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Biomedical subjects

R Das

Publications and source records attributed to R Das.

At least 73 records · Page 4Linked to original sources

Prolactin as a mitogen in mammary cells.

Prolactin (PRL) acts as both a mitogen and a differentiating agent in the breast. The decision to respond to PRL as a mitogen by breast cells depends on the hormonal milieu in which the epithelial cell resides. In addition, PRL's action on the breast is regulated (1) at the level of the hormone itself; (2) at the receptor level; (3) at the level of selection of signaling pathway; and, (4) by combinations of these aspects. The development of cell lines containing only one class of the PRL receptors and showing qualitative differences in response and signaling pathways will help in understanding the pleiotropic nature of PRL action.

Adaptor Proteins, Signal Transducing↗

Technetium-MIBI as a glioma imaging agent for the assessment of multi-drug resistance.

OBJECTIVE: To explore the presence of MDR-1 drug resistance in human glioma utilizing a Single Photon Emission Computerized Tomography (SPECT) imaging agent, sesta-MIBI, and testing cases interpreted as positive for drug resistance with molecular characterization of subsequent tissue biopsy, including RNA, Northern blot analysis, and polymerase chain reaction, and in situ hybridization. METHODS: Six patients that carried a diagnosis of biopsy-proven glioma underwent dual isotope SPECT imaging with thallium 201 and technetium sesta-MIBI. All six patients underwent subsequent surgical reexcision of their tumors, and tissue was immediately flash frozen for further analysis. PolyA RNA was isolated and subsequently analyzed by both Northern blot analysis and RT-PCR utilizing an MDR-1 probe (ATCC) and MDR-1 primers. RESULTS: Four patients with SPECT concordance yielded tumors without MDR-1 expression whereas two patients with SPECT discordance yielded tumors with MDR-1 gene expression. In one discordant case we subsequently performed RT-PCR in situ amplification/ hybridisation and immunohistochemistry with, respectively, an MDR-1 sense primer with Biotin labeled probes and an MDR-1 monoclonal antibody, and both analyses revealed MDR-1 expression in tumor cells. CONCLUSION: These data support the use of SPECT technetium sesta-MIBI to evaluate the presence of MDR-1 gene expression in gliomas.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Evaluation of efficacy of methylprednisolone, prednisolone and chlorambucil in idiopathic glomerulonephritis.

Thirty adults with steroid resistant idiopathic glomerulonephritis were randomly assigned to symptomatic treatment only or to a 6-month course of methylprednisolone and prednisolone alternated with chlorambucil every other month. Patients were followed up for a period of 6 months. At the end of follow-up, 11 out of 15 treated patients were in complete or partial remission as compared with only 3 of 15 control patients. Three of the treated patients were in complete remission, as compared with none of the controls. In the treated group there was a significant improvement of renal functions during follow-up, whereas in the control group renal functions did not show any significant change. None of the patients was dropped from the study because of side-effects. Therefore, it is concluded that pulse steroid and chlorambucil treatment for 6 months favours remission of idiopathic glomerulonephritis in adults and it leads to improvement of renal function.

Adult↗

Involvement of SHC, GRB2, SOS and RAS in prolactin signal transduction in mammary epithelial cells.

The peptide hormone prolactin (Prl) regulates proliferation of normal and malignant mammary cells. In the present study we demonstrate that two Prl responsive cell lines, NOG-8 and T47D, activate the JAK2-SHC-MAPK pathway in a rapid and transient manner. Within 1 min of Prl treatment there was an increase in association of JAK2 with SHC, followed by rapid phosphorylation of both the 52 kDa and 46 kDa SHC proteins. Grb2 and Sos associated with the SHC proteins within 1-3 min of Prl treatment in these mammary cells. Within 5 min of hormone treatment we observe an increase in ras-GTP suggesting activation of ras. We also showed a rapid and transient tyrosine phosphorylation of STAT5 in proliferating T47D cells which reached its peak after 30 min of Prl treatment. These results indicate that Prl receptors, after binding the ligand, activate several pathways for signal transduction leading to mitogenesis.

Adaptor Proteins, Signal Transducing↗

Identification of a novel Bcl-2 related gene, BRAG-1, in human glioma.

Programmed cell death (apoptosis) plays a major role in embryogenesis, in mature organ homeostasis and in many disease states including cancer. Apoptosis occurs as an orderly cell-intrinsic suicide program regulated by a family of genes related to Bcl-2. Here, we describe the cloning and molecular characterization of a gene homologous to Bcl-2 from a human glioma. This gene named BRAG-1 (for brain-related apoptosis gene) has an open reading frame that encodes for a protein of 31 kDa sharing significant sequence homology with the Bcl-2 family of genes in the BH1 and BH2 regions. Northern blot analyses revealed that BRAG-1 is expressed in human gliomas as a 1.8 kb message. This gene, interestingly, was found to be expressed predominantly in normal human brain as a 4.5 kb transcript which is different in size from the message found in tumor tissues. These results suggest that BRAG-1 may be rearranged in human gliomas leading to its over-expression as a truncated transcript. Utilizing a bacterial expression vector, we produced BRAG-1 protein which was found to cross-react with a Bcl-2 monoclonal antibody, further suggesting structural and immunological similarity to Bcl-2.

Amino Acid Sequence↗

Activation of raf-1, MEK, and MAP kinase in prolactin responsive mammary cells.

The polypeptide hormone prolactin (Prl), acting through its cell surface receptors, promotes growth and differentiation in normal and malignant breast cells. We demonstrate herein that two Prl-responsive cell lines, NOG-8 normal mouse mammary epithelial and T47D human breast cancer cells, respond to Prl by rapid and transient activation of a series of kinases. Raf-1 was activated within 2-5 min of Prl treatment. This was followed rapidly by activation of MEK (MAP kinase kinase) and MAP kinase activity in these cells. Increased MAP kinase activity was accompanied by tyrosine phosphorylation of both the 42 kDa and 44 kDa isoforms. The tyrosine kinase inhibitors genestein and tyrphostin blocked the increase in MAP kinase activity as well as Prl induced growth of the T47D cells. These results indicate that the Prl receptor, after binding to Prl in mammary cells, activates the raf-MEK-MAP kinase pathway for signal transduction leading to mitogenesis.

Animals↗

Aseptic cerebral venous thrombosis associated with idiopathic ulcerative colitis: a report of two cases.

Two cases of cerebral venous thrombosis with ulcerative colitis with complete autopsy findings are reported. The diagnosis of cerebral venous thrombosis with ulcerative colitis was made during life in one case and at autopsy showed active chronic ulcerative colitis with recent cerebral venous thrombosis with cerebral infarction. In the other case active chronic ulcerative colitis and old cerebral venous thrombosis with cerebral infarction were diagnosed at autopsy. Although rare the importance of recognising cerebral venous thrombosis as a complication of ulcerative colitis has been emphasised in view of the high mortality of this complication.

Adult↗

Intraluminal brachytherapy in bile duct carcinomas.

BACKGROUND: Cholangiocarcinoma of the biliary tract is a rare tumour which has been treated with surgery, radiotherapy, chemotherapy, bypass procedures and stenting. Surgery remains the only curative treatment for these tumours, but a large proportion are unresectable. Intraluminal brachytherapy has been reported as an effective treatment for localized cholangiocarcinoma of the biliary tract. The purpose of our study was to analyse the survival of patients with biliary tract carcinoma treated with iridium-192 brachytherapy. METHODS: A retrospective review of patients treated at Peter MacCallum was undertaken. From 1989 to 1994, 16 patients underwent brachytherapy via transhepatic approach for cholangiocarcinoma. There were 12 male and four female patients. The median age was 65 (range 40-83). All patients had cholangiocarcinoma. Prior treatment included complete resection in three, partial resection in one, bypass procedures in eight, endoscopic stents in five and external biliary drainage in 15 of the 16 patients. One patient had received external beam irradiation. RESULTS: The median survival was 23 months and 61% survived 1 year. The most common acute complication was cholangitis seen in four patients and the most common late complications were duodenal ulcer seen in two patients and cholangitis seen in two patients. CONCLUSIONS: We conclude that iridium-192 brachytherapy is a safe effective treatment for biliary tract carcinoma but a comparison between surgery and stenting would be of value. However, the cost of brachytherapy is not cheap and its value in this regard should be carefully analysed.

