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Biomedical subjects

S Nair

Publications and source records attributed to S Nair.

At least 181 records · Page 10Linked to original sources
PubMed1996

The role of ductography in patients with nipple discharge.

The main objective of this study is to illustrate the role of ductography in the management of nipple discharge. Thirty-six patients had ductography for the investigation of blood-stained or serous nipple discharge. The ductogram findings were reviewed. Ductography showed an intraductal lesion in 13 patients, duct ectasia in 16 and normal ducts in 7. Fourteen patients had surgery. Eight had preoperative ductography using a mixture of methylene blue and contrast media. Histology revealed 5 cases of duct papilloma, 2 cases of epithelial hyperplasia, 4 cases of fibrocystic change and 3 cases of duct ectasia. Twenty had follow-up without surgery and of these, the nipple discharge ceased in 11 patients. Two patients did not come for follow-up. Ductography has a significant role in the management of nipple discharge. Firstly, surgery might be averted in patients with normal ducts or duct ectasia on ductography. Secondly, intraductal methylene blue will demonstrate the abnormal ductal system to the surgeon and allow for a less radical surgery.

Breast Diseases↗
PubMed1996

Intraventricular cryptococcal cysts.

The case of a 55-year-old immunocompetent woman with central nervous system cryptococcosis and multiple intraventricular cysts is presented. The cysts did not enhance on MR and had signal characteristics similar to cerebrospinal fluid on T1- and T2-weighted images; their intensity was lower than cerebrospinal fluid on proton density-weighted images.

Cerebral Ventricles↗
PubMed1996

Diet intervention for modifying cancer risk.

Considerable evidence suggests that dietary differences between populations account for a significant proportion of the variation in cancer occurrence in different parts of the world. A major problem has been identifying the particular dietary components which predispose or protect individuals against cancer. For example, the high rates of breast and colon cancer in the United States have been associated with numerous dietary patterns including high fat, high dietary energy, and low fruit and vegetable intakes. Our laboratories have attempted to identify mechanisms whereby diet may modify cancer and it is anticipated that future studies will determine which of these potential mechanisms may be relevant in humans. A promising lead in understanding the mechanism of high dietary fat/high dietary energy promotion of cancer was the impact of these diets on cellular protein kinase C (PKC). PKC is important in cellular signaling events which are critical to tumor promotion. Our studies demonstrated increased PKC activity and/or protein expression observed in epidermis and pancreatic epithelial cells of rodents fed high fat/energy diets. The inverse association between cancer at a number of sites and fruit and vegetable intake may be due to both micronutrient and non-nutrient components of fruits and vegetables. We have studied the prevention of skin tumor promotion by apigenin, a plant flavonoid. Apigenin may block several points in the process of tumor promotion, including inhibiting kinases, reducing transcription factors and regulating cell cycle. The complexity of our diets and the multitude of potential dietary effects which may be important in cancer development make this a fertile area for future study.

Anticarcinogenic Agents↗
PubMed1996

Informatics integration in a medical residency program: early experiences.

In 1992, Informatics training was integrated into the medical residency program at Norwalk Hospital. The program objective was to familiarize the residents with clinical applications of information technology that could enhance their productivity in clinical practice. In its first year, the curriculum was theory oriented. Evaluation of the program at the end of the first year led to a significant restructuring of the program format and curriculum. The trainees did not find theory to be of immediate clinical value, in the second year the program emphasis was redirected toward the development of practical skills. Next year, in 1993, 'Informatics Clinics' were initiated to develop practical Informatics skills that would be useful in a clinical setting. This approach was more successful but did not offer a complete solution. The degree to which the concepts and methods learned are clinically utilized by residents will depend upon the degree of reinforcement provided in the clinical residency years. In addition, there is a need for the development of assessment standards for the evaluation of Informatics literacy levels. In the absence of assessment standards the level of Informatics literacy in medical graduates remains undetermined Consequently, it is difficult to determine whether the training received has transformed expectations into reality.

Connecticut↗
PubMed1996

Non Hodgkins lymphoma of ethmoidal sinus with rhinoorbital myiasis.

A patient with primary non-hodgkins lymphoma of the paranasal sinuses presenting as rhinoorbital myiasis is reported. The myiasis causing species was identified as Chrysomia bezziana Villeneuve. This case demonstrates the extreme destruction caused by myiasis and the inadequacy of therapeutic options available in such patients.

