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E Holtzman

Publications and source records attributed to E Holtzman.

At least 37 records · Page 2Linked to original sources
PubMed1987

Peroxisomes in wild-type and rosy mutant Drosophila melanogaster.

This study shows that peroxisomes are abundant in the Malpighian tubule and gut of wild-type Oregon R Drosophila melanogaster and that the peroxisomal population of the rosy-506 eye-color mutant differs from that of the wild type. Catalase activity in wild-type flies is demonstrable in bodies of appearance and centrifugal behavior comparable to the peroxisomes of vertebrate tissues. Xanthine oxidase (xanthine:oxygen oxidoreductase, EC 1.1.3.22) activity of the Malpighian tubule of wild-type flies is demonstrable cytochemically in bodies like those containing catalase. The rosy-506 mutant flies, with a deletion in the structural gene for xanthine dehydrogenase (xanthine:NAD+ oxidoreductase, EC 1.1.1.204), lack cytochemically demonstrable peroxisomal xanthine oxidase activity. In addition, peroxisomes in the rosy-506 mutants show less intense cytochemical staining for catalase than those in wild-type flies, and biochemical assays indicate that catalase in the rosy mutant is much more accessible to substrate in the absence of detergent than in the wild type. Thus, the rosy-506 mutation appears to affect peroxisomes and may mimic aspects of the defects of peroxisomes in some human metabolic disorders.

Animals↗
PubMed1987

Enhanced risk of coronary heart disease mortality in lean hypertensive men.

A recently presented hypothesis contends that the excess coronary heart disease mortality associated with hypertension is more prominent in lean men than in overweight men. This hypothesis was addressed using data collected in the Israeli Ischemic Heart Disease Study (n = 10,059). The ratios of age-adjusted 15-year death rates in hypertensive and normotensive men were 4.7, 2.8, 2.0, and 1.9 in the Quetelet index groups of less than 2.29, 2.29 to 2.56, 2.56 to 2.83 and greater than 2.83 g/cm2, respectively. The corresponding ratios for all-cause mortality were 2.2, 2.1, 2.0, and 1.7, respectively. The group with the highest all-cause age-adjusted mortality, at 33.6%, was that of the leanest (less than 2.29 g/cm2, bottom 20% of the Quetelet index distribution) hypertensive subjects. The same group also displayed the highest coronary heart disease mortality (age-adjusted rate, 18.2%). The findings persisted for both smokers and nonsmokers and after exclusion of men with coronary heart disease or diabetics at intake, men on antihypertensive medication, or those who died in the first 2 years of follow-up (1963-1965). A multivariate risk score for developing myocardial infarction was calculated, based on levels of age, systolic blood pressure, total cholesterol, high density lipoprotein cholesterol, cigarette smoking, diabetes mellitus, and Quetelet index. This score varied little across the four Quetelet index groups in hypertensive men: 5-year mean estimated risks of myocardial infarction were between 70 and 74/1000. In normotensive men the scores increased from 19/1000 in the leanest subjects to 29/1000 in the overweight ones.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Do beta-blockers alter lipids and what are the consequences?

The unpredictable effect of antihypertensive therapy on coronary risk resulting from changes in lipid levels is an increasingly recognized problem. Different drugs have been shown to exert varying effects on lipids. This problem is particularly evident in young hypertensive patients who may be candidates for lifelong therapy. The effects of chlorthalidone and metoprolol on fasting plasma lipids and lipoprotein levels were compared in two similar nonrandomized groups of patients with mild hypertension. Chlorthalidone therapy was associated with an increase in serum cholesterol of 8.1% (17 mg/dl), mainly reflecting an increase in low-density lipoprotein (LDL) cholesterol. Serum triglycerides increased by 16% (20 mg/dl) and high-density lipoprotein (HDL) cholesterol levels decreased by 10% (3 mg/dl, not significant). Metoprolol therapy induced no changes in total, low, very low, or high-density lipoprotein. Serum triglyceride concentration increased by 22% (28 mg/dl). Application of the Israel Ischemic Heart Disease Study data to these findings indicates a slight decrease at most in the 5-year estimated probability of myocardial infarction in the chlorthalidone-treated group, whereas a clearly favorable influence on the calculated risk of coronary heart disease was observed for those treated with metoprolol. These data suggest that the different forms of therapy for mild hypertension carry varying degrees of significance in terms of risk of coronary heart disease, which should be considered when choosing medication.

Adrenergic beta-Antagonists↗
PubMed1986

Peroxisomes in infantile phytanic acid storage disease: a cytochemical study of skin fibroblasts.

Cultured skin fibroblasts from six patients demonstrating clinical signs and biochemical characteristics of infantile phytanic acid storage disease (IPSD) were examined by electron microscopy, using cytochemical procedures for the demonstration of peroxisomal catalase activity. In four of the six fibroblast cell lines peroxisomes strongly reactive for catalase were present in numbers similar to those found in normal fibroblasts. Liver biopsy tissue from one of these patients showed no typical hepatic peroxisomes, but did show small, marginally reactive bodies. In two other IPSD fibroblast cell lines peroxisomes with appreciable cytochemical reactivity were rare or absent. It seems, therefore, that infantile phytanic acid storage disease is heterogeneous with respect to the presence of cytochemically recognizable peroxisomes, at least in the cases studied here. Furthermore, peroxisomes may be markedly affected in one cell type - liver - and yet not affected in another - skin fibroblasts - within a single individual.

Catalase↗
PubMed1986

Malignant fibrous histiocytoma complicating mitral valve replacement.

A 67 year old woman developed a fatal febrile illness 8 years after mitral valve replacement for rheumatic valvular heart disease. The final disease persisted for 1 year and was characterized clinically by weakness, weight loss, congestive heart failure and multiple embolic events to the central nervous system and abdominal organs. The source of the emboli was a tumor, malignant fibrous histiocytoma of the left atrium, originating from the anulus fibrosus around the covered base of the prosthetic valve. This unique case suggests the possibility that chronic exposure to materials, such as Dacron, covering prosthetic valves may induce local malignant tumors.

Aged↗
PubMed1986

Functional domains of the nicotinic acetylcholine receptor.

The nicotinic acetylcholine receptor is a multisubunit, membrane-spanning protein that contains a gated, cation-conducting channel. Our approach to the understanding of the function of this receptor in molecular terms has been to locate its functionally significant sites in the sequences of its subunits and in its three-dimensional structure. In addition, we have tried to correlate transitions in the properties of these sites with functional transitions of the receptor. On binding acetylcholine, the nicotinic acetylcholine receptor enters at least two transient states, the open state and the rapid-onset desensitized state, and, in the continued presence of agonist, finally subsides into the slow-onset desensitized state. The transitions of the receptor between these various states are susceptible to regulation by acetylcholine and its congeners acting at one type of site and by a broad class of noncompetitive inhibitors (NCIs), including local anesthetics, acting at other sites. The chain composition of the receptor is alpha 2 beta gamma delta. The two acetylcholine binding sites are on the alpha chains, and two residues contributing to these sites, Cys-192 and Cys-193, have been identified. Furthermore, these adjacent Cys residues are cross-linked by a disulfide bond. In the quaternary structure of the receptor, the chains appear to be arranged in the order alpha gamma alpha beta delta around a central channel. Both the alpha and beta chains contribute to functionally significant NCI binding sites. The addition to receptor-rich membrane from Torpedo electric tissue of agonists (but not competitive antagonists) renders these NCI sites susceptible to photolabeling by the NCI quinacrine azide (QA). Furthermore, this susceptibility is transient, arising in milliseconds and subsiding in hundreds of milliseconds. These transiently susceptible sites are protected by other NCIs against photolabeling by QA. The time-course of the susceptibility and its dependence on agonist-concentration suggest that it might be the transient, rapid-onset desensitized state of the receptor that is most susceptible to photolabeling by QA.

Acetylcholine↗
PubMed1986

Elevated systolic blood pressure as a predictor of long-term cancer mortality: analysis by site and histologic subtype in 10,000 middle-aged and elderly men.

The association of a casual reading of blood pressure (BP) in 1963 to subsequent 15-year cancer mortality was examined in a cohort of 10,059 middle-aged and elderly men. Systolic BP (SBP), but not diastolic BP, predicted significantly long-term cancer mortality occurring in 369 subjects. The covariate-adjusted relative risk (RR) estimated by Cox's proportional hazard model was 1.10 [95% confidence interval (CI), 1.00-1.21]. In patients aged less than 60 at the beginning of the study, increased cancer mortality was mainly observed in association with SBP of more than 150 mm Hg. In subjects aged 60 or above, the estimated RR was 1.21 (95% CI, 1.03-1.42). Exclusion of 40 men in whom diagnosis made prior to 1963 or death occurred through 1965 did not alter the results. An excess mortality in men who reported pharmacologic treatment for hypertension while under follow-up was fully accountable by their age, BP, and smoking habits. Analysis by site suggested that the association was mainly due to increased mortality from cancer of the digestive and genitourinary organs (estimated RR's, respectively, 1.20 and 1.26; 95% CI's, respectively, 1.03-1.39 and 0.99-1.59). Analysis by histologic subtype suggests an association with adenocarcinoma (RR = 1.19, 95% CI, 1.04-1.37) but not squamous cell or transitional cell carcinomas, myeloma, lymphomas, and leukemias.

Adult↗
PubMed1985

Total and high density lipoprotein cholesterol in the serum and risk of mortality: evidence of a threshold effect.

The association of serum total and high density lipoprotein cholesterol values with 15 year mortality was examined in a cohort of 10 059 Israeli male civil servants and municipal employees aged 40 and above. In 618 of 1664 deaths in the cohort (37%) coronary heart disease was documented as the cause of death. Risk of mortality was analysed by quintiles. Neither total mortality nor coronary heart disease mortality rose with serum cholesterol concentrations up to 5.6 mmol/1 (216 mg/100 ml), representing 60% of the sample. Rates rose appreciably only in the highest quintile (cholesterol concentration greater than 6.2 mmol/1; greater than 241 mg/100 ml). High density lipoprotein cholesterol was similarly, although inversely, associated with total mortality when expressed as a percentage of total cholesterol. The inverse association of high density lipoprotein cholesterol with coronary heart disease mortality was, in contrast, continuous. These data support the hypothesis that over most of the range of cholesterol values coronary mortality risk and total mortality risk are nearly independent of total cholesterol and most probably independent of low density lipoprotein cholesterol values. In multivariate analysis a low concentration of high density lipoprotein cholesterol appeared to be more predictive of mortality than a high concentration of total cholesterol. The latter was very weakly related to mortality from all causes after multivariate adjustment. It is concluded that the findings of this and other major epidemiological studies support the notion of a "threshold effect." Success in reducing mortality through the pharmacological reduction of serum cholesterol in hypercholesterolaemic patients does not warrant a similar approach in people with average or slightly above average values. These findings appear to provide support for a "high risk strategy" in reducing the risk of coronary heart disease.

Adult↗
PubMed1985

Peroxisomes in the nervous system of Aplysia californica: a cytochemical study.

We have studied the distribution of peroxisomes in the abdominal ganglion of Aplysia californica using electron microscopic cytochemical methods. Reaction product for catalase was observed in small ovoid or dumb-bell-shaped bodies in the perikarya of many of the neurons. The abundance of these catalase-reactive peroxisomes is considerably greater than is the case in vertebrate neurons. While the non-neuronal cells of the Aplysia abdominal ganglion do contain appreciable peroxisome populations, there were few peroxisomes in glial cytoplasm directly adjacent to the perikarya, again contrasting with vertebrate ganglia in which the satellite cells are a principal site of peroxisomes. Peroxisomes are present throughout the perikaryal cytoplasm. In the regions in which lipochrome granules abound, peroxisomes are frequently seen closely associated with these granules; glycogen is abundant nearby. The association of peroxisomes, lipochrome granules and glycogen is interesting in view of the propinquities of peroxisomes to lipid droplets and lipofuscin granules reported for non-neuronal vertebrate tissues, and in view of the growing evidence indicating that some of the roles of peroxisomes are in lipid metabolism and in gluconeogenesis. Some of the lipochrome granules themselves show reaction product in ganglia incubated to demonstrate catalase activity and some react in tissue incubated to demonstrate acid phosphatase activity. Such observations suggest that the enzymatic capacities of the lipochrome granules merit further studies, and that the granules may be of complex or heterogeneous nature.

