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Biomedical subjects

M Menon

Publications and source records attributed to M Menon.

At least 55 records · Page 3Linked to original sources
PubMed1995

Oxalate-induced damage to renal tubular cells.

Our own studies and those of others have shown that the incidence of calcium oxalate stones and plaques is markedly increased by nephrotoxins. The possible role of oxalate as a nephrotoxin has not been fully appreciated. However, recent studies in experimental animals and in cultured cells support this possibility. The results of these studies led us to hypothesize that hyperoxaluria promotes stone formation in several ways: by providing a substrate for the formation of the most common form of renal stones, calcium oxalate stones, and by inducing damage to renal epithelial cells. Damaged cells in turn would produce an environment favorable for crystal retention and provide membranous debris that promotes crystal nucleation, aggregation and adherence. The present report summarizes evidence for oxalate nephrotoxicity and discusses the potential importance of oxalate toxicity in the pathogenesis of stone disease.

Animals↗
PubMed1994

Oxalate-induced initiation of DNA synthesis in LLC-PK1 cells, a line of renal epithelial cells.

These studies examined the effects of oxalate, a constituent of renal stones, on the growth of LLC-PK1 cells. Exposure to oxalate resulted in an initiation of DNA synthesis in serum-starved, growth-arrested cells as measured by 3H-thymidine incorporation. The effects of oxalate were comparable to those observed in response to 10% serum. Moreover, exposure to oxalate plus 10% serum stimulated DNA synthesis to a greater extent than oxalate or serum alone. These studies indicate that oxalate promotes the progression of cells from the G0/G1 to the S phase of the cell cycle. However, the increase in DNA synthesis was not always followed by an increase in cell number since high concentrations of oxalate led to a reduction in cell number.

3T3 Cells↗
PubMed1994

Simultaneous quadruple immunosuppression with cyclosporine induction therapy in high risk renal transplant recipients.

High risk renal transplant recipients experience excess graft loss despite overall improvements in the results of cadaveric renal transplantation. We evaluated a novel immunosuppression regimen consisting of simultaneous administration of OKT3, cyclosporine, azathioprine and prednisone. Of the 12 high risk patients studied 5 received 2 transplants, 1 received 3 transplants and 8 had peak panel reactive antibodies of greater than 60%. The protocol consisted of cyclosporine (7 mg./kg. orally or 3 mg./kg. intravenously per day) starting from the day of transplant regardless of graft function; 5 mg. OKT3 per day for 10 to 14 days starting intraoperatively; 5 mg./kg. azathioprine per day for 2 days, then 1.5 mg./kg. per day and adjusted according to white blood cell counts, and prednisone taper at 2 to 0.4 mg./kg. per day on day 10. The dose of cyclosporine was increased to 14 mg./kg. per day orally when serum creatinine was less than 3 mg./dl. The cyclosporine whole blood levels (measured by high performance liquid chromatography) were maintained between 250 and 400 ng./ml. in the first 3 months. Followup evaluations ranged from 3 to 28 months (median 8.5). Seven patients (58.3%) had acute tubular necrosis and required dialysis support for 2 to 5 weeks. Six patients (including 5 with acute tubular necrosis) experienced 1 episode of acute rejection in the first 3 months (2 of these were due to accelerated vascular rejection). Two rejections responded to pulse steroid treatment, while 4 (including 2 with vascular rejection) were treated with antilymphoblast globulin rescue therapy for 10 to 14 days. Symptomatic cytomegalovirus pneumonia occurred in 3 patients (25%). There were no deaths or graft losses. No case of malignancy was observed to date. The serum creatinine is less than 2 mg./dl. in 9 patients, and 2.5 to 2.9 mg./dl. in the remaining 3. We conclude that simultaneous quadruple immunosuppressive regimen that includes induction cyclosporine and OKT3 is a highly effective therapy for high risk patients, yielding excellent short-term and intermediate success rates. Long-term results of this regimen, including neoplastic potentiation, cannot be addressed because of the limited followup of these patients.

Adult↗
PubMed1994

Effects of sialoadenectomy and epidermal growth factor on testicular function of sexually mature male mice.

The effect of sialoadenectomy (Sx) and epidermal growth factor (EGF) administration on testicular function was investigated in 8-week old C3H mice. Animals were divided initially into three groups: sham operated controls, Sx, and Sx + EGF treated (100 micrograms./kg./day subcutaneously for 28 days). Sialoadenectomy completely depleted the circulating levels of EGF and reduced body weight and reproductive organ weights. However, kidney weight was not affected. Quantitative analysis of spermatogenesis showed a decrease in preleptotene and pachytene spermatocytes and round spermatids, which resulted in a decrease in sperm counts. Sperm motility and fertility were also significantly decreased. Endocrinologic studies showed a 2- and 6-fold elevation in intratesticular and serum levels of testosterone and a decrease in luteinizing hormone (LH) levels. Follicle stimulating hormone levels were not altered. Administration of EGF to the Sx animals maintained reproductive organ weights, spermatogenesis and levels of LH and testosterone closer to control values; however, sperm motility was not maintained at control value. That sialoadenectomy resulted in a decline in androgen-dependent parameters, in spite of an elevation in testosterone levels, and EGF maintained them closer to the control value suggested that EGF may modulate androgen action. A comparison was therefore carried out between the effects of Sx and administration of flutamide (F), an androgen receptor blocker. Animals were subjected to Sx, F treatment (100 mg./kg./day subcutaneously for 28 days), Sx + F, or Sx + F + EGF. The effects of Sx and F treatment on organ weights, sperm counts and sperm motility were more or less similar. As expected, flutamide treatment increased LH and FSH levels, and testosterone levels were normal. The Sx + F animals showed no further decrease in organ weights, sperm count and motility. Treatment with Sx + F increased intratesticular and serum levels of testosterone by 2- and 10-fold. Circulating levels of LH and FSH were the same as in the flutamide-treated group. Administration of EGF to Sx + F maintained all these parameters, except sperm motility, closer to the control value. These results suggest that EGF either bypasses flutamide effects and acts directly or that EGF modulates androgen action at one or more steps in the signal transduction pathway in the male reproductive organs.

