ICMR BULLETIN VOL.11-No.-9-SEPTEMBER-1981.pdf
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Vol. 11 No. 9
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September, 1981
CURRENT STATUS OF INHIBIN
Although much has been said about the
need for a chemical contraceptive for the
male, so far, not a single systemic male
contraceptive has been developed and brought
to the stage _ of serious clinical testing.
Initially efforts were directed at inter
ruption of spermatogenesis by chemical means.
However, studies were hindered by the limited
knowledge of
male reproductive physiology
and during the subsequent 30 years,
the
development of a male contraceptive did not
advance beyond the confines of research lab
oratories.
Production of an azoospermic state would
undoubtedly be the most effective means of
male contraception. In several species, it is
well documented that FSH regulates germinal
cell function, while LH is concerned with
testosterone production. Any agent which could
selectively, inhibit spermatogenesis by supp
ression of FSH without affecting androgen
secretion from the testis would have potential
use for male contraception.
‘ Inhibin’ is a
peptidic factor of gonadal origin that select
ively and specifically lowers the rate of
secretion of FSH.
In simple terms, two pituitary gonado
tropins act on the testis, FSH stimulates the
seminiferous tubules while LH stimulates the
Leydig cells; the Leydig cells produce andro
gens (particularly testosterone) which control
LH secretion by negative feedback and the
seminiferous tubules produce inhibin which
controls FSH secretion
by negative feedback.
Evidence for Existence of Inhibin:
Circulating levels of FSH and LH have
been found to be altered in certain pathologic
conditions of the human testis.
Serum FSH
levels are elevated without altering LH and
testosterone levels in patients with distur
bance of spermatogenesis and normal Leydig
cell function1*2.
It was found that a subs
tance produced by the seminiferous tubules
was involved in the regulation of. FSH secre
tion.
The existence of such a substance was
first postulated by McCullagh3, who named it
‘Inhibin’. Evidence for inhibin activity in
human seminal plasma was shown by Franchimont4. Since FSH inhibiting activity was found
in seminal plasma of normal and oligosvermic
men, but not in the semen of azoospermic
patients, spermatids were postulated to be
the most likely source of inhibin1*
Other
investigators
could
not
demonstrate a
correlation between specific
spermato genic
stages and serum FSH levels, which suggested
that the Sertoli cells could be the cellular
source of inhibin5.
In the rat, it has been
demonstrated that Sertoli cells in culture
secrete a factor - Sertoli cell factor (SCF) which selectively suppresses FSH production by
cultured pituitary cells6. However, no direct
evidence for secretion of an FSH inhibit
ing substance by the human Sertoli cell is
available.
Interest in inhibin as a potential male
contraceptive was stimulated by virtue of its
Division of Publication & Information, ICMR, New Delhi-110 029
ability to suppress FSH secretion.
However,
reports over the last decade have merely
established the- existence of inhibin
in
gonadai secretion of several species without
making any spectacular studies on its chemis
try or physiology.
Interest in its physiological and bio
chemical properties nas resulted in the need
for purification of inhibin in sufficient
quantity.
Various investigators have used
different sources for
inhibin extraction
(Table).
SOUFCES OF INHIBIN
Sources
Molecular weight
Human seminal plasma
<5,000
Franchimont et at1
19,000
Thakur et at8
Ovine rete testis fluid
<5,000 to >160,000
Ovine testicular lymph
90,000
30,000
Bovine seminal plasma
Ram testis
15,000 to 19,000
1,500
A variety of extraction methods have been
used including some which might be expected to
lead to a loss of low molecular weight subs
tances, e.g. ethanol precipitation, charcoal
treatment.
The evidence from a number of
groups that inhibin like activity is destroyed
by heat and by enzymatic treatment with tryp
sin, pepsin or pronase, has established that
the material is peptide or proteinaceous in
nature. There is, however, considerable con
fusion regarding the molecular weight of the
active material even when prepared by different investigators from the same starting
material.
This discrepancy has been attri
buted to polymer formation, association with
a carrier protein or purification artifacts.
Measurement of Inhibin:
The evidence for the existence of in
hibin which has been disputed since several
investigators have been able to reverse com
pletely the changes in gonadotropin levels
which follow castration by the administration
of steroids combinations, rests on various
assay methods.
Given the definition, the
obvious response metameter for any biological
106
Investigators
)
)
)
)
)
Baker et at^
Chari et at^
Sairam et alll
Sheth et at^2
assay is the reduction in FSH secretion, which
can be measured indirectly by the assessment
of a biological effect of FSH or directly by
FSH assay.
The major problem with inhibin
assays is that of specificity; all the bio
assays are based on suppression of FSH secre
tion and/or synthesis, which can be affected
by a variety of cell toxins, or by other bio
logically active substances.
Using a homogeneous inhibin preparation
of human origin (human seminal
plasma) a
sensitive and specific radioimmunoassay for
inhibin13 has been developed at the Institute
for Research in Reproduction (IRR), Bombay.
None of the purified hormones tested, such as
LH, FSH and prolactin from different species
showed any cross-reaction in this radioimmuno
assay. Steroid hormones such as testosterone,
dihydrotestosterone, estradiol 17B and pro
gesterone did not interfere with the assay.
