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Biomedical subjects

M Menon

Publications and source records attributed to M Menon.

At least 19 recordsLinked to original sources
PubMed1992

Epidermal growth factor: receptor binding and effects on the sex accessory organs of sexually mature male mice.

The role of epidermal growth factor (EGF) in maintaining the integrity of the male sex accessory glands was investigated in the mouse. In the sexually mature male C3H mouse, EGF levels were highest in the submandibular gland, followed by the seminal vesicles and the prostate. Twenty eight days after sialoadenectomy (Sx), EGF fell below detectable limits in the serum and in the seminal vesicles. However, the prostate still retained 22% of its immunoreactive EGF. There was a seven-fold increase in serum testosterone after sialoadenectomy. Despite this drastic rise in testosterone, both prostatic and seminal vesicular weights were reduced, serum levels of LH were suppressed only by 37% and FSH levels were not altered. All these changes were abolished by the simultaneous administration of exogenous EGF at 100 micrograms./kg./day for 28 days. Both prostatic and seminal vesicular membranes contained binding sites for 125I-EGF. Binding was maximal after one hour of incubation at room temperature. Two classes of binding sites were shown for either organ (Kd = 1.2 nM, n = 56 fmol/mg. and Kd = 74 nM, n = 540 fmol/mg. for prostate; Kd = 0.9 nM, n = 29 fmol/mg. and Kd = 93 nM, n = 150 fmol/mg. for seminal vesicle). The binding of 125I-EGF was displaced by excess EGF and TGF-alpha but not by insulin, ILGF-2 and PDGF. These data suggest that EGF may have an important role in maintaining the integrity of the seminal vesicle and the prostate in the mouse. While the seminal vesicle appears to acquire EGF by uptake from the environment, the prostate may have the ability to synthesize EGF locally.

Animals↗
PubMed1992

Short term effects of cis-platinum on male reproduction, fertility and pregnancy outcome.

In order to find out the short term effects of cis-platinum treatment on reproductive function of the treated male rats and their progeny, sexually mature male Sprague-Dawley rats were given a single intra-peritoneal injection of either saline or cis-platinum (2, 4, 8 mg./kg.body wt.). One week following the treatment, the animals were mated with proestrus females of proven fertility. The females were scored positive or negative depending upon whether or not spermatozoa were seen in the vaginal smear after mating. However, all the females were watched until day 18, and on day 19, the females that became pregnant were subjected to laparotomy, and the number of corpora lutea, implantation sites and fetuses were counted. The fetuses were weighted and observed for the presence of any morphological abnormalities. Significant pre-implantation loss was seen in the treated groups. The weights of the fetuses were also significantly lower than those from the control group. Analysis of the effects of cis-platinum on the reproductive system of treated males revealed that cis-platinum reduced the reproductive organ weights, sperm counts, sperm motility, fertility and the levels of testosterone, LH and FSH. These results suggest that cis-platinum has a profound deleterious effect on the reproductive system and on the fertility potential of the treated male rats.

Animals↗
PubMed1992

The mechanism of cyclosporine's action in the inhibition of testosterone biosynthesis by rat Leydig cells in vitro.

We have previously demonstrated that cyclosporine inhibits testosterone (T) biosynthesis in vivo. To better understand the mechanism by which CsA inhibits T synthesis, interstitial cells were isolated from rat testes and incubated in the standard medium 199 with or without CsA (0-10 micrograms/ml) in the presence or absence of human chorionic gonadotropin (hCG, 10(-7) M) and 8-bromo cyclic AMP (cAMP, 0.5 mM) for 3 hr at 32 degrees C. The levels of cAMP and T were determined by RIA. CsA did not inhibit the basal secretion of T, but inhibited hCG-stimulated T production in a dose-dependent manner (4 ng/10(6) cells vs. 10 ng/10(6) cells at a CsA dose of 5 micrograms/ml, P less than 0.05). Radioligand binding of 125I-hLH to testicular membranes was not affected by CsA, as CsA did not compete with hCG/LH for binding sites (25-28% binding with or without CsA). Similarly, the MIX-stimulated cAMP production was not affected by CsA (24.03 +/- 1.09 vs. 20.60 +/- 0.38 pmol/10(6) cells), suggesting that CsA does not inhibit the accumulation of the second messenger. However, when interstitial cells were incubated with CsA in the presence of cAMP, a significant dose-dependent decline in T secretion was observed (7 ng/10(6) cells vs. 20 ng/10(6) cells at a CsA dose of 5 micrograms/ml). To determine whether CsA inhibits the steps beyond cAMP stimulation of T secretion, the kinetic parameters (Km and Vmax) of steroidogenic enzymes, delta 4-3 keto-17 alpha hydroxylase (17 alpha-hydroxylase), and delta 4-3 keto-17 beta hydroxy steroid dehydrogenase (17B-HSD) were determined by using Michaelis Menten analysis. Results are shown in the presence of CsA vs. no CsA: Km and Vmax values for 17 alpha-hydroxylase were (2.32 vs. 7.98 microM) and (27.96 vs. 100.97 pmol/mg protein/min), respectively. For 17B-HSD the Km and Vmax were (2.14 vs. 1.52 microM) and (15 vs. 15 pmol/mg protein/min), respectively. These results indicate that CsA inhibits the activity of 17 alpha-hydroxylase uncompetitively and 17B-HSD activity competitively. In conclusion the primary site for CsA inhibition is the cAMP stimulation and, CsA inhibits T synthesis at multiple sites.

