ICMR BULLETIN VOL. 24-No.-3-MARCH-1994.pdf
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ISSN 0377-4910
Vol. 24, No. 3
March, 1994
IMMUNITY IN LEPROSY : III. CELL MEDIATED IMMUNITY
Understanding the Mechanism of Unresponsiveness
Macrophage/ Antigen Presenting Cell
It is known that M. leprae is an obligatory parasite
and resides inside the macrophages/ Schwann cells and
produces a granuloma in the host. The claim253 that
macrophages from lepromatous patients are incapable
of killing M. leprae in vitro was contradicted later254*255.
While studying the capability of M. leprae antigen
presentation by the macrophages of LL patients,
Hirschberg256 pointed out that due to the defect in the
macrophage presentation of antigen, LL patients are
unable to respond to M. leprae. Nath et al251 further
confirmed this-observation in HLA-D matched co
cultured situations. They showed that the macrophages
from LL patients inhibited the lymphoproliferation of
peripheral blood in M. leprae responding individuals.
Nath et al251 further showed that lymphocytes of LL
patients were capable of undergoing proliferation when
macrophages from tuberculoid patients were added in
Che culture, indicating thereby that antigen reactive T
cells are- present in the peripheral blood of LL patients.
However, a study258 in HLA-D identical siblings
completely negated the role of monocyte population257
and suggested a T cell defect being responsible for the
unresponsiveness. More data are now available259
indicating that the adherent cells in the peripheral blood
of lepromatous individuals having macrophage
characteristics, induce a suppressive effect on the
antigen induced lymphoproliferation in HLA-D
identical tuberculoid patients and healthy contacts. It
was further concluded that the suppression induced by
these macrophages is due to some soluble factors
liberated by these cells259. In support of this view,
Salgame et aPM had already established tl)at lysates of
LL macrophages inhibit protein synthesis of normal
macrophages in addition to the inhibition of
lymphoproliferation261. Recently, the soluble factor was
characterised262 and was found to be heat-stable,
indomethacin resistant and of >25 kDa.
It has been shown that the macrophages after
phagocytosis of live M. leprae downregulate their own
Fc receptor expression, biochemical and other
functions263. In addition, the macrophagesx of LL
patients have been shown to have a selective (fepression
in leucine uptake and exhibited a reduction of Fc
receptors only when exposed to M. leprae1^.
Mahadevan and Antia264 proposed that macrophages
after phagocytosis of M. leprae lose their capacity to
process antigen leading to a CMI defect. At the same
time it has been noted that Schwann cells after
phagocytosis of M. leprae lose their capacity to
synthesise DNA and are unable to associate themselves
with axon thereby inducing a defect in C-fibre function.
Recently, Marolia et al265 noted that macrophages from
the peripheral blood of patients of paucibacillary and
multibacillary leprosy, but not of healthy individuals,
are inefficient in killing phagocytosed M, leprae due io
their inability to produce superoxide (Of) and hydroxyl
radicals (OH").
D i v i $ i o n of Publication & Information, I C M R, New Delhi - I I 0 029
Immune responses are controlled partially by
soluble factors liberated by the lymphoreticular system.
IL-1 liberated by macrophages, acts upon T cells in the
early GI phase of the cell cycle and prepares the T cells to
respond to the subsequent signals. Initial report by
Horwitz el a/266 of lowered production of cytokine by
macrophages of lepromatous patients has been further
confirmed and characterised by Watson er a/261 while
studying the IL-1 production in LPS stimulated
monocytes. They noted that 38.5 per cent of BL/ LL
patients failed to produce IL-1 while TT/BT patients
were able to either produce IL-1 in the normal range
spontaneously or upon stimulation. Similar findings
were also reported ina M.
stimulated situation268.
Tumour necrosis factor (TNF-a) is a secretory pro
duct of macrophages269 and activated mononuclear cells
of the peripheral blood270#27!. Higher levels of TNF-a
have been seen to be associated with malaria and kalaazar272. Using a bioassay higher levels of TNF in
serum273 and higher TNF production by antigen induced
mononuclear cells274 have been noted in tuberculoid
patients as compared to patients with various
lepromatous forms. However, a higher level of TNF-a in
sera of lepromatous patients275 could be due to the
presence of inhibitors in the sera of such patients. The
presence of such inhibitors has already been reported in
tuberculosis and sarcoidosis276. Moreover, the presence
of higher number of TNF containing cells277, higher
concentration of TNF mRNA by in situ
hybridization278, and PCR amplification252 in
tuberculoid skin lesions than in lepromatous lesions
have already been reported. The protective role of TNF
can further be explained by the finding of its inhibitory
role in mycobacterial multiplication in murine and
human macrophages279. Moreover, TNF has been
recently, shown to enhance the production of nitric
oxide in mouse macrophages280 which in turn have been
shown to kill M, leprae2^. Further the finding of high
levels ofTNF274 in active ENL patients could explain the
clinical manifestations of fever and nerve damage which
have been noted by TNF inoculation in mice281 and by/n
vitro experiments282^283 respectively.
