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S K Martin

Publications and source records attributed to S K Martin.

At least 37 records · Page 2Linked to original sources
PubMed1997

Preoperative androgen-deprivation therapy for clinical stage T3 prostate cancer.

The widespread availability of luteinizing hormone-releasing hormone analogues has renewed interest in androgen-deprivation therapy (ADT) before radical prostatectomy. Neoadjuvant ADT in patients with clinically localized tumors has resulted in decreased margin-positive rates and increased rates of organ-confined disease. Unfortunately, the pathological effects of ADT in patients with locally advanced (cT3) prostate cancer have been less marked. This article reviews our experience with neoadjuvant hormonal therapy in patients with clinical stage T3 prostate cancer. In a case-control study of cT3 patients undergoing radical retropubic prostatectomy between 1985 and 1992, 72 patients receiving preoperative ADT were compared with a matched group of 144 untreated patients in terms of pathological outcome and long-term disease-free survival. A local downstaging effect in hormonally treated patients was suggested by lower rates of extracapsular extension, but only 31% had organ-confined disease. Hormonally treated patients showed no benefit in survival or disease progression compared with patients who did not receive this therapy. Although preoperative ADT may decrease the incidence of extracapsular extension in clinical stage T3 prostate cancer, our data suggest that it has no significant effect on survival or disease progression in patients with locally advanced disease.

Aged↗
PubMed1996

Contributions of liver and kidneys to glycerol production and utilization in the dog.

The classical concept holds that liver and kidneys are the main sinks of glycerol released by adipose tissue. However, rates of glycerol appearance (Ra) exceed the rate of glycerol delivery to liver and kidneys. We measured the hepatic and renal contributions to glycerol production and utilization in anesthetized dogs that were fasted either overnight or for 24 h after 3 days on a carbohydrate-free diet. Dogs were infused with [2H5]glycerol, and the concentration and 2H enrichment of glycerol were measured across liver and kidney. After a baseline period, either norepinephrine or glucose plus insulin was infused to alter the rate of glycerol production. Our study shows that the production of glycerol by liver and kidneys amounted to 4-9% and 4-7% of the Ra of glycerol, respectively. Uptake of glycerol by liver and kidneys amounted to 26-30 and 10-19% of the Ra of glycerol, respectively. Thus, contrary to the classical concept, the bulk of glycerol utilization occurs in nonhepatic, nonrenal tissues that have very low glycerol kinase activity per gram.

Animals↗
PubMed1996

The periurethral glands do not significantly influence the serum prostate specific antigen concentration.

PURPOSE: The periurethral glands are known to produce prostate specific antigen (PSA). With ultra-sensitive assays now routinely available, it is necessary to determine if the periurethral glands significantly influence serum PSA concentration after radical prostatectomy. MATERIALS AND METHODS: Serum PSA levels of 46 men, 51 to 89 years old (median age 67) who underwent radical cystoprostatectomy and total urethrectomy, were compared with those of 92 men 46 to 91 years old (median age 67) who underwent radical cystoprostatectomy only. All men had transitional cell carcinoma of the bladder without gross or microscopic evidence of prostate cancer and all underwent ileal conduit diversion. Serum was obtained at least 1 year postoperatively. Each specimen was analyzed using the Tosoh, Immulite, and Yu and Diamandis ultra-sensitive PSA assays with analytical detection limits of 0.02 ng./ml., 0.004 ng./ ml. and 0.002 ng./ml., respectively. RESULTS: Median PSA for the radical cystoprostatectomy with urethrectomy group was 0.00 ng./ml. (range 0.00 to 0.14) for each of the 3 assays. For the radical cystoprostatectomy only group the median Tosoh and Immulite PSA assay levels were 0.01 ng./ml. (range 0.00 to 0.22), and median Yu and Diamandis PSA assay level was 0.00 ng./ml. (range 0.00 to 0.31). CONCLUSIONS: The greatest difference in median PSA levels that could be found between men with and without periurethral glands when using 3 different ultra-sensitive assays was 0.01 ng./ml., indicating that the periurethral glands do not have a clinically significant effect on serum PSA concentration after radical prostatectomy. Thus, a serum PSA level above the residual cancer detection limit following radical prostatectomy, even if obtained with a ultra-sensitive assay, reflects either malignant or benign residual prostatic tissue, rather than the presence of periurethral glands.

