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Publications and source records attributed to S Grossman.
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The effects of dietary vitamin E and beta-carotene were studied on enzymes involved in arachidonic acid metabolism and other related enzymes in the rat testis. Groups of rats were fed various soybean oil-based semi purified diets. Group 1 was fed a vitamin E-supplemented diet (+E - beta); Group 2 was fed a beta-carotene-supplemented diet (-E + beta); Group 3, the control group (-E - beta) was fed a vitamin E-deficient diet; and Group 4, the standard diet group (S), was fed vitamin E plus beta-carotene-standard diet. Soybean oxidized oil was added to the three diet groups - (+E - beta), (- E + beta) and (- E - beta), whereas the diet of S group contained non-oxidized oil. After 8 weeks rats were killed, blood and testis samples were collected for biochemical determinations. Vitamin E deficiency caused significant increase in testis thiobarbituric acid value and activities of testis NADPH oxidase, testis 15-lipoxygenase and in plasma pyruvate kinase. In contrast, significant decreases were observed in activity of testis prostaglandin synthetase, compared with antioxidant-supplemented diet groups. We also found a significant increase in 15-lipoxygenase activity in (- E + beta) diet group, compared with (- E - beta) diet group. Fatty acid analysis of testis parenchyma indicated decrease in palmitate (16:0) and arachidonate (20:4(n - 6)), and increase in oleate (18:1(n-6)) linoleate (18:2(n - 6)) and linolenate (18:3(n - 3)), when compared (-E - beta) diet group with vitamin E-supplemented diet groups. The results suggest that dietary vitamin E has a role in both enzymatic and non-enzymatic peroxidation of polyunsaturated fatty acids in the testis.
The acrosome reaction (AR) in bull spermatozoa was induced by the Ca2(+)-ionophore A23187, by dilauroylphosphatidylcholine or by arachidonic acid in the presence of Ca2+ in the incubation medium. The occurrence of AR was determined by following the release of acrosin from the cells. Nordihydroguaiaretic acid (NDGA), an inhibitor of both lipoxygenase and prostaglandin-synthetase, caused 35%, 43% and 69% inhibition of AR at concentrations of 1, 10 or 100 microM, respectively. Eicosatetraynoic acid (ETYA), an analogue of arachidonic acid, caused 17%, 61% and 77% inhibition of AR at concentrations of 20, 40 or 80 micrograms/ml, respectively. When AR was induced by arachidonic acid, ETYA, causes 36% and 58% inhibition at concentrations of 2 or 20 micrograms/ml, respectively. Under identical conditions, 100 microM indomethacin, a specific inhibitor of prostaglandin-synthetase, showed no inhibition but rather 35% stimulation at acrosin release rate. The fact that AR is inhibited by NDGA and not by indomethacin indicates that the lipoxygenase, rather than prostaglandin-synthetase, is involved in the mechanism of AR. Since the inhibition by NDGA is seen in the presence of the Ca-ionophore, we suggest that lipoxygenase activity is not involved in enhancing calcium transport into the cell, but rather at other steps in AR mechanism. A thin-layer chromatography revealed the presence of 15-HETE, the classical product of 15-lipoxygenase activity, which was identified by HPLC. Under AR conditions, there is an elevation of lipoxygenase products and the addition of NDGA caused a reduction in their levels. The inhibition of acrosin release by NDGA can be eliminated by adding 15-HETE or 15-HPETE to the incubation medium. In conclusion, we suggest here for the first time, a physiological role for 15-lipoxygenase in the mechanism of AR in mammalian spermatozoa.
The spatial distribution of phosphate metabolites and pH within subcutaneously implanted RIF-1 tumours was determined by 1-dimensional phosphorus chemical shift imaging. 31P spectra from two to three 4 mm thick cross-sectional slices were obtained for each tumour. Quantitative morphometry was used to estimate the amount of necrosis within those slices. A spatially heterogeneous distribution of phosphate metabolites and pH was detected in most of the tumours. Levels of necrosis ranged from 0-24% for the tumours in this study. There was no significant correlation between the extent of necrosis over this range and levels of metabolites or pH, suggesting that factors besides necrosis can contribute to spectral heterogeneity.