Ethmoid Sinus↗
PubMed1995

Pilot study of human recombinant interferon gamma and accelerated hyperfractionated thoracic radiation therapy in patients with unresectable stage IIIA/B nonsmall cell lung cancer.

PURPOSE: Gamma interferon has a wide range of properties, including the ability to sensitize solid tumor cells to the effects of ionizing radiation. The North Central Cancer Treatment Group has previously completed pilot studies of accelerated hyperfractionated thoracic radiation therapy (AHTRT) in patients with unresectable Stage IIIA/B nonsmall cell lung cancer (NSCLC). This Phase I study was designed to assess the toxicity of concomitant gamma interferon and AHTRT in a similar patient population. METHODS AND MATERIALS: Between December 1991 and May 1992, 18 patients with unresectable Stage IIIA/B NSCLC were treated with daily gamma interferon (0.2 mg subcutaneously) concomitant with AHTRT (60 Gy given in 1.5 Gy twice daily fractions). All patients had an Eastern Cooperative Oncology Group performance status of 0 or 1 with weight loss < 5%. Eight patients had Stage IIIA and 10 had Stage IIIB disease. RESULTS: Nine patients (50%) experienced severe, life-threatening, or fatal toxicities. Eight of the patients (44%) developed significant radiation pneumonitis, which was severe in six patients and fatal in two patients (11% treatment-related mortality). Two patients (11%) developed severe radiation esophagitis. With follow-up of 15-21 months, 2 patients are alive, and 16 have died. The median survival time and 1-year survival rate is 7.8 months and 38%, respectively. CONCLUSION: Gamma interferon appeared to sensitize normal lung tissue to the effects of radiation, as demonstrated by the high incidence of severe or fatal radiation pneumonitis. We do not recommend pursuing gamma interferon as a radiosensitizer in this setting.

Adult↗
PubMed1995

Surface-associated proteins from Staphylococcus aureus demonstrate potent bone resorbing activity.

Staphylococcus aureus infections are associated with rapid bone destruction in conditions such as osteomyelitis, bacterial arthritis, and infected orthopedic implant failure. How this bacterium induces bone destruction has not been defined. In studies of the role of oral Gram-negative bacteria in periodontal pathology, we have established that cell surface-associated proteins (SAPs) are potent stimulators of bone resorption. The surface-associated components from S. aureus have now been isolated and demonstrated to be extremely potent stimulators of bone resorption in the murine calvarial bone resorption assay. Bone resorption appears to be due to proteins, is not the result of contamination with lipoteichoic acid or muramyl dipeptide, and is potently inhibited by indomethacin and can be completely blocked by high concentrations of interleukin-1 receptor antagonist or TN3-19.12, a neutralizing monoclonal antibody to murine TNF. The SAP fraction can stimulate fibroblasts or monocytes to release osteolytic cytokines, but only at high concentrations. Fractionation of the SAPs by high performance liquid chromatography demonstrated that a number of fractions were osteolytically active. The most active contained a heterodimeric protein of molecular weight 32-36 kD. The presence of this osteolytically active surface-associated fraction may account for the bone resorption associated with local infection with S. aureus.

Animals↗
PubMed1995

Expression of cytokine mRNA in murine splenic dendritic cells and better induction of T cell-derived cytokines by dendritic cells than by macrophages during in vitro costimulation assay using specific antigens.

Among antigen-presenting cells dendritic cells (DC) have the unique ability to generate primary T cell response. The reasons for the superior inductive property of DC still remain obscure. The explanations offered include higher expression of CD80, MHCII, and ICAMI on DC surface which allows effective cluster formation with T cells. It is also possible that additional cellular characteristics of DC, i.e., their ability to release critical mediators involved in the induction of effective immune response, are important. We examined the ability of DC to express IL-1, IL-6, and IL-12 using the highly sensitive reverse transcription-quantitative polymerase chain reaction. Our data show that highly purified (97-99% pure) murine splenic DC were capable of expressing IL-1, IL-6 and IL-12 mRNA upon stimulation with lipopolysaccharide. We also compared the ability of DC and macrophages to induce T cell-derived cytokines IL-2 and IFN-gamma in an in vitro antigen-specific costimulation assay. In naive T cells stimulated with antigen presented via DC or macrophages, the levels of mRNA for IL-2 and IFN-gamma were 2- to 4-fold higher when cells were stimulated with DC. Overall, our data add additional support to the description of DC as superior antigen-presenting cells for the activation of naive T cells.