Animals↗
PubMed1992

Clinical and social problems in young women with breast carcinoma.

Studies have noted that Asian women tend to have invasive breast cancer at a younger age compared with their Western counterparts. This is a rising trend among women in Singapore. This study compares 46 women less than or equal to 35 years with 313 women greater than 35 years who were treated in a teaching hospital between January 1983 and December 1989. Despite better education, the younger women (less than or equal to 35 years) were no different from their older counterparts in delaying medical consultation for more than 3 months after self-detection (39 vs 38.6%) though a higher percentage of older women procrastinated for over a year (16.6 vs 6.5%). As a result, 28% of younger women and 21.6% of older women presented with late disease (TNM Stage III and IV). Primary healthcare physicians contributed towards further delay among 65% of women less than or equal to 35 years. They were more suspicious when breast lumps were detected in women greater than 35 years and only 8% had delayed referrals. Failure in advising early biopsy added further delay (greater than 3 months) in 27.6% of younger patients whereas it was seldom delayed for the other older group (0.3%). Eight patients less than or equal to 35 years were initially reluctant to undergo definitive surgery. These cumulative delays resulted in progression of disease in seven patients of the 11 patients whose therapy was delayed more than 6 months.

Adolescent↗
PubMed1992

Modification of liver and serum enzymes by paraquat treatment in rabbits.

Paraquat (PQ) is known to cause progressive interstitial fibrosis in the lungs. Previous investigations have indicated that PQ acts by lipid peroxidation of the membrane. However, there are few reports on the action of PQ on hepatic enzymes. This work was carried out to investigate the modulation of various hepatic enzymes by PQ in rabbits. Paraquat was administered at a dose of 3, 6 or 12 mg/kg b. wt/day intraperitoneally to male rabbits for different periods of time. Administration of paraquat resulted in a significant decrease in plasma activities of transaminase enzymes, alkaline phosphatase and liver transketolase. No significant change was found in the activities of plasma and hepatic lactate dehydrogenase and alkaline phosphatase. A marked increase in blood glucose was noticed 48 hours after paraquat administration.

Alanine Transaminase↗
PubMed1991

A new model of nephrolithiasis involving tubular dysfunction/injury.

To better understand the pathogenesis of nephrolithiasis, we developed a new animal model that closely mimics human calcium oxalate stone disease. Rats were treated with a regimen that combines moderate hyperoxaluria (produced by 10 days of feeding with 3% ammonium oxalate) with mild proximal tubular injury/dysfunction (produced by 8 daily injections of gentamicin sulfate -40 mg./kg.). This combined treatment caused a marked increase in the incidence of calcium oxalate crystals and stones over that seen in animals treated with oxalate or gentamicin alone. Using a semiquantitative scoring system for estimating the abundance of crystals in coronal sections of kidneys, we found that 63% of animals receiving gentamicin plus oxalate showed "moderate" numbers of crystal, as compared to 8% of animals receiving oxalate alone; and the majority of the crystals occurred in the papilla, a pattern similar to that seen in human stone disease. Untreated rats and rats treated with gentamicin alone did not exhibit calcium oxalate crystals or stones. Despite the abundance of crystals and stones, animals receiving gentamicin plus oxalate retained relatively normal renal function as judged by creatinine clearance. Thus, the model has several advantages over preexisting models of nephrolithiasis. Crystal and stone deposition develop rapidly (within 14 days). The pattern of deposition resembles that seen in human stone disease and renal function remains relatively normal. These findings indicate that this model of nephrolithiasis may prove useful for studies of the pathogenesis of stone disease. Moreover, they suggest that renal tubular injury and/or dysfunction may produce conditions conducive to the formation and growth of calcium oxalate stones.