Acid Phosphatase↗
PubMed1985

Pericardial effusion as the sole manifestation of infectious mononucleosis.

A 56-year-old patient presented with fever, dyspnoea and large pericardial effusion, which were the only features of infectious mononucleosis. Atypical cases or infectious mononucleosis are common in older patients. Such a well documented case of effusive pericarditis, however, has not been previously recorded.

Dyspnea↗
PubMed1985

Uncommon presentation of pheochromocytoma: case studies.

Twelve patients with pheochromocytoma have shown unusual clinical and laboratory presentation. These include three patients with cardiac manifestations (sick sinus syndrome, obstructive cardiomyopathy and ischemic ECG changes). Two patients with gastrointestinal problems (acute abdomen due to ischemic bowel and constipation). One child with sudden blindness and one, non diabetic patient with polyuria. Laboratory findings included four patients with diabetes mellitus, four patients with hypercalcemia two of them with concomitant hyperreninemia and one patient with hypokalemia. Awareness of the illness leads to the discovery of unusual cases and even a most severely sick patient can make a complete recovery.

Adolescent↗
PubMed1985

Peroxisomes in fibroblasts from skin of Refsum's disease patients.

Skin fibroblasts were cultured from young adult patients with Refsum's disease, an inherited metabolic disorder characterized by a deficiency in oxidation of phytanic acid and by increased serum and tissue concentrations of this fatty acid. These cultures were compared to cultures of normal fibroblasts in terms of the number and distribution of peroxisomes demonstrable cytochemically in preparations incubated for catalase activity. Refsum's fibroblasts were found to contain 1-10 peroxisome profiles per 100 micron 2 of cytoplasm; the controls contained 1-2 profiles per 100 micron 2. The peroxisomes in normal fibroblasts were found in all regions of the cytoplasm. In the Refsum's material they were relatively scarce in the perinuclear region, where many of the cells showed numerous large inclusions containing lipid-like material and myelin figures. Our findings indicate that in the adult form of Refsum's disease, which is the more thoroughly studied variety, peroxisomes in fibroblasts are not diminished in number. This contrasts with a recent report concerning a case of what is thought to be an infantile form of the disorder, in which no peroxisomes were detected in a liver biopsy. If phytanic acid accumulations in the adult form are a consequence of peroxisomal defects, the defects presumably are at the level of specific enzymatic deficiencies and do not involve a generalized absence of peroxisomes.

Adult↗
PubMed1985

Oxidation of oxalate and polyamines by rat peroxisomes.

During renal failure, polyamines and oxalate levels are elevated in the serum and the glomerular filtrate and are dumped by the kidney. Both of these compounds can be catabolized by oxidative reactions. We have, therefore, investigated the intracellular distribution of oxalate oxidase and of a polyamine oxidase in normal female rat kidney and liver. Polyamine oxidase was demonstrable, using spermidine as substrate in the cerous peroxyhydrate procedure of Briggs et al., in peroxisomes of kidney tubule cells and of hepatocytes. Oxalate oxidase could not be studied with this technique due to precipitation of cerium oxalate in the incubation medium. To demonstrate oxalate oxidase, and to confirm the polyamine oxidase localization, we incubated aldehyde-fixed tissue in a diaminobenzidine medium at pH 8, following the approach of Veenhuis et al., in which oxidases are demonstrated by virtue of their production of H2O2, which then serves as a substrate for endogenous catalase. Using oxalate or spermidine as substrate with this approach, we found reaction product in typical renal peroxisomes; we also found reaction product, with the polyamine substrate, in hepatocyte peroxisomes. To strengthen the conclusion that the oxidases themselves are present in peroxisomes, we used a light microscopic method, based on the tetrazolium procedures of Allen and Beard to demonstrate polyamine and oxalate oxidase activities in bodies with the distribution of renal peroxisomes.

