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Biomedical subjects

A Zuckerman

Publications and source records attributed to A Zuckerman.

At least 37 records · Page 2Linked to original sources

Regional renal nitric oxide release in stroke-prone spontaneously hypertensive rats.

Diminished nitric oxide (NO) production has been implicated in the pathogenesis of salt-sensitive hypertension. We questioned whether such a defect is responsible for the malignant hypertension and nephrosclerosis in stroke-prone spontaneously hypertensive rats (SHRSP) fed a high-salt/stroke-prone diet (S) versus a regular diet (R). NO release from 30-minute incubates of cortex and outer and inner medulla were studied in SHRSP at 10, 12, and 16 weeks of age on the S diet versus R diet. SHRSP-S (n=16) exhibited a marked age-dependent increase in NO release, especially in the cortex. Increases were only modest in SHRSP-R (n=21). At 16 weeks, cortical NO was 93+/-25 versus 6+/-1 pmol/mg tissue in SHRSP-S versus SHRSP-R (P<.001). Immunohistochemical staining increased mostly for neuronal, slightly for endothelial, and negligibly for inducible isoforms of NO synthase and was predominantly in the cortex of SHRSP-S versus SHRSP-R. Despite similar hypertension in SHRSP-S versus SHRSP-R (mean arterial pressure, 174+/-7 versus 177+/-2 mm Hg), malignant nephrosclerosis was seen only in SHRSP-S, affecting 22+/-6% of glomeruli and 23+/-4 vessels per 100 glomeruli by 16 weeks. N omega-nitro-L-arginine (15 mg/kg per day) in SHRSP-S (n=6) abrogated the increase in cortical NO but further augmented the hypertension and accelerated lesion development. Wistar-Kyoto rats at 16 weeks on the R diet (n=8) had NO levels similar to those of SHRSP-R, showed increased cortical NO to only 28+/-10 pmol/mg on the S diet (n=9) (P<.05 versus SHRSP-S), but remained normotensive and lesion-free. We conclude that hypertension and lesion development in SHRSP are not due to deficient renal NO. Accelerated onset of malignant nephrosclerosis by NO synthase inhibition suggests that NO is protective in these animals, mitigating the effects of hypertension and S diet on renal pathology.

Aging↗

Transjugular intrahepatic portosystemic shunt for the management of severe venoocclusive disease following bone marrow transplantation.

Hepatic venoocclusive disease (VOD) is a common, life-threatening complication of bone marrow transplantation (BMT). Portal hypertension is usually present and accounts for many of the clinical manifestations of this syndrome. We describe the results of transjugular intrahepatic portosystemic shunt (TIPS) for the management of VOD after BMT TIPS was performed in six patients with histologically confirmed VOD who had progressive jaundice and ascites. Portal hypertension was improved by TIPS in all patients (mean portal pressure gradient before TIPS, 20.2 +/- 4.6 vs. 6.7 +/- 1.9 mm Hg post-TIPS, P < .004). Three patients who underwent TIPS late in the course of VOD did not demonstrate any clinical improvement after TIPS and expired within 2 weeks of the procedure. The remaining three patients had less advanced disease and demonstrated decreases in serum bilirubin, improvement in coagulopathy, and decreased ascites after TIPS. Two patients subsequently expired, one with persistent histological changes of VOD. The lone survivor continues to do well with resolution of ascites, jaundice, and coagulopathy as of her last outpatient visit. TIPS was an effective method for portal decompression in patients with VOD after BMT, and was associated with clinical improvement in some patients. However, these effects may be transient and may not improve overall survival.

Adult↗

Analysis of the antibody response in humans with a new inactivated hepatitis A vaccine.