The production of a factor with interleukin-3-like activity (IL-3-LA) by cultured human peripheral-blood mononuclear cells has been studied. Culture supernatants spontaneously derived from lymphocytes or monocytes stimulated the proliferative activity of 3 IL-3-dependent cell lines. Purification of this factor by gel filtration-high-pressure liquid chromatography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric focusing demonstrated the presence of a glycoprotein with a molecular weight of 25-30 kilodaltons and an isoelectric point of 7.6. The biochemical characteristics of the IL-3-LA derived from human monocytes and lymphocytes were very similar. The biological activity of the semipurified factor was tested on mononuclear cells from fetal cord blood. It was found that after 21 days 40% of the cells in the culture were mature basophils which released 15-18 ng histamine/10(6) cells.
Colonoscopic screening has been recommended for all persons who have had a colorectal adenoma or carcinoma. Such persons have been assumed to be at increased risk of having additional, asymptomatic colorectal neoplasms, the removal of which would reduce morbidity and mortality from colorectal cancer. In this prospective study, initial colonoscopy was performed on 544 asymptomatic subjects with past histories of colorectal index lesions ranging from small tubular adenomas to invasive cancers. In 402 subjects whose worst index lesion was an adenoma, the prevalence of neoplasms detected at colonoscopy, above the reach of the rigid sigmoidoscope, increased with age, male sex, black race, and the number and size of their index adenomas. In 142 subjects whose worst index lesion was invasive cancer, colonoscopy findings were marginally related to age and white race. A subgroup of 133 subjects whose worst index lesion was a single, small (less than 10 mm) tubular adenoma and who had no first-degree relatives with colorectal cancer had only a 3% prevalence of advanced colonic neoplasms (tubular adenomas greater than or equal to 10 mm in diameter; tubulovillous, villous, or severely dysplastic adenomas; or invasive cancers) found on colonoscopy--no greater than would be expected in the general population. Subgroups of the remaining 411 subjects, who had advanced or multiple index lesions, had prevalences of advanced neoplasms ranging from 8% to 18%. These findings indicate that for persons whose only risk factor is a single small tubular adenoma, current screening guidelines could be modified to recommend techniques less costly and less invasive than colonoscopy.
1. Arachidonic acid was metabolized by lipoxygenase and prostaglandin synthetase enzymes systems in the perfused ram testis. 2. The major product of the prostaglandin synthetase was 6-keto-PGF1 alpha (6KF). 3. Addition of testosterone resulted in a significant increase in the 6KF. 4. Arachidonic acid (AA) as well as testosterone penetrated the perfused testis. 5. Both 15-HPETE and 15-HETE, the products of the 15-lipoxygenase enzyme, were detected. 6. Addition of 0.1% BSA changed the pattern of the oxidized arachidonic acid metabolism.
A prospective, randomized, double-blind trial was designed to compare the duration of analgesia produced by intravenous morphine and methadone. Patients with intractable cancer-related pain were studied for 5-6 days. One-eighth of the patient's daily opiate requirement was supplied as an i.v. infusion of either morphine or methadone over a period of 15 min. when initiated by the patient using a patient-controlled analgesia device. Dosing intervals, pain intensity assessments and toxicity were evaluated. Twenty-three patients were randomized; 18 were fully evaluable. Ten of the evaluable patients received morphine, 8 received methadone. Dosing intervals did not change over the 5 days for either group. The mean dosing interval for the last 10 doses was 3.9 +/- 0.85 h for patients receiving morphine and 3.9 +/- 1.6 h for patients receiving methadone (P = NS). One patient receiving morphine and one taking methadone required only 2-3 doses/day for pain control. Pain intensity and relief were similar for both groups. All patients had adequate analgesia as determined by at least a 50% difference in pain intensity at peak relief. The duration of pain relief when repeated intravenous doses of these analgesics were given was similar throughout the entire study period although morphine and methadone have different serum half-lives (3 vs. 25 h). Parenteral methadone does not offer a clinically significant increase in the duration of analgesia in patients with severe pain secondary to cancer.
