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Biomedical subjects

H Goldberg

Publications and source records attributed to H Goldberg.

At least 37 records · Page 2Linked to original sources

Case of the month: March 1998--48 year old man with back pain and weakness.

A 48 year old man with long history of end stage renal disease (ESRD) and secondary hyperparathyroidism presented with back pain and incontinence. MRI and CT showed T2 expansion with bony destruction and spinal cord compression. Other vertebral bodies showed destructive lesions as well. Microscopic examination showed a brown tumor composed of multinucleated giant cells and bone uninvolved by tumor showed "tunneling" resorption. Brown tumors are an exaggerated form of "local" osteitis fibrosa cystica in patients with ESRD and secondary hyperparathyroidism, but spinal cord compression is rare.

Back Pain↗

[Optic glioma in children with type 1 neurofibromatosis].

During the period 1985-95 we treated 5 girls and 13 boys with optic glioma associated with Type 1 neurofibromatosis (median age 3 years, range 2-10 years). 6 were treated with radiotherapy alone, 1 with surgery and radiation therapy and 1 with chemotherapy in order to postpone irradiation to an older age; 1 is being followed with no therapy. All children are alive, 2-10 years from diagnosis (mean follow-up time 5.4 years). 3 had improvement of vision following therapy and in 4 visual ability stabilized, including the child being followed without treatment. In 1 vision deteriorated despite therapy.

Child↗

Nationwide telecare for diabetics: a pilot implementation of the HOLON architecture.

This paper presents results from a demonstration project of nationwide exchange of health data for the home care of diabetic patients. A consortium of industry, academic, and health care partners has developed reusable middleware components integrated using the HOLON architecture. Engineering approaches for multi-organization systems development, lessons learned in developing layered object-oriented systems, security and confidentiality considerations, and functionality for nationwide telemedicine applications are discussed.

Computer Communication Networks↗

HOLON: extending Web document libraries via objects in order to support the health information infrastructure. Health Object Library Online.

In HOLON, user clients, applications, data servers, and fine-grained elements are all objects in a document library. To that end, this paper reviews the past year of progress and lessons learned in HOLON for integrating the Web, HL7, CORBA, Arden, KQML, UMLS Thesaurus, and other standards to determine if object technology reduces common problems in document-centric libraries such as indexing, searching/retrieving, complex data type management, and maintenance, among others.

Computer Systems↗

Requirements for transforming growth factor-beta regulation of the pro-alpha 2(I) collagen and plasminogen activator inhibitor-1 promoters.

Experiments were designed to clarify the role of several proteins, junB, retinoblastoma protein (RB), and the transforming growth factor-beta (TGF-beta) receptors that are potential intermediates in TGF-beta activation of the alpha 2(I) collagen promoter. Treatment of NIH-3T3 cells with TGF-beta increased the activity of a transiently transfected murine alpha 2(I) collagen promoter (nucleotides -350 to +54) fused to a luciferase reporter gene 9-fold. Cotransfection of a junB stimulated the basal activity of the alpha 2(I) collagen promoter 93-fold, respectively. Expression of antisense junB RNA attenuated the effect of TGF-beta. Simian virus 40 large T antigen, an inhibitor RB function, did not prevent TGF-beta effects on the alpha 2(I) collagen promoter. A chimeric receptor containing the extracellular domain of the colony-stimulating factor-1 receptor and the intracellular domain of the type I TGF-beta receptor enhanced alpha 2(I) collagen promoter activity 4.8-fold, whereas a similar chimera containing the type II receptor intracellular domain had much weaker effects. Similar results were obtained with a plasminogen activator inhibitor-1 promoter, previously shown to be activated by TGF-beta through AP-1 elements. We conclude that TGF-beta activates the alpha 2(I) collagen and plasminogen activator inhibitor-1 promoters in NIH-3T3 cells through junB and the type I TGF-beta receptor kinase domain.

3T3 Cells↗

Transmembrane signaling in kidney health and disease.

Transmembrane signal transduction is the process whereby a ligand binds to the external surface of the cell membrane and elicits a physiological response specific for that ligand and cell type. It is now appreciated that numerous disease states represent disturbances in normal transmembrane signaling mechanisms. In the current paper, we focus our attention on the mesangial cell of the glomerular microcirculation as a prototypical model system for understanding normal and abnormal transmembrane signaling processes. Among the major receptor and effector mechanisms for transmembrane signal transduction in the mesangial cell, this paper emphasizes the phospholipase effector response to growth factors and vasoactive hormones. The post-translational and transcriptional pathways for regulation of phospholipase C and phospholipase A2 are described, including consideration of perturbations in these systems that characterize two disease models, namely: acute cyclosporine nephrotoxicity and early diabetic glomerulopathy.

Animals↗

The implementation of first-trimester scanning at 10-13 weeks' gestation and the measurement of fetal nuchal translucency thickness in two maternity units.