Sera from subjects vaccinated with the Pasteur Merieux (PM) inactivated hepatitis A vaccine (AVAXIM) have been analysed in order: (1) to assess comparability of the results provided by a modified radio-immunoassay (mRIA) in the different laboratories involved in testings of sera during clinical trials and by enzyme-linked immunoabsorbent assay (ELISA) used during development of other inactivated hepatitis A vaccines; (2) to describe the IgM responses elicited by this vaccine compared with one control vaccine [HAVRIX, 720 ELISA antigens units; Smithkline Beecham (SB), Rixensart, Belgium]; (3) to provide comparative data between the PM vaccine and the SB vaccine on neutralizing activities of vaccine-induced antibodies. Vaccine-induced antibody titres evaluated by a mRIA in different laboratories correlated well and validated the comparability of the results obtained in various vaccine trials conducted by PM. Geometric mean titres (GMTs) expressed as milli-international units (mlU/ml) were higher with ELISA especially after the first dose, but seroconversion rates were similar and a good correlation was found between the two assays. IgM vaccine-induced antibodies were detectable in nearly all vaccinated subjects from week 2 after vaccination, with a peak titre between weeks 2 and 4 after the first dose. Comparison of GMTs by the Student Fisher t-test was statistically significant (P < 0.05) only at week 2 with higher titres in PM vaccinees. Neutralizing antibodies were detected after vaccination with the PM inactivated hepatitis A vaccine. The titres gradually increased between the second week after the first dose and the booster dose (week 24). A strong booster effect of the second dose on neutralizing titres was observed. Seroneutralizing titres induced at week 2 in subjects vaccinated with the PM inactivated hepatitis A vaccine were statistically significantly higher (P < 0.05) from those induced by the SB vaccine.

Adolescent↗

Dehydroepiandrosterone augments M1-muscarinic receptor-stimulated amyloid precursor protein secretion in desensitized PC12M1 cells.

Epidemiologic studies suggest that the age-related decline in dehydroepiandrosterone (DHEA) levels may be associated with Alzheimer's disease (AD). Cholinergic markers also decline with age, and are associated with AD pathology. Activation of m1AChR-transfected PC12 cells (PC12M1) with cholinergic agonists results in secretion of Alzheimer's beta-amyloid precursor protein (APP) which in turn reduces beta-amyloid production. This study examined whether DHEA affects APP processing in m1AChR-transfected PC12 cells. DHEA treatment did not significantly alter basal or m1AChR-stimulated APP secretion. However, DHEA (0.1 microM) significantly diminished the desensitization of APP secretion in cells exposed to carbachol for 24 h. The effect of DHEA on APP processing is probably not related to up-regulation of m1AChR or increased m1AChR-activated phosphoinositide hydrolysis since these parameters did not change following DHEA treatment. These findings imply a possible involvement of DHEA in APP processing. Thus, the age-associated decline in DHEA levels may contribute to decreased APP secretion and a consecutive increase in beta-amyloid deposition, which in turn may play a role in the development of AD.

Amyloid beta-Peptides↗

Immunogenicity and safety of a new inactivated hepatitis A vaccine in a comparative study.

A multicentre, controlled, randomised, open, comparative trial including 839 healthy adult volunteers was carried out in order to compare the immunogenicity and reactogenicity of two vaccines against hepatitis A virus (HAV) during primary immunization and after booster injection. The first vaccine was produced by Pasteur Mérieux (PM), and the second vaccine by Smith-Kline Beecham (SKB). The vaccination schedule consisted of 2 doses (months 0, 6) for PM and 3 doses (months 0, 1, and 6) for SKB. Two weeks after the first dose, the seroconversion rates among initially HAV seronegative subjects (n = 608) were 93.4% and 76.1% for the PM and SKB vaccines, respectively, the corresponding geometric mean titres (GMTs) were 59.0 mIU/ml versus 30.8 mlU/ml (modified RIA HAVAB assay, Abbott Laboratories). Two months after the beginning of immunization (one dose versus two doses) the GMTs were 138.4 and 161.6 mlU/ml, respectively. At month 7, the seroconversion rates were 100% for both vaccines, and the GMTs were 4,189 and 3,163 mlU/ml, respectively. After the first dose of vaccine, 24.6% and 19.6% of the PM and SKB vaccines reported local reactions. The rates for systemic reactions were 27.2% and 25.0%, respectively. Lower rates for local and systemic reactions were seen after booster injections and statistical differences were not observed between the two vaccines. The study also demonstrated that vaccination was as well tolerated in subjects with anti-HAV antibodies as in HAV seronegative subjects. Logistic regression analysis revealed a significant vaccine effect on seroconversion rates only at week 2 (P < 10(-4). The same conclusions were drawn from the analysis of GMT by multivariate regression.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Changes in intestinal tunica muscularis following dietary fiber feeding in rats. A morphometric study using image analysis.