Using this radioimmunoassay, inhibin has been
measured in various biological fluids and
tissues. Normospermic semen is found to con
tain significantly higher levels of inhibin
than the oligospermic semen11*. Similar results
have been reported with bioassay
(Berger
et at. Personal communication).
Physiological Characterization of Inhibin:
The half-life of inhibin is much shorter
in adult rats than in immature rats (2.4 min
for adult rats and 90 min for immature rats).
The metabolic clearance rate of inhibin is
greater in adult rats as compared to the
immature rats (0.12 ml/min in adult rats and
0.019 ml/min in immature rats).
The slower
clearance of inhibin in immature rats leads to
longer half-life.
The levels of inhibin are much higher in
immature rats as compared to adult rats15.
Inhibition of FSH binding was more pronounced
in immature rats as compared to the mature
rat testicular receptor preparation at the
same dose of inhibin 6. The role of FSH in
spermatogenesis indicates that the initiation
of spermatogenesis at puberty and also the
reinitiation of spermatogenic cycle in re
gressed testis requires the presence of FSH.
It appears that inhibin may control puberty
in men.
Half-life studies were carried out in
castrated and testosterone treated groups with
labelled inhibin.
The half-life is prolonged
in these two groups as compared to the intact
rats. It is tempting to speculate that there
are some testicular factors which shorten the
half-life or affect the metabolism of inhibin.
It is also postulated that inhibin acts in
synergism with androgens in the male and
estrogens in the female17. If so, then inhibin
alone or in combination with steroids, can be
used to bring about 80-90 per cent suppression
of FSH.
Site of Action:
The in vitro evidence, from a number of
laboratories, indicates that inhibin prepara
tions exert suppressive effects on FSH secre
tion by cultured pituitary cells of rats,
while limited experiments in sheep also indi
cate that a major effect of inhibin contri
buting to its in vivo effect of lowering FSH
levels,is a direct one on the pituitary gland.
The effect is seen on basal release and cell
content as well as on LHRH stimulated release.
Action at the testicular level has been
postulated by Franchimont and co-workers7.
IRR has provided
the first
experimental
evidence of this by demonstrating that inhibin
inhibits the binding of FSH to its testicular
receptor16* 18,19.
Simultaneous incubation of inhibin and
ovine FSH (6 x 10-8M) with testicular slices
resulted in reduction of cAMP accumulation as
compared to controls.
When testicular slices
were incubated with inhibin the phospho
diesterase (PDE) activity was increased in a
dose related manner.
This suggests that
the observed inhibition of cAMP accumulation
is due to reduction in adenyl cyclase and/or
increase in PDE activity.
When inhibin was
incubated in the presence of labelled hCG with
testicular receptor, inhibin was unable to
inhibit the binding of hCG to its receptor.
This suggests that the observed inhibition
with inhibin is specific to FSH.
From the
contraceptive point of view, this is advanta
geous because inhibin does not affect the LH
action at the testicular level.
Recently,
Daume stat.,20 have also reported the
presence of a low molecular weight factor from
human follicular fluid that inhibits in vitro
binding of FSH to ovarian granulosa cells.
Other mechanisms of action may also be
operating.
Inhibin preparations have been
found to decrease the endogenous LHRH content
of isolated rat hypothalami after short term
incubation7.
Similarly, studies at the IRR
have shown suppression of hypothalamic LHRH
content on administration of low molecular
weight testicular
inhibin preparation to
castrated adult male rats.
It may be difficult to correlate the
effects on hypothalamic LHRH with the observed
specificity of inhibin action on FSH release
and the question must again be raised that
more than one gonadal peptide is involved in
gonadotropin regulation or that the hypothala
mic effects represent a non-specific toxic
effect.
However, in a number of experimental
situations, it has been shown that effects on
LH release are earlier and of shorter duration
than effects on FSH. This would be consistent
with acute effects on LHRH with more prolonged
effects on FSH synthesis.
Site of Synthesis:
The probable cell type responsible for
inhibin production
still remains contro
versial. The general view is that the Sertoli
cells are the probable site of its synthesis
in the testis.
It has also been demonstrated
in in vitro culture of pituitary and Sertoli
cells21*22.
However, Krenger et al. 23, have
suggested that Sertoli cells in association
with germ cells are responsible for inhibin
production. Experimental evidence shows high
amounts of bioactive and immunoreactive in-
107
hibin in enriched spermatid fraction obtained
from rat testis extract (Sheth et al.3 unpub
lished data). Recently, in vitro localization
of inibin in spermatid region has been shown
by immunofluorescent technique (Arbatti et at,
unpublished observations).
Role of Inhibin in Female:
Using identical extraction procedures,
inhibin has been purified from sheep testis
and ovaries19.
Daily treatment of adult female or
immature male rats for periods longer than
5 days did not result in prolonged suppression
of circulating FSH concentrations, LH levels
were significantly increased.
Female rats
showed cyclic vaginal smear changes and normal
ovulation; in the male rat, testis weight and
number of spermatogenic cells were reduced.
It was, therefore, concluded that testicular
and ovarian inhibin-like activities are
similar.
Injections of follicular fluid into
male and female rats caused similar effects on
FSH and LH. The effect of follicular fluid in
unilateral ovariectomized animals suggests
that inhibin could play a role in the short
term regulation of the number of developing
follicles in the ovary.
Injection of folli
cular fluid into male rats caused a probably
transient
impairment
of spermatogenesis
through an initial suppression of FSH.
Erickson and Hsueh24 have demonstrated
that granulosa cell cultures secrete inhibinlike
material
which acts directly upon
cultured pituitary cells.
In view of the
preclusive relationship that FSH has on
granulosa cells, it would be physiologically
meaningful for the specific target cell to
provide a selective signal in the modulation
of its trophic (FSH) secretion.
Thus, an
exclusive feedback control system of granulosa
cell - FSH axis may operate through follicular
inhibin.
An inverse correlation between FSH
inhibiting activity and follicular size has
been observed25.
Depalo and associates26,
employing an in vitro bioassay, used ovarian
venous plasma to estimate inhibin activity.
Similarities of inhibin of testicular and
ovarian origin have been recently estab
lished19. It is not surprising that antigenic
similarities were observed between ’female
inhibin1 and human
seminal plasma
’male
inhibin’ as reflected by the parallel dose
responses
obtained
in radioimmunoassay
developed for human seminal plasma inhibin.
Inhibin levels showed cyclic variations during
menstrual cycles.
In all the six cycles
108
studied, an inhibin peak was observed during
late follicular phase, 2 to 3 days earlier
than the LH peak27.
The role of FSH in the female is more
pronounced as compared to the male. Prelimi
nary studies from IRR, Bombay, on inhibin
revealed that it has an anti-inplantation
effect in mice.
It would thus appear that
inhibin may be potentially useful for female
contraception.
From the reported studies at IRR, Bombay,
and other laboratories,
it appears
that
inhibin perhaps exist in multiple forms.
Since inhibin is a native hormone, toxicity
will be minimal.
From various studies, it
has been shown that inhibin is capable of
suppressing only 70-80 per cent of the FSH
secretion. It is possible that inhibin and a
steroid (estrogen or androgen) may be involved
in the physiological regulation of FSH.
To
suppress completely circulating FSH levels,
administration of either a combination of
inhibin and a steroid or a powerful synthetic
analogue of inhibin may be necessary. Studies
at IRR, Bombay, have demonstrated the identi
cal characteristics of male and female
inhibin.
Preliminary studies indicate the
anti-implantational activity of inhibin.
Studies clearly indicate that inhibin has
a very short half-life in the adult animal,
which may be due to the involvement of other
testicular factors. Apart from its possible
contraceptive application in the male or the
female, inhibin can help to understand the
basic role of FSH in reproductive disorders.
The availability of synthetic inhibin would
certainly solve some of the existing contro
versies in this field.
References:
1.
De Krester, D.M., Burger, H.G., Fortune,
D., Hudson, B., Long, A.R., Paulsen, C.A.
and Taft, H.P. Hormonal, histological and
chromosomal studies in adult males with
testicular disorders.
J Clin Endocrinol,
Metab 35: 392, 1972.
2.
Franchimont, P. Human gonadotrophin secre
tion. J R Cott Physicians 6: 282, 1972.
3. McCallagh, D.R.
Dual endocrine activity
of testis. Science 76: 19, 1932.
4.
Franchimont, P., Millet, D., Venderely,E.,
Legross, J.J. and Nelter, A. Relationship
between spermatogenesis and serum gonado-
trophin levels in azoospermia and oligo
spermia.
J Clin Endocrinol Metab 34:
1003, 1972.
5.
Van Thiel, D.H., Sher ins, J. R., Myers, G.H.
and De Vita, V.T. Evidence for a specific
seminiferous
tubule
factor affecting
follicle stimulating hormone secretion in
man. J Clin Invest 51: 1009, 1972.
6.
Steinberger, A. and Steinberger, E.
In
hibition of FSH by a Sertoli cell factor
in vitro.
In: The Testis in Normal and
Infertile Men, eds.
P. Troen and H P.
Nankins, p. 271, Raven Press, New York,
1977.
7.
Franchimont, P., Demoulin,A., VerstraelenProyard, J.,
Hazee-Hagelstein,
M.T.,
Walton, J.S. and Waiter, G.M.H.
Nature
and mechanism of action of
inhibin:
Perspectives in regulation of male ferti
lity. Int J Androl (Suppl) 2: 69, 1978.
8.
9.
Thakur, A.N., Vaze, A. Y., Dattatreyamurthy,
B., Arbatti, N.J. and Sheth, A.R.
Isola
tion and characterization of" inhibin from
human seminal plasma.
Indian J Expt Biol
16: 854, 1978.
Baker, H.W.C., Bremner,W.J., Burger, H.G.,
De Kretser, D.M.,
Dulmanis, A.,
Eddie,
L.W., Hudson, B., Keogh, N.J., Lee, V.W.K.
and Rennie, G.C.
Testicular control of
FSH secretion.
Recent Prog Horm Res 32:
329, 1976.
10. Chari, S., Duraiswami, S. and Franchimont,
P.
Isolation and characterization of
inhibin from bull seminal plasma.
Acta
Endocrinol 87: 434, 1978.
