ICMR BULLETIN VOL. 27-No.-7-JULY-1997
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ICMR
BULLETIN
Vol. 27, No. 7
July, 1997
PROGRAMMED CELL DEATH IN THE OVARY: DEVELOPMENT TO DISORDER
In the body of an eukaryotic animal a cell either pro
liferates by mitosis or remains in a non proliferative stage.
During the development and growth of the animal the ratio
of cell proliferation to non proliferation is high, in adult
hood it decreases while in aged individuals the ratio is
inversed. Non proliferation can lead to cell death which
can either be accidental (necrosis) or programmed
(apoptosis). Kerr and co-workers1 first coined the word
apoptosis which in Greek means ‘falling off of leaves from
trees or petals from flowers’.
Researchers and clinicians have now realised that a
proper balance between cell proliferation and apoptosis is
essential for the maintenance of normal body function. An
imbalance may lead to diseases such as acquired immune
deficiency syndrome (AIDS), in which apoptosis of the
immune cells is enhanced, or cancer, where apoptosis is
inhibited (increased cell proliferation).
Morphological changes during apoptosis involve cell
shrinkage changes in nuclear chromatin followed by
nuclear deoxyribonucleic acid (DNA) fragmentation
(apoptotic bodies). The apoptotic bodies can be phagocytosed by macrophages or neighbouring cells. Biochemi
cally, increase in intracellular Ca^ can cause stimulation
of endonucleases which cleave the intemucleosomal DNA
to form fragments of DNA-180 bp or its multiples. This is
the basis for detecting apoptosis by agarose gel electro
phoresis of the extracted DNA from cells. Ladder like
bands of multiple base pairs of 180 to 2300 are formed
which can be visualized after staining with fluorescent dyes
such as ethidium bromide. Different investigators have
reported various techniques for detecting apoptosis. These
include morphological changes observed by staining of
cells by dyes such as acridine orange, flow cytometry analy
sis by staining DNA with 4,6 diamidino-2-phenylindole
(DAPI) or propidium iodide. In addition to the agarose gel
electrophoresis; DNA ladder formation, microelectro
phoresis (comet assay) has also been used to detect DNA
fragmentation. Recently, in situ dUTP 3' nich end label
ling (TUNEL) of DNA fragments has been' used to local
ize apoptotic cells in an organ with heterogenous popula
tion of cells while cellular DNA fragmentation enzyme
linked immunosorbent assay (ELISA) has been employed
for quantitation of apoptosis.
A number of genes have been identified that promote
or inhibit apoptosis eg. interleukin ip converting enzyme
(ICE) or bcl-22,3, respectively.
Apoptosis during Development
In the human ovary, about 7 x 106 oogonia are present
at 20 weeks of gestation, 2 x 106 oocytes are present at
Division of Publication & Information, ICMP
Nvu Delhi - 110029
birth which are further reduced to 4 x 10s at the time of
puberty. Thus, there is a significant reduction in the num
ber of oocytes from the foetal to the adult ovary due to
degeneration. In fact, of 7 x 106 Oogonia present during
the gestation period, only 450 oocytes can ovulate while
the remaining 99.9 per cent are destined to die in situ.
Though it is well documented that the pituitary gona
dotropins, FSH and LH stimulate follicular maturation and
ovulation, 99.9 per cent of the follicles undergo atresia in
the presence of gonadotropins. Studies are underway to
elicit information on the factors responsible for oocyte
degeneration, and on their origin-intraovarian or other
wise.
Intraovarianfactors
It is well established that oestrogens secreted by the
ovarian follicles stimulate follicular growth while high an
drogen levels lead to follicular atresia. It is suggested that
inhibins/activins regulate folliculogenesis either by their
regulatory action on pituitary FSH or by direct autocrine/
paracrine effect on granulosa cell steroidogenesis4.