The morphological changes in the intestinal tunica muscularis induced by prolonged dietary fiber intake were determined in rat small intestine and colon with the aid of computerized image analysis. Thirty male Sprague-Dawley rats were fed either a fiber free, 15% cellulose or 15% pectin diet for 8 weeks. Intestine length was measured and stained cross sections of the jejunum, ileum, and colon were quantitated using image analysis. In the distal colon, muscle cell size was also determined. Despite lower weight gain in the pectin fed rats, both the small intestine and colon length were significantly increased. Cellulose feeding had a lesser effect on intestine length. Pectin fed rats had significantly increased relative tunica muscularis area (37.2 +/- 2.2 mm2) in ileum cross sections when compared to control (24.3 +/- 1.8 mm2) and cellulose fed rats (26.1 +/- 1.1 mm2). In the mid-colon, the tunica muscularis area was found to be pectin > cellulose > control (33.5 +/- 2.2; 29.7 +/- 1.7; 25.8 +/- 1.5 respectively) with significant differences reached between pectin and control rats. In jejunal samples, no differences were observed among the groups. Circular smooth muscle cell size in the distal colon was significantly increased following cellulose feeding but was less pronounced in the case of pectin. We conclude that fiber supplementation leads to morphological changes in the rat intestine including changes in length and tunica muscularis volume.

Animals↗

Correlation of Ag-NOR protein measurements with prognosis in canine transmissible venereal tumour.

Ten canine transmissible venereal tumour (TVT) cases were studied by digital image analysis quantification on sections stained with silver to demonstrate nucleolar organizer regions (Ag-NORs). In each animal, 100 neoplastic cells were randomly selected for evaluation. The following parameters were measured or calculated: area of nucleus, area of Ag-NOR dot, the mean number of Ag-NOR dots per nucleus, the mean area of Ag-NOR dots per nucleus and the ratio of mean nuclear dot area to nuclear area. All 10 cases were treated with vincristine at a dose of 0.6 mg/m2 intravenously once a week. Two, which showed malignant characteristics (i.e. uncontrolled growth, local invasion or metastasis), did not respond to multiple (12) treatments and had a fatal outcome. Of the remaining eight cases, seven responded to two to six treatments and one required 12 treatments. The average number of Ag-NORs per nucleus and the area of Ag-NORs per nucleus were lower in the seven cases that responded to two to six treatments than in the other three cases, but the difference was not significant. However, there was a significant difference in the ratios of Ag-NOR area to nuclear area between the two groups of cases. Thus, poor prognosis was (1) possibly correlated with an increase in the mean number of Ag-NORs per nucleus and an increase in the mean area of Ag-NORs per nucleus, and (2) definitely correlated with an increase in the mean ratio of Ag-NOR area to nuclear area.

Animals↗

A framework for studying personality in the stress process.

This article presents a framework for studying personality in the stress process. The framework specifies that personality may affect both exposure and reactivity to stressful events and that both processes may explain how personality affects health and psychological outcomes. The framework also specifies that personality differences in reactivity may be due to differential choice of coping efforts and differential effectiveness of those efforts. In a 14-day daily study of 94 students, this framework was used to analyze the links among neuroticism, daily interpersonal conflicts, coping with conflicts, and distress. Results showed that high-neuroticism participants had greater exposure and reactivity to conflicts. Furthermore, high- and low-neuroticism participants differed both in their choice of coping efforts and in the effectiveness of those efforts, a possibility not considered in previous models of personality in the stress process.

Adaptation, Psychological↗

Pathology of lymphoid organs in low birth weight infants subjected to antigen-related diseases: a morphological and morphometric study.

