PubMed Health⌕ Search

Biomedical subjects

D Hirsch

Publications and source records attributed to D Hirsch.

At least 55 records · Page 3Linked to original sources
PubMed1993

Colocalization of cholesterol and hydroxyapatite in human atherosclerotic lesions.

Cholesterol and calcium phosphate, the latter in the form of hydroxyapatite, accumulate in atherosclerotic lesions. In this report, we demonstrate that these organic and inorganic constituents of lesions can accumulate together, closely associated in crystal agglomerates. Using the fluorescent cholesterol probe, filipin, we identified unesterified cholesterol that was associated with calcium granules in tissue sections of lesions. We also have shown that small crystallites of cholesterol can associate with preformed hydroxyapatite crystals in vitro. Scanning electron microscopy coupled with energy-dispersive X-ray analysis demonstrated the physical association of many small crystallites of cholesterol with larger crystals of hydroxyapatite. These small crystallites of cholesterol associated with hydroxyapatite stained with filipin. This contrasted with the lack of filipin staining of unassociated larger cholesterol crystals or hydroxyapatite alone. How cholesterol and calcium come to be closely associated in crystal agglomerates within atherosclerotic lesions remains to be determined.

Aorta↗
PubMed1993

Does carotid eversion endarterectomy and reimplantation reduce the risk of restenosis?

Two hundred twelve eversion endarterectomies of the internal carotid artery and reimplantation in the common carotid artery were performed between January 1985 and July 1990. A total of 206 patients with stenosis of 75% or more and with redundancy and tortuosity of the internal carotid artery underwent this procedure. Cumulative mortality and neurologic morbidity were 2.4%. Forty patients died during the course of follow-up, seven of neurologic causes (17.1%). Duplex scans of 107 operated carotid arteries were obtained an average of 27.1 months after surgery. Restenosis of > 50% was encountered in three patients (1.9%), two asymptomatic patients (1.3%) with > 75% restenosis and one symptomatic patient with occlusion (0.6%). These results contrast with a 13.5% rate of restenoses > 50% (including 5.9% of restenoses > 75% and 1.7% occlusions) observed after 156 consecutive endarterectomies performed and closed by direct suture by the same surgical team in 1987 at a mean follow-up of 44 months. We believe that this technique can be used more often because the the operative and long-term risks are not any greater than those of the other methods of carotid revascularization. Eversion endarterectomy associated with reimplantation is especially indicated when the internal carotid artery is elongated, is < 4 mm wide, and occurs in women.

Aged↗
PubMed1993

Effects of metallic ions and diphosphonates on inhibition of pericardial bioprosthetic tissue calcification and associated alkaline phosphatase activity.

This study focused on the association of extrinsic alkaline phosphatase (AP) activity with both early and advanced calcification of glutaraldehyde-pretreated bovine pericardial bioprosthetic (GPBP) tissue, and the inhibition of both calcification and AP activity by pre-incubation in diphosphonates (sodium-ethanehydroxydiphosphonate [NaEHDP], aminopropanehydroxydiphosphonate [APD]) and metallic salts (FeCl3, Ga(NO3)3, AICI3). GPBP specimens were implanted subcutaneously in 3 wk old male rats after pre-incubation. Following explantation of the tissue at 72 h and 21 d, calcification was assessed morphologically by light microscopy and chemically by atomic adsorption spectroscopy for calcium content and by molybdate complexation for phosphorus. AP activity was characterized by enzymatic hydrolysis of paranitrophenyl phosphate and by histochemical studies. In both control and pretreated groups, AP levels were greater in 72 h explants than 21 d retrievals, which demonstrated extensive calcification in control explants. All pre-incubations that resulted in inhibition of calcification after 21 d, except for APD, were associated with 72 h AP content which was lower than control specimens. The typical time of initiation of calcification was 72 h, as determined by previous studies with this model system. Covalently bound APD inhibited calcification. Increased AP activity in the APD group may be due to the toxicity of this agent with resultant acute inflammation, or other incompletely understood effects of diphosphonates on calcification and AP. Furthermore, EHDP and Ga3+ incubations were also associated with decreased GPBP AP at 72 h compared to control, but were not effective for inhibiting calcification after 21 d. We concluded that inhibition of peak GPBP AP activity is not necessarily associated with the prevention of GPBP mineralization.

