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Biomedical subjects

J Goldstein

Publications and source records attributed to J Goldstein.

At least 73 records · Page 4Linked to original sources
PubMed1998

Response to pneumococcal immunization in children with and without recurrent infections.

Many children with recurrent sinopulmonary infections fail to mount an adequate humoral response following immunization with polysaccharide antigens. At present there are no controlled studies comparing responses to pneumococcal immunization in children with recurrent infections and a healthy, age-matched cohort. Immunological evaluation was performed on 66 children with recurrent sinopulmonary infections, aged 2-5 years (mean 3.06 +/- 0.92). A control group included 28 healthy, age-matched controls (mean 3.14 +/- 0.88 years). Both groups were immunized with 23 valent pneumococcal vaccine, and titers were measured before and 4 weeks after immunization. Antibody levels to 12 pneumococcal serotypes were measured via radioimmunoassay. Geometric preimmunization mean titers in the control group were 215.5 +/- 157 ngAbN/ml rising to 989.5 +/- 745 ngAbN/ml compared to 77.71 +/- 38.4 ngAbN/ml increasing to 446.7 +/- 406 ngAbN/ml in the study group (p < .05). Serotypes 3, 4, 7F, 8, 9N, and 18C were the most immunogenic, while serotypes 6A and 14 were the least. Overall, the control group responded to 7.71 +/- 1.24 serotypes versus 5.1 +/- 2.0 in the study group (p < .05), where postimmunization titers at least doubled and rose to > or = 300 ngAbN/ml. All controls responded to at least five or more serotypes, 26/28 responded to 6 or more. In contrast, only 38/66 (57%) of study patients responded to five or more serotypes, and only 27/66 (41%) responded to at least 6 of 12. Preimmunization titers of greater than 300 ngAbN/ml were present in 30% (102/336) of the control serotypes; however, only 53 of these (52%) doubled post immunization; 22% of the elevated titers decreased post immunization. Markedly elevated titers > or = 500 ngAbN/ml were present in 20% (69/336) of the preimmunization serotypes, only 39% of these doubled post immunization. Twenty-three valent pneumococcal vaccine is immunogenic in young, healthy children. A significant percentage of children with recurrent sinopulmonary infections fail to produce adequate serotype specific antibodies following pneumococcal immunization.

Antibodies, Bacterial↗
PubMed1998

Distribution of GABA in the golden hamster retina. An immunocytochemical study.

Distribution of the inhibitory neurotransmitter GABA was studied in the golden hamster retina using immunocytochemistry at cellular and subcellular levels. GABA-immunoreactivity was observed in somata of amacrine, displaced amacrine and horizontal cells. GABA immunoreactive fibers were abundant in the inner plexiform layer. Ultrastructural analysis exhibited dense GABA-immunoreactive deposits in amacrine cell somata, processes and terminals. Immunolabelling was also observed in the cytoplasm of horizontal or interplexiform cells and displaced amacrine cells. In every case DAB deposits were observed in the cytosolic compartment, attached to the inner surface of cell membranes and to outer mitochondrial membranes. Immunolabeled terminals predominated in the inner plexiform layer and immunoprecipitates were also observed attached to the outer face of vesicle membranes as well as completely filling synaptic vesicles. Both clear and dense core vesicles were observed. The present results are similar to those obtained in other mammalian species showing GABA immunoreactivity in amacrine, displaced amacrine and horizontal cells.

Animals↗
PubMed1997

Modified total lymphoid irradiation and low dose corticosteroids in progressive multiple sclerosis.

In a double-blind prospective randomized trial, we assessed the efficacy and safety of modified total lymphoid irradiation (TLI) plus low dose prednisone (TLI-LDP) as compared to sham TLI plus identical prednisone therapy (sham TLI-LDP) in 46 patients with progressive forms of multiple sclerosis (MS). No significant difference existed between groups at study entry in patient age, sex, duration of MS, or disability status. However, following treatment, significantly fewer TLI patients showed a sustained one point decline in the Expanded Disability Status Scale, the primary study endpoint, as compared to the sham TLI group using the Kaplan-Meier Product-limit survival analysis, (P<0.005). Risk for relapse requiring treatment with intravenous methylprednisolone was reduced by 54% in the TLI-treated group (P<0.05). Significantly fewer TLI-LDP patients had gadolinium enhancing plus new T2-weighted lesions (P=0.018) when compared to the sham group post-treatment. There was also a substantial and significant decrease in blood lymphocytes in the TLI-LDP group when compared to either pretreatment values or to sham TLI-LDP through at least 12 months post-therapy. Side effects secondary to TLI were generally mild and well-tolerated. These results further support the hypothesis that TLI and systemic immunosuppression have a beneficial effect in progressive forms of MS.

Adult↗
PubMed1997

Notch-1 controls the expression of fatty acid-activated transcription factors and is required for adipogenesis.

Notch, a transmembrane receptor member of the homeotic epidermal growth factor-like family of proteins, participates in cell-to-cell signaling to control cell fate during development. Activated Notch-1 constructs lacking the extracellular region prevent differentiation of several mammalian cells in vitro. This effect, however, bypasses the normal mechanisms of cell-to-cell interactions in which Notch-1 participates. We investigated the role of Notch-1 in the hormone-induced adipocyte differentiation of 3T3-L1 fibroblasts, a paradigmatic model of adipogenesis that requires cell-to-cell contact. Unlike other differentiation models, Notch-1 expression and function were necessary conditions for adipogenesis. Impaired Notch-1 expression by antisense Notch-1 constructs prevented adipocyte differentiation. Strategies aimed at blocking putative Notch/ligand interactions also blocked adipogenesis, implicating Notch as a critical molecule in cell-to-cell signaling necessary for differentiation. Inhibition of Notch-1 expression or function decreased the expression of peroxisomal proliferator-activated receptors delta and gamma, transcription factors that control adipocyte differentiation and that are up-regulated at cell confluence. These results implicate Notch in the commitment of 3T3-L1 cells to undergo adipogenesis by controlling the expression of the principal regulators of this process.

3T3 Cells↗
PubMed1997

Neuronal and macrophagic nitric oxide synthase isoforms distribution in normal rat retina.

A detailed study about the distribution of nitric oxide synthase (NOS) isoforms, neuronal NOS (nNOS) and macrophagic NOS (mNOS), in normal rat retina was performed using immunocytochemistry by employing specific antibodies. The nNOS immunocytochemistry showed immunoreactive amacrine cells, fibres in inner and outer plexiform layers (IPL and OPL) and an immunostained band corresponding to inner photoreceptor segments (IPS). This was in agreement with NADPH-d histochemical results. mNOS immunoreactivity was found in cell somas localized in both, inner nuclear layer (INL) and ganglion cell layer (GCL), in slender Müller cell processes along IPL and GCL and also in the band corresponding to IPS. A different distribution of nNOS and mNOS was found in rat retina although both isoforms of NOS are co-localized in IPS.

Animals↗
PubMed1997

Changes in NADPH diaphorase reactivity and neuronal nitric oxide synthase in the rat retina following constant illumination.

The distribution of nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) reactivity and neuronal nitric oxide synthase immunoreactivity (nNOS-IR) was investigated in the rat retina during photoreceptor regeneration. Photoreceptor damage and the disappearance of a NADPHd reactive/nNOS-IR band corresponding to inner photoreceptor segments were observed after continuous exposure to light irradiation. Both events were reversible after 20 days of total darkness. Also a progressive decrease in the number and in the staining intensity of NADPHd reactivity in amacrine cells were found along the first 3-6 days of darkness stabilizing thereafter in both illuminated and control groups. However, staining intensity in the former group remained more elevated than in the latter one. NOS activity in the retina varies depending on functional and pathological states.

Adaptation, Ocular↗
PubMed1997

Association of the Epstein-Barr virus with Hodgkin's disease in Southern Israel.

Epstein-Barr virus (EBV) has been frequently documented in the putative neoplastic Hodgkin-Reed-Sternberg (HRS) cells, in lymph nodes from patients with Hodgkin's disease (HD). This association varies in different geographic areas and between industrialized and developing countries, as does the epidemiological pattern of the disease. In the present study of 106 cases of HD from the Soroka Medical Center in Beer-Sheva, which serves as the only hospital for most of the southern part of Israel, we found an association with EBV expression in only 30% of the patients; 45% of mixed cellularity (MC) cases compared with 21% of nodular sclerosis (NS) cases were positive for EBV. The number of patients in the 0-14-year-old age group was limited; however, 8 of these II children were EBV positive. This low association rate of HD with the presence of EBV sequences is probably related to the small number of children in our series. A low proportion of EBV-associated disease in older adults may be contributory. Other factors may be involved.

Adolescent↗
PubMed1997

Cytolytic and cytostatic properties of an anti-human Fc gammaRI (CD64) x epidermal growth factor bispecific fusion protein.