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A family history of colorectal cancer is believed to place persons at increased risk for development of the disease. It is unclear, however, how "strong" a family history must be to increase this risk or to make colonoscopic screening appropriate. We performed initial colonoscopy in 154 asymptomatic subjects whose only suspected risk factor was one or two first-degree relatives with colorectal cancer; 48 of these subjects also had affected second- and third-degree relatives. We found 45 adenomas in 28 subjects (18%). One subject had a 3-cm villous adenoma. In 6 subjects, the most advanced findings were tubular adenomas 5-9 mm in diameter; in 21 subjects, we found only tubular adenomas that were 2-4 mm in diameter. The prevalence of adenomas increased significantly with age of subjects (p less than 0.01). Although the overall prevalence of colorectal neoplasms in our group was no greater than might be expected in the general population, subjects with two first-degree relatives tended to have more diminutive adenomas than those with one such relative. Our findings suggest that colonoscopy is not an appropriate first step in screening persons with one affected first-degree relative. For those with more complex family histories, more data are needed--particularly on the prevalence of advanced neoplasms--to determine whether a screening technique that is less costly and less invasive than colonoscopy may be adequate.
The noncoding region of human papillomavirus type 18 (HPV-18) is shown to contain at least three enhancer elements. Two of these elements are responsive to papillomavirus-encoded trans-acting factors, and the third element functions as a constitutive enhancer, requiring only cellular factors for activity. The first enhancer (IE2) is located proximal to the E6 cap site and is responsive to papillomavirus E2 trans-activator. The second enhancer (IE6) is located approximately 500 base pairs upstream of the E6 cap site and is dependent upon the viral E6 gene product for function. A third enhancer (C) is located between 200 and 400 base pairs upstream of the E6 cap site and possesses a constitutive activity, requiring no HPV-18-encoded factors for function. The constitutive enhancer element exhibits some cell type preference for epithelial cell lines, but also functions in rodent fibroblast lines. Each of these enhancers manifests activity independent of the other elements and may reflect separate transcriptional control elements for different stages of the HPV-18 virus life cycle.
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In a previous study, we demonstrated that the red blood cell Na+ concentration and Na+,K+-ATPase activity are sex-dependent and race-dependent: a higher intracellular Na+ concentration in blacks and men was associated with a lower Na+,K+-ATPase activity. To examine whether the low Na+,K+-ATPase activity is due to a decreased number of enzyme units, altered structure of the enzyme, or the presence of an endogenous digoxinlike substance, ouabain binding studies were performed on the same subject group. The measurements included displacement of [3H]ouabain from its specific binding sites by unlabeled ouabain or potassium. The results demonstrate that groups with lower enzyme activity manifest lower numbers of total specific ouabain binding sites on the surface of the red blood cell (mean +/- SD: blacks, 654 +/- 24.4; whites, 806 +/- 18.3; women, 806 +/- 26.9; men, 728 +/- 21.2). Other kinetic parameters of [3H]ouabain displacement appear to be the same among the groups. The respective red blood cell Na+ and K+ concentrations were negatively and positively correlated with the number of ouabain binding sites. Our findings suggest that the lower activity of red blood cell Na+,K+-ATPase in blacks and men is a function of a lower number of Na+-K+ pump units. The results also indicate that sex and race should be considered when red blood cell ouabain binding is examined.
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Prior to Jackson v. Indiana, psychiatric hospitalization of those found to be incompetent to stand trial often led to an inordinately long confinement, a particularly invidious consequence if the patient had been accused only of a misdemeanor. After a highly publicized murder perpetrated by a patient originally in this category, New York State instituted a rather cumbersome set of procedures designed to assure several layers of review, including involvement of the legal system, prior to increasing privileges or discharging someone committed pursuant to a criminal court order. The effect of this new law on patient care is examined by looking at the hospital course of 52 incompetent misdemeanants at one state facility. They are demographically and clinically quite similar to a control group of persons civilly committed, except for an increased length of inpatient stay. When compared with those sent to the county penitentiary after conviction, the study population differs on several important parameters. Looking like a patient, the incompetent misdemeanant is, however, treated more as a criminal with no indication that public safety is thereby increased or that individual therapeutic objectives are enhanced.