Scientists at the Institute of Research in Reproduction
(IRR), Mumbai, have purified a peptide that inhibits bind
ing of FSH (FSHBI) to granulosa cells in vitro5. In vivo,
the peptide suppressed ovulation and induced follicular
atresia in cycling mice6. Experiments were further planned
to understand whether in these animals the granulosa cells,
due to non availability of FSH (binding inhibited)
underwent apoptosis. Immature mice were injected with
pregnant mares’ serum gonadotropin (PMSG) and autopsied 48 h later. Another group was injected with PMSG
and 20 pg FSHBI on the following day and autopsied 48 h
after PMSG (24 h after FSHBI injection). The granulosa
cells, punctured and collected from ovarian follicles, were
studied, for apoptosis using 4 parameters viz (i) morpho
logical changes by staining with acridine orange for fluo
rescent microscopy; (ii) DNA staining with DAPI for flow
cytometry; (iii) DNA fragmentation (a) agarose gel elec
trophoresis, and (b) TUNEL technique; and (iv) DNA cel
lular fragmentation ELISA. All the parameters revealed
that FSHBI is responsible for apoptosis in granulosa cells7.
Recent studies have shown that a number of intraovarian
factors which include growth factors and cytokines8 may
be responsible in programming cell death in ovarian granu
losa cells. It is therefore suggested that a cocktail of
intraovarian factors may bring about apoptosis in granu
losa cells of ovarian follicles. A number of genes/proteins
70
reported to be involved in granulosa/luteal cell apoptosis
are listed in the Table. AH the genes, except bcI-2 possibly
alone or together induce apoptosis in granulosa/luteal cells
to cause follicular atresia or luteal regression in rodents
and primates.
Table: Genes involved in ovarian cell apoptosis
Genes/Proteins
Ceil Type
Authors
c-myc
granulosa cells
Li er a/9
c-myc
luteal cells
Fraser et aP
bcl-2
granulosa cells
Tilly er o/11
p53
granulosa ceils
Tilly et al2
Fas
granulosa cells
Quirk et aP
Fas/Fas ligand
granulosa cells
Harkuno et al14
Sakamaki et aP
bax, ICE
granulosa cells
Rueda et aP
ICE-interleukin 10 converting enzyme.
Superscript nos. refer to the si. nos. in the reference list
In an ovarian follicle the granulosa cells are the major
cell type which undergoes proliferation of apoptosis to
decide the fate of the follicle/oocyte for ovulation or
atresia. After ovulation the egg may be fertilized in the
oviduct or may degenerate, if not fertilized. Recently.
Takase et>alP, have reported that degenerative changes in
the unfertilized oocyte are apoptotic and are enhanced 32
h after ovulation.
The follicular cells, granulosa and theca, are lutein
ized after the release of the ovum. The corpus luteum is
functional and short lived if the pregnancy does not occur.
Prostaglandins are known to cause luteolysis in cattle but
not in rodents and primates. Changes in luteal cells during
luteal regression are apoptotic10. The granuhsa cells in the
follicle are devoid of blood supply while luteal cells are
flooded with capillaries. Possibly, growth factors such as
tumour necrosis factor and cytokines eg. interleukin,
locally regulate luteal maintenance or regression in rodents
as well as primates.
Apoptosis in Diseases
Polycystic ovary syndrome
Polycystic ovary syndrome (PCO) is a heterogenous
clinical entity characterized by distinct symptoms, elevated
androgen concentration and polycystic ovaries.
Hyperandrogenaemia, a crucial etiological factor in PCOS
Wz
is caused by increased androgen production by the ovary
or adrenal or both under the influence of elevated serum
LH concentration. The arrest in follicular maturation and
function of polycystic ovaries is not due to absence of
aromatase activity, the enzyme responsible for the con
version of androstenedione to estradiol, as observed in in
vitro and in vivo studies. An abnormal regulation of the
activity of the enzyme 17 oc hydroxylase in PCOS18 leads
to high androgen concentration in the follicular fluid caus
ing apoptosis of granulosa cells which in turn leads to the
arrest of follicular maturation. Multiple small antral/cystic follicles observed in PCOS are viable19 but they may or
may not ovulate for being apoptotic.
follicles (referred to as resistant ovary syndrome). In these
patients circulating immunoglobulins interfere with FSH
binding to its receptor23. Recently in some individuals with
POF antibodies against multiple steroidogenic enzymes
were found in circulation24, specifically to the key enzyme,
A5 3 p hydroxysteriod dehydrogenase (PHSD)25 required
for conversion of pregnenolone to progesterone. Mutation
of CYP19 aromatase gene can elevate serum gonadotro
pin concentrations inducing formation of ovarian cysts26.