Aged↗
PubMed1994

Regulation by glucose of the biosynthesis of PC2, PC3 and proinsulin in (ob/ob) mouse islets of Langerhans.

The prohormone convertases PC2 and PC3 have been shown to catalyze the processing of proinsulin to insulin in pancreatic beta-cells. In these studies we have compared the effects of glucose on PC2 and PC3 biosynthesis in freshly isolated islets from normal and hyperglycemic (ob/ob) mice. In contrast to normal islets [Alarcón, et al. (1993) J. Biol. Chem. 268, 4276] the biosynthesis of both PC2 and PC3 is stimulated by glucose, parallel to the stimulation of proinsulin in the (ob/ob) islets. Inhibition of PC2 biosynthesis by glucose in normal islet non beta-cells may obscure stimulation of PC2 biosynthesis in normal islet beta-cells.

Animals↗
PubMed1994

Proglucagon is processed to glucagon by prohormone convertase PC2 in alpha TC1-6 cells.

Proglucagon is processed differentially in the pancreatic alpha cells and the intestinal L cells to yield either glucagon or glucagon-like peptide 1, respectively, structurally related hormones with opposing metabolic actions. Here, we have studied the processing of proglucagon in alpha TC1-6 cells, an islet-cell line transformed by simian virus 40 large tumor (T) antigen, a model of the pancreatic alpha cell. We found that these cells process proglucagon at certain dibasic cleavage sites to release glucagon and only small amounts of glucagon-like peptide 1, as demonstrated by both continuous and pulse-chase labeling experiments. Both normal islet alpha cells and alpha TC1-6 cells were shown to express the prohormone convertase PC2 at high levels, but not the related protease PC3. Expression of PC2 antisense RNA in alpha TC1-6 cells inhibited both PC2 production and proglucagon processing concomitantly. We conclude that PC2 is the key endoprotease responsible for proglucagon processing in cells with the alpha-cell phenotype.

Animals↗
PubMed1994

Biochemical diagnosis of fatty acid oxidation disorders by metabolite analysis of postmortem liver.

At least 12 fatty acid oxidation disorders are known to be responsible for cases of sudden and unexpected death in early childhood. A specific diagnosis of these disorders is essential for genetic counseling and for the screening of siblings potentially at risk for life-threatening episodes of fasting intolerance. Postmortem blood and urine samples often are not available for further biochemical studies, and currently only medium-chain acyl-CoA dehydrogenase (MCAD) deficiency can be diagnosed by the molecular analysis of tissues. We developed a postmortem screening method for fatty acid oxidation disorders by the simultaneous measurement of C8-C20 fatty acids, glucose, lactate, and other metabolites from the methanol wash of a pellet obtained by ultracentrifugation of liver homogenate. Cis-4-decenoic acid was present in five confirmed cases with MCAD deficiency and in one case with glutaric aciduria type II and was absent in 97 of 100 randomly chosen sudden death cases, at least 81 of which were diagnosed as sudden infant death syndrome (SIDS). C14-C18 monounsaturated fatty acids were significantly elevated in the one examined case affected with long-chain acyl-CoA dehydrogenase (LCAD) deficiency. The metabolite profiles in two cases with carnitine uptake deficiency were less informative, but they shared with all the other disease controls a very low glucose concentration, a finding compatible with premortem hypoglycemia. This method is proposed as a simple and practical means of biochemical screening to follow up the postmortem finding of liver fat infiltration.

Acyl-CoA Dehydrogenase↗
PubMed1994

Radical prostatectomy for clinically localized prostate cancer: long-term results of 1,143 patients from a single institution.