Hyperprolactinemia is common in patients with renal failure. Because radiographic contrast material given during a computed tomographic (CT) scan of the sella as part of the evaluation for prolactinoma worsens renal insufficiency, we attempted to define the point at which hyperprolactinemia becomes an expected finding in patients with renal insufficiency in this study. Of 59 patients with serum creatinine levels of 1.5 to 12 mg/dL, 16 (27.1%) were hyperprolactinemic. Of these 16, nine were not taking medications known to raise prolactin levels and their prolactin levels were less than 100 ng/mL. In the eight patients taking medications prolactin levels were much higher. In one patient the prolactin level fell from 2,210 to 100 ng/mL when methyldopa was discontinued. In patients with chronic renal failure prolactin levels were similar regardless of the method of dialysis. We conclude that in the absence of medications known to affect prolactin secretion, hyperprolactinemia occurs infrequently (18.3%) and, when it occurs, is mild (less than 100 ng/mL). Marked hyperprolactinemia may occur in patients taking such medications. These should be stopped and the prolactin level rechecked before a CT scan is performed.
Several reports indicate that erythrocytes (RBCs) from blacks and men have higher sodium concentrations than those from whites and women. One possible mechanism to explain this finding is a difference in the activity of Na+-K+-ATPase. To explore this possibility, we have studied the Na+ and K+ kinetics of RBC Na+-K+-ATPase and RBC Na+ and K+ concentrations in 37 normotensive blacks and whites, both males and females. The maximal initial reaction velocity (Vmax) values for RBC Na+-K+-ATPase were lower in blacks and men as compared with whites and women. Higher RBC Na+ levels were observed in blacks and males vs. whites and females. Significant inverse correlations were noted between the Na+-K+-ATPase activity and RBC Na+ concentrations. These findings indicate that cellular Na+ homeostasis is different in blacks and men as compared with whites and women. Since higher RBC Na+ concentrations have also been observed in patients with essential hypertension as compared with normotensive subjects, the higher intracellular Na+ concentrations in blacks and men may contribute to the greater predisposition of these groups to essential hypertension.
The effect of methylmercuric iodide modification of sulfhydryl groups in soybean lipoxygenase-1 on linoleate oxidation, carbonyl production and beta-carotene and chlorophyll alpha bleaching were determined under aerobic and anaerobic conditions. Linoleate oxidation at pH 9.0 was strongly inhibited by modification of the enzyme. On the other hand, pigment bleaching was enhanced with the modified enzyme. Unmodified lipoxygenase-1 was not sensitive to chlorophyll inhibition, but activity of modified lipoxygenase-1 was affected. Linoleate oxidation was inhibited up to 70% when 2.2 microM chlorophyll was present in the reaction mixture. Chlorophyll inhibition was similar with affinity chromatography-purified lipoxygenase-2 and modified lipoxygenase-1. Unmodified lipoxygenase-1 exhibited high bleaching activity under anaerobic conditions and relatively low activity under aerobic (oxygen or air) conditions. Modified lipoxygenase-1 showed a significant increase in carotene and chlorophyll bleaching under both anaerobic and aerobic conditions. Under anaerobic conditions in the presence of either pigment, both modified and unmodified lipoxygenase-1 exhibited high 285 nm absorbing material production. Antioxidants (butylated hydroxyanisole, butylated hydroxytoluene, alpha-tocopherol, propyl gallate and tertiary butylated hydroxyquinone ) were powerful inhibitors of pigment bleaching by modified lipoxygenase-1. However, only tertiary butylated hydroxyquinone and propyl gallate blocked the increase in the rate of absorbance at 285 nm.