11. Sairam, M.R., Ranganathan, M.R.,
Ramasharma, K. and Lamo th, P.
Isolation and
characterization
of a
bovine seminal
plasma protein inhibiting pituitary FSH
secretion.
Mol Cell Endocrinol 22: 231,
1981.
12. Sheth, A.R., Joshi, L.R., Moodbidri, S.B.
and Rao, S.S.
Characterization of a
gonadal factor involved in the control of
FSH secretion. J Reprod Fertil (Suppl) 26:
71, 1979.
13. Vaze, A.Y., Thakur, A.N. and Sheth, A.R.
Development of radioimmunoassay for human
seminal plasma inhibin.
J Reprod Fertil
(Suppl) 26: 135, 1979.
14. Asch, R.H., Vaze, A.Y., Thakur, A.N. and
Sheth, A.R.
Concentrations of immuno
reactive inhibin in seminal plasma and
serum from normospermic,
oligospermic,
vasectomized, Klinefelters’ syndrome and
Sertoli-cell only syndrome subjects. J
Androl 1: 252, 1980.
15. Sheth, A.R., Vaze, A.Y. and Thakur, A.N.
Development of a radioimmunoassay for
human seminal plasma inhibin and its
application for physiological studies.
In: Recent Advances in Reproduction and
Regulation of Fertility, ed. G.P. Talwar,
Elsevier/North-Holland Biochemical Press,
Amsterdam, 1979.
16. Vijayalakshmi, S., Moodbidri, S.B., Bandivdekar, A H. and Sheth, A.R.
Modulation
of FSH action by inhibin. Arch Androl 5:
231, 1980.
17. Hopkinson, C.R.N., Fritze, F., Chari, S.,
Stum, G. and Hirschhauser, C. Interaction
between testosterone and inhibin prepara*tion in male rats. IRCS Med Sci 5: 83,
1977.
.18 . Moodbidri,S.B., Joshi,L.R. and Sheth, A.R.
The mechanism of action of low molecular
weight inhibin from rat testis.
Indian
J. Expt Biol 18: 100, 1980.
19. Vijayalakshmi, S,,
Bandivdekar, A.H.,
Joshi, L.R., Moodbidri, S.B. and Sheth,
A.R.
Isolation and characterization of
ovine testicular and ovarian inhibin.
Arch Androl 5: 179, 1980.
20. Daume, E., Chari, S,, Hopkinson, C.R.N.,
Sturn,G. and Hirschhauser, C.
Existence
of inhibin activity in human follicular
fluid. Acta Endocrinol (Suppl) (Copenh)
212: 85, 1979,
21. Steinberger, A. and Steinberger, E. Secre
tion of a FSH inhibiting factor by cul
tured Sertoli cells. Endocrinology 99:
918, 1976.
22. De Jong, F.H., Welschen, R., Hermans,W.P.,
Smith, S.D. and
Van der Molen, H.J.
Effects of factors from ovarian follicular
fluid and Sertoli cell culture medium on
in vivo and in vitro release of pituitary
gonadotrophins in the rat: An evaluation
of systems for the assay of inhibin.
Reprod Fert (Suppl) 26: 47, 1979.
23. Krueger, P.M., Hodgen, G.D. and Sherins,
R.J.
New evidence for the role of the
Sertoli cell and spermatogenesis in feed
back control of FSH secretion in male
rats. Endocrinology 95: 955, 1974.
24. Erickson, G.F. and Hsueh, A.J.W. Secretion
of inhibin by rat granulosa cells in
vitro. Endocrinology 103: 1960, 1978.
25. Lorenzen,J.R., Channing,C.P. and Schwartz,
N.B.
Partial characterization of FSH
suppressing activity (folliculastalin) in
porcine follicular fluid using the metaestrous rat as an in vivo bioassay model.
Biol Reprod 19: 635, 1978.
26. Depalo, L.V.,
Shander, P.,
Wise, P.M.,
Barrac longer, C.A.
and Channing, C.P.
Identification of inhibin like activity in
ovarian venous plasma of rats during the
estrous cycle.
Endocrinology 105: 647,
1979.
27. Sheth, A.R., Vaze, A.Y., Thakur, A.N.,
Arbatti, N.J., Hazari, K., Mehta, S. and
Joshi, J. Inhibin levels in women during
the menstrual cycle. Indian J Med. Res (In
Press).
contributed by Dr. A.R.Sheth and colleagues of
the Institute for Research in Reproduction,
Bombay.
ABSTRACTS
Some Research Projects completed recently
Role of hypersensitivity in intestinal/hepatic
amoebiasis
indicating thereby that inhibition did not
reflect the humoral antibody response.
With a view to assess the role of speci
fic amoebic and/or non-specific prior sensiti
zation on the outcome of intestinal/hepatic
amoebiasis this study was undertaken.
V.K. Vinayak
Department of Experimental
Medicine
Postgraduate Institute of
Medical Education and
Research
Chandigarh.
All the animals studied, became hyper
sensitive with monoaxenic amoebic antigen and
developed fulminating caecal ulcers while
approximately 13 per cent animals developed
hepatic abscesses.