Alkaline Phosphatase↗
PubMed1993

Synergistic inhibition of the calcification of glutaraldehyde pretreated bovine pericardium in a rat subdermal model by FeCl3 and ethanehydroxydiphosphonate: preincubation and polymeric controlled release studies.

Calcification is a frequent cause of the clinical failure of bioprosthetic heart valves fabricated from glutaraldehyde-pretreated porcine aortic valves or glutaraldehyde-pretreated bovine pericardium (GPBP). We investigated the hypothesis that ferric chloride (FeCl3) and sodium-ethanehydroxydiphosphonate (EHDP) may act synergistically to prevent bioprosthetic tissue calcification. Pre-incubations and controlled release systems were studied individually. FeCl3-EHDP polymeric controlled release matrices were formulated using silicone rubber and evaluated for in vitro release kinetics at pH 7.4 and 37 degrees C. The effects of Fe-EHDP synergism on GPBP calcification were investigated with 21 d subdermal implants in 3 wk-old male rats. Results demonstrated that levels of Fe3+ and EHDP uptake, measured in GPBP tissues pre-incubated first in an FeCl3 solution (10(-5) M) followed by an EHDP solution (0.1 M), were higher than in the reverse order of incubation. In the first series of rat implants, GPBP was pre-incubated in either FeCl3 or Na2EHDP solutions, or sequential pre-incubations of first FeCl3 and then Na2EHDP solutions, or the reverse. The inhibition of calcification was greatest when FeCl3 (first pre-incubation, 10(-5) M) was combined with Na2EHDP (second pre-incubation, 0.1 M) (1.78 +/- 0.2 micrograms of Ca2+/mg of dried tissue) compared with the other pre-incubation groups: EHDP (first pre-incubation) combined with FeCl3 (second pre-incubation) (21.7 +/- 6.4), FeCl3 solution alone at 10(-5) M (27.9 +/- 10.7), Na2EHDP solution alone at 0.1 M (52.3 +/- 11.9) and the control group (72.3 +/- 10.2). In a second series of implants, GPBP specimens were co-implanted with individual controlled release systems containing one of the following formulations (weight percentage in silicone rubber): 1% FeCl3, 20% CaEHDP, 20% protamine sulphate, 1% FeCl3-20% CaEHDP, and 1% FeCl3-20% protamine sulphate. The 1% FeCl3-20% CaEHDP silicone-rubber matrices were the most effective for inhibiting GPBP mineralization (13.7 +/- 3.0 micrograms Ca2+/mg of dried tissue) compared with non-drug silicone co-implant controls (74.7 +/- 5.58 micrograms Ca2+/mg of dried tissue) and other polymeric treatment groups (32.3 +/- 2.3-80.0 +/- 19.7). No adverse effects on bone or overall growth of any treatment protocols were noted. Thus, combinations of FeCl3 and EHDP, using either pre-incubations or polymeric controlled release, were synergistic for inhibiting GPBP calcification.

Animals↗
PubMed1993

Regulation of pyelonephritis-associated pili phase-variation in Escherichia coli: binding of the PapI and the Lrp regulatory proteins is controlled by DNA methylation.