Animals↗
PubMed1984

Uptake of calcium by the endoplasmic reticulum of the frog photoreceptor.

We studied retinal photoreceptors of Rana pipiens by using techniques designed to investigate calcium localization. Particularly useful were methods in which intracellular sites of calcium uptake were detected by incubation of saponin-treated isolated retinas in calcium-containing media, with oxalate present as a trapping agent. With these procedures, cell compartments accumulate deposits, which can be shown to contain calcium by x-ray microanalysis. Calcium accumulation was prominent in the rough endoplasmic reticulum in the myoid region. In addition, deposits were observed in agranular reticulum and in certain Golgi-associated compartments of the myoid region, in mitochondria, in axonal reticulum, and in agranular reticulum of presynaptic terminals. Calcium was also detected in the endoplasmic reticulum of retinas fixed directly upon isolation, by a freeze-substitution method. The factors influencing accumulation of calcium in the endoplasmic reticulum were evaluated by a semiquantitative approach based on determining the relative frequency of calcium oxalate crystals under varying conditions. Calcium accumulation was markedly enhanced by ATP. Studies with a nonhydrolyzable ATP analogue (adenylyl- imidodiphosphate ) and with inhibitors of the sarcoplasmic reticulum Ca2+-Mg2+ ATPase (mersalyl and tetracaine) indicated that this ATP-dependent calcium uptake reflects an energy-dependent process roughly comparable to that in the sarcoplasmic reticulum.

Adenosine Triphosphate↗
PubMed1984

A comparative study of infective endocarditis.

A survey of hospitalizations at the Chaim Sheba Medical Center, covering two nonconsecutive decades (1951-60 and 1970-79), included 213 patients (228 episodes) with infective endocarditis. The increase in the age of patients and in the frequency of atherosclerotic heart disease, as well as the introduction of techniques such as heart catheterization and open-heart surgery, are responsible for the differences in clinical course, microbiology and therapy. Despite the changed pattern, rheumatic heart disease remained the principal underlying disease in both periods and Streptococcus viridans remained the most common pathogen. Not a single case of drug addiction appeared in our material, despite its increasing frequency in Israel.

Adolescent↗
PubMed1984

Different effects of metoprolol and chlorthalidone on serum lipoprotein levels in mild hypertension. Possible implications for coronary heart disease risk status.

The effects of chlorthalidone and metoprolol on fasting plasma lipids and lipoprotein levels were compared in two similar nonrandomized groups of patients with mild hypertension. Chlorthalidone therapy was associated with an increase in serum cholesterol of 8.1% (17 mg/dl), mainly reflecting an increase in low-density lipoprotein (LDL)-cholesterol. High-density lipoproteins (HDL)-cholesterol decreased, but the difference between pre- and posttreatment levels did not reach statistical significance. Serum triglyceride (TG) concentration increased by 16% (20 mg/dl). Metoprolol therapy was not associated with changes in total, very low-density lipoprotein (VLDL)-, LDL- and HDL-cholesterol levels. Serum TG concentration increased by 22% (28 mg/dl), mainly due to an increase in VLDL-TG. Application of the Israel Ischemic Heart Disease Study data to these findings could predict only a very slight decrease in the 5-year estimated probability of myocardial infarction in the chlorthalidone-treated group. Metoprolol therapy has, theoretically, a more favorable influence on coronary heart disease risk status. These data suggest that the different forms of therapy for mild hypertension have a different effect on the theoretical coronary heart disease risk status, a fact that should be taken into consideration in the choice of medication.

Body Weight↗