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Biomedical subjects

D Suri

Publications and source records attributed to D Suri.

12 recordsLinked to original sources

A case of ACTH-independent bilateral macronodular adrenal hyperplasia and severe congestive heart failure.

Cortisol secretion in ACTH independent bilateral macronodular adrenal hyperplasia (AIMAH) can be regulated by aberrant adrenal receptors. We describe a patient with Cushing's syndrome (CS) due to AIMAH and concomitant Class IV congestive heart failure (CHF). Clinical testing for the presence of aberrant receptors revealed a pronounced serum cortisol (257%) and aldosterone response (212%) to the administration of ACTH and a partial serum cortisol (35%) and aldosterone (106%) response to upright posture. This suggested the possible presence of aberrant hormone receptors for ACTH [melanocortin 2 receptor (MC2-R)], vasopressin, catecholamines or angiotensin II (AT-II) on the patient's adrenal glands. Adrenal tissue from the patient demonstrated an eight-fold increased expression of MC2-R compared to normal adrenal tissue. This increased expression was consistent with the increase in cortisol and aldosterone seen in response to exogenous ACTH. We propose that the severe CHF resulted in activation of the renin-angiotensin system, with an increased production of AT-II. The elevated circulating levels of AT-II may have led to increased expression of MC2-R on the patient's adrenal glands and increased responsiveness to ACTH. This unusual case of CS may elucidate a heretofore unknown mechanism for the development of AIMAH.

Adrenal Glands↗

Non-cytolytic inhibition of hepatitis B virus replication in human hepatocytes.

BACKGROUND/AIMS: Interferon-gamma (IFN-gamma) has been shown to abolish hepatitis B virus (HBV) gene expression and replication in HBV transgenic mice without destroying infected hepatocytes. We investigated the characteristics of IFN-gamma induced non-cytolytic inhibition of viral replication in human HBV infection. METHODS: We used an in vitro model where lymphocytes from 15 HBsAg positive patients were co-cultured with transfected hepatocytes supporting HBV replication. The effector and target cells were separated by a membrane, which allowed transfer of soluble factors only, to determine whether IFN-gamma produced from antigen-specific CD4+ T cells or mitogen stimulated lymphocytes inhibits HBV replication. RESULTS: IFN-gamma produced following lymphocyte stimulation reduced cytoplasmic HBV DNA in the target cells. The degree of HBV DNA reduction correlated with the level of IFN-gamma in the supernatants. Further investigations using naturally infected human hepatocytes confirmed that recombinant IFN-gamma reduces HBV DNA and HBV RNA in these cells as well, in parallel with the induction of cellular interferon-responsive genes. This antiviral effect was without significant cytotoxicity and was more pronounced in hepatocytes from patients with low HBV replication. CONCLUSIONS: These results provide direct evidence that IFN-gamma can inhibit both HBV transcription and replication in human hepatocytes without cell lysis.

Adult↗

Influence of donor factors on early function of graft kidneys.

Factors which influence graft function can be divided into donor factors that affect both kidneys from the same donor equally and postdonor factors that affect each kidney individually. This study assessed the influence of donor factors on graft function early after transplantation. Sixty-one donors who provided kidneys that were transplanted locally into two separate recipients were identified. Recipient creatinine clearance values were estimated from serum creatinine concentrations using a computer model. Pairwise ANOVA showed that donor factors accounted for 35 to 45% of the variation in recipient creatinine clearance from 2 d to 2 wk posttransplantation. Although donor factors had a large aggregate effect during this period, individual factors that influenced graft function could not be identified from analysis of donor medical records. At 6 mo after transplantation, the effect of donor factors on graft function was no longer discernible. These results show that the condition of the donor exerts an important influence on graft function early after transplantation. More detailed study is required to identify individual factors that contribute to this effect.

Adolescent↗

Responses in animals vaccinated with the Theileria annulata (Hisar) cell culture vaccine.

Bovine tropical theileriosis caused by Theileria annulata is an economically important disease of cattle in India. The disease has assumed paramount importance with the intensification of cross-breeding programmes aimed at enhancing milk production in the country. To control this disease, a cell culture vaccine was developed in this department by continuous passaging of T. annulata (Hisar) schizonts in vitro. Current work in this department has concentrated on the epidemiology of theileriosis: development of the cell culture vaccine for very young calves and pregnant cows; evaluation of serological responses using immunofluorescent antibody (IFA) tests and Enzyme-linked immunosorbent antibody assays (ELISA); studies on the duration of immunity stimulated by the cell culture vaccine; the immune/susceptible status of calves born to vaccinated dams. Results have shown the following. Clinical cases of theileriosis were mainly observed in young calves below two months of age followed by adults in exotic and cross-bred animals. Amongst indigenous animals, only young calves below two months of age suffered from clinical disease. Clinical cases of theileriosis mainly occurred between the months of April to October. The T. annulata schizont cell culture vaccine developed in the department was extensively used in the susceptible calves and pregnant/lactating cows in the field. Sufficiently high antibody titres were detected by both schizont as well as piroplasm antigen using both ELISA and IFAT. The results indicated that the vaccine was safe, potent and effective for all breeds and age groups of cattle under field conditions. ELISA was standardised for T. annulata using three antigens, viz.: soluble piroplasm, soluble schizont and cellular schizont antigens. Comparison of results with IFAT showed that ELISA is more sensitive, objective, reliable and specific as well as less cumbersome than IFAT. Piroplasm, cellular schizont and soluble schizont antigens were found to be suitable for the detection of antitheilerial antibodies as per their order in ELISA. Studies on the duration of immunity stimulated by the T. annulata schizont cell culture vaccine indicated that immunity started waning after six months. Calves born of dams immunised against T. annulata with the cell culture vaccine were found to be fully susceptible to theileriosis soon after birth. This indicated that there was no passive transfer of immunity from dams to their offspring through colostrum.