PURPOSE: To determine the efficacy and complication rate of radical prostatectomy (RP) as a treatment option for clinically localized prostate cancer (clinical stage < or = T2c). METHODS: The study was a retrospective analysis of 1,143 consecutive patients (median age, 64 years; range, 38 to 79 y) who underwent RP at one institution (mean follow-up time, 9.7 years). Complications for this study population were compared with those of a contemporary group of 1,000 consecutive patients. RESULTS: Of 1,143 patients, 83 (7%) had a low clinical stage (T1) and 160 (14%) had a low histologic grade (Gleason score < or = 3); 648 (57%) had a high clinical stage (T2b or T2c) and 204 (18%) had a high histologic grade (Gleason score > or = 7). Only 113 (10%) died of prostate cancer, and 177 (15%) developed metastasis. Adjuvant treatment (androgen deprivation or radiation therapy) was given in 197 (17%) patients (> or = pT3) and provided virtually identical results as without adjuvant treatment. The 10- and 15-year crude survival rates for 1,143 patients were 75% +/- 1.5% (SE) and 60% +/- 2.2%, respectively; the cause-specific survival rates were 90% +/- 1.1% and 83% +/- 1.9%, respectively; and the metastasis-free survival rates were 83% +/- 1.3% and 77% +/- 1.9%, respectively (398 men at risk at 10 years and 138 men at risk at 15 years). The 10-year survival rate for patients with Gleason score > or = 7 was 74% +/- 3.9%. Only tumor grade was a significant predictor for disease outcome. The hospital mortality rate decreased from 0.7% for the 1,143 study patients to 0% for the more recent 1,000 patients. Severe incontinence declined to 1.4% for the more recent 1,000 patients. Most patients who underwent RP were healthy (Charlson comorbidity index). CONCLUSION: Survival at 15 years was similar to the expected survival rate. Current morbidity and mortality rates associated with RP were extremely low. Thus, RP has been a viable management option for men with clinically localized prostate cancer who have a life expectancy of more than 10 years.

Adult↗
PubMed1994

Relationship between personality disorders and clinical symptoms in psychiatric inpatients as measured by the Millon Clinical Multiaxial Inventory.

The Millon Clinical Multiaxial Inventory is a 175-item psychodiagnostic instrument which is based on Millon's theory of psychopathology, in which Millon suggests clinical symptoms result from an exacerbation of an individual's personality style when under stress. The purpose of the present study was to examine the relations of personality disorders to clinical symptoms as measured by the inventory. The sample of 245 inpatients from a state psychiatric hospital completed the Millon inventory between January, 1987 and April, 1989. Stepwise multiple-regression analyses were conducted to ascertain the relationship between personality disorders and symptoms. The 9 clinical symptom scales served as criterion variables while the personality-disorder scales served as predictor variables. The results were generally consistent with expectation and are discussed in terms of Millon's theory.

Adult↗
PubMed1994

Determination of fifty percent inhibitory concentrations (IC50) of antimalarial drugs against Plasmodium falciparum parasites in a serum-free medium.

Plasmodium falciparum chemosensitivity to the various antimalarial drugs is presently determined in the laboratory by setting up multiple microcultures of the parasite and estimating the amount of growth inhibition caused by known concentrations of drug. Parasite growth inhibition is assessed either by microscopy, radiolabeled substrate uptake, or calorimetrically. The obligate requirement for serum in this assay presents difficulties in the direct comparison of results among laboratories. We now have evidence that antimalarial drug sensitivity assays can be reliably performed in a serum-free medium. The overall comparison of 50% inhibitory concentration (IC50) values obtained with serum-free media (bovine albumin, Cohn fraction V [BAM] and BAM combined with glucose and lipids-cholesterol-rich mixture) and those obtained in serum-supplemented medium was r = 0.56; n = 60; P < 0.01.

Animals↗
PubMed1994

Correlation of phosphoinositide hydrolysis with exflagellation in the malaria microgametocyte.