T Cells
The understanding of suppressor function of a
subpopulation of T cells in mice, which regulates the
immune response, prompted researchers to work on
normal and diseased states of human beings.
Investigators engaged in leprosy research also generated
data on the T suppressor (0KT8+) cells in leprosy. A
38
preliminary study284 in an Ethiopian population
indicated that M. leprae antigens generally suppress the
in vitro PHA-induced lymphoproliferation in leprosy
patients and their household contacts. While working
with ConA induced lymphoproliferation in leprosy
patients and healthy individuals, Mehra et。网 noted
that Dharmendra antigen suppressed the Co nA induced
proliferation selectively in majority of lepromatous and
borderline patients and not in tuberculoid and healthy
individuals. These authors further pointed out that the
suppression was induced by the generation of the
classical T8+ and TH2+ phenotype markers bearing
suppressor cells2^87.
Although these studies
demonstrated that suppressor T cells were responsible
for the suppression of CMI in lepromatous leprosy.
Stoner et al1^ could not establish such a role, rather they
noted a lack of these cells in most of the Ethiopian
patients. Further, from their observations on
subclinically infected healthy individuals these workers
established that there is an association of suppressor cell
activity with resistance to M. leprae infection289. To
prove the role of suppressor cells in leprosy, Nath et aP90
have done extensive work in untreated leprosy patients
belonging to both hyperendemic and low endemic areas
of India. It was noted in a 4-day culture condition that
ConA induced suppressor cells selectively suppressed
the autologous mitogenic responses of tuberculoid
patients. Further, this ConA stimulated lymphoproli
feration was suppressed by addition of M. leprae antigen
in a large number of tuberculoid patients but not in all
the lepromatous patients. On the other hand, many of
the lepromatous patients showed enhancement in the
lymphoproliferative response. However, when the
cultures were continued for 6 days the differences in
suppression in various groups were abolished and the
suppressive effect was noted uniformly in all subjects291
as earlier noted by Bjune284. Earlier studies, where T cell
bearing Fc receptors for IgG used to be considered as
suppressor T cell subset, also indicated the presence of
normal levels of these cells in tuberculoid patients292
with a reduction in their number in lepromatous
patients293.
The results of these studies on the suppressor cell
activity are very divergent in their views. The suppressor
cell activity in tuberculoid type of leprosy gains support
from only one observation wherein the suppressor cell
generation was mostly associated with a strong CMI
response294, which might possibly play a role in the
suppression of unwanted antibody production 295. On
the other hand, with the understanding of murine
TH 1 /TH2 subsets and their biological function29S297
more evidence is being accumulated to show that TH1
lymphocyte proliferation alongwith IFN-y secretion are
associated with acute stage of the disease whereas TH2
lymphocyte proliferation w
*th
increase of lL4and ILIO
are associated with chronic disease298-300. Recently,
Salgame et aP01 categorised the functional subsets of T
cells in leprosy. They established that CD4+ cells cloned
from tuberculoid patients produced more IFN-y,
whereas those obtained from lepromatous patients
produced more IL4. In addition, CD8+ T suppressor
clones producing IL4 isolated from lepromatous
patients were found to be essential for suppression of in
vitro responses to antigen in these patients. However,
more recently the role of contrasuppressor (Cs) cells for
antagonising the suppressor function in leprosy, has also
been reported302. Cs cells are known to interact with
CD44- cells and render them unresponsive to the signals
of CD8+ cells303. Cs-like functional activity has also
been noted in CD8+ cells in leprosy302.
T cel! unresponsiveness to M. leprae stimulation in
lepromatous leprosy has also been attributed to the lack
of lymphokine production by the immune ceils26^30*307.
Several workers308*310 have noted T cells in LL patients
are incapable of specific antigen stimulated proliferation
due to deficiency of IL-2. However, in spite of
exogenous supply of IL-2 in about one third of the
patients. T cell unresponsiveness could not be
corrected308. All these studies have also indicated that in
most lepromatous leprosy patients, there is no clonal
deletion of M. leprae specific T cells which was opined
earlier by Godal et j/171. This unresponsiveness may be
either due to lack of required number of M. leprae
reactive T cells being circulated307 or to the presence of
monocytes which are liberating suppressive factors311.