Animals↗

Race and clinical outcome in breast cancer in a series with long-term follow-up evaluation.

PURPOSE: To compare the outcome of African American (AA) and Caucasian (C) breast cancer patients who had equivalent disease extent and were similarly treated. PATIENTS AND METHODS: We compared prognostic characteristics, treatment, and outcome of 1,037 C and 481 AA breast cancer patients treated with mastectomy between 1946 and 1987. The median follow-up duration was 15.6 years. RESULTS: During the study period, there was a successive increase in the percent of patients who presented with early breast cancer. Between 1980 and 1987, 35.1% AA versus 47.6% C patients had < or = 2-cm tumors and 50.0% AA versus 61.9% C patients were node-negative, while between 1946 and 1959, 27.7% AA and 31.3% C had < or = 2-cm tumors and 41.5% AA versus 40.4% C patients were node-negative. The treatments were similar during the study period. The 20-year disease-free survival (DFS) rate of AA compared with C patients with node-negative < or = 2-cm, 2.1- to 4-cm, and greater than 4-cm tumors and of patients with one to three and > or = four positive nodes was not significantly different. Equal-size tumors had similar proportion of positive axillary nodes in AA compared with C patients. The DFS for AA patients compared with C patients was similar in the periods 1946 to 1959, 1960 to 1969, and 1970 to 1979, but was lower between 1980 and 1987 (P = .02). In multivariable analysis, race was not a significant variable. CONCLUSION: In this large group of uniformly treated breast cancer patients, race was not an independent factor that influenced outcome. The racial differences seen between 1980 and 1987 are likely because of a larger percent of greater than 2-cm and node-positive tumors in AA patients. Education and access to early diagnosis should reduce or eliminate the racial differences seen.

Actuarial Analysis↗

Stimulation of alpha 1 (I) procollagen gene expression in NIH-3T3 cells by the human T cell leukemia virus type 1 (HTLV-1) Tax gene.

The mechanisms that regulate the expression of genes encoding extracellular matrix proteins in fibroblasts and other mesenchymal cells have remained elusive. Studies from several laboratories have indicated that Tax, a trans-regulatory protein from the human T cell leukemia virus type I not only augments viral gene expression but also triggers the expression of various cellular genes. Here, we examined the hypothesis that the expression of collagen genes may also be modulated by Tax. NIH-3T3 cells were simultaneously transfected with a Tax expressor plasmid and a chimeric construct containing regulatory sequences (-804 to +42 bp) of the alpha 1(I) procollagen gene (COL1A1) promoter. The results indicated that the promoter activity of the -804 to bp COL1A1 fragment increased up to 12-fold in cells expressing Tax. Deletion analysis revealed that the region of COL1A1 encompassing nucleotides -174 to -84 contained the Tax-responsive elements. A gene segment encompassing nucleotides -187 to -67, which contained this region, proved sufficient to confer Tax inducibility (2.5-fold) to a herpes simplex virus thymidine kinase promoter. Stably transfected NIH-3T3 cell clones that constitutively produce Tax displayed elevated levels of alpha 1(I) procollagen and fibronectin transcripts and increased production and accelerated processing of type I procollagen. These findings suggest that retroviral proteins may be involved in the pathogenesis of idiopathic diseases accompanied by collagen overproduction.

3T3 Cells↗

The pituitary gland is capable of responding to two successive doses of growth hormone releasing hormone (GHRH)

We have studied the serum growth hormone (GH) response to two consecutive doses of growth hormone releasing hormone (GHRH) (50, 100, 200 micrograms) given 1, 2 or 3 h apart in seven adult males. The serum GH profile was analysed by deconvulution incorporating a variable half-life for GH. All three doses of GHRH stimulated maximal GH secretion: 50 micrograms, 146.0 mU/min (SEM 24.0); 100 micrograms, 128.1 mU/min (SEM 14.3); 200 micrograms, 134.1 mU/min (SEM 20.5) (one-way ANOVA, P = NS). The magnitude of the second secretory burst after the second dose of GHRH was less than that induced by the first injection of GHRH, particularly when doses of 200 micrograms were used. Factors influencing the response to the second dose were the GH secretory status at the point that the stimulus was applied and the time interval between administration of the first and second doses. These studies demonstrate that the pituitary gland is capable of responding to two consecutive doses of GHRH although the second response is always less than the first. The data demonstrate the importance of using methods of assessing GH secretion and not relying simply on measured serum GH concentration values.

Adult↗

The interaction between clonidine and growth hormone releasing hormone in the stimulation of growth hormone secretion in man.

Six normal adult males were given clonidine and GHRH either separately, or in combination, in random order. The peak serum GH concentrations elicited by clonidine or GHRH were variable but one factor influencing the GH response to GHRH was the GH secretory status in the hour prior to the administration of the GHRH. Peak serum GH concentrations attained were significantly greater when serum GH concentrations were rising (mean 52.9 mU/l, SD 17.2) than if they were falling (mean 27.5 mU/l, SD 13.3) or unchanged/undetectable (mean 20.6 mU/l, SD 9.8) (one-way ANOVA, F = 8.77; P = 0.004). The GH response to clonidine was not influenced by the secretory status in the hour prior to administration of clonidine. Pretreatment with clonidine did not augment the peak serum GH response to GHRH but the direction of response was more predictable than when GHRH was administered separately or repeatedly. Prior treatment with GHRH(1-29)-NH2 led to a marked attenuation of the peak serum GH response to clonidine. These results suggest that the alpha-2 adrenergic agonists probably stimulate GH secretion through pathways other than just GHRH.

Adult↗