Adult↗

Modelling epidemics with variable contact rates.

In this paper we look at models for epidemics where the contact rate is a monotone increasing function of the population density. The background death rate also depends on the population density. We first examine the case of a constant contact rate (motivated by AIDS) and here obtain some global stability results. We consider an SIR model where a typical individual starts off susceptible, at some stage catches the disease and after a short infectious period becomes permanently immune. We also look at the effects of vaccination. First we perform an equilibrium and local stability analysis. Next we reformulate the model in terms of the proportions of individuals susceptible, infected, and immune to obtain some global stability results. We find three possible equilibrium values: one where the population is extinct, one where the disease has died out but the population has not died out, and a unique equilibrium where disease is present. We determine conditions for global stability of these equilibria. For certain parameter values none of these equilibria are locally stable. In this case there is a formal proportional endemic equilibrium with a strictly positive proportion of infected individuals. We expect the population size to die out but the proportions of susceptible, infected, and immune individuals to tend to this endemic proportional equilibrium. We find two critical contact rates which help determine the behaviour of the system. Next we extend some of these results to the case where the contact rate depends on population density. Finally the paper examines these results further using numerical methods.

Acquired Immunodeficiency Syndrome↗

Transduction of prolactin's (PRL) growth signal through both long and short forms of the PRL receptor.

The genes for the long form of the human and the short form of the mouse PRL receptors were transfected independently into NIH 3T3 cells. Reverse transcriptase-polymerase chain reaction indicated that the transfectant designated LFH contained message for only the long form and the transfectant designated SFM had message for only the short form of the receptor. Both transfectant cell lines specifically bound lactogenic hormones with high affinity and responded to PRL in culture with a 2- to 3-fold increase in cell number preceded by transient activation of mitogen-activated protein kinase. After a PRL-responsive casein-chloramphenicol acetyl transferase (CAT) construct was introduced into both LFH and SFM cells, CAT activity was induced by PRL only in the LFH-CAT cells. Thus, while the long form of the receptor can transduce the differentiation signal, both the long and the short forms of the receptor can signal the cells to grow.

3T3 Cells↗

Health of the elderly in a community in transition: a survey in Thiruvananthapuram City, Kerala, India.

Results of a survey to assess the health and functional status of the elderly (defined as those who are 60 years or older) in Thiruvananthapuram city, the capital of Kerala state, India, are discussed. As the process of development results in longevity without concomitant economic success, traditional support systems break down. The differences in status of the elderly dependent on gender and socioeconomic class are highlighted. Women are poorer and generally suffer more morbidity than men in old age, even though their death rates are lower. The better-off among the elderly enjoy a quality of life much superior to their poor brethren. Thus, in transitional societies such as Kerala, socioeconomic status and gender play a significant role in determining the quality of life of the elderly, a finding which may have some policy implications.

Aged↗

Persistent respiratory health effects after a metam sodium pesticide spill.

STUDY OBJECTIVE: To report the occurrence of persistent respiratory disorders, including irritant-induced asthma, among adults living and working near an environmental spill of the pesticide, metam sodium, after the derailment of a tank car. DESIGN: Retrospective clinical case series. SETTING: California communities situated within one-half mile of the Sacramento River, from Mt. Shasta City to Shasta Lake. PATIENTS: 197 adults referred to a university occupational/environmental health clinic or to a private occupational/environmental health practitioner for evaluation of health problems potentially related to the spill. MEASUREMENTS AND RESULTS: History, physical examination, review of medical records, spirometry, and methacholine challenge testing revealed 20 cases of persistent irritant-induced asthma and 10 cases of persistent exacerbation of asthma. CONCLUSIONS: This is the first reported series of cases of persistent irritant-induced asthma involving both community residents and occupationally exposed individuals.

Adult↗

Structure, spectroscopic, and redox properties of Rhodobacter sphaeroides reaction centers bearing point mutations near the primary electron donor.