A bispecific fusion protein (H22-EGF) that binds simultaneously to the epidermal growth factor receptor (EGF-R) and to the high affinity receptor for the Fc portion of human IgG, Fc gammaRI (CD64), has been successfully constructed and expressed. For this construction, genomic DNA encoding the Fd fragment of humanized anti-Fc gammaRI mAb, H22, which binds Fc gammaRI at an epitope that is distinct from the Fc binding site, was fused to cDNA encoding human epidermal growth factor (EGF), a natural ligand for EGF-R. The resulting H22Fd-EGF-expressing vector was transfected into a myeloma cell line that was transfected previously with a vector containing DNA encoding the H22 kappa-light chain. SDS-PAGE analysis of purified H22-EGF demonstrated that the fusion protein was secreted predominantly as H22Fab'-EGF monomer (approximately 55 kDa), even though a free Cys residue exists in the hinge region of the H22 Fab' component. Using a novel bispecific flow cytometry-binding assay, we demonstrated that the purified bispecific fusion protein, H22-EGF, was able to bind simultaneously to soluble Fc gammaRI and EGF-R-expressing cells. H22-EGF inhibited the growth of EGF-R-overexpressing tumor cells and mediated dose-dependent cytotoxicity of these cells in the presence of Fc gammaRI-bearing cytotoxic effector cells. These results suggest that this fusion protein may have therapeutic utility for EGF-R-overexpressing malignancies.

Antibodies, Bispecific↗
PubMed1997

Restoration of patency of left internal mammary artery graft with progression of the underlying left anterior descending coronary artery disease.

The use of the left internal mammary artery (LIMA) to graft a borderline lesion in the left anterior descending coronary artery (LAD) has been associated with distal narrowing and occlusion of the LIMA. We present a patient in whom the LIMA occluded 1 year after coronary artery bypass, but was found to be fully patent 4 years later, after progression of the native LAD disease.

Angioplasty, Balloon, Coronary↗
PubMed1997

Comparison of the histopathology of culprit lesions in chronic stable angina, unstable angina, and myocardial infarction.

BACKGROUND: The etiology of unstable angina (UA) and myocardial infarction (MI) both involve rupture of an atherosclerotic plaque in a coronary artery. It has been suggested that the two syndromes differ because MI results if a red occlusive permanent thrombus occurs and UA occurs only if a nonocclusive platelet (white) thrombus occurs. HYPOTHESIS: The purpose of this study was to determine the differences between coronary lesion pathology in MI and UA and compare them with lesions of chronic stable angina (CSA). METHODS: We reviewed the pathologic specimens of culprit lesions obtained by directional coronary atherectomy in 27 patients with MI, 29 patients with UA, and 16 patients with CSA. RESULTS: The incidence of ruptured plaque was high and identical in patients with MI (77.8%), and UA (75.8%), and significantly lower in patients with CSA (25.0%) (p < 0.001). Similarly, the incidence of red thrombus was the same in MI (92.6%) and UA (82.7%), and significantly less in CSA (p < 0.001). CONCLUSIONS: The underlying pathophysiology of both UA and MI appears to be the same, with red thrombus playing an important role in both syndromes. The only difference is in the degree of occlusiveness of the red thrombus on the ruptured plaque and whether the occlusion is transient (UA) or persistent (MI). The balance between thrombosis and endogenous clot lysis determines which syndrome occurs. Lytic therapy is not effective in UA, probably because the clot is not occlusive or because endogenous lysis has already achieved the degree of coronary opening that eventuates from tissue plasminogen activator or streptokinase administration. Prompt catheterization and revascularization may be as indicated in patients with MI if there remains viable myocardium as in patients with UA.

Aged↗
PubMed1997

Naive alloreactive CD8 T cells are activated by purified major histocompatibility complex class I and antigenic peptide.

In this report, we demonstrate stimulation of T cell receptor (TCR) transgenic CD8 T cells by isolated major histocompatibility complex (MHC) class I H-2Ld complexes and antigenic peptide. This is the first demonstration of CD8 T cells activated by MHC and antigenic peptide in the absence of antigen priming. Furthermore, isolated MHC and a potent peptide antigen can stimulate phenotypically naive CD44- T cells to become CTL effectors and to produce interleukin-2 in nanogram per milliliter amounts. These results demonstrate that particular TCR antigen pairs may overcome the need for specialized antigen-presenting cells and have implications for mechanisms of autoimmunity and tolerance induction.