The aim of this prospective screening study was to evaluate the implementation of an additional ultrasound examination, incorporating the measurement of fetal nuchal translucency thickness, at 10-13 weeks' gestation in two maternity units providing routine antenatal care. During the 1 year prior to the introduction of the first-trimester scan, the major indication for fetal karyotyping was maternal age > or = 35 years and only two out of the total of 11 cases of trisomy 21 were identified. In the first 5 months of the study, 70% of the women delivering in these hospitals attended for measurement of fetal nuchal translucency thickness and the measurement was obtained in all cases. This was achieved without an increase in the number of sonographers or ultrasound machines. The incidence of fetal nuchal translucency thickness > or = 2.5 mm was 3.6% (63 of 1763), and this group included three of the four fetuses with trisomy 21. The findings of this study demonstrate the feasibility of introducing scanning at 10-13 weeks' gestation and the measurement of fetal nuchal translucency thickness in routine maternity units. The sensitivity and specificity of this method of screening are at present being evaluated in a large multicenter study.

Abortion, Legal↗

Efficacies of dexfenfluramine and fluoxetine in preventing weight gain after smoking cessation.

We tested whether 14 wk of dexfenfluramine (30 mg) or fluoxetine (40 mg) treatment would prevent weight gain after subjects quit smoking. Normal-weight women (n = 144) were randomly assigned to drug or placebo on a double-blind basis for 2 wk before quitting smoking and 12 wk thereafter. The fluoxetine group had more dropouts (28/49, 57.1%) than the dexfenfluramine group (17/47, 36.2%), with an intermediate number of dropouts from the placebo group (21/48, 43.8%). All groups gained weight during treatment, but their amount and pattern of weight gain differed. In the first month after quitting smoking, the placebo group gained more weight than either the dexfenfluramine or fluoxetine group (P < 0.05). By 2 mo postcessation, dexfenfluramine still suppressed weight gain in comparison with placebo (P < 0.05); weight gain with fluoxetine was not differentiable from either dexfenfluramine or placebo. By 3 mo postcessation, the dexfenfluramine group had gained 1.0 +/- 0.7 kg, significantly less than either the placebo (3.5 +/- 0.7 kg) or fluoxetine (2.7 +/- 0.5 kg) groups. Three months after drug discontinuation, formerly medicated, but not placebo patients, showed additional weight gain, eliminating differences between groups. Results indicate that weight gain, an adverse accompaniment of smoking cessation, can be minimized to some degree by serotoninergic drugs, although only for the duration of drug treatment.

Adult↗

Betaxolol eye drops. A clinical trial of safety and efficacy.

OBJECTIVE: To study the cardiopulmonary safety and ocular hypotensive efficacy of topical betaxolol hydrochloride 0.5% (a selective beta-1 blocker) in patients with unacceptably elevated intraocular pressure (IOP) and respiratory dysfunction. METHODS: Thirty-one patients with poor control of elevated IOP were selected on the basis of coexistent respiratory disease which could be exacerbated by beta-antagonist administration and/or who had past adverse reactions to topical timolol. Using an open-label design, the ophthalmic, cardiovascular and pulmonary parameters of these patients were measured before betaxolol therapy, for four hours immediately after the first administration of the drug, and after one, four and 12 weeks of therapy. The screening and 12-week examinations included a bronchial challenge with methacholine, a non-specific bronchoconstricting agent. RESULTS: IOP reduction was significant at all time points measured after first instillation of betaxolol, with a mean maximum fall of 8.4 (SD, 3.2) mmHg (95% Cl -9.545 to -7.261) from a baseline mean IOP of 23.9 (SD, 3.8) mmHg. Over 12 weeks of therapy, the mean reduction from baseline in IOP was 3.9 (SD, 2.6) mmHg (95% Cl -4.908 to -2.988). After first instillation of betaxolol, mean arterial pressure (MAP) fell transiently to a mean maximum fall of 3.9 (SD, 9.3) mmHg (95% Cl -7.159 to -0.582), from a mean baseline MAP of 107.7 (SD, 9.4) mmHg. Heart rate did not change. There were no changes in any of the respiratory parameters measured: forced expiratory volume in one second, forced vital capacity and peak expiratory flow rate. Over 12 weeks of betaxolol therapy, there were no changes in any of the above systemic parameters and no change in mean bronchial reactivity as measured by methacholine challenge. Of the 31 patients, who included 13 patients with previous intolerance to timolol (a non-selective beta-antagonist), only one showed intolerance to betaxolol. CONCLUSIONS: Betaxolol appears to be an effective and well tolerated ocular hypotensive agent in a typical glaucoma population, which includes many patients with cardiopulmonary disease. Individual intolerance to betaxolol will continue to occur and care is always required when patients with cardiac or respiratory dysfunction are exposed to any beta-antagonist.

Aged↗

Modulation by Gly, Ca, and acidosis of injury-associated unesterified fatty acid accumulation in proximal tubule cells.

We have examined the dependence of unