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Biomedical subjects

S Kaur

Publications and source records attributed to S Kaur.

At least 91 records · Page 5Linked to original sources
PubMed1999

Prolactin controls mammary gland development via direct and indirect mechanisms.

The inactivation of the prolactin receptor gene by homologous recombination has made it possible to investigate the role of prolactin signaling in mammary gland development without resort to ablative surgery of the endocrine glands. In knockout mice lacking the prolactin receptor, mammary development is normal up to puberty. Subsequently, the ducts branch less frequently than those of wild-type animals. While terminal end buds differentiate to alveolar buds in wild-type females by the end of puberty, in knockout females terminal end bud-like structures persist at the ductal ends. To distinguish between the developmental defects that are intrinsic to the epithelium and those that result from systemic endocrine alterations in prolactin receptor knockout mice, mammary epithelium from prolactin receptor knockouts was transplanted into mammary fat pads of wild-type mice. In virgin mice, the knockout epithelial transplants developed normally at puberty, indicating an indirect effect of prolactin on ductal development. Prolactin receptor knockout females are infertile due to multiple reproductive defects, but epithelial transplants allowed us to assess the extent to which the absence of prolactin receptor is limiting, under systemic conditions that allow full mammary gland development. During pregnancy, the prolactin receptor knockout transplants showed normal side branching and the formation of alveolar buds, but no lobuloalveolar development. Thus, prolactin affects mammary morphogenesis in two different ways: it controls ductal side branching and terminal end bud regression in virgin animals via indirect mechanisms, but acts directly on the mammary epithelium to produce lobuloalveolar development during pregnancy.

Animals↗
PubMed1999

Genotoxicity of wastewater samples from sewage and industrial effluent detected by the Allium root anaphase aberration and micronucleus assays.

The genotoxicity of wastewater samples from sewage, and industrial effluent from the Amritsar, India, area were investigated using the Allium micronucleus and anaphase aberration assays. Raw sewage samples and acetone extracts of the dehydrated sewage were use for treatment of the Allium roots. Industrial effluents were collected and stored in the form of sludge (semi-dried matter). The acetone extracts of the sludge samples were also used for treatment of the Allium roots. From the Allium root micronuclei tests on the sewage extracts, no significant increase in the number of micronuclei was found in comparison with negative controls. All the other extracts from industrial effluent showed positive responses both in the micronucleus and anaphase aberration assays.

Allium↗
PubMed1999

Importance of the carboxyl terminus in the folding and function of alpha-hemolysin of Staphylococcus aureus.

The physical state of two model mutants of alpha-hemolysin (alphaHL), alphaHL(1-289), a carboxyl-terminal deletion mutant (CDM), and alphaHL(1-331), a carboxyl-terminal extension mutant (CEM), were examined in detail to identify the role of the carboxyl terminus in the folding and function of native alphaHL. Denatured alphaHL can be refolded efficiently with nearly total recovery of its activity upon restoration of nondenaturing conditions. Various biophysical and biochemical studies on the three proteins have revealed the importance of an intact carboxyl terminus in the folding of alphaHL. The CDM exhibits a marked increase in susceptibility to proteases as compared with alphaHL. alphaHL and CEM exhibit similar fluorescence emission maxima, and that of the CDM is red-shifted by 9 nm, which indicates a greater solvent exposure of the tryptophan residues of the CDM. In addition, the CDM binds 8-anilino-1-naphthalene sulfonic acid (ANS) and increases its fluorescence intensity significantly unlike alphaHL and CEM, which show marginal binding. The circular dichroism studies point that the CDM possesses significant secondary structure, but its tertiary structure is greatly diminished as compared with alphaHL. These data show that the CDM has several of the features that characterize a molten globule state. Experiments with freshly translated mutants, using coupled in vitro transcription and translation, have further supported our observations that deletion at the carboxyl terminus leads to major structural perturbations in the water-soluble form of alphaHL. The studies demonstrate a critical role of the carboxyl terminus of alphaHL in attaining the native folded state.

Bacterial Toxins↗
PubMed1999

Size fractionation of bacterial capsular polysaccharides for their use in conjugate vaccines.

We have developed a chromatographic method suitable for the fractionation of polysaccharides having a negatively charged group. The method permits the removal of all those polysaccharide fragments having a short sequence and which are likely unsuitable for conjugate vaccine construction. The selected polysaccharide fragments can be used to produce glycoconjugate vaccines containing a restricted saccharide polydispersion. We have applied this chromatographic method to three different antigens, Haemophilus influenzae type b and Neisseria meningitidis group A and group C polysaccharides. The method is easily adapted for manufacturing purposes.