In contrast to the above findings Mohagheghpour et
aPn could not find IL-2 deficiency in lepromatous
patients； they suggested that the unresponsiveness could
be due to the lack of IL-2 receptor on the T cells. An
interesting observation313 recently made relates to
CD44- cells of LL patients which were found to respond
to M. leprae stimulation after culture for 48 hours in
medium alone. They further noted that the recovery of
this T cell reactivity was blocked by the presence of M.
leprae in preculture medium. These authors reasoned
the unresponsiveness to be due to the persistence of
antigen which renders unresponsive the antigen
responsive T cells.
Downregulation of T cell response specially by M.
leprae modulating the CD2 has been recently postulated
by Muthukkaruppan ei a/,88>189. Using OKTII and
0KT3 monoclonal antibodies they showed that
bacillifcrous lepromalous leprosy patients while
exhibiting low levels of CD2+ cells show normal levels
of CD3+ cells. Further, when M. leprae (Dhannendra
lepromin only) were exposed to the suspension of
peripheral blood T lymphocytes obtained from normal
healthy individuals. CD2+ cells were reduced in number
while the CD3+ cell number remained intact. These
observations indicated that M. leprae antigens by
modulating the E-receptor of T cells, might be inducing
the suppression. Contrary to this. Wong et aP14 while
looking for expression of CD2+ and CD3+ receptors on
lymphocytes in lepromatous skin lesions and peripheral
blood found that virtually all the CD3+ cells express
CD2 in both situations.
Other Factors
Serum /plasma
From time to time, the presence of some unknown
factors in the blood plasma/serum of leprosy patients
which are capable of inhibiting the in vitro growth of
autologous lymphocytes have been reportedi勺76朋7
Bullock and Fasal170 and others17^318 described that
some LL sera are lymphocytoioxic and these sera also
suppress the lymphoproliferation induced by PH A.
Later Potts et r?/316 and Kerr et a" showed that the
inhibition in lymphoproliferation is due to the decrease
in number of cells responding io mitogen. On the other
hand, Kerr et al311 have recently shown that the putative
inhibitory factor(s) is (are) not cytotoxic. The
suppression in the proliferative response may be due to
an inherent cellular defect or to factors in the serum
which inhibit lymphocyte activation. They further
characterised317 the inhibitory factor which was resistant
at 60° C for 30 minutes and was denatured at iOO°C. A
very interesting report319 is available showing that LL
sera bring down some chromosomal aberrations of
normal lymphocytes in culture, leading to a lowering in
the mitotic index and thus inhibiting
lymphoproliferation.
Although the presence of such scrum/plasma
fauiors in leprotic patients, has been reported by
diff rent workers, these factors need further chemical
and structural characterisation to substantiate the
findings.
Mycobacterial component
In addition to the isolation from lepromatous
lesions, of T-cell clones having suppressor functions520.
39
M, leprae soluble products have also been shown to
suppress lymphoproliferation to the antigen not only of
lepromatous but also of tuberculoid patients321. It is also
possible that a nonspecific suppressive function by
microbial fraction may be responsible for the
suppression as noted by Molloy et al322. Holzer et al323
noted that M. leprae, as a whole, fails to stimulate
human blood monocytes, neutrophils and murine
peritoneal macrophages to generate superoxide anions
(respiratory burst). Vachula et aP24 pointed out the role
played by phenolic g!ycolipid-I (PGL-I) in blocking the
respiratory burst of human macrophages. Recently,
Parkash and Sengupta325 have hypothesised that the
failure of oxidative burst exhibited by M. leprae
phagocytosed macrophages is probably due to the
complement mediated entry of M. leprae into the
monocytes. Such a view has already been favoured by
workers using various particulate materials including
Leishmania major as a pathogen326*330. With regard to
the PGL-1 induced suppressive function by
macrophages further evidence has accumulated from
the work of Neill and Klebanoff331 who showed that
both purified PGL・1 and its deacylated form abolished
the antimicrobial effect by blocking the xanthine
oxidase system which is essential for the release of OH .
Blocking effect on the myeloperoxidase-HzOz-halide
system was also observed using this lipid.
Another cell-wall associated lipid of mycobacterial
species, lipoarabinomannan (LAM), which has been
shown to inhibit antigen responsiveness of human
peripheral blood leucocyte332 and antigen induced
proliferation of CD4+ T cell clones333, has also been
found to block the activation of macrophages without
any change in their capability of phagocytosis334. The
same group of workers further demonstrated335 that
LAM is able to block the activation of mouse
macrophages induced by IFN-y.
M. leprae protein components and 12 kDa protein
antigen of M. leprae have been shown by Sengupta et
a/187 to suppress the tuberculin induced DTH response
in vivo in leprosy patients. However, such a suppression
could not be reproduced by Fine et "36 This
discrepancy may be due to the differences in the typePf
leprosy patients studied and the differences in the
genetics of- the ethnic group included in these studies.
All the above studies proved beyond doubt that
there are several M. leprae components which are
suppressive for cell immune functions and these
components may be playing a major role in the
pathogenesis of leprosy.
40
Antibodies/immune complexes
It is known that entry of M. leprae leads to host
immune response by production of antibodies and CMI
against the pathogen. This is also known that there is an
inverse correlation between CMI and M. leprae
antibody levels in leprosy patients6*311. It could be
expected that when the protective antigens are capable
of eliciting both CMI and antibody in the host, the
antibodies can mask the M. leprae antigens expressed on
the membranes of antigen presenting cells and this could
result in the lowering of CMI337. Further, preliminary
evidence has been provided by Tyagi et aPiS to suggest
that circulating immune complexes from leprosy
patien s could suppress the M. leprae induced
lymphocyte proliferation.
Antigenic Mimicry
M. leprae has been known to have afflicted human
beings since biblical time. It is possible that during these
many years the organism has adapted to the human
host, in a way that it generally does not evoke a strong
host immune respons已 The unresponsiveness of the host
is possible if M, leprae share or "mimic" some of their
antigens with the host tissues. Such a possibility is not
far fetched, as it has been reported that human tissues
possess proteins which are almost similar to
mycobacterial 65 kDa heat shock protein when
compared on the basis ,of their
aminoacid
sequences33^40. Recently,Naafs er aP41 have shown that
8 monoclonal antibodies '(MAb) against M. leprae
determinants (12 kDa, 18 kDa and 65 kDa) reacted with
dermal determinants. If at all these similarities are
founded then these M. leprae antigens would be
recognised as self and due to the presence of some minor
dissimilarities in some sequences from the host proteins,
they would evoke an autoimmune reaction. Evidence
exists for such a situation in other diseases like Group A
streptococcal myocarditis342, rheumatoid arthritis in M.
tuberculosis infection343, myasthenia gravis344 and
neuropathy/cardiomyopathy in Chagas disease344*545.
An attempt has been made in this review to cover
various aspects of studies on the humoral and cellular
immunology on which studies have been carried out to
understand the disease process. It is known that there
are genes for immune responses as well as for immune
suppression346 It has not yet been established whether a
genetic mechanism also plays a role in modulating the
host immune response. However, a significant
association of HLA-DR2347*352 and HLA-DR3350
molecules with various types of leprosy has been
claimed. The role played by .HLA-DR antigens in
modulating the immune response to M. leprae antigens
calls for separate mention.
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1987.
284. Bjune, G. In vitro lymphocyte stimulation in leprosy; simultaneous stimulation with Mycobacterium leprae antigens and
phyto-hemagglutinin. Clin Exp Immunol 36: 479, 1979.
•
•
285. Mehra, V.» Mason, L.H., Fields, J.R and Bloom, B.R, Lepromininduced suppressor cells in patients with leprosy. J
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42
298. Boom, W.H., Leibster, L.» Abbas, A.K. and Titus, R.G.
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*
An alternative Explanation fur the immune re
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This write-up (in 3 parts) was contributed by Dr. U. Sengupta,
Central Jalma Institute for Leplrosy, Agra.
ABSTRACTS
Some Research Projects Completed Recently
A study of toxocariasis.
The study was carried out to prepare and purify
excretory-secretory (ES) antigens from second stage
larvae of Toxocara canis, assess the antigenicity of crude
44
ES antigens and fractions, and for comparative
evaluation of enzyme linked immunosorbent assay
(ELISA) and indirect haemagglutination assay (1HA)
for serodiagnosis and seroepidemiology of toxocariasis.
Second stage larvae of T. canis were cultured in
vitro in RPM 1-1640 media at larval concentration of IX
104 ml for collection of ES antigens. The SDS-PAGE
of crude ES antigenic extract of larvae revealed eight
protein fractions with molecular weights ranging from
42 to 117 kDa. However. SDS-PAGE of the sephadex
G-25 fractionated crude antigen revealed seven protein
fractions with molecular weights ranging from 15 to 169
kDa; 42 kDa fraction proved to be very specific for the
detection of toxocara antibody and for skin testing.
Seroprevalence and seroepidemiological studies
for toxocariasis were carreid out on 169 individuals
clinically suspected to have toxocariasis and 150 healthy
blood donors (control). The overall seropositivity in
clinically suspected individuals wasfound to be 29.5 and
18.4 per cent with ELISA and IHA respectively, where
as in controls only 2.6 per cent were positive (ELISA).
The IgG levels were significantly higher than IgM in
clinically suspected subjects while both were
significantly higher compared to controls.
In an attempt to study the effect of visceral larva
migrans. histopathology of different organs of rabbits,
infected with different doses of infective T canis eggs.
was done. High eosinophilic infiltration, accumulation
of macrophages, inflammation and oedema of the
intestine was seen. Lungs showed peribronchiolar
accumulation of eosinophils with eosinophilic exudates
in the bronchioles and alveoli together with diffused
interalveolar eosinophilic infiltration. Liver showed
hepatic tissue destruction with haemorrhage and
leukocyte infiltration followed by oedema and
production of fibroblasts.
Seroepidemiological studies in 100 stray dogs using
ELISA with larval ES as well as adult somatic antigens.
showed 64 per cent seropositivity with larval ES
antigens, and 50 per qent positivity with adult somatic
antigen. Thus, the ES antigen appeared to be more
specific than the somatic antigen.
U.K. Baveja
Department of Microbiology
Maulana Azad Medical College
New Delhi.
strain albino rats and rhesus monkeys exposed to
different he pa t oca rci noge nic agents. Morphological
and cytochemical profiles of preneoplastic cells were
also studied.
Rats were treated with dimethylnitrosamine (single
dose of 0.4 mg/100 g body wt. intraperitoneally 24 h
after partial hepatectomy) or acetylaminofluorene (3
doses of 3 mg/100 g body wt. i.p. at 24 h intervals
followed by partial hepatectomy 24 h after the last dose).
A total of 5 rats and 4 monkeys were treated with
aflatoxin Bi.
Qualitatively and quantitatively the sequence of
preneoplastic and neoplastic events were similar in rats
irrespective of the carcinogen used. Structurally altered
hepatocytes occurred usually as small foci which later
evolved into larger areas as nodules of altered liver cells.
In monkeys treated with aflatoxin Bi changes were mild
and the lesions few. Histochemical localization of
enzymes of carbohydrate metabolism viz glycogen
synthetase, glycogen phosphorylase or glucose-6
phosphate dehydrogenase revealed no significant
change in these enzymes. No signiGcant changes were
also noticed with the other enzymes. The acidophilic
cells showed a variable pattern of staining for various
enzymes.
It appears that chemical carcinogenesis induces
multifocal hepatic glycogenosis which may be related to
development of multicentric tumours. It is probable that
metabolic disturbances leading to hepatocellular
glycogenosis might be related to the neoplastic
transformation of the hepatocytes.
Liver sections prepared from livers obtained from
medico-legal autopsies of 114 cases (55 from Madras
and 59 from New Delhi) were studied for the presence of
altered hepatocytes. Altered cell foci were observed in 19
(34.5%) cases from Madras compared to 14 (23.7%) in
New Delhi. The commonest cell type was the clear
(glycogen rich) cell and some of these foci had acidophil
cells admixed. The number of foci with acidophil cells
were more in livers obtained from Madras compared to
New Delhi.
Frequency and nature of preneoplastic hepatocellular
lesions in human and animal liver.
The study was carried out to determine the
frequency of hepatocytic alterations of preneoplastic
nature in livers of population groups with different
incidences of hepatocellular carcinoma and Wister
疙整UNITY
P. Chopra
Department of Pathology
All India Institute
of Medical Sciences
a/X
New Delhi.
故》
LIBRARY、
(
AND
\ documentation
、
UNfT
a I 八口仁
'
45
Effects and nature of corticosteroid treatment on
various serological and bronchoalveolar lavage
abnormalities in patients with sarcoidosis.
A total of 29 patients with sarcoidosis (mean age
39.5 yr) were studied to assess immunological
abnormalities in serum and bronchoalveolar lavage
(BAL) fluid. Attempts were also made to study the
relationship, if any, between these abnormalities and
clinical, physiological and radiological parameters in
patients and the effect of corticosteroid treatment on
various immunological abnormalities. None of the
patients had any evidence of mycobacterial, fungal or
parasitic infection or history of exposure to organic or
inorganic material known to cause granulomatous lung
disease. Controls (20 healthy individuals, matched for
age) had normal chest radiographs and ancillary
investigations including CT chest and bronchoscopy.
Pretreatment,' the patients with sarcoidosis had
increased total cell count, proportion of lymphocytes
and helper/inducer cells (CD4+) and CD4+/CD阡
ratio in the BAL fluid. But the proportion of B cells in
the BAL fluid was not significantly different from that
of normal subjects. Absolute lymphocyte count,
proportion of lymphocytes and helper/inducer cells
(CD4+) were decreased significantly in the peripheral
blood in patients of sarcoidosis. Levels of IgG, IgA and
IgM as also whole complement (CH50) and C3 and C4
were increased in both peripheral blood and BAL fluid
in patients. The circulating immune complexes (CICs)
were increased in the peripheral blood in patients.
Patients had /ow carbon monoxide diffusing capacity
(DLco.) Their forced vital capacity (FVC) and forced
expiratory volume in one second (FEVi) were normal.
mg/week until maintenance dose of 0.25 mg/ kg. day
was reached. Maintenance dose was given for 4-6
months. Twenty patients were followed up for clinical.
physiological and radiological improvement.
Treatment brought about significant fall in the
levels of IgG, IgA, IgM, C3.C4 and CH50 in both BAL
fluid and peripheral blood. Absolute lymphocyte
counts, the percentage of.lymphocytes as also CD3+.
CD44-, CD8+ and B cells in BAL fluid showed
significant fall. But absolute lymphocyte counts and
percentage of CD3+ and CD44- cells in the peripheral
blood increased significantly. However, in the
peripheral blood, the proportion of lymphocytes did
not change significantly after treatment whereas the
percentage of B cells decreased significantly.
Of the 20 patients who were followed up. 14
responded to treatment. Total cell counts and ihc
percentage of lymphocytes in both BAI. fluid and
peripheral blood and alveolar macrophages in BAL
fluid did not differ significantly in responders and non
responders. The proportion of CD3t cells and levels of
CH50 were higher and IgG and Ci lower in BAL tluid in
responders. Levels of IgG, IgA and CU50 were
significantly lower while IgM. C4 and CbCs were higher
in peripheral blood in responders.
Treatment resulted in significant increase in FVC
and DLco. The FEVJFVC ratio remained unchanged.
S.K. Sharma
Department of Medicine
All India Institute of
Medical Sciences
New Delhi.
Patients were treated with prednisolone, 30
mg/day (for 6 weeks), and tapered at the rate of 2.5
ICMR NEWS
The following meetings of various Expert
Groups/Task Forces of the Council were held at New
Delhi.
Expert Group on Pan Masala
February 22,. 1994
Task Force on District level
Project for Control of
Cervical Cancer
March 2-3, 1994
Task Force on Child
Psychiatric Epidemiology
March 16-17, 1994
46
Participation of ICMR Scientists in Scientific Events:
Dr. S.P. Pani, Dy. Director, Vector Control
Research Centre, (VCRC), Pondicherry, participated in
the meeting of the Steering Committee on Applied Field
Research in Tropical Diseases (of the WHO Special
Programme for Research and Training in Tropical
Diseases) at Geneva (February 7-11, 1994).
Dr. D.A. Gadkari, Dy. Director, National AIDS
Research .Institute (NARI), Pune, visited Johns
Hopkins University, Baltimore, in co. ..cction with the
preparation of a draft proposal for the next phase of
PAVE (Preparation for AIDS Vaccine Evaluation)
Project. (February 14-23, 1994)
Dr. S.P. Tripathy, Director-General, 1CMR,
participated in the meeting of the Apex Committee of
the Indo-US Vaccine Action Programmeat New Delhi
(February 21. 1994).
Dr. G.V. Satyavati, Senior Dy. Director-General,
1CMR. New Delhi, gave a Guest Lecture on"Rasayana
Concept of Ayurxeda- How Relevant is it Today?
**
a nd
also chaired the session on 'WhitherAyurveda' at the
'Update Ayurveda Conference
*
at Bombay (February
24-25, 1994). She aiso chaired the session on Medicinal
Plant Products at the 2nd International Symposium on
Innovations in Pharmaceutical Sciences, and
Technology at Ahmedabad (February 26-27, 1994).
Dr. K.N. Panicker, Dy. Director, VCRC,
Pondicherry, participated in the International
Conference on Community based Vector Control at
San Pedro Sula (March 6-9, 1994).
Dr. V. Kumaraswami, Asstt. Director,
Tuberculosis Research Centre, Mddras, participated in
the Meeting of the Filariasis Field Triafs Task Force of
the Special Programme for Research and Training in
I ropical Diseases at Geneva (March 14-16, 1994).
included various items like—display/demonstration of
specimens of medicinal plants/household herbal
products used in day-to-day practice; and
display/demonstrations of various common food items
of daily use. In addition, general science quiz and
computerized general health quiz were organised for
school children. A general health quiz competition was
held for the non-scientific employees of the ICMR
Headquarters.
Students from four Delhi Schools participated in
various quiz programmes conducted and winners in all
the competitions were given suitable prizes.
Technology Transfer Programme:
The 1CMR organized, in collaboration with the
Directorate General of Health Services, New Delhi, a
workshop for the transfer of technology for the control
of Rheumatic Fever and Rheumatic Heart Diseases at
the Primary Health Care Level at New Delhi (March 79, 1994).
Appointments:
Dr. C.R. Ramachandran, Director Grade
Scientist, has been appointed as Senior Deputy
Director-General, Division of Non-Communicable
Diseases, ICMR Headquarters.
***
National Science Day Celebrations:
The Indian Council of Medical Research
Headquarters celebrated the National Science Day at its
campus on February 28, 1994. The celebrations
***
***
The Council announces with regret the sudden
demise of Dr. Anil R. Sheth, formerly Director of its
Institute for Research in Reproduction, Bombay, on
March 13, 1994 (Please see obituary).
ICMR AIDED SYMPOSIA/SEMINARS/WORKSHOPS/COURSES/CONFERENCES
Symposium/Seminar/ Workshop/
Course/ Conference
Date & Place
Contact Address
International Conference on Safe Motherhood
in South Asia : Challenges Ahead.
March 3-5. 1994;
(at Chandigarh)
Dr. R.S. Goyal. Conference Director, SID Inter
national Conference on Safe Motherhood. SCO-809810. Chandigarh.
Indo-German Training Course and Workshop
on Application of Flow-Cytometry in Cellular
and Molecular Biology.
March 14-16. 1994;
(at Delhi)
Dr. V.P. Bhardwaj. Course Coordinator, Institute of
Nuclear Medicine and Allied Sciences. Delhi.
National Symposium on Cellular and Mole
cular Biophysics.
March 15-17, 1994：
(at Chandigarh)
Dr. M.P. Bansal. Organising Secretary, Biophysics
Symposium. Department of Biophysics. Punjab
University. Chandigarh.
47
COUNCIL'S TRAINING PROGRAMMES FOR 1994-95
...
Virology
At the National Institute of Virology, Pune:
...
Diploma in
Mayl995).
Medical
Virology (June
1994-
Medical Entomology
At the Vector Control Research Centre, Pondicherry:
Reproductive Biology
...
M>Sc in Medical Entomology (from August 1994:
for 2 years).
...
Short-term Course on Malaria, Filariasis and
Urban Vector Control for in-service candidates
(June 1994).
At the Institute for Research in Reproduction, Bombay:
...
Workshop on Gynaecologic Cytology and Immu
nocytochemistry (September 26-October 1, 1994).
Endocrinology
Laboratory Animal Technology
At the National Institute of Nutrition, Hyderabad:
…
Annual Training Course on Endocrinological
Techniques and their Applications (August 1September 16, 1994).
Nutrition
At the Laboratory Animal Information Service Centre,
National Institute of Nutrition, Hyderabad:
...
Training Course for Laboratory Animal Techni
cians (June I5-July31, 1994).
...
Training Course for Laboratory Animal Super
visors (September 12- December 10, 1994).
At the National Institute of Nutrition, Hyderabad:
...
...
Training Course in Pesticide Residue Analysis
(December 5-9, 1994).
M.Sc in Applied Nutrition (June 1,1994-February
28, 1995).
Annual Training Course in Nutrition (December 1,
1994-February 28, 1995).
Occupational Health
Clinical Pharmacology
At the Seth G.S. Medical College, Bombay:
...
Training Course in Clinical Pharmacology (March
1-25, 1994).
Haematology
At the National Institute of Occupational Health,
Ahmedabad:
...
Orientation Course on Occupational Health for
Industrial Medical Officers (September 19-24,
1994).
...
Training Course on Air Pollution Monitoring and
Risk Assessment (October 19-25, 1994).
At the Institute of Imm unohaematology, Bombay:
Training Course in Blood Group Serology and
Blood Bank Methodology for Technicians (August
、9-September 8, 1994).
...
...
Training Course in Blood Group Serology and
Blood Bank Methodology for Medical Officers
(August 9-Octobcr 7. 1994).
SOME AVAILABLE ICMR PUBLICATIONS
Price
Rs.
Nutritive Value of Indian Foods (1985), by C. Gopalan,
B.V. Ramasastri and S.C. Balasubramaniam, Revised and Updated (1989),
by B.S. Narasinga Rao, K.C. Pant and Y.G. Deosthale
18.00
Growth & Physical Development of Indian Infants and Children (1972), Reprinted 1989
10.00
Studies on Weaning & Supplementary Foods (1974), Reprinted 1984
6.00
Studies on Pre-School Children (1974), Reprinted 1984
6.00
A Manual of Nutrition . Second Edition (1974), Reprinted 1990
4.50
Low Cost Nutritious Supplements , Second Edition (1975), Reprinted 1990
3.00
Menus for Low Cost Balanced Diets and School Lunch Programmes Suitable for North India.