Cellular responses to growth factors, hormones, and other agonists have been shown in many animal cell systems to be mediated by the signal transduction cascade controlled by phospholipase C. One such response, calcium mobilization, is regulated by the concerted effect of several specific inositol (poly)phosphates. Another response, protein phosphorylation, is regulated by other phospholipase C (PLC) hydrolysis products. Mature gametocytes are specialized cells primed for transformation into gametes immediately upon removal from the vertebrate bloodstream, thereby initiating the sexual cycle in a vector mosquito. This study showed that PLC hydrolysis products, inositol (1,4,5)triphosphate and diacylglycerol, are correlated with the initial events of flagellar development; they are implicated in synchronizing this crucial transformation for the parasite and hence the continued transmission of the parasite, which leads to this debilitating disease.

Animals↗
PubMed1993

Use of pharmacological agents to implicate a role for phosphoinositide hydrolysis products in malaria gamete formation.

The kinetics of phosphoinositol 4,5 bisphosphate hydrolysis products in activated Plasmodium falciparum gametocytes suggests a role for inositol trisphosphate [Ins(1,4,5)P3] and diacylglycerol (DAG) in the signal transduction pathway of malaria gametocytes. To investigate further this role, compounds that have an effect on the metabolism and biologic functions of these second messengers were tested in an in vitro system. Gentamycin, 2,3 diphosphoglycerate (2,3 DPG) and magnesium ion (Mg2+), inhibitors of Ins(1,4,5)P3 5' phosphatase, all stimulated gametocytes to exflagellate in suspended animation buffer, pH 7.4, at room temperature. In addition, methylxanthines, caffeine and theobromine, calcium ionophore (A-23187), and external calcium also stimulated exflagellation. In contrast, neomycin, an aminoglycoside that inhibits phospholipase C activity, and heparin, an antagonist of Ins(1,4,5)P3 binding to its receptor, inhibited microgamete formation. Quinine and chloroquine which can inhibit both phospholipase A and C activity also inhibited gametocyte exflagellation. The consistent manner in which these various compounds affect gametocyte activation further implicates phosphoinositol turnover in the signal transduction pathway of falciparum gametocytes.

2,3-Diphosphoglycerate↗
PubMed1993

The use of prostate-specific antigen in staging patients with newly diagnosed prostate cancer.

OBJECTIVE: To assess the need for obtaining radionuclide bone scans in the staging evaluation of patients with newly diagnosed, untreated prostate cancer. This determination was made on the basis of presenting prostate-specific antigen (PSA) levels. DESIGN: Retrospective review. PARTICIPANTS: The medical records of 2064 consecutive patients with prostate cancer who were evaluated at the Mayo Clinic in Rochester, Minn, from January 1989 through December 1990 were reviewed. Eight hundred fifty-two patients with newly diagnosed, untreated disease and a serum PSA concentration less than 20.0 micrograms/L at presentation comprised the study population. MAIN OUTCOME MEASURE: The rate of false-negative results associated with using the serum PSA concentration to predict bone scan findings. RESULTS: Five hundred sixty-one patients had a serum PSA concentration of 10.0 micrograms/L or less; only three had an abnormal bone scan result, and one had an indeterminate scan result. Of the 467 men whose PSA value was 8.0 micrograms/L or less (two times the upper limit of the reference range), none had bone scan results that were either abnormal or indeterminate. The rate of false-negative results for an abnormal bone scan result was 0% with a serum PSA value of 8.0 micrograms/L or less and 0.5% with a cutoff level of 10.0 micrograms/L. The 95% upper confidence limit for the rate of false-negative results for all PSA cutoff levels less than 20.0 micrograms/L was less than 2%. CONCLUSIONS: For patients with newly diagnosed, untreated prostate cancer, a serum PSA concentration of 10.0 micrograms/L or less, and no skeletal symptoms, a staging radionuclide bone scan does not appear to be necessary. This clinical situation applies to 39% of all patients presenting with newly diagnosed prostate cancer. Since more than 130,000 new cases are diagnosed each year, approximately 50,000 patients are affected annually. If the $600 staging bone scan were eliminated for these patients, a significant economic savings to the health care system in this country would be effected.