Growth hormone-insulin like growth factor (GH-IGF-1)
system has been shown to be crucial for intraovarian
regulation of steroid synthesis and follicular development27.
A mutational defect in the system leads to ovarian failure.
Hypogonadism
Ageing
In hypogonadism the gonadotropic levels are low and
follicular development is arrested. Hypogonadism may
occur due to lack of hypothalamic secretion of GnRH, due
to deletion of GnRH gene, or mutation of GnRH receptor
gene observed during puberty20. Mutation of LH p gene or
LH receptor gene can also lead to ovarian dysfunction.
Premature ovarianfailure
In premature ovarian failure (POF) the follicles may
or may not be present and the levels of FSH are high. Where
follicles are present it is not clear whether these follicles
lack FSH receptors21 or are apoptotic? A decrease in the
number of follicles at an early age (<35 years) in POF
patients possibly is due to some local factors responsible
for the ageing/apoptotic effect on the follicle/oocyte.
As the body ages, reproductive organs also simulate
ageing effect. Fujino et aP* have observed apoptotic
changes in the oocyte of ageing mice.
Ovarian tumours
Inhibins and activins belong to a large group of trans
forming growth factors-p. Inhibins and activins exist as
heterodimers composed of oc and p chains. The p subunit
is common to inhibin and activin while oc is specific for
inhibin. Interestingly, deletion of inhibin oc gene in em
bryonic stem cell increases ovarian tumours in mice29.
Gonadotropins modify the action of inhibin30 indicating
that local factor as well as gonadotropin together are
responsible for regulating ovarian tumours.
Truncated point mutation of FSHP, or change in FSH
glycosylation can fail to activate FSH receptor thereby
leading to POF. FSH receptor (mutation of DNA sequence)
defect is also observed in some of the patients with POF.
These patients have characteristic early age ovarian dys
function, elevated serum gonadotropins and low estradiol
concentration due to apoptosis in granulosa cells of the
follicles.
In conclusion, the granulosa cells, the oocytes and the
luteal cells undergo apoptosis during normal ovarian func
tion. The dysregulation of the ovarian function by alter
ation in the concentration of gonadotropins, local factors
such as steroids, growth factors, or their receptors cause
ovarian disorders31 by enhanced apoptosis in these cell
types.
Enlarged hypoanaemic ovaries have been observed in
patients lacking estrogen responsiveness due to disruption
of estrogen receptor gene in granulosa cells22 possibly due
to programmed cell death.
References
1.
Kerr, J.F., Willie, A.H. and Currie A Apoptosis: A basic biologi
cal phenomenon with wide ranging implications in tissue kinet
ics. Br J Cancer 26:239,1972.
2.
Lee, B.S. and Yeh, J. The Molecular basis of follicular atresia:
Apoptosis as a possible mechanism. Adv Contracept Del Syst 12:
269,1996.
3.
Vaux, D.L. and Strasser, A. The molecular biology of apoptosis.
Proc Natl Acad Sci USA 93:2239,1996.
Autoimmunity
In patients with hypergonadotropin, hypogonadotropic
amenorrhoea elevated levels of FSH failed to stimulate
71
4.
Hillier, S.G. Regulatory functions for inhibin and activin in
human ovaries. J Endocrinal 131:1711991.
18.
Fauser, B.C.J.M. and Hsueh, A.J.W. Genetic basis of human re
productive endocrine disorders. Human Reprod 10: 826, 1995.
5.
Shahid, J.K., Nandedkar, T.D., Iyer, K.S.and Mahale, S.D. Effect
of ovarian follicular fluid peptide (OFFP) on FSH and EGF bind
ing to granulosa cells. Horm Metab Res 23:456, 1991.
19.
Homburg, R., Guidice, L.C. and Chang, R.J. Opinion: Polycystic
ovary syndrome. Human Reprod 11: 465, 1996.