Animals↗
PubMed1991

Oxalate transport in renal tubular cells from normal and stone-forming animals.

To investigate the cellular mechanism(s) underlying kidney stone disease, we examined oxalate uptake in suspensions of renal cortical and papillary cells derived from control and stone-forming animals. In control animals, both cortical and papillary cells exhibited a time-dependent accumulation of oxalate. This uptake was mediated both by passive diffusion and by one or more transport processes sensitive to the anion transport inhibitor, DIDS. Oxalate uptake was also markedly sensitive to extracellular pH, showing increased uptake at acidic pH outside (pHo) (6.0), and reduced uptake at alkaline pHo (8.0). In renal tubular cells from stone-forming animals, oxalate uptake was markedly altered. Uptake was significantly reduced in cortical cells, whereas it was significantly stimulated in papillary cells from the same animals. Since the observed changes in oxalate handling occurred only in stone-forming animals, it is possible that alterations in renal cell oxalate transport contribute to calcium oxalate stone formation.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1990

Reversal of the toxic effects of cyclosporine on male reproduction and kidney function of rats by simultaneous administration of hCG + FSH.

We have shown earlier that the administration of cyclosporine impairs testicular function and causes a decrease in sperm counts, sperm motility and fertility. In order to determine whether or not the deleterious effects of CsA could be reversed by hormonal therapy, we injected sexually mature male Sprague Dawley rats with cremaphor + saline or CsA (40 mg./kg./d) alone or in combination with human chorionic gonadotropin (hCG; five micrograms./d/rat) and follicle stimulating hormone (FSH; five micrograms./d/rat). The injections were given subcutaneously for 14 days. As expected, CsA administration decreased the body and reproductive organ weights, testicular and epididymal sperm counts, sperm motility and fertilizing ability. Serum levels of LH were elevated and testosterone was decreased. The administration of FSH + hCG to the CsA treated rats restored the body and reproductive organ weights, sperm counts and motility. Seventy five percent of gonadotropin treated males were fertile as compared to 25% in the CsA treated group. In the hormone treated group, the blood levels of CsA were 50% of that of CsA treated group. In order to verify whether or not the decline in the blood levels of CsA was the cause for the amelioration of CsA-induced changes in the reproductive function, we compared the CsA + hormone treated group with another group treated with five mg./kg./d CsA which had blood levels of CsA comparable to the former group. In the five mg./kg./d group the reproductive functions were significantly lower than the CsA + hormone treated group suggesting, therefore, that the restoration of reproductive functions in the CsA + hormone treated group is a result of hormonal treatment. Administration of CsA (40 mg./kg./d) reduced the kidney weight and increased the levels of serum creatinine: these changes were also ameliorated by the administration of hCG + FSH.

Animals↗
PubMed1979

Progesterone binding by human endometrial tissue during the proliferative and secretory phases of the menstrual cycle and by hyperplastic and carcinomatous endometrium.

Cytosol receptors for progesterone were assayed in human endometrial tissue during the proliferative and secretory phases of the menstrual cycle and in the hyperplastic and carcinomatous endometrium. The assays were performed utilizing a technique involving prior treatment of the cytosol extract with dextran-coated charcoal to remove endogenous progesterone. The results showed that the progesterone receptor activity was higher during the later proliferative and early secretory phases of the menstrual cycle. Hyperplastic and carcinomatous endometrium also contained specific cytosol receptor for progesterone, and the binding activity of the hyperplastic endometria and endometrial polyps was comparable to that found during the later proliferative phase of the menstrual cycle. No apparent correlation between the progesterone receptor level and the morphologic degree of differentiation in Grades 1 and 2 adenocarcinomas of the endometrium was observed.

Adenocarcinoma↗
PubMed1979

Search for blocking factors in sera of patients with prostatic cancer.

Sera from patients with carcinoma of the prostate were screened for the presence of blocking factors by measuring the inhibition of phytohemagglutinin-induced blastogenesis of normal lymphocytes. The blastogenic index obtained in cancer sera is not significantly different from that obtained in sera of patients with benign prostatic hypertrophy (control group). Determination of alpha-2-globulins in the cancer sera by cellulose acetate electrophoresis revealed slightly elevated levels in patients with metastatic disease but it did not correlate with the inhibitory blocking activity of the serum.

Adult↗
PubMed1979

Androgen, estrogen and progesterone receptors of the R3327H Copenhagen rat prostatic tumor.