Thirty eight per cent of
the animals developed granulomatous lesions as
well. Animals sensitized with axenic amoebic
antigen showed protection in 30 per cent of
animals; caecal lesions were seen in 70 per
cent and hepatic lesions in 7 per cent ani
mals.
It seemed that axenic amoebic antigen
could protect as well as make some of the
animals hypersensitive depending upon the
concentration of functional antigenic deter
minants. Animals Sensitized with live amoebae
developed lesions only in 20-30 per cent
animals indicating that live amoebae act as
better immunogen.
Circulating antibodies
seemed to have no role in protection as the
animals with lesions had as high antibody
titres as the
infected animals without
lesions.
Cell mediated immune response was
altered • in animals with amoebic Liver
abscess.
In human studies analysis of the relationship between serum antibodies and the
degree of macrophage inhibition did not show
much correlation between the two parameters,
110
Publications:
1.
Jain, P., Sawhney, S. and Vinayak, V.K.
Experimental amoebic infection in animals
immunized with low grade amoebic infec
tion. Trans R
Soc Trop Med Hyg 74:
347, 1980.
2.
Vinayak, V.K., Jain, P., Gupta,B., Kaushik,
S.P. and Sawhney, S. Cellular and humoral
immune response in amoebic patients. Trop
Geogr Med 32: 298, 1980.
3.
Jain, P., Sawhney, S. and Vinayak, V.K.
Effect of specific and non-specific prior
sensitization on the outcome of amoebic
infection. Trans R
Soe Trop Med Hyg
75; 25, 1981.
Effect of lipid composition on the virulence
of Mycobacterium tuberculosis
The alterations in the lipid composition
in response to low temperature and fatty acid
supplementation in saprophytic avirulent and
virulent
strains of M. tuberculosis were
studied, if was observed that total lipids
(total phospholipids as well as the glyce
rides) increase at lower growth temperature in
M. smegmatis 607 and M. phtei whereas in the
pathogenic strain H37RV, total phospholipids
were found to decrease.
Among the individual
phospholipid components, a general trend of
decrease in phosphatidylinosoto 1mannosides and
increase in phosphatidyl ethanolamine was
observed. In addition, cardiolipin was found
to increase significantly in M. tuberculosis
H37R.. Unsaturated fatty acids showed a marked
increase at low temperature. The supplementa
tion of exogenous fatty acids produced complex
changes with different fatty acids in differ
ent strains.
No significant changes were
observed in lipids of BCG strain (avirulent)
under these conditions.
Comparison of human strain of H37Rv (iso
lated from human sputum)
with the stock
vulture (NCTC London), revealed the presence
of high contents of total lipids as well as
total phospholipids in virulent human strains
as compared to NCTC strain.
It was also
interesting to note that the total lipids of
the human H37Rv strains increased significant
ly when the cells were grown in media supple
mented with exogenous fatty acids.
Furthermore, virulence was observed to be
related with the lipid composition of cells to
some extent.
M. tuberculosis H37RV cells
grown in the presence of palmitoleic acid were
found to be more virulent than the control
cells.
G. K. Khul l er
Department of Biochemistry
Postgraduate Institute of
Medical Education and
Research
Chandigarh.
Publication:
Taneja, R., Malik, U. and Khuller, G.K. Effect
of growth temperature on the lipid composition
of Mycobacterium smegmatis A ICC 607.
J Gen
Microbiol 113: 413, 1979.
SUMMARY OF THE BASANTI DEVI AMIR CHAND PRIZE (1981) ORATION
Dr. N.C. Nayak, Professor of Pathology, All
India Institute of Medical Sciences, New Delhi,
delivered the Basanti Devi Amir Chand Prize
(1981) Oration on ‘Immunological Aspects of
Viral Hepatitis with Particular Reference to
Immune Response against Liver Specific Pro
tein1 at the Indian Council of Medical Research, New Delhi, on September 10, 1981.
Infections with hepatitis viruses are
responsible for the majority of acute and
chronic hepatitis - health problems of consi
derable magnitude in India and the South-East
Asia region.
These viruses do not appear to
be cytopathic and the mechanism of hepato
cellular injury
induced by them remains
unknown.
Immune reactions against the virus
or against altered or normal cellular consti
tuents subsequent to infection have been
considered to have important bearing on the
pathogenesis of hepatitis.
An attempt was made at the AIIMS, New
Delhi,
to explore the
latter facet by
investigating the role of immune responses
against the specific liver cell
membrane
protein (LSP) in human patients and in mice.
Antibodies to LSP circulating in blood as
well as fixed on hepatocytes can be demon
strated not only in patients with acute and
chronic hepatitis but also in those with some
other liver diseases.
Development of these
antibodies appears to result from rather than
causing liver injury.
High lymphocyte mediated
hepatocytotoxicity is present in the first 3 weeks of
jaundice due to acute hepatitis. The values
touch control levels at around 6 weeks or
later. Some patients including a few going on
to chronicity show resurgence of cytotoxicity.
Mice immunised with rat LSP
(1 or 2
doses) manifest both humoral and cellular
immune response against this protein as
measured by immunofluorescence and cytotoxi
city (51Cr release and morphologic cell
loss) respectively. These reactions seem to
have two humps, a small one at 3 to 4 weeks
and a larger at 14 to 18 weeks.