The pathology of lymphoid organs in 38 low birth weight (LBW) human infants has been evaluated by morphological and morphometric features. The gestational ages of infants ranged from 22 to 32 wks and their age at death varied from 1 hr to 153 days post partum. Infants were divided into 3 groups: 1) without antigenic effects, 2) with mild (bronchopneumonia), and 3) with severe antigenic effects, mainly sepsis. In mildly affected LBW infants, the fetal type of the immune reaction was found. It continued during the period studied (till 5 mths) and was manifested in the reaction of macrophages and the transformation of lymphocytes to lymphoblasts. Reactive centres of follicles and mature plasmocytes were not found. During the first months of postnatal development, an increase in the amount of lymphocytes in the lymphoid organs and in the rate of proliferation of reticular epithelium and a decrease in the area of the cortex in the thymus were found in all infants. In severely affected infants, the number and the size of follicles in the spleen decreased significantly and the total number of cells decreased more than 3 times. Similar changes were found in lymph nodes. These changes as well as the weak reaction of the thymus are the main features of the insufficiency and fast devastation of the lymphoid system. A compensatory increase in the number of neutrophils and eosinophils in the red pulp of the spleen and lymph nodes was found after the second week.

Bronchopneumonia↗

The content and cost of cataract surgery.

Although more than 1 million cataract surgeries are performed annually in the United States, little is known about the frequency of use or cost of various services provided in connection with this procedure. To assess the frequency with which various ophthalmic, optometric, anesthesia, and medical services are provided in conjunction with cataract surgery and to estimate the cost to Medicare associated with those services, we analyzed 1985 through 1988 Medicare claims records of a nationally representative 5% sample of Medicare beneficiaries. The experience of 57,103 Medicare beneficiaries who underwent extracapsular cataract surgery in 1986 or 1987 that was not combined with another ophthalmologic procedure formed the basis of our analysis. Projections for current costs were performed using 1991 charges allowed by Medicare for physician services. We estimate that the median charge allowed by Medicare for a "typical" episode of cataract surgery in 1991 was approximately $2500. In addition to the $3.4 billion that Medicare spent in 1991 on such "typical" episodes, Medicare spent more than $39 million on miscellaneous "atypical" preoperative ophthalmologic tests, such as specular microscopy (14% of cases) and potential acuity testing (8% of cases), more than $7 million on postoperative ophthalmologic diagnostic tests, such as fluorescein angiography (3% of cases), and more than $18 million on perioperative medical services (most commonly electrocardiography and chest roentgenography). The major determinants of the cost to Medicare associated with cataract surgery are the rate of performance of cataract surgery and neodymium-YAG laser capsulotomy and the charges allowed for these procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

Cataract Extraction↗

Mouse mesangial cells produce colony-stimulating factor-1 (CSF-1) and express the CSF-1 receptor.

CSF-1 stimulates the survival, proliferation, and differentiation of mononuclear phagocytes and may also play a role in placental development. The expression of CSF-1 and the CSF-1 receptor (CSF-1R) and their regulation were examined in cultures of mouse mesangial cells (MC). The concentration of CSF-1 in the medium of cultured MC increased linearly with time over 24 h. IFN-gamma stimulated and dibutyryl cyclic AMP inhibited CSF-1 production in a dose-dependent manner. MC expression of CSF-1 mRNA was shown by Northern blot analysis, and CSF-1 mRNA levels were increased within 4 h of IFN-gamma addition and inhibited within 4 h of dibutyryl cyclic AMP addition. Indirect immunofluorescence indicated that 90% of the untreated cultured MC expressed CSF-1. In addition, CSF-1R expression by MC was demonstrated by immunofluorescence with anti-receptor antibody, specific binding of [125I] CSF-1, and expression of the CSF-1R mRNA by Northern blot analysis. Thus, mouse MC, specialized pericytes of non-bone marrow origin, not only produce CSF-1 but also express receptors for CSF-1. The effects of CSF-1 on MC may be important in the control of immune function in the glomerulus.

Animals↗

Quantitative evaluation of chlortoluran-induced splenic hemosiderosis by means of an image analyzer.

This study investigated a technique for the quantification of hemosiderin layed down in the spleen. The model used was the rat to which the urea-based herbicide chlortoluran was fed for 90 days. There was good correlation between hematological, biochemical, histological and image analytical techniques when splenic hemosiderosis was of a moderate to severe degree. Where hemosiderosis was of a slight nature, only the technique of image analysis was able to detect the on-going changes.

Animals↗