Animals↗
PubMed1997

Short-term changes in NADPH-diaphorase reactivity in rat brain following perinatal asphyxia. Neuroprotective effects of cold treatment.

Perinatal asphyxia (PA) produces changes in nitric oxide synthase (NOS) activity in neuronal and endothelial cells of the striatum and neocortex. The changes were examined using a histochemical NADPH-diaphorase (NADPH-d) staining method. Newborn rats were exposed to severe PA at 37 degrees C and other groups were subjected to severe PA under hypothermic condition (15 degrees C) for 20 or 100 min, respectively. Quantitative image analysis was performed on the striatum and neocortex in order to count cell number of reactive neurons and to compare the pattern of staining between the different groups of animals. Severe asphyctic pups showed an important neuronal loss in striatum and neocortex that was reduced by hypothermia. NADPH-d(+) neurons with reactive processes were found in the lateral zone of the striatum and neocortex in asphyctic pups. Controls and hypothermic striatum showed rounded cells without reactive process, while no cells were stained in cortex. There was also an increase in NADPH-d activity in endothelial cells in severe asphyctic pups in striatum and neocortex vs control and hypothermically treated animals. Our data evidenced that an inappropriate activation of NOS in neuronal and endothelial cells induced by PA is related to neuronal injury. Hypothermia inhibits neuronal injury and may be a valuable neuroprotective agent.

Animals↗
PubMed1997

The effect of omeprazole pretreatment on acetaminophen metabolism in rapid and slow metabolizers of S-mephenytoin.

Omeprazole, a widely used and potent gastric proton pump inhibitor, induces cytochrome P450 (CYP) 1A2 in humans. Induction is most pronounced in slow metabolizers of S-mephenytoin because CYP2C19 (S-mephenytoin hydroxylase) is responsible for the elimination of omeprazole. Acetaminophen (INN, paracetamol), a widely used and effective analgesic and antipyretic agent, causes serious hepatic and renal toxicity at high doses by conversion of acetaminophen to the toxic intermediate N-acetyl-p-benzoquinone imine (NAPQI) through CYP1A2, CYP2E1, and CYP3A4. This study evaluated whether omeprazole pretreatment in five rapid and five slow metabolizers of S-mephenytoin could increase thioether (an estimate of NAPQI production) metabolite formation from acetaminophen. The results of this study show that, despite induction of CYP1A2 activity in slow metabolizers (a 75% increase in plasma clearance of caffeine), the formation of NAPQI from acetaminophen was not increased after 7 days of omeprazole administration (40 mg/day). This suggests that induction of CYP1A2 activity by omeprazole is unlikely to increase the risk of acetaminophen hepatotoxicity.

Acetaminophen↗
PubMed1997

Size exclusion HPLC method for the determination of acidic fibroblast growth factor in viscous formulations.

A size exclusion HPLC method has been developed to determine the protein concentration of pharmaceutical formulations of recombinant acidic fibroblast growth factor (aFGF). These topical aFGF formulations not only contain low levels of protein mass (50 micrograms ml-1), but also include buffer ions, polysaccharide polyanions to conformationally stabilize aFGF and 1% hydroxyethylcellulose to increase the solution's viscosity. A cesium chloride mobile phase is utilized during SEC-HPLC to dissociate aFGF from the pharmaceutical excipients and to minimize nonspecific interaction of the protein with the column matrix. The protein content of a viscous aFGF formulation is determined by comparison of aFGF peak areas to standards of known concentration. Fluorescence spectroscopy was utilized to directly demonstrate that the protein remains in its native conformation during sample preparation and analysis.

Chemistry, Pharmaceutical↗
PubMed1997

Natural history and management of the asymptomatic, moderately stenotic internal carotid artery.