6.
Nandedkar, T.D., Kadam, A.L. and Moodbidri, S.B. Control of
follicular maturation in mouse by a nonsteroidal regulator from
sheep follicular fluid. Int J Fertil 33: 52, 1988.
20.
Rosenfleld, R.L. Puberty and its disorders in girls. Endocrinol
Metab Clin North Am 20: 15, 1991.
21.
Maxson, W.S. and Wentz, A.C. The gonadotropin resistant ovary
syndrome. Semin Reprod Endocrinol 1: 147, 1983.
22.
Lubahm, D.B., Moyer, J.S., Golding, T.S., Couse, J.F., Korach,
K.S. and Smithies, O. Alterations of reproductive function but not
prenatal sexual development after insersional disruption of the
jnouse estrogen receptor gene. Proc NatlAcad Sci USA 90:11162,
1993.
23.
Wilkin, T.J. Receptor autoimmunity in endocrine disorders. NEngl
J Med 323: 1318, 1990.
24.
Uibo, R., Aavik, E., Petersen, P., Perheentupa, J., Avanko, S.,
Pelkonen, R. and Krohn, K.J.E. Autoantibodies to cytochrome
P450 enzymes P450scc, P450cl7 and P450c21 in autoimmune
polyglandular disease types I & II and in isolated Addison’s dis
ease. J Clin Endocr Metab 78: 323, 1994.
25.
Arif, S., Vallian, S., Farzanch, F., Zonome, M.M., James, S.L.,
Pietropaolo, M., Hettiarachchi, S., Vergani, D., Conway, G.S. and
Peakman, M. Identification of 30 hydroxysteroid dehydrogenase
as a novel target of steroid cell autoantibodies: Association of au
toantibodies with endocrine autoimmune disease. J Clin Endocr
Metab 81:4439, 1996.
26.
Conte, F.A., Grumbach, M.M., Ito, Y., Fisher, C.R. and Simpson,
E.R. A syndrome of female pseudohermaphrodism, hypergo
nadotropic hypogonadism, and multi-cystfc ovaries associated with
missense mutations in the gene encoding aromatase (P450 arom.).
J Clin Endocr Metab 78: 1287, 1994.
27.
Guidice, L.C., Insulin-like growth factors-and ovarian follicular
development. Endocr Rev 13:641, 1992.
28.
Harkuno, N., Koji, T.-, Yano, T., Kobayashi, N., Tsutsumi, O.,
Taketani, Y. and Nakane, P.K. Fas/Apo-1/CD95 system as a me
diator of granulosa cell apoptosis in ovarian follicular atresia.
Endocrinology 137:1938, 1996.
Fujino, Y., Ozaki, K., Yamamasu, S., Ito, F., Matsuoka, I., Hayashi,
E., Nakamura, H., Ogita, S., Sato, E. and Inoue M. DNA fragmentation of oocytes in aged mice. Human Reprod 11: 1480,
1996.
29.
Sakamaki, K., Yoshida, H., Nishimura, Y., Nishikawa, S.I.,
Manabe, N. and Yonehara, S. Involvement of Fas antigen in ova
rian follicular atresia and luteolysis. Mol Reprod Dev 47:11,1997.
Matzuk, M.M., Finegold, M.J., Su, J-G. J., Hsueh, A.J.W. and
Bradley, A. a inhibin is a tumour-suppressor gene with gonadal
specificity in mice. Nature 360:313, 1992.
30.
Rueda, B.R., Tilly, K.I., Botros, I.W., Jolly, P.D., Hansen, T.R.,
Hoyer, P.B. and Tilly J.L. Increased bax and interleukin-10.con
verting enzyme mRNA levels coincide with apoptosis in the bo
vine corpus luteum during structural regression. Biol Reprod 56:
186,1997.
Rajendrakumar, T., Wang, Y. and Matzuk, M.M. Gonadotropins
are essential modifier factors for gonadal tumour development in
inhibin-deficient mice. Endocrinology 137:4210, 1996.
31.
Tilly, J.L. Apoptosis and the ovary: A fashionable trend or food
for thought? Fertil Steril 67:226, 1997.