Antigens, Bacterial↗
PubMed1999

Calcium metabolism in pre-eclampsia.

OBJECTIVES: To study calcium metabolism in pre-eclampsia and normotensive gravid women. METHOD: Ten milliliters of heparinized blood samples and 24-h urine samples were collected from 50 pre-eclamptic and 50 normotensive primigravidae. Blood samples were studied for calcium uptake, intracellular calcium level and calcium-dependent adenosine triphosphatase activity of red blood cell ghost. Urinary calcium excretion was estimated from the 24-h urine samples. These values were compared in the two groups. RESULTS: The mean gestational age at recruitment was similar in both the groups. The mean maternal age was 24.28 +/- 2.41 years in pre-eclamptic and 23.48 +/- 4.16 years in normotensive women. In pre-eclampsia 24-h urinary calcium excretion (71.20 +/- 22.95 mg/day) and calcium-dependent ATPase activity (10.78 +/- 2.40 nmol/Pi/mg protein/min) was significantly lower compared to normotensive primigravidae (calcium excretion = 189.24 +/- 57.06 mg/day; Ca2+-dependent ATPase = 12.64 +/- 2.42 nmolPi/mg /protein per min; P < 0.001). Intracellular calcium levels and calcium uptake at 10 min by red blood cells were significantly higher in pre-eclampsia (P < 0.05). Calcium uptake by red blood cells at 20 and 30 min was similar in both groups. CONCLUSION: Pre-eclampsia is associated with increased levels of intracellular calcium, decreased calcium-dependent ATPase activity of erythrocytes and hypocalciuria.

Adult↗
PubMed1999

Role of GABA-A receptor in the preoptic area in the regulation of sleep-wakefulness and rapid eye movement sleep.

The role of GABA in medial preoptico-anterior hypothalamic area in the regulation of spontaneous sleep-wakefulness and rapid eye movement sleep was investigated in this study. Local microinjection of picrotoxin, a GABA-A antagonist, into this area increased quiet wakefulness but significantly reduced deep sleep and rapid eye movement sleep. Both the frequency of generation and duration per episode of the latter were significantly reduced. It is concluded that GABA-ergic neurotransmission in the medial preoptic area is spontaneously active in modulating the hypnogenic function including rapid eye movement sleep and the action is mediated by GABA-A receptor.

Animals↗
PubMed1999

Transjugular intrahepatic portosystemic shunt (TIPS) for Budd-Chiari syndrome or portal vein thrombosis: review of indications and problems.

OBJECTIVE: The aim of this study was to evaluate the role of transjugular intrahepatic portosystemic shunt (TIPS) in patients who present with portal vein thrombosis (PVT) or Budd-Chiari Syndrome (BCS). METHODS: Nine patients with recent PVT and four patients with BCS underwent TIPS. The diagnosis was confirmed by color Doppler ultrasound and by angiogram in most patients. Patients were followed clinically and had TIPS checked periodically for patency. The end point was mortality, subsequent surgical shunting or orthotopic liver transplantation (OLT). RESULTS: TIPS was placed in 13 of 15 (87%) patients with BCS or PVT. The mean decrease in pressure gradient was 56%. Median and mean follow-up were 14 months and 16.9 months. Procedure related complications occurred in two of 13 (15%), both in the PVT group. Direct procedural mortality was one of 13 (8%). The majority of patients with PVT (five of eight) underwent OLT. Of the remaining three, one patient subsequently developed a cavernous transformation of portal vein but is stable, one patient is stable, without further variceal bleeding, and one patient died because of multiple organ failure. In patients with BCS, three of four (75%) did well with TIPS, but one patient required immediate surgical shunting after occlusion of the TIPS. Two patients underwent OLT and the fourth patient is stable 2 yr later but has cirrhosis on biopsy. CONCLUSIONS: In patients with BCS, TIPS placement is effective and can be used as a bridge to liver transplantation. TIPS in the noncavernous PVT group should only be recommended when cirrhosis and uncontrollable variceal bleeding are present.

Adult↗
PubMed1999

Colorectal liver metastasis thymidylate synthase staining correlates with response to hepatic arterial floxuridine.