Animals↗
PubMed1995

Priming for virus-specific CD8+ but not CD4+ cytotoxic T lymphocytes with synthetic lipopeptide is influenced by acylation units and liposome encapsulation.

Synthetic peptides of the herpes simplex virus glycoprotein B synthesized either as a free form or derivatized with one (PAM1) or three palmitic acids (PAM3Cys) were used to assess the in vivo priming efficacy of high affinity virus-specific CTL induction. The peptide and its derivatives were delivered in vivo with or without liposome encapsulation. Neither the free peptide nor the PAM1 derivative primed for high affinity virus specific CD8+ CTL induction, whether delivered via liposomes or not. On the other hand, the PAM3Cys derivative was able to prime for low levels of high affinity virus specific CD8+ CTL induction in the absence of liposome encapsulation. However, the efficiency of virus-specific CD8+ CTL induction with PAM3Cys derivative was enhanced following encapsulation in the liposomes. In contrast, all forms of the peptides induced both CD4+ T cell proliferative response as well as high affinity virus-specific CD4+ CTL. In addition, the efficiency of the PAM3Cys derivative to prime for CD4+ or CD8+ CTL was found to be influenced by the liposome encapsulation. When delivered via liposomes, the PAM3Cys derivative effectively primed for CD8+ CTL. However, liposomal delivery was not necessary for efficient priming for CD4+ CTL induction. Thus, both the acylation units as well as liposomal delivery appear to influence the in vivo priming of CD4+ and CD8+ T cell responses with synthetic peptides.

Acylation↗
PubMed1995

Mechanisms of neuronal plasticity as analyzed at the single cell level.

This chapter has highlighted how correlates of neuronal plasticity such as electrophysiological responsiveness and changes in gene expression may be examined in defined CNS regions as well as in single cells. The ability to simultaneously measure the mRNA levels for hundreds of different genes, to clone novel genes, and to characterize the physiology and morphology of the cell promises to provide insight into molecular mechanisms of plasticity. The importance of understanding how one gene product changes relative to another (coordinated changes) as well as subcellular distribution of mRNAs cannot be overstated. It is only through an analysis of both the molecular and cellular processes associated with plasticity that a thorough understanding of the mechanisms of neuronal plasticity can be gained.

Animals↗
PubMed1995

Role of macrophages and dendritic cells in primary cytotoxic T lymphocyte responses.

The successful induction of class I restricted cytotoxic T lymphocytes (CTL) responses with soluble non-replicating antigens relies upon vehicles which deliver antigen in vivo appropriately to antigen presenting cells (APC), which for CTL may be dendritic cells (DC). In this study, we have followed the distribution of liposomes and their incorporated antigen and compared the efficacy of splenic macrophages (Mo) and DC at inducing primary CTL responses in vitro. Our results show that whereas liposomes locate predominantly in the splenic red pulp and marginal zone locations, some of their soluble antigen contents redistribute to the central white pulp, comprising mainly DC and T cells. Such antigen redistribution was most apparent following administration of pH-sensitive liposomes. In comparisons of the APC activity of Mo and DC taken at various times post-injection, DC were always superior to Mo. However, if Mo were depleted prior to antigen exposure, DC were ineffective APC for CTL induction. Furthermore, addition of supernatant from OVA-liposome treated Mo to naive DC-T cell cultures in vitro resulted in OVA-specific T cell responses. These studies indicate a role for Mo in enhancing the antigen presenting function of DC.

Animals↗
PubMed1995

Lipid A-associated proteins from periodontopathogenic bacteria induce interleukin-6 production by human gingival fibroblasts and monocytes.