Takase, K., Ishikava, M. and Hoshiai, H. Apoptosis in the degen
eration process ofunfertilized mouse ova. TohokuJExp Med 175:
69,1995.
This write-up has been contributed by Dr. T.D. Nandedkar,
Deputy Director, Institute for Research in Reproduction,
Mumbai.
7.
8.
9.
10.
Nandedkar, T.D., Parkar, S.G., Iyer, K.S., Mahale, S.
D., Moodbidri, S.B., Mukhopadhyaya, R.R. and Joshi, D.S.
Regulation of follicular maturation by human ovarian follicular
fluid peptide. J Reprod Fertil (Suppl) 50: 95, 1996.
Vinatier, D., Dufour, Ph. and Subtil, D. Apoptosis: A programmed
cell death involved in ovarian and uterine physiology. EurJObstet
Gynaecol Reprod Biol 67: 85, 1996.
Li, S., Manio, T., Ladines-Llave, C.A., Kondo, H. and Mochizuki,
M, Stage limited expression of c-myc oncoprotein in human ovary
during follicular growth, regression and atresia. Endocrine J 41:
83, 1994.
Fraser, H.M., Lunn, S.F., Cowen, G.M., and Illingwo'rth, P.J. In
duced luteal regression in the primate: Evidence for apoptosis and
changes in c-myc protein. J Endocrinol 147: 131, 1995.
11.
Tilly, J.L., Tilly,%K.I., Kenton, M.L. and Johnson, A.L. Expres
sion of members of the bcl-2 gene family in the immature rat ovary:
Tequine chorionic gonadotropin mediated inhibition of granulosa
cell apoptosis is associated with decreased bax and constitutive
bcl-2 and bcl-x lon messenger ribonucleic acid levels. Endocrinol
ogy 136:232,19§5.
12.
Tilly, K.I., Baneijee, S., Banerjee, P.P. and Tilly, J.L. Expression
of the p53 and Wilms’ tumour suppression genes in the rat ovaiy:
Gonadotropin repression in vivo and immunohistochemical local
ization of nuclear p53 protein to apoptotic cells of atretic follicles.
Endocrinology 136: 13*94, 1995b.
13.
Quirk, S.M., Cowan, R.G., Joshi, S.G. and Henrikson, K.P. Fas
antigen-mediated apoptosis in human granulosa/luteal cells. Biol
Reprod 52: 279, 1995.
14.
15.
16.
17.
72
ABSTRACTS
Some Research Projects Completed Recently
Chronic calcific pancreatitis: A prospective study of
response to surgical treatment
Patients with a clinico-radiological diagnosis of
chronic calcific pancreatitis (CCP) were studied to
evaluate the effect of surgical intervention on pain and the
exocrine and endocrine functions.
Of the 126 patients (104 males and 22 females; mean
age 36.98 years), 40 had alcoholic pancreatitis,
81 tropical calcific pancreatitis, 3 had carcinoma of the
pancreas initially presented as chronic pancreatitis and
2 had pancreas divisum. One hundred and twenty patients
presented with abdominal pain (of pancreatitis) with an
average duration of 4.63 years, 33 had diabetes mellitus,
19 had pancreatic steatorrhoea, 23 obstructive jaundice and
10 patients had left sided portal hypertension (LtPHT).
Pancreatic calcification was observed in 37 of the 126
(29.4%) patients on plain x-ray of the abdomen, while
ultrasonography showed dilated pancreatic duct and cal
cification in 49 (33.6%) patients. Endoscopic retrograde
cholangio pancreatography (ERCP) done on 50 patients
revealed dilated duct and/or calcification in all 50 patients.