Histologi
cally, there is lymphocytic infiltration in
the liver parallel in intensity to the immune
reactions,
but no significant hepatocytic
damage is seen.
It is concluded that even though LSP is
actively immunogenic there is, as yet, no
evidence to indicate a significant in vivo
cyto pathogenic
role of anti LSP immune
reactions in man or mouse.
ICMR NEWS
Advisory Group/Study Group meetings:
The following ICMR Advisory Group/Study
Group meetings were held at the Council during
the month:
Advisory Group on Mater
nal and Child Health
September 22-24,
1981
Study Group on Diarrhoeal
Diseases and Acute Res
piratory Diseases
September 28-29,
1981
***
***
Dr. S.C. Pal, Director, National Insti
tute of Cholera and Enteric Dis eases,Calcutta,
participated in the Steering Committee meeting
of the WHO Scientific Working Group on Bacte
rial Enteric Infections held at Geneva between
September 2-4, 1981.
He also participated in
the International Symposium on Recent Advances
in Enteric Infections held at Brugge, Belgium,
from September 8-11, 1981.
Dr. B.C. Deb, Deputy Director, National
Institute of Cholera and Enteric Diseases,
Calcutta, participated in a training course
on Health Services Research Evaluation with
emphasis on Diarrhoeal Diseases Control, held
at Dacca, Bangladesh, between September 7-18,
1981.
Dr. V. Ramalingaswami, Director-General,
Indian Council of Medical Research, New Delhi,
inaugurated the XII Biennial Conference of the
Indian Association of Leprologists at Agra on
September 9, 1981.
Dr. S.P. Tripathy, Director, Tuberculosis
Research Centre, Madras, participated in the
meeting of the WHO/IUAT Joint Study Group on
Tuberculosis Control at Geneva between Septem
ber 14-18, 1981.
Dr. V. Ramalingaswami participated in the
meeting of the Scientific and Technical Advi
sory Committee of the WHO Special Programme
for Research and Training in Tropical Diseases
at Geneva between September 15-19, 1981.
He
also participated in the meeting of the WHO
ACMR Sub-Committee on Cancer, between Septem
ber 28-30, 1981.
Dr. Usha K. Luthra,
Senior Deputy
Director-General, ICMR, visited various centres
of Cytology/Cytopathology in the USSR between
September 15-22, 1981.
New Appointments:
Dr. A.J. Baxi, Assistant Director, Blood
Group Reference Centre, Bombay,
has been
appointed as Deputy Director at the Centre.
ICMR AIDED SYMPOSIA/SEMINARS/WORKSHOPS/CONFERENCES
Date
Sympos ium/Seminar/Workshop/
Conference
Workshop on Scientific
Morphosciences.
Methods
in
UNESCO-IBRO Workshop on New Tech
niques in Neurosciences with special
reference to the Neurophysiology of
Higher Nervous Activity.
Symposium on
Society.
112
Science,Technology and
Institution/Department
August/September, 1981
Department of Anatomy,
Maulana Azad
Medical
College, New Delhi (Delhi
Association of Morpho
logical Sciences).
August 30 September 12, 1981
National
Institute of
Mental Health and Neurosciences, Bangalore.
September 7-12, 1981
Bombay
(Indian ' Women
Scientists Association).
Symposium/ Seminar/Workshop/
Conference
Date
Institution/Department
September 9-12, 1983
Central Jalma Institute
for Leprosy, Agra (Indian
Association of Leprologists).
September 19, 1981
Department of Gastro
enterology, Medical Coll
ege, Trivandrum (Society
of Gastrointestinal Endo
scopy of India).
September 25-27, 1981
Medical College, Nagpur.
Conference on Drug
September 28 October 1, 1981
and
October 3, 1981
Department of Psychiatry,
All India Institute of
Medical
Sciences,
New
Delhi.
JN Medical College, Ali
garh Muslim University,
Aligarh.
Symposium on Leprosy,
Workshop on Gastrointestinal
scopy.
Endo-
Seminar on Involvement of Medical
Colieges/Institutions in the Deli
very of Comprehensive Health Care
to the Rural Community.
Third National
Abuse.
Symposium on Fertility Control
Teratology.
Symposium on Regulation of Fertility.
October 3-5, 1981
School of Life Sciences,
University of Hyderabad,
Hyderabad
(Endocrine
Society of India).
National Symposium on
Corneal Disasters.
and
October 12-17, 1981
Dr.Rajendra Prasad Centre
for Ophthalmic Sciences,
New Delhi.
4th All India Congress of Cytology
and Genetics, 1981.
October 17-21, 1981
University of Bhagalpur,
First National Conference on Environ
mental Biopollution.
October 19-21, 1981
Marathwada
University,
Aurangabad (Indian Aerobiological Society).
Seminar-cum-Work shop in Surgery for
Postgraduates and Surgeons.
October 31 November 1, 1981
All India Institute of
Medical Sciences,
New
De Ihi.
Second Workshop on in vitro Cultivat ion of Erythrocytic Forms of P.
faiciparwn and Preparation of Antigens for Serology of Malaria.
November 2-15, 1981
Department of Microbiology, St. John’s Medical
College, Bangalore.