The aim of this study was to determine whether lipid A-associated proteins (LAP) from two periodontopathogenic species of bacteria were able to stimulate interleukin-6 (IL-6) release from human gingival fibroblasts and myelomonocytic cells. LAP and lipopolysaccharide (LPS) were extracted from Porphyromonas gingivalis and Prevotella intermedia and added to cultures of human gingival fibroblasts and mono-mac-6 monocytic cells. Release of IL-6 into the culture supernatants was determined by ELISA. LAP and LPS from Por. gingivalis, but not from Prev. intermedia, stimulated IL-6 release from both cell types in a dose-dependent manner although LPS was less potent than LAP in inducing IL-6 release from the fibroblasts. IL-6 was detectable in cultures of both cell types following stimulation with LAP from Por. gingivalis at a concentration as low as 10 ng/ml. In response to LAP from Prev. intermedia, IL-6 was produced by mono-mac-6 cells but not by fibroblasts. Our results show that bacterial cell wall components other than LPS can induce IL-6 release from cells of the periodontium in vitro. The production of such potent immunomodulatory agents in vivo may contribute to the connective tissue breakdown characteristic of chronic periodontitis.

Bacterial Proteins↗
PubMed1995

Anamnestic development of lymphocytic infiltration in murine experimental autoimmune oophoritis is primarily localized in the stroma and theca.

PROBLEM: Neonatal thymectomy performed on day 3 of life (NTX3) induces autoimmune oophoritis and ovarian failure in B6A mice. These mice develop high-titer autoantibodies specific to oocytes, and ultimately the ovaries become fibrotic and devoid of primordial follicles. These findings implicate the oocyte as a primary target of the autoimmune process. However, in previous work we demonstrated that in developing disease the lymphocytic infiltration was confined to the stroma and theca, and not found involving oocytes. Here, we investigate the possibility that lymphocytic infiltration involving oocytes develops as part of end-stage disease. METHOD: We transplanted normal syngeneic ovaries to B6A mice with confirmed autoimmune ovarian failure, and, as a control, to normal oophorectomized mice. We then defined the time course and histologic distribution of lymphocytic infiltration in the transplanted ovaries. Lymphocytes were identified by morphology with the aid of an immunohistochemical leukocyte marker (CD45). RESULTS: Autoimmune oophoritis developed by 7 days after transplantation to the NTX3 mice. Compared to control mice, in these mice we found significantly increased stromal and thecal lymphocytic infiltration. In no case did we observe lymphocytic infiltration involving oocytes. CONCLUSIONS: Our findings agree with our previous report and suggest that the ovarian failure in this model is not mediated by a direct lymphocytic attack against intact oocytes. Other immune-mediated mechanisms are responsible. The paradoxical development of high-titer oocyte-specific antibodies despite the stromal and thecal location of the lymphocytic infiltration remains to be explained.

Animals↗
PubMed1995

Murine experimental autoimmune oophoritis develops independently of gonadotropin stimulation and is primarily localized in the stroma and theca.

PROBLEM: Neonatal thymectomy performed on day 3 of life (NTX3) induces experimental autoimmune oophoritis in certain strains of mice. The disease has its onset around the time of the first estrous, suggesting the process may be gonadotropin dependent. Furthermore, one study reported that gonadotropin stimulation exacerbated the ovarian lymphocytic infiltration in NTX3 mice. Here we examine the possibility that gonadotropin stimulation of the ovary plays a role in the development of post-thymectomy autoimmune oophoritis. METHOD: Using immunohistochemistry we defined the time course and histologic distribution of the post-thymectomy ovarian lymphocytic infiltration that develops in B6A mice ([C57BL6 X A/J]F1). We detected ovarian leukocytes using a monoclonal antibody against mouse CD45/T200 and counted those positive staining cells that had the morphologic appearance of lymphocytes. We then treated NTX3 mice to determine if gonadotropin stimulation could exacerbate the disease or cause the disease to appear earlier. We also treated NTX3 mice to determine if gonadotropin suppression could reduce the severity of the disease. RESULTS: Ovarian lymphocytic infiltration was observed as early as 3 weeks after thymectomy, and, during the course of the disease, was primarily located in the stroma and theca. Gonadotropin stimulation did not exacerbate existing disease or induce an earlier onset of severe disease. Furthermore, gonadotropin suppression did not reduce the degree of lymphocytic infiltration or oocyte destruction. CONCLUSIONS: Our findings suggest that murine experimental autoimmune oophoritis develops independently of gonadotropin stimulation of the ovary.

Amino Acid Sequence↗