All. patients with pain were initially managed conser
vatively with abstinence from alcohol, small frequent
carbohydrate rich diet, oral pancreatic enzymes and H
receptor blockers. Sixty nine of the 126 patients not
responding to conservative treatment underwent surgerymodified Puestow’s operation in 56, Duval’s operation in
seven and distal pancreatectomy in six. Internal drainage
for symptomatic pancreatic pseudocysts was carried out
in 17, biliary enteric anastomosis for obstructive jaundice
in 22 and splenectomy for L-PHT in 10 patients. A total of
50 patients could be followed up for periods ranging upto
5 years. Postopertive relief of pain was recorded in 45
(90%) patients. Pain recurred in 4 (8%) patients at the end
of the 5 years. Five of the 11 (45.4%) patients with overt
diabetes mellitus improved in terms of insulin requirement
and normalisation of blood glucose values. It is thus con
cluded that the drainage operations for CCP do result in a
consistent long-term improvement in abdominal pain and
diabetes mellitus.
Quantitative estimation of inorganic and organic con
stituents of 8 pancreatic stones showed that Ca2+ (31.37 ±
4.07 mg/dl) and oxalate (5.06 ±2.18 mg/dl) were the major
inorganic constituents and proteins (83.0 ± 13.5 pg %)
and mucopolysaccharides (6.96 ± 1.77 mg %) the major
organic constituents.
Rakesh Tandon
Department of Gastroenterology
and Human Nutrition,
All India Institute of Medical Sciences,
New Delhi
Publications:
1.
Sidhu, S.S., Shah, P.» Srikant, S. and Tandon, R.K. Ketosis resis
tant diabetes of the young: A profile of its exocrine and endocrine
pancreatic dysfunction. Indian J Physiol Pharmacol 38:289,1994.
2.
Sidhu, S.S., Shah, P., Prasanna, B.M., Srikanta, S.S. and Tandon,
R.K. Chronic calcific pancreatitis of the tropics (CCPT):
Spectrum and correlates of exorine and endocrine pancreatitic dys
function. Diabetes Res Clin Pract 27\ 127,1995.
3.
Sidhu, S. and Tandon, R. Chronic pancreatitis: Diagnosis and treat
ment. Postgrad Med J 72’. 327, 1996.
c-myc localization in premalignant and malignant le
sions of human colon
The correlation of the expression of c-myc oncogene
with the degree of differentiation of premalignant and ma
lignant lesions of the colon was examined immunohistochemically using monoclonal antibodies against c-myc
protein and by morphometry. The colonic lesions studied
included polyps with dysplasia, well differentiated, mod
erately differentiated and poorly differentiated carcinomas,
signet ring carcinoma, mucinous carcinoma and adeno
squamous carcinoma. Paraffin sections from normal
colonic mucosa served as controls.
Sections representing the normal colonic mucosa
showed the highest nuclear c-myc positivity (84%). The
percentage of nuclear positivity declined with the increase
in histologic grades-the highest (59%) and lowest (2%)
nuclear c-myc positivity being recorded in cases of well
differentiated carcinoma and adenosquamous carcinoma
respectively. There was a significant increase in the
cytoplsmic positivity of the c-myc oncoprotein in various
lesions (except for signet ring carcinoma which showed
zero cytoplasmic positivity) as compared to controls.
The nuclear diameter was found to be a reliable
cytological variable in distinguising severe dysplasias with
well differentiated carcinomas. Moderately and poorly
differentiated carcinomas and adenosquamous carcinoma
showed significantly higher values for nuclear diameter
compared to controls and well differentiated carcinoma.
There was a significant decline in nuclear volume with an
increase in the histological grade. With an increase in
nuclear volume the nuclear expression of c-myc
oncoprotein declined. Well differentiated carcinomas
showed nearly equal distribution of c-myc positivity in
the nucleus and cytoplasm. Moderately differentiated
carcinomas showed predominantly cytoplasmic c-myc
positivity. Poorly differentiated carcinomas showed very
weak nuclear but intense cytoplasmic positivity.
It may be concluded that cytoplasmic c-myc over
expression is related to the aggressive behaviour of the
tumour as it is a growth regulating protein. Hence the
assessment of c-myc over expression by immuno
cytochemistry is an additional prognostic indicator.
Combining immunocytochemistry of c-myc oncogene with
morphometric analysis will give new dimensions in
predicting the prognosis of colonic neoplasms. However,
a large number of cases need to be studied for a more
reliable assessment of c-myc expression.