Expression of pyelonephritis-associated pili (Pap) in Escherichia coli is under a phase-variation control mechanism in which individual cells alternate between pili+ (ON) and pili- (OFF) states through a process involving DNA methylation by deoxyadenosine methylase (Dam). Methylation of two GATC sites (GATC1028 and GATC1130) within the pap regulatory region is differentially inhibited in phase ON and phase OFF cells. The GATC1028 site of phase ON cells is non-methylated and the GATC1130 site is fully methylated. Conversely, in phase OFF cells the GATC1028 site is fully methylated whereas the GATC1130 site is non-methylated. Two transcriptional activators, PapI and Lrp (leucine-responsive regulatory protein), are required for this specific methylation inhibition. DNA footprint analysis using non-methylated pap DNAs indicates that Lrp binds to a region surrounding the GATC1130 site, whereas PapI does not appear to bind to pap regulatory DNA. However, addition of Lrp and PapI together results in an additional DNaseI footprint around the GATC1028 site. Moreover, Dam methylation inhibits binding of Lrp/PapI near the GATC1028 site and alters binding of Lrp at the GATC1130 site. Our results support a model in which Dam and Lrp/PapI compete for binding near the GATC1028 site, regulating the methylation state of this GATC site and, consequently, the pap transcription state.

Bacterial Proteins↗
PubMed1993

Growth hormone-releasing activity of growth hormone-releasing peptide-1 (a synthetic heptapeptide) in children and adolescents.

The heptapeptide growth hormone-releasing peptide-1 (GHRP-1), one of a series of recently synthesized small growth hormone (GH)-releasing peptides, was administered as an iv bolus (1 microgram/kg) to 15 (six prepubertal, nine pubertal) short but healthy children and adolescents and to eight juvenile patients with pituitary insufficiency (four with isolated growth hormone deficiency, two with multiple pituitary hormone deficiencies, one with partial GH deficiency and one with GH-releasing hormone (GHRH) deficiency). Eleven out of 23 subjects also underwent an in GHRH (1-29) test (1 microgram/kg). All the healthy children responded with a progressive rise in plasma human GH (hGH) peaking at 15-30 min, with a significantly higher rise (p < 0.05) in the pubertal than prepubertal group. The hGH response to GHRH (1-29) in these children was similar or slightly higher. Six hypopituitary patients had no response to either GHRP-1 or GHRH; the patient with partial GH deficiency had a hGH peak of 6.5 micrograms/l (at 5 min) to GHRP-1 and 9.2 micrograms/l (at 15 min) to GHRH. One patient had no response of hGH to hypoglycemia, clonidine and GHRP-1, but the plasma hGH rose to 10 micrograms/l after GHRH. Following the GHRP-1 bolus there was a significant (p < 0.01) rise in plasma free thyroxine and a decrease of thyrotropin (p < 0.01), both in the limits of normal values. There was also a transitory rise of plasma cortisol (p < 0.05). Plasma prolactin, luteinizing hormone and follicle-stimulating hormone did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Liposome interactions with hydroxyapatite crystals: a possible mechanism in the calcification of atherosclerotic plaques.

Some stages in the calcification of atherosclerotic plaques may involve associations between lipids and hydroxyapatite (HA) by surface interactions. Liposomes, artificial membranous lipid vesicles, have been used in this study as model structures for biological calcification processes. Liposome (containing cholesterol and phosphatidylcholine in most cases) suspensions were prepared by sonication, after which HA seed crystals were added to the suspensions and stirred at 37 degrees C. Aliquots of the liposome suspensions were analyzed for particle size distribution and by transmission electron microscopy and electron diffraction. The results showed that HA induced aggregation of liposomes and modifications of the microscopic shapes of the liposomes in the aggregates. These data can be explained by the electron diffraction pattern where superimposition of liposome reflection and crystal reflection exists and may suggest organic-inorganic interaction. The potential of HA crystals to induce formation of liposome aggregates may be seen as a step in atherosclerotic plaques calcification.

Arteriosclerosis↗
PubMed1992

Acute skin and fat necrosis during sepsis in a patient with chronic renal failure and subcutaneous arterial calcification.

Calcification of small subcutaneous arteries and arterioles is commonly found in patients with chronic renal failure (CRF), but the syndrome of acute ischemic necrosis of the skin and subcutaneous fat supplied by these vessels is relatively uncommon. The necrosis occurs during dialysis and after successful renal transplantation, and it is often fatal. Occlusion of the calcified arteries and associated microvessels by thrombi is reported infrequently, but it is relevant to the necrosis. However, the pathogenesis remains enigmatic. In the patient described here, who had CRF, bacteremia, and laboratory evidence of disseminated intravascular coagulation (DIC), the distribution of thrombi and necrosis was mainly that of the calcified arteries which, therefore, probably played a role in the localization of the thrombi. An increased susceptibility of the endothelium of calcified vessels to the procoagulant effects of sepsis may be a contributing factor.

Acute Disease↗
PubMed1992

Factitious hemiplegia and Munchausen's syndrome.

We report a case of a thirty-year-old woman suffering from chronic factitious disorder with hemiplegia. Such a pathomimia is very uncommon in Munchausen's syndrome. Indeed, most often, the clinical picture is characterised by acute abdominal pain, fainting, haemoptysis, precordialgia, hematemesis or dermatological lesions.

Adult↗
PubMed1991

[Genetics and schizophrenia].

Studies of twins, adoption and familial incidence have demonstrated that heredity plays a role in the genesis of schizophrenia. Owing to recent advances in molecular biology and computerized statistical models, analyses of pedigrees and genetic linkage have made it possible to progress in the identification and mode of transmission of genetic factors in schizophrenia. The methodology and conflicting results of these studies are reviewed, together with modern hypotheses on the mode of transmission of schizophrenia. The contribution of genetic studies to the concept of schizophrenia clinical spectrum and the new strategies of research in genetics are presented.

Genetic Linkage↗
PubMed1991

Crescentic IgA nephropathy as a manifestation of human immune deficiency virus infection.

A 37-year-old Caucasian male homosexual presented with hematuria and rapidly progressive acute renal failure. He was found to have proteinuria and microscopic hematuria as well as RBC casts. Investigations revealed polyclonal gammopathy with five times normal serum IgA levels as well as elevated serum IgG. Renal biopsy showed evidence of crescentic IgA nephropathy with ultrastructural changes of tubuloreticular inclusions described in HIV nephropathy. He was found to be positive for human immunodeficiency viral antibodies. Renal function improved during follow-up after two doses of 1 g each of methylprednisone. In our opinion, this is the first case of HIV-related crescentic IgA nephropathy. HIV testing should be performed more frequently in patients presenting with acute glomerular diseases.

AIDS-Associated Nephropathy↗
PubMed1991

Absence of linkage between chromosome 11p15 markers and manic-depressive illness in a Belgian pedigree.

OBJECTIVE: The original finding of genetic linkage in an Old Order Amish pedigree has been contradicted by the results of several subsequent studies. Using the same genetic parameter values, diagnostic criteria, and 11p15 genetic markers as those used to study the initial Amish population, the authors performed a linkage study of a four-generation informative pedigree in Belgium. METHOD: Recombinant DNA technology was used to analyze three markers for the chromosome 11p15 location: the genes for tyrosine hydroxylase (TH) and insulin (INS) and the c-Harvey-ras oncogene (HRAS). Diagnoses of the relatives of a proband with bipolar affective disorder were determined with the Schedule for Affective Disorders and Schizophrenia--Lifetime Version and based on the Research Diagnostic Criteria. Relatives were considered affected if they had bipolar disorder, unipolar disorder, or cyclothymia; a diagnostic hierarchy was developed to include unipolar disorder and cyclothymia in the linkage analysis. RESULTS: Pairwise analyses of the disease locus and each of the three polymorphisms excluded the possibility of close linkage between manic-depressive illness and the three chromosome 11p15 markers. Multipoint linkage analysis combining the information from all three genes also excluded linkage. CONCLUSIONS: The conflict between the original results from the Amish study and the many negative reports on chromosome 11 linkage of manic-depression has been interpreted as indicating genetic heterogeneity, but heterogeneity has not been documented for the 11p15 locus. Conversely, the linkage approach has major drawbacks, so other genetic strategies should also be considered.

Adolescent↗
PubMed1991

Risk of death among Honolulu fire fighters.

To examine possible health risks associated with fire fighting, a 20-year Proportionate Mortality Ratio (PMR) study was conducted involving all male fire fighters with at least one year of service in the City of Honolulu Fire Department. The observed cause of death, as determined by the death certificates, was compared statistically to the expected numbers of deaths for all males over age 20 in Hawaii's general population. Significant increases in risk of death were found for brain cancer (Risk Ratio = 3.78), prostate cancer (Risk Ratio = 2.61), and cirrhosis of the liver (Risk Ratio = 2.3). A significant decrease in mortality was found for lung disease with a risk ratio of 0.37. No deaths were attributed to suicide nor to a category which included allergic, endocrine and nutritional diseases. Since fire fighters are known to suffer exposure to carcinogens and toxins, additional studies would be helpful in order to clarify possible risks to health associated with fire fighting on a long-term exposure basis.

Adult↗
PubMed1989

Alpha-2-adrenoreceptor binding as a possible vulnerability marker for affective disorders.

The affinity (1/Kd) and density (Bmax) of alpha 2-adrenoreceptors in platelet membranes were studied in patients with major depressed illness (n = 10), affected first-degree relatives (n = 17), nonaffected first-degree relatives (n = 44) and controls (n = 31). The alpha 2 selective antagonist 3H-yohimbine was used as the radioligand. The mean Bmax values of affected subjects (probands and relatives) were significantly lower than those of controls. There was no difference in Kd values between the controls and affected subjects. There was a positive gradient of the mean Bmax values from the groups of probands to affected relatives, unaffected relatives and control subjects. A familial effect of Bmax values between members of the same families confirms a genetic control of alpha-receptor affinity. These results support the hypothesis that the density of alpha 2-adrenoreceptors, evaluated by 3H-yohimbine binding on human platelets, could be a potential vulnerability marker for affective disorder.

Adult↗
PubMed1988

DSC, X-ray and NMR properties of cholesterol-cholestanol-dihydrate crystals.

The melting point, X-ray diffraction and longitudinal relaxation time (T1) of cholesterol-cholestanol-dihydrate crystals (CC2W) were studied in an effort to produce new experimental data related to atherosclerotic plaques. The crystals were precipitated from ethanolic solutions at several cholesterol: cholestanol (CS:CN) ratios. The melting point of CC2W crystals obtained at the CS:CN ratio 75:25, 50:50, 25:75 was 122-124 degrees C. The X-ray patterns recorded from these crystals of the same CN:CS ratios showed two additional diffraction peaks, as compared to those of CN and CS patterns. On the other hand, the values of T1 relaxation time measured by proton magnetic resonance were different for every CS:CN ratio for the various solution compositions. This latter method seems to be more precise for the detection of the presence of coprecipitated components in the CC2W mixed crystals than X-ray or thermal analysis. The results suggest that CN and CS do not have to be present in equimolar quantities in order for CC2W crystals to be formed. The presence of CC2W in the blood may have significance in the nucleation of cholesterol crystals in atherosclerotic plaques.

Arteriosclerosis↗
PubMed1986

Dependence of the substrate specificity and kinetic mechanism of horse-liver alcohol dehydrogenase on the size of the C-3 pyridinium substituent. 3-Benzoylpyridine-adenine dinucleotide.

The kinetic mechanism and the substrate specificity of liver alcohol dehydrogenase are changed when 3-benzoylpyridine-adenine dinucleotide is used as coenzyme. Only primary alcohols are substrates of the enzyme and with ethanol the mechanism becomes rapid-equilibrium random bi-bi. According to model building experiments on a graphic display, the benzoyl group partially enters the substrate binding site, whereas the essential interactions between coenzyme and enzyme are preserved. This restraint on the substrate binding site provides a molecular explanation for the observed dependence between coenzyme and substrate chemical structures.

Alcohol Dehydrogenase↗