Conference on Industrial and Environ
mental Toxicology.
November 6-7, 1981
Industrial Toxicology Re
search Centre,
Lucknow
(Society of Toxicology,
India).
Cataract
Bhagalpur.
113
Date
Institution/Department
Symposium on the Heart.
November 6-8, 1981
Sree
Chitra
Tirunal
Institute for Medical
Sciences and Technology,
Trivandrum (Indian Aca
demy of Sciences).
Satellite Congress on Diabetes in the
Young.
November 21-22, 1981
Ootacamund(The Coimbatore
Branch of the Diabetes
Association of India).
Symposium on Tropical Immunology.
November 23, 1981
Cancer Research
Insti
tute,
Tata
Memorial
Centre, Bombay
(Indian
Immunology Society).
International
Symposium on Early
Diagnosis and Prevention of Disabi
lity.
November 26-28, 1981
Department of Pediatrics,
B.J.
Medical College,
Pune (Indian Society of
Human Genetics).
Seminar on Teaching and Research
Medical Sociology in India.
November, 1981
University
Jodhpur.
International Symposium on Incidence
of Infections and Chronic Diseases Geographical Perspectives.
December 1-4, 1981
Department of Geography,
University of Madras,
Madras.
National Seminar on Health for All A National Dialogue on Operational
Aspects of Comprehensive Primary
Health Care and Rural Development.
December 12-13, 1981
Birla Institute of Medi
cal Research, Gwalior.
International
Conference on the
Applications of Mossbauer Effect.
December 14-18, 1981
Jaipur (Indian National
Science Academy).
Symposia on Nutrition § Environment
and Current Concepts in Membrane
Bio chemi stry.
December 21-24, 1981
Department of
Biochem
istry, University Coll
ege of Sciences,Calcutta.
30th Annual Conference of the Anato
mical Society of India.
December 28-30, 1981
Gandhi Medical College,
Bhopal.
International Workshop on Nutrition
and the Development of the Child.
January 8-15, 1982
Department of Biochemis
try, M.S.
University,
Baroda.
Workshop on Evaluation of Mutagenic
Potential of Environmental Agents:
Microbial and Mammalian Systems.
February 15-19, 1982
Division of Biochemistry
and
Food Technology,
Bhabha Atomic
Research
Centre, Bombay (Environ
mental Mutagen Society of
India).
Symposium/ Seminar/Work shop/
Conference
114
in
of Jodhpur,
PROGRAMME OF SCIENTIFIC LECTURES AT THE
INDIAN COUNCIL OF MEDICAL RESEARCH, NEW DELHI
Speaker
Topic
Date
10.9.1981
Immunological Aspects of Viral Hepatitis
with particular reference to Immune Response
against Liver Specific Protein
(Basanti Devi Amir Chand Prize Oration,1981)
Dr. N.C. Nayak
New Delhi
24.9.1981
Influenza,the Perennial Scourge: A Challenge
to Mankind by a Changing Virus
(Dr. J.B. Srivastav Oration, 1981)
Dr. B. Lalitha
Rao,
Pune.
29.10.1981
Evaluation of Methods for Fertility Regulation
Dr. K. Prema,
Hyderabad.
(Kshanika Oration Award, 1980)
COUNCIL’S TRAINING PROGRAMMES FOR 1981
Leprosy:
At the Central J al ma Institute for Lep
rosy, Agra:
Training course in Leprosy for medical
officers: (February 15 to March 28, 1981,
and August 31 to October 14, 1981).
(2)
M.Sc. (Applied Nutrition) course: (June 1,
1981 to February 28, 1982).
(3)
Annual certificate course in Public
Health Nutrition:(October/November,1981).
(4)
Annual certificate course in Nutrition:
(December 1, 1981 to February 28, 1982).
Virology:
At the National
Pune:
(1)
Institute of Virology,
Haematology:
At the Blood Group Reference Centre,
Bombay:
Diploma course in Medical Virology of
Poona University: (July, 1981).
in
(1)
A certificate course in Blood Banking
Technology and Basic Haematology for
medical officers: (February 1 to March
15, 1981).
At the National Institute of Nutrition,
Hyderabad:
(2)
Training course in Blood Banking Methodo
logy for technicians: (May 12-26, 1981).
Annual certificate course in Endocrino
logical Techniques and their Application:
(August to September, 1981).
Mental Health:
(2) * Workshop
India.
on Japanese
Encephalitis
Endocrinology:
Nutrition;
At the National Institute of Nutrition,
Hyderabad:
At Bangalore, Chandigarh and Delhi:
Training course on Extension of Mental
Health Services in the Community: (July,
18 - August 29, 1981).
Occupational Health:
(1) . Annual certificate course in Human Nutri
tion for teachers from Agricultural Uni
versities:.. (June/July, 1981).
At the National Institute of Occupational
Health, Ahmedabad:
NIOH/WHO Training Course on Air Pollution
and Health: (December 1-10, 1981).
Cnclogy:
At the Cancer Research Institute,
Memorial Centre, Bombay:
Tats
Training course on Carcinogenicity, Muta
genicity and Teratogenicity:
December,
1981).