J. Suresh Durai
K. Baba Krishnan
Department of Pathology,
Dr. A.L.M. Postgraduate Institute of
Basic Medical Sciences,
Chennai
ICMR NEWS
Participation of ICMR Scientists in Scientific Events:
Dr. V.P. Sharma, Director, Malaria Research Centre,
Delhi, participated in the V Neem Awareness Workshop
at Mbite, Kenya (June 15-24, *1997).
Dr. G.V. Satyavati, Director-General, ICMR,
participated in the XX session of the Joint Coordinating
Board of the TDR/WHO at Geneva (June 23-24, 1997).
Dr. G.V. Satyavati delivered the Key-note Address on
“Opportunities for Women and Biomedical Sciences” at
the Silver Jubilee symposium of the Indian Women
Scientists’ Association at Mumbai (June 27,1997).
Dr. Jayashree Nandi, Senior Research Officer, National
Institute of Virology, Pune, participated in the workshop
on AIDS in Africa at Dar-es-Salaam, Tanzania (June 2528,1997).
Dr. P.K. Das, Director, Vector Control Research Centre
(VCRC), Pondicherry and Dr. V. Kumaraswamy, Dy.
Director, Tuberculosis Research Centre (TRC), Chennai,
participated in the UNDP/World Bank/WHO Special
Programme for Research and Training on Tropical
Diseases meeting on Rapid Assessment of Lymphatic
Filariasis at New Delhi (July 3-5, 1997).
74
Dr. P.K. Das, Director, Dr. S.P. Pani, Dy. Director and
Dr. K.D. Ramaiah, Research Officer, VCRC, Pondicherry;
Dr. A.P. Das, Dy. Director and Dr. B.V. Babu, Sr. Research
Officer, Regional Medical Research Centre, Bhubaneswar;
and Dr. V. Kumaraswamy, TRC, Chennai, participated in
the UNDP/World Bank/WHO Special Programme for
Research and Training on Tropical Diseases meeting on
Protocol Development for Community Directed Treatment
of Lymphatic Filariasis at New Delhi (July 7-11,1997).
Dr. M.D. Gupte, Director, Institute for Research in
Medical Statistics, Chennai and Officer-in-Charge, CJIL
Field Unit, Avadi, Chennai, participated in the meetings
of the (i) WHO Task Force on Monitoring and Evaluation
of Elimination of Leprosy (July 14, 1997), (ii) WHO
Steering Committee on Special Action Projects (July 15,
1997); (iii) Leprosy Elimination Advisory Group (July 1617, 1997); and (iv) Joint ILEP/WHO Workshop on
Reaching Undetected Leprosy Patients in Endemic
Countries (July 18-19) at Geneva.
Dr. N.V. Giridharan, Sr. Research Officer, National
Centre for Laboratory Animal Science, Hyderabad,
participated in the VI International workshop on Lessons
from Anifnal Diabetes at Bagsvaerd, Denmark (July 1417,1997).
ICMR AIDED SYMPOSIA/SEMINARS/WORKSHOPS/COURSES/CONFERENCES
Symposium/Seminar/Workshop/
Contact Address
Date & Place
Course/Conference
Workshop on Intellectual Property Rights
August 13, 1997;
(at Ahmedabad)
Dr. H.N. Saiyed, Director, National Institute of
Occupational Health, Ahmedabad-380016.
Symposium on Recent Trends in Tropical Disease
Research
September 5-6, 1997;
(at Sevagram)
Dr. M.V.R. Reddy, Organising Secretary of the
Symposium, J.B. Tropical Disease Research Cen
tre and Department of Biochemistry, Mahatma
Gandhi Institute of Medical Sciences, Sevagram,
Wardha-442102.
III National Conference of the Alzheimer’s and
Related Disorders Society of India, Hyderabad
August 31, 1997;
(at Hyderabad)
Mr. K.R. Gangadharan, Organising Secretary of
the Conference, Alzheimer’s and Related Disor
ders Society of India, 7-1-59/4 & 8, Ameerpet,
Hyderabad-500016.