We assessed whether intensity of colorectal liver metastasis staining with the thymidylate synthase (TS) antibody TS106 predicted response to hepatic arterial infusion (HAI) of floxuridine chemotherapy. Liver metastasis biopsies were taken during laparotomy for hepatic arterial cannulation and stained using the TS106 monoclonal antibody. Staining intensity was designated at histological examination by two independent assessors as either "high" or "low." Patients were treated by HAI, and liver metastasis response was assessed by comparison of computed tomography scan tumor volume before and after 4 months of treatment. A significant correlation (Fisher's exact test, P = 0.01) was noted between partial response to HAI and TS106 staining intensity in patients with colorectal liver metastases. Seventy-five percent of patients with evidence of a partial response had low TS staining compared with 29% of nonresponders. There was a significant difference (Fisher's exact test, P = 0.01) in the proportion of low (9 of 16) compared with high (3 of 20) TS staining tumors in which a partial response occurred. There was no significant difference (logrank test, P = 0.4) in survival from hepatic cannulation and HAI treatment of high (median, 322 days; interquartile range, 236-411) compared with low (median, 335 days; interquartile range, 301-547) TS staining patients. This study demonstrates an inverse correlation between TS immunohistochemical staining intensity in colorectal liver metastases and response to HAI. The results suggest that a prospective assessment of TS staining intensity in colorectal liver metastases would be useful to determine whether this method can be used to define patients who will benefit from HAI chemotherapy.

Aged↗
PubMed1999

Immunohistochemical co-expression of c-erbb-2/Neu oncoprotein, altered tumour suppressor (p53) protein, EGF-R and EMA in histological subtypes of infiltrating duct carcinoma of the breast.

Carcinoma of the breast has an unpredictable biological behaviour. Several oncogenes have been implicated in the progression of breast cancer. Immunohistochemical staining of c-erbB-2 (Neu) oncoprotein and mutant p53 protein on 45 cases of infiltrating duct carcinoma (IDC) of the breast revealed 33% membrane positivity of c-erbB-2 oncoprotein, 46% nuclear positivity of mutated p53 protein, 33% and 84% membrane positivity of EGF-R and EMA respectively. Staining profile of c-erb-B2 oncoprotein in various histological subtypes of IDC of the breast indicated a high positivity rate in comedo followed by NOS and cibriform subtype. Similarly, high incidence of immunopositivity of mutated p53 protein was observed in comedo and cibriform subtypes while papillary carcinoma were found exclusively positive for mutated p53 protein. Interestingly, tubular subtype of IDC was not positive for c-erbB-2 oncoprotein as well as p53 mutant protein. Further, comedo and cibriform subtypes of IDC revealed 'high grade' histological features of tumour of the breast with high mitotic count, presence of marked pleomorphism and multinucleation thus, reflecting a positive relationship with overexpression of c-erbB-2 (Neu) oncoprotein as well as mutant p53 protein. The results on immunoexpression of c-erbB-2 oncoprotein and mutated p53 protein in various histological subtypes of IDC of the breast demonstrated c-erbB-2 status as an important predictor and also indicated that oncogene product may be involved in growth factor response pathway.

Breast Neoplasms↗
PubMed1999

Epichlorohydrin induced biochemical changes in the rose-ringed parakeet, Psittacula krameri Scopoli.

Intraperitoneal administration of epichlorohydrin (ECH) at the dose level of 20 and 50 mg/kg body weight inhibited spermatogenesis in the testis of parakeet during breeding season. A total load of 60 mg/kg body weight of ECH given on 3 consecutive days proved to be lethal. Testicular proteins, nucleic acids (DNA and RNA), phospholipids and acid phosphatase activity were decreased, while the lipids, total cholesterol and alkaline phosphatase activity increased after ECH administration. The results suggest that the testicular atrophy caused by ECH was associated with an alteration in the activities of macromolecules and enzymes related to specific events of spermatogenesis.

Animals↗
PubMed1998

Antimutagenicity of hydrolyzable tannins from Terminalia chebula in Salmonella typhimurium.