Animals↗
PubMed1994

Oxalate transport in a line of porcine renal epithelial cells--LLC-PK1 cells.

The present studies examined oxalate handling in LLC-PK1 cells, an epithelial cell line of porcine origin. These cells appear to express transport systems for oxalate, as evidenced by the fact that uptake was saturable, time dependent and sensitive to the anion transport inhibitor DIDS (4,4'-diisothiocyanostilbene-2,2'-disulfonic acid). Oxalate uptake in these cells was also affected by the presence of certain inorganic anions (Cl-, SO4(2-), or HCO3-) but not by organic anions (para-aminohippurate, urate, malate, phenylsuccinate, succinate). This uptake was Na independent and unaffected by changes in membrane potential but was affected by external pH, with acidic pH stimulating and alkaline pH inhibiting oxalate accumulation. These findings suggest that LLC-PK1 cells express oxalate transporters similar to those observed in the mammalian renal cortex. Further studies using these cells may prove useful in defining the conditions that govern transcellular oxalate flux in renal epithelial cells.

Animals↗
PubMed1994

Polarized distribution of oxalate transport systems in LLC-PK1 cells, a line of renal epithelial cells.

Although oxalate is a major component of kidney stones, the factors affecting renal oxalate handling are poorly understood. This uncertainty stems in part from complexities inherent to available preparations; thus the present studies examined oxalate handling in a simpler model system, LLC-PK1 cells, an epithelial cell line of porcine origin. Initial studies on monolayers in dishes demonstrated that these cells accumulate oxalate via a process or processes sensitive to the anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). Subsequent studies using LLC-PK1 monolayers on membrane filters examined the characteristics and distribution of these transporter(s). At the apical surface, DIDS-sensitive uptake was sensitive to [Cl-] but not [SO4(2-)] or [HCO3-] and was unaffected by alterations in pH or membrane potential. At the basolateral surface, oxalate uptake was [Cl-] insensitive but markedly affected by variation in pH, [SO4(2-)], or [HCO3-]. Uptake at the two membrane surfaces was also differentially affected by transport inhibitors and organic acids. Thus LLC-PK1 cells appear to express unique transporters at each membrane surface: oxalate/Cl- exchange at the apical surface and oxalate/SO4(2-) (or HCO3-) exchange at the basolateral surface.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1994

Posttransplant lymphocele presenting as 'acute abdomen'.

Lymphoceles occurring after renal transplantation are frequently asymptomatic and are usually identified on routine ultrasonography of the allograft. A small percentage of them may increase in size and manifest due to their compression effects on adjacent structures or as lymphocutaneous fistula. An infected lymphocele would, in addition, give rise to local and systemic features. A case of infected lymphocele occurring 4.5 months after cadaveric renal transplant is reported. The patient presented in septicemia and features of generalized peritonitis. Emergency diagnostic laparoscopy revealed fluid collection in the peritoneal cavity. However, on exploratory laparotomy no intra-abdominal pathology was detected. Further evaluation revealed a large perigraft lymph collection which was drained percutaneously. Fluid and blood cultures grew Staphylococcus aureus. The patient recovered completely following external drainage and antibiotic administration.

Abdomen, Acute↗
PubMed1993

[Active uptake of oxalate in a renal tubular cell line (LLC-PK1)].

The oxalate uptake was studied in LLC-PK1 cells, an epithelial cell line originated in proximal tubular cells of porcine kidney. It was clear that the cells contain an oxalate exchanger highly sensitive to 4,4-diisothio-cyanostilbene-2-' disulfonic acid (DIDS). The uptake was inhibited by the addition of inorganic anions (chloride, sulphate and bicarbonate) to the reaction system, but was unaffected by sodium ion. The data suggest the possibility that it should be consistent with at least two transport systems for oxalate in LLC-PK1 cells, a SO4-/oxalate/HCO3- exchanger and a Cl-/oxalate exchanger.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1993

[Some effects of pH, diuretics and organic acids on the uptake of oxalate in a renal tubular cell line (LLC-PK1)].

The effects of changes in extracellular pH and treatments with diuretics or some organic acids on the uptake of oxalate were studied in an epithelial cell line of renal origin (LLC-PK1 cells). The oxalate uptake into the cells exhibited a marked sensitivity to extracellular, pH, in the present results with acidic pH stimulating and alkaline pH inhibiting the DIDS sensitive uptakes. The uptake of oxalate was clearly inhibited by DIDS, proportionally to the concentrations from 10 microM to 1 mM. Furosemide, chlorothiazide, probenecid and acetazolamide inhibited the oxalate uptake significantly. Probenecid has the most potency on the inhibition of the uptake in high concentrations, and acetazolamide needed a high concentration for the small effect. However, allopurinol has no effect on the uptake as well as dicarboxylates (malate, succinate and phenyl succinate) and organic acids (urate and para-amino hippurate). We discussed the mechanisms of the inhibition against the oxalate uptake concerning with each drug. It was suggested that probenecid may inhibit the oxalate carriers directly, while furosemide, chlorothiazide and acetazolamide may inhibit then by the direct actions and some secondary effects which are provided by those drugs.

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