National Symposium-cum-Workshop on
Leptospirosis
September 11-13, 1997;
(at Port Blair)
International Symposium on Recent Trends in
Mental Health
September 19-20, 1997;
(at Sevagram)
Dr. Prakash D. Behere, Organising Secretary of
the Symposium, Department of Psychiatry, Maha
tma Gandhi Institute of Medical Sciences, Seva
gram, W ardha-442102.
IV National Conference of the Society of Bio
materials and Artificial Organs on New Horizo
ns in Biomaterials Research
October 3-4, 1997;
(at Hyderabad)
Dr. P.R. Chatterjee, Convenor of the Conference,
Indian Institute of Chemical Technology, Hydera
bad-500007.
Seminar on Current Status of Thalassemia in
India and National Workshop on Carrier
Detection and Antenatal Diagnosis of
Thalassemia
November 13 and
14-15,1997;
(at Lucknow)
Dr. Sarita Agarwal, Organising Secretary, Dep
artment of Medical Genetics, Sanjay Gandhi
jPostgraduate Institute of Medical Sciences, Lucknow-226014.
International Conference on Advances in
Reproductive Medicine
November 15-18, 1997;
(at Calcutta)
Dr. Sudersan Ghosh DastidarJOrganising Secretary-ICARM’97, Infertility Clinic and I.V.F. Cen
tre, 208, Rash Behari Avenue, Calcutta-700029.
Asia-Pacific Congress on Head and Neck Cancer
December 11-14, 1997;
(at Mumbai)
Dr. Ashok R. Mehta, Chairman of the Congress,
Department of Surgery, Tata Memorial Hospital,
Mumbai-400012.
.
Dr. V.G. Kao, Organising Secretary of the Symposium, Regional Medical Research Centre, Port
Blair-744101.
INDIAN COUNCIL OF MEDICAL RESEARCH
Grant-in-aid for organising Seminars/Symposia/Workshops
The Council provides partial financial assistance for organising Seminars/Symposia/Workshops.
Applications for grant of financial assistance (complete in all respects in the prescribed proforma), will
be considered only if furnished at least four months before the date of commencement of the
Seminar/Symposium/Workshop, etc.
75
COUNCIL’S TRAINING PROGRAMMES FOR 1997-98
Leprosy
Occupational Health
At the Central JALMA Institute for Leprosy, Agra:
At the National Institute of Occupational Health,
Ahmedabad:
•
Training Course on National Leprosy Eradication
Programme for Medical Officers (September 15-26,
1997).
Reproductive Biology
•
Orientation Course on Occupational Health for Indus
trial Medical Officers (September 30-October 11,
1997).
•
Training Course on Environmental Hygiene Practice
(November 10-14,1997).
At the Institutefor Research in Reproduction, Mumbai:
•
•
Workshop on Genotoxicity (August 18-29, 1997).
Workshop on Basic Molecular Biology for Clinicians
(December 2-11, 1997).
Laboratory Animal Technology
At the National Centre for Laboratory Animal Science,
National Institute ofNutrition, Hyderabad:
•
Training Course for Laboratory Animal Supervisors
(September 1-November 29, 1997).
Endocrinology
Haematology
At the National Institute of Nutrition, Hyderabad:
•
Annual Certificate Course on Endocrinological Tech
niques and their Applications (August I-September
15, 1997)’.
Nutrition
At the Institute of Immunohaematology, Mumbai:
•
Training Course in Transfusion Medicine for Blood
Bank Medical Officers (August 27-October 24,
1997).
•
Training Course in Blood Group Serology and Blood
Bank Methodology for Blood Bank Technicians (Au
gust 27-September 26, 1997).
•
Training Course in Advanced Haematology and
Immunohaematology (October 6-24,1997).
At the National Institute of Nutrition, Hyderabad:
•
Postgraduate Certificate Course in Nutrition (Decem
ber 1,1997-February 28,1998).
EDITORIAL BOARD
Dr. G.V. Satyavati
. Chairperson
Dr. Badri N. Saxena
Member
Dr. Bela Shah
Member
Dr. N. Medappa
Editor
Printed and Published by Shri J.N. Mathur for the Indian Council of Medical Research, New Delhi
at the 1CMR Offset Press, New Delhi-110 029
R.N. 21813/71
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