Sucrose density gradient analysis of the R3327H tumor cytosol demonstrated the presence of both androgen and estrogen binding proteins. Competitive binding analysis with 17 beta-estradiol, 5 alpha-dihydrotestosterone, R1881, cyproterone acetate, and cortisol was consistent with the presence of 2 different binding sites for androgens and estrogens. Scatchard binding analysis was performed in the dorsal-lateral prostate as well as the R3327H tumor from normal Copenhagen rats. High affinity receptors for androgen and estrogen but not progesterone were found. However, in R3327H tumors relapsing following castration, the presence of high affinity receptors for progesterone were readily detectable.

Animals↗
PubMed1979

Deae-dextran and T-cell rosette formation.

Use of DEAE-dextran (a polycation) increases and stabilizes the rosettes formed between sheep red cells and human peripheral blood lymphocytes. Under its influence, reproducible stable rosettes are formed after one hour of incubation in an ice bath instead of the usually required 18 to 24 hours. We have shown that rosettes are specific for T-cells and not due to "co-rosetting" of nonrosette forming cells into the T-cell rosette clusters. Only the cells from normal controls consistently show an increase in rosette formation hence routine use of this 'stabilizer' in clinical immunology is not recommended.

Adult↗
PubMed1979

Consideration and implications of tumor antigenic expression.

This review is an attempt to simplify the myriad descriptions of tumor antigens, by considering such antigens in the perspective of their mechanisms of formation. We believe that most and possibly all tumor antigens previously described and currently under study will ultimately fit into one of the categories discussed in this article, since there are only a finite number of biochemical mechanisms for producing new antigens in any cell--cancerous or otherwise. Pragmatically, we view the vagaries of expression of tumor antigens as among their most important properties, and the search for tumor antigens has in fact opened a Pandora's box of molecular variability. Large tumor masses consisting of multiple subclones with different karyotypes, chromosomal anomalies and mutations would appear to be capable of expressing a motley group of tumor antigens. To the best of our knowledge, no tumor antigen has been shown to be necessary and causal in transformation, except in virally-induced tumors. The presence of tumor antigens appears to be coincidental and reflects dedifferentiation and karyotypic, metabolic and nutritional variations occurring in tumors. Undoubtedly, some antigens may give a tumor a selective advantage of growth, metabolism or metastatic potential, but many antigens may simply reflect the vagaries of the tumor cell. The intratumor and intertumor variations of tumor antigens, their mechanisms of origin and their rather uncanny capabilities to change their phenotype--antigen expression--secondary to environmental selection during tumor expansion or following therapy should be kept in mind when tumor antigens and immunotherapy are considered.

Animals↗
PubMed1978

Cell-mediated immune competence in patients with prostatic carcinoma.

The immune competence of 65 patients with prostatic cancer was evaluated by 2 in vivo and 2 in vitro tests to study the contribution of host factors to the progress of the disease. Patients with benign prostatic hypertrophy served as controls. Our results indicate that the delayed skin hypersensitivity response to common microbial recall antigens (streptokinase/streptodornase, purified protein derivative, dermatophytin 0 and dermatophytin) is unaltered in advanced stages of malignancy. The ability to be sensitized by dinitrochlorobenzene declines significantly in patients with metastatic disease. Blastogenic response of peripheral blood lymphocytes to phytohemagglutinin stimulation is not depressed in late stages of malignancy, although in the circulating T cells per cent and absolute values are somewhat lower in patients with metastases. Herein we show that immune competence (measured by the 4 tests) of patients with prostatic carcinoma does not decrease markedly even in the late stages of the disease. Primary sensitization to dinitrochlorobenzene is the only test showing a decline in responsiveness related to the tumor stage.

Carcinoma↗
PubMed1978

Changes in pheromone production, release, mating behaviour and reproductive ability of the gamma-irradiated cockroach Nauphoeta cinerea (Olivier).

Mature males of Nauphoeta cinerea produce a sex pheromone 'seducin' which has short-range effects in attracting mature females of the same species. Exposure of newly-emerged adult males to 3.5, 7, 14 or 21 krad of gamma-radiation decreased their life expectancy and affected their mating behaviour. Bioassay of dichloromethane extracts of males showed that radiation doses (14 krad) sufficient to induce sterility did not affect the ability to produce pheromone but significantly reduced the release of pheromone by inhibiting wing-raising. The sterile-male technique using males sterilized by ionizing radiation in air may not be the method of choice for control of Nauphoeta cinerea.

Animals↗