A tannin fraction (TC-E) from the dried fruit pulp of Terminalia chebula was obtained by successfully extracting with 95% ethyl alcohol and ethyl acetate. TC-E was subjected to silica gel chromatography which yielded four fractions, viz., TC-EI, TC-EII, TC-EIII and TC-EIV. Thin layer chromatography (TLC) and 13C-NMR revealed that TC-EI was gallic acid (GA) derivative while the other fractions were tannin in nature. TC-E and its fractions were evaluated for their antimutagenic potential against two direct-acting mutagens, 4-nitro-o-phenylenediamine (NPD) and 4-nitroquinoline-N-oxide (4NQNO), and S9-dependent mutagen, 2-aminofluorene (2AF) in TA98 and TA100 strains of Salmonella typhimurium. The study revealed that the extract (TC-E) and its fractions were highly significant against S9-dependent mutagen, 2AF. The effect was found to be more or less corresponding with the nature of the fractions, as the monomeric TC-EI (a GA derivative) was least effective as compared to other fractions which were oligomeric, and the order of their effectiveness as per their IbD50 value being TC-EIV (8.9 micrograms)>TC-EIII (17.8 micrograms)>TC-EII (45 micrograms)>TC-EI (320 micrograms) in TA98; TC-EIV being 40 times more effective than TC-EI in inhibiting his+ revertants. A similar effect was noticed in TA100 too, where TC-EI was the least effective and TC-EII had the maximum effect. A similar result was noticed when the antimutagenicity of GA (a monomeric) was compared with tannic acid (TA, an oligomeric). However, chebula tannins were found to be partly effective against NPD but not at all effective against 4NQNO.

Antimutagenic Agents↗
PubMed1998

The granulin/epithelin precursor abrogates the requirement for the insulin-like growth factor 1 receptor for growth in vitro.

3T3 cells null for the type 1 insulin-like growth factor receptor are refractory to stimulation by a variety of purified growth factors that are known to be required for the stimulation of other 3T3 cells. However, these cells, known as R- cells, grow in serum-supplemented medium and also in media conditioned by certain cell lines. We report here the purification of a growth factor that stimulates DNA synthesis (and growth) of R- cells. The growth factor, purified to homogeneity by SDS-polyacrylamide gel electrophoresis, was identified as the granulin/epithelin precursor by an accurate determination of the masses of endoproteinase Lys-C peptides using matrix-assisted laser desorption ionization mass spectrometry, followed by a data base search. The granulin/epithelin precursor is a little known growth factor, secreted by a variety of epithelial and hemopoietic cells. It is at present the only purified growth factor that can stimulate the growth of mouse embryo fibroblasts null for the type 1 insulin-like growth factor receptor.

3T3 Cells↗
PubMed1998

Ethnic differences in expression of susceptibility marker(s) in rheumatic fever/rheumatic heart disease patients.

The ability of monoclonal antibodies (MAb) against a human B lymphocyte alloantigen has been suggested to discriminate between rheumatic fever "susceptible" individuals and persons with a lower risk of developing RF. However, while such MAb have been reported to identify a majority of RF/RHD patients in some populations, a reduced discriminatory ability has been observed in others. Antigenic variation in the RF marker(s) may exist among ethnic groups which reduce the discriminatory ability of these monoclonal antibodies. We developed MAb using B lymphocytes from RF patients of North Indian ethnic origin. In this same population we compared the new MAb (PGI/MN II) with a previously described MAb of Caucasian ethnic origin (D8/17). In three groups: acute rheumatic fever patients (no evidence of previous attacks of rheumatic fever), patients with chronic rheumatic heart disease and normal controls from the same population, we found a greater discriminating ability of PGI/MNII MAb to identify Indian RF/RHD patients than with the D8/17 MAb. Further, sixty percent of 142 siblings of the RF/RHD patients were "positive" when tested with PGI/MN II. The data from these studies suggest that before such MAb can be used for identification of RF "susceptibles" in public health programs, variation among ethnic populations must be assessed.

Adolescent↗
PubMed1998

Alterations in early biochemical events following T cell activation in leprosy patients.

The early events of activation and cytokine profiles (IL-2, 4, and 6) were studied in lymphocytes of paucibacillary (TT/BT) and multibacillary (BL/LL) leprosy patients after stimulation with PMA/A23187 and Mycobacterium leprae antigen (PGL-1). Lymphocytes from BT/TT patients showed proliferation in response to both PMA/A23187 and PGL-1 compared to BL/LL. The levels of early activation signaling molecules such as IP3, calcium, and protein kinase C (PKC) in the particulate fraction were found to be elevated in BT/TT and BL/LL patients and showed a further significant increase after stimulation with PMA/A23187 in BT/TT patients. PGL-1 marginally increased the IP3 levels in BT/TT patients, whereas in BL/LL patients, it had no effect. The levels of IL-2 were enhanced in lymphocytes of BT/TT leprosy patients and were further augmented by PPD and PGL-1, while the levels of IL-4 and IL-6 were increased in LL/BL lymphocytes and further augmented by PGL-1. Thus PGL-1 seems to be a major culprit in inducing the TH2-type cytokine response observed in lepromatous leprosy patients.

Antigens, Bacterial↗