1 hird Edition (1977), Reprinted 1984
4.50-
Menus for Low Cost Balanced Diets and School Lunch Programmes Suitable for South India,
Third Edition (1977). Reprinted 1991
4.50
Some Common Indian Recipes and their Nutritiv Value, Fourth Edition (1977),
Reprinted 1991, by Swaran Pasricha and L.M. Rebello
10.00
Nutrition for Mother and Child, Third Edition (1978), Reprinted 1991,
by P.S. Vcnkatachala in a nd I..M. Rebello
9.00
Japanese Encephalitis in India ,Revised Edition (1980)
5.00
Some Therapeutic Diets , Fourth Edition (19X1)： Reprinted 1983, Revised 1988,
by Swaran Pasricha
4.50
Nutrient Requirements and Recommended Dietary Allowances for Indians (1990)
13.00
Lathyrism: A Preventable Paralysis, Revised Edition (1983)
3.50
A Manual of Laboratory Techniques (1983), Edited by N. Raghuramulu, K. Madhavan Nair
and S. Kalyanasundaram
30.00
Fruits (1983), by Indira Gopalan and M. Mohan Ram
7.00
Count What You Eat (1989), by Swaran Pasricha
9.00
Dietary Tips for Elderly (1992), by Swaran Pasricha
and B.V.S Thimmayamma
3.50
* Depressive Disease (1986), by A. Venkoba Rao
58.00
**The Anophelines of India Revised Edition (1984), by T. Ramachandra Rao
150.00
**Medicinal Plants of India, Vol.2 (1987)
136.00
• 10 per cent discount allowed to individuals.
• 25 per cent discount allowed to individuals.
*
These publications arc available on prepayment of cost by cheque or postal order (bank and postal charges will be extra) drawn in favour of the DirectorGeneral. 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 No.4508. Ansari Nagar, New Delhi-! 10029.
Unpriced Publications
(for limited distribution)
Proceedings of the Indo-UK Workshop on Leishmaniasis (1983)
Collaborative Study on Blindness, 1971-74 (1987)
National Task Force Study on Problems of the Aged Seeking Psychiatric Help, 1981-84 (1987)
Endomyocardial Fibrosis in India (1983)
Epidemiological Survey of Endemic Goitre and Endemic Cretinism (1989)
Illegal Abortion in Rural Areas (1989),
Perinatal Determinants of Child Survival (1989)
Contraceptive Research Today & Tomorrow (1989)
Collaborative Study on Phenomenology and Natural History of Acute Psychosis (1989)
Melatonin (1991) by Dr. S. Parvathi Devi
Field Supplementation Trial in Pregnant Women with 160mg, 120mg and 180mg of iron with 500/jg
of Folic Acid (1992)
钓
Dr. Anil. R. Sheth, PhD, FASc, FNA
(August 5, 1933—March 13, 1994)
A TRIBUTE
Dr. Anil R. Sheth, former Director, Institute for Research in Reproduction (IRR) of ICMR at Bombay,
passed away on March 13, 1994, leaving behind a vacuum which will not be easy to fill.
Dr. Sheth dedicated his entire life to research in the area of reproductive biology and to the service of the IRR.
Along with the late Dr. Shanta S. Rao, he was instrumental in bringing the Institute to its present status of national
and international repute. Through his dedicated efforts spanning over nearly four decades. Dr. Sheth contributed
significantly to the development of reproductive biology as a discipline in India, particularly through his
contributions in areas like male and female fertility regulation, studies on protein hormones, characterization, assay
and mechanism of hormone action, sperm physiology etc. He was one of the pioneers in the field of research in
Inhibin.
Dr. Sheth was Fellow of a number of major and reputed professional scientific Societies/ Associations in India
including the National Science Academy. He was a prolific science communicator and published over400 research ；
papers in both National and International Journals. He also guided many young students for their postgraduate (
degrees (25) and doctorate theses (14).
Dr. Sheth was the recipient of many honours/awards for his outstanding contributions to medical science :
including the Oration Award of the Endocrine Society of India (1985). Oration Award of the Geriatric Society of :
India (1986), Dr. Subhas Mukherjee Memorial Lecture Award of the Cryogenics Council (1988). the prestigious !
Basanti Devi Amir Chand Award of ICMR (1987), among others. He was elected Fellow of various Science :
Academies eg Indian Academy of Sciences (1988); Indian National Science Academy (1993); Maharashtra
Academy of Sciences (1989) and Gujarat Science Academy (1991).
With the sudden departure of Dr. Anil Sheth, the IRR has lost a friend, philosopher and Guide as also a
genuine well-wisher. His great desire to develop Inhibin as an antifertility agent andasa diagnostic tool for prostatic
cancer remains unfulfilled. His colleagues at the Institute will endeavour to complete this unfinished task.
Dr. Sheth has left behind many sweet lingering thoughts and memories of his jovial nature for all to cherish.
Dr. H.S. Juneja
Director
Institute for Research in Reproduction
Bombay
Editorial Board
Members
Dr. Badri N. Saxena
Dr. C.R. Ramachandran
Chairman
Dr. S.P. Tripathy
Director-General
Chief, Publication & Information
Dr. G.V. Satyavati
Editor
Dr. N. Medappa
Printed and Published by Shri J.N. Mathur for the Indian Council of Medical Research
New Delhi at the ICMR Offset Press, New Delhi
R.N. 21813/71
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