Bone Neoplasms↗
PubMed1993

Factors affecting exflagellation of in vitro-cultivated Plasmodium falciparum gametocytes.

The environment of Plasmodium falciparum gametocytes changes when they make the transition from the vertebrate to the invertebrate host. Gametocytes of this species cultivated in vitro were used to evaluate the effect of serum, pH, pCO2 tension, bicarbonate ion, and temperature on gamete formation. Temperature was the only factor responsible for keeping P. falciparum gametocytes in the inactivated state. Mature gametocytes held at temperatures above 30 degrees C remained quiescent in 10% serum, even at low ambient pCO2 tension, alkaline pH, and in the presence of 25 mM bicarbonate ion. When the temperature of the medium was allowed to drop below 30 degrees C, gametocytes emerged from the red blood cells and microgametocytes consistently exflagellated at pH 7.4, even in the absence of bicarbonate ion. With regard to bicarbonate ion, exflagellation in P. falciparum is similar to P. berghei and different from P. gallinaceum gametocytes, which have an obligate requirement for bicarbonate ion.

Animals↗
PubMed1993

Cultivation of Plasmodium falciparum parasites in a serum-free medium.

The elimination of serum from Plasmodium falciparum culture media could decrease costs, enhance procurement, and improve the feasibility of large-scale production of parasite material. We provide a semi-defined, serum-free formulation, of commercially available constituents that supports P. falciparum parasite growth at rates comparable with those obtained with serum-supplemented media. The medium is composed of RPMI 1640 to which HEPES, extra glucose, bicarbonate, and hypoxanthine have been added. Bovine albumin and serum-derived, lipids-cholesterol-rich mixture are then used in place of serum.

Animals↗
PubMed1993

Response of falciparum malaria to chloroquine and three second line antimalarial drugs in a Kenyan coastal school age population.

Ambulatory rural school children in the Mombasa area with P. falciparum parasitaemia were examined and randomly assigned to treatment with one of three second-line antimalarials--amodiaquine, pyrimethamine/sulphadoxine (P/SD) and pyrimethamine/sulfalene (P/SL). Clinical signs and parasitaemia were followed daily for the first week and on days 14 and 28. WHO Mark II schizont inhibition tests were performed for all the above 3 drugs and chloroquine. The total number of cases was 73. The mean parasite density was 142.1 +/- 207; 102.7 +/- 166; 82.74 +/- 93 parasites per 300 WBC for amodiaquine, P/SD, and P/SL, respectively. In vitro tests showed a chloroquine resistance rate of 60% and no resistance to all of the second line drugs. Also, all children treated successfully cleared their parasitaemia with mean clearance rates of 2.05 +/- 0.57; 1.86 +/- 0.47; 2.05 +/- 0.50 days for amodiaquine, P/SD and P/SL, respectively. Even though, no difference in the effectiveness between the second line drugs used was found, reinfection rates as depicted by day 28 parasitaemia differed--amodiaquine 16%; P/SD 0%; and P/SL4.35%. This difference could be attributed to the difference in the pharmacokinetic properties of the drugs.

Adolescent↗
PubMed1992

Treatment of chloroquine-resistant malaria in monkeys with a drug combination that reverses resistance in vitro.

Compounds that inhibit the P-glycoprotein-related efflux mechanism of multidrug-resistant cells reverse chloroquine resistance in vitro. Hence, the co-administration of chloroquine and an efflux-blocking drug could potentially treat chloroquine-resistant malaria infections. We administered a drug combination (chloroquine and a tiapamil analogue), that has been shown to reverse chloroquine resistance in vitro, to Aotus monkeys but failed to safely clear experimentally-induced chloroquine-resistant Plasmodium falciparum parasitaemias.

Animals↗