Single mutations of three amino acid residues in the vicinity of the primary electron donor, P, in the reaction center (RC) from Rhodobacter (Rb.) sphaeroides were constructed and characterized in order to study the effects of hydrogen-bonding on the physical properties of P. The mutations, Phe M197-->Tyr, Met L248-->Thr, and Ser L244-->Gly, represent single amino acid changes near P designed to introduce residues found in Rhodopseudomonas (Rps.) viridis and to, thus, probe the effects of nonconserved residues. The mutations were designed to change the nonconserved H-bonding interactions of P in Rb. sphaeroides, at the level of a C2 acetyl, a C9 keto, and a C10 ester carbonyl of P, respectively, to those present in Rps. viridis. The Fourier transform (pre)resonance Raman (FTRR) spectra of P, in its reduced and oxidized states, from reaction centers of these mutants were studied to determine modifications of H-bond interactions of the pi-conjugated C2 acetyl and C9 keto carbonyl groups and the C10 carbomethoxy ester carbonyl groups of P. The vibrational spectra of reduced P in the Met L248-->Thr and Ser L244-->Gly mutants reveal no evidence for changes in the H-bonding pattern of P; this suggests that for Rb. sphaeroides wild type, Ser L244 is not H-bonded to the C10 ester carbonyl of PL. The vibrational spectrum of reduced P from the Phe M197-->Tyr mutant compared to that of wild type can unambiguously be interpreted in terms of the formation of a new H-bond with an acetyl carbonyl of P, specifically PM. Correlating with the new H-bond, the Phe M197-->Tyr mutant exhibits an electronic absorption spectrum where the P absorption band is significantly perturbed. Intact cell and chromatophore photobleaching spectra of the same mutant indicate that the P absorption band has red-shifted by ca. 10 nm; no such behavior is observed for the other mutants. As well, the P-->BPheL electron transfer rate does not seem to strongly depend on the H-bonding of the C2 acetyl carbonyl of PM to a tyrosine residue. The EPR zero-field splitting parameters, E and D, of the primary donor triplet are only slightly modified in the mutant reaction centers, on the order of 1%.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacteriochlorophylls↗

What is vestibular papillomatosis? A study of its prevalence, aetiology and natural history.

OBJECTIVES: To clarify the prevalence, aetiology, symptoms and natural history of vestibular papillomatosis. DESIGN: Study in two parts: 1. prevalence assessed by colposcopic examination of the vulva of unselected patients by one doctor (J.M.W.); 2. patients selected by clinical appearance as having vestibular papillomatosis (by J.M.W. and other doctors) assessed in a research clinic. SETTING: Outpatient genitourinary medicine clinic in South London. SUBJECTS: Part 1 study: 295 female clinic attenders; part 2 study: 18 women with clinical vestibular papillomatosis. MAIN OUTCOME MEASURES: Part 1 study: number of unselected patients found to have vestibular papillomatosis. Part 2 study: associated symptoms, histology, DNA hybridisation and polymerase chain reaction on vulval biopsies. Clinical regression of lesions. Cervical cytology and colposcopy. RESULTS: Part 1 study: Vestibular papillomatosis was identified by colposcopic examination of the vulva in 3/295 (1%) of women. Part 2 study: 9/18 (50%) women with vestibular papillomatosis were asymptomatic; the other nine had intermittent mild symptoms. Thirteen (72%) had a history of genital warts. Vulval biopsies had features suggestive of wart virus infection on histology in 17/18 (94%) and HPV16 was found by DNA hybridisation studies or polymerase chain reaction in 7/18 (39%). On follow up (mean duration 9 months) the vulval lesions had regressed in 9/12 patients. Ten patients had cervical wart virus infection or intraepithelial neoplasia (CIN), or both, and five needed laser treatment for this. CONCLUSIONS: In this study vestibular papillomatosis was associated with human papillomavirus (HPV) infection. This study suggests that vestibular papillomatosis need not be treated, but patients with it may be at increased risk for CIN.

Adolescent↗

Myxoid variant of primary cutaneous malignant melanoma.

We report a rare case of primary cutaneous myxoid melanoma. Histologically, the tumour was composed of spindle and stellate-shaped cells, embedded in a myxoid stroma. Positivity for S-100 protein and the presence of melanosomes were demonstrated in the tumour. Primary cutaneous myxoid melanoma is rare. This is the second report of such a case.

Aged↗

Lymphoma.

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Hodgkin Disease↗