PURPOSE: Although it has been widely accepted as the evidence supporting prophylactic carotid endarterectomy, aspects of the Asymptomatic Carotid Atherosclerosis Study have left unease among clinicians who must decide which individuals without symptoms should undergo surgery. Additional confusion has been created by the fact that the several large randomized trials investigating the efficacy of carotid endarterectomy have classified and analyzed different categories of carotid stenosis. In an effort to provide more information on the natural history of asymptomatic, moderate carotid artery stenosis (50% to 79%), we have reviewed data on approximately 500 arteries. METHODS: Records of our vascular laboratory from 1990 to 1992 were reviewed. We identified 425 patients with asymptomatic, moderate carotid artery stenosis; 71 patients had bilateral stenoses in this category, resulting in 496 arteries for study. RESULTS: The mean length of follow-up was 38 +/- 18 months. New ipsilateral strokes occurred in 16 (3.8%) patients. New ipsilateral transient ischemic attacks occurred in 25 (5.9%) patients. Documented progression of stenosis occurred in 48 (17%) of the 282 arteries for which a repeat duplex examination was available. Arteries that progressed to > 80% stenosis were significantly more likely to have caused strokes than those that remained in the 50% to 79% range (10.4% vs 2.1%, p < 0.02). Conversely, arteries that remained stable in the degree of stenosis were significantly more likely to have remained asymptomatic than those that progressed (92.7% vs 62.5%, p < 0.001). With life-table analysis the estimated cumulative ipsilateral stroke rate was 0.85% at 1 year, 3.6% at 3 years, and 5.4% at 5 years. The respective estimated cumulative transient ischemic attack rates were 1.9%, 5.5%, and 6.3%. The respective estimated cumulative rates for progression of stenosis were 4.9%, 16.7%, and 26.5%. Life-table comparison of ipsilateral stroke revealed a significantly higher cumulative rate among arteries that progressed in the degree of stenosis than among those that remained stable (p < 0.001). CONCLUSIONS: Based on the low rate of permanent neurologic events in these cases, prophylactic carotid endarterectomy for the asymptomatic, moderately stenotic internal carotid artery cannot currently be recommended. The only factor that appears to predict increased risk for future stroke is progression of stenosis. Careful follow-up with serial repeat duplex examinations must be performed in these patients. Until there are widely accepted duplex parameters that can provide all clinicians with accurate identification of arteries with narrowing corresponding to 60% stenosis as defined by the Asymptomatic Carotid Atherosclerosis Study, all surgeons will need to be aware of specifically how their noninvasive laboratories are deriving their results. For the many laboratories that continue to use the University of Washington criteria, 80% should remain the level above which prophylactic carotid endarterectomy is warranted.

Aged↗
PubMed1997

Twenty-four-hour effectiveness of BMS 180048 in the acute treatment of migraine headaches.

The efficacy of BMS 180048, a 5-HT1 agonist in the acute treatment of a migraine headache, was evaluated in 216 patients. Three doses of the study drug were compared to placebo. Patients received a single test dose in the physician's office while being evaluated with a Holter monitor during a headache-free day. They then treated a migraines headache with a single dose of the study drug as an outpatient. The 150 mg- and 200-mg doses of BMS were significantly superior to placebo on change in pain intensity at 2 hours. Patients treated with BMS 180048 had a longer duration of response than placebo-treated patients. At the 24-hour point, only 24% of the 150-mg group and 25% of the 200-mg group had relapsed, compared to placebo which had a 42% relapse rate. It is concluded that BMS 180048 is an effective compound for the treatment of migraine headaches with a prolonged duration of response.

Acute Disease↗
PubMed1997

Mutations in the COL3A1 gene result in the Ehlers-Danlos syndrome type IV and alterations in the size and distribution of the major collagen fibrils of the dermis.

Ehlers-Danlos syndrome type IV (EDS type IV) results from heterozygosity for mutations in the COL3A1 gene that encodes the chains of type III procollagen. By using light, transmission, and scanning electron microscopy, we examined skin biopsies from 22 individuals with EDS type IV in whom the COL3A1 mutations had been identified. The most striking changes in EDS type IV were correlated with point mutations that substituted a residue for a glycine near the carboxyl-terminal end of the triple-helical domain of pro alpha1(III). In three cases with the mutation G1012R, G1018V, or G1021E, cells in the dermis had extremely dilated rough endoplasmic reticulum (RER), the dermis was thin, and there was a reduced proportion of collagen although the proportion of elastic fibers appeared increased. In these tissues, collagen fibrils were small (65-80 nm) compared to normal (95-110 nm). Fibrils 80-90 nm in diameter and moderately dilated RER were found with mutations G769R, G373R, and G061E and with exon-skipping mutations of exons 34 and 45. With mutations G034R and G016C and exon-skipping mutations that deleted the sequences of exons 7, 8, 14, 18, 24, and 27, fibrils were more variable in size (85-120 nm). The composite collagen fibrils characteristic of EDS types I and II were not found in EDS type IV. These findings indicate that mutations in the COL3A1 gene have effects on secretion, fibrillogenesis, and skin architecture that reflect the position and nature of the mutation.

Adult↗