Clinical Pharmacology:
*At the Department of Pharmacology, Seth
G.S. Medical College, Bombay.
(1)
Laboratory Animal Supervisors Training
Course: (January 2 to March 31, 1981).
(2)
Laboratory Animal Technicians Training
Course: (August 1 to September 30, 1981).
COURSES FOR TALENT SEARCH SCHEME FELLOWS
Cell-Biology and Cyto-Genetics:
At the
Indian Institute of Science,
Bangalore: (March, 1981).
Use of Radioisotopes in Medicine:
At the National Institute
Hyderabad: (July, 1981).
Biostatistics:
At the Institute for Research in Medical
Statistics, New Delhi:
(1)
Certificate course in Planning and Evalu
ation of Health Programmes: (April,1981).
(2)
Diploma course in Biostatistics: (Septem
ber, 1981).
(3)
Certificate course in Orientation to Biostatistics: (September, 1981).
(4)
Certificate course in Statistical Tech
niques in Medical Research: (January,
1982).
of Nutrition,
4
Immunological Techniques:
At the Central Jal ma Institute for Lep
rosy, Agra: (November, 1981).
Haematological Techniques:
*At the Department of Pathology, Christian
Medical College, Vellore.
Clinical Endocrinology:
*At the Institute for Research in Reproduct ion, Bombay.
Laboratory Animal Technology:
At the National Institute of Nutrition,
Hyderabad:
*Dates to be announced later.
SOME ICMR PUBLICATIONS
Price
Rs.
Menus for Low-Cost Balanced Diets and School Lunch Programmes suitable for
South India (1959), Third Edition 1977, Reprinted 1978
Menus for Low-Cost Balanced Diets and School Lunch Programmes suitable for
North India (1959), Second Edition 1977
Nutrition for Mother and Child (1962), Third Edition 1978
Some Common Indian Recipes and Their Nutritive Value (1964), Fourth Edition 1977,
Reprinted 1980
Nutritive Value of Indian Foods (1971), Reprinted 1981
Dietary Allowances for Indians (1971), Reprinted 1980
Diet Atlas of India (1971)
Nutrition Atlas of India (1971)
116
1.50
1.50
4.50
6.50
9.00
5.50
8.00
10.50
Price
Rs.
Atlas of Histopathology of Liver: Hepatitis and Cirrhosis (1974)
Studies on Pre-School Children (1974), Reprinted 1977
Studies on Weaning and Supplementary Foods (1974), Reprinted 1977
Medicinal Plants of India Vol. 1 (1976)
Research in Malaria - An Outline (1977)
Health Hazards of Mycotoxins in India (1978)
Japanese Encephalitis in India, Revised Edition 1980
Recommended Dietary Intakes for Indians (1981)
10.00
3.50
4.00
30.00
Gratis
5.00
5.00
4.00
These publications are available on prepayment of cost by cheque or postal order (postal
charges will be extra) drawn in favour of the Director-General, Indian Council of Medical
Research, New Delhi.
Money orders are not acceptable. All correspondence in this regard
should be addressed to the Chief, Division of Publication and Information, Indian Council
of Medical Research, Post Box 4508, Ansari Nagar, New Delhi-110029.
TISSUE CULTURE
A Workshop on "Animal Cell Culture and Differentiation” (November
20 - December 15, 1981) will be held at the Department of Zoology,
University of Poona,Pune, in collaboration with the National Institute
of Virology, Pune.
Prof. S.P. Modak, Department of Zoology, University of Poona,
Pune-411007, may be contacted for details on or before 3rd October,
1981.
117
RADIOIMMUNOASSAY KITS AVAILABLE
The reagents listed below (procured under the Indo-US Sub-Commission
Programme) are available at the Reagent Bank, Institute for Research in Repro
duction, Bombay, in limited quantities, free of charge, to qualified investi
gators for research and diagnostic purposes only:
RIA Kits:
Human
Rat
Subhuman
h TSH
h LH
h FSH
h GH
h CG
B hCG
r LH
primate pregnancy
test kits
r FSH
r Prol
Supplies of these materials - may be obtained on request from the Director,
Institute for Research in Reproduction, Parel, Bombay-400 012, with a copy
endorsed to the Director-General, ICMR, Ansari Nagar, New Delhi-110029.
The
request must include: (i) A description of the proposed use of the materials,
to justify the kind and amount of request; (ii) experience with RIA; and (iii) a
progress report and/or recent publication of results from materials previously
supplied by the Reagent Bank, if any.
Only one vial, or one kit (one kit = one vial of antigen (50 ug) and one
vial of antiserum) of the reagents, animal or human for RIA will be supplied at
a time. Request for larger amounts may also be considered.
EDITORIAL BOARD
Chairman
Members
Dr. V. Ramalingaswami
Director-General
Chief, Publications
Dr. S. V. Apte
Dr. N. D. Datta Banik
Dr. N. P. Gupta
Dr. Usha K. Luthra
Dr. Badri N. Saxena
Dr. G. V. Satyavati
Editor
Dr. N. Medappa
. Printed and Published by Shri Prem Chand for the Indian Council of Medical
Research, New Delhi, at the ICMR Offset Press, New Delhi.
R.N. 21813/71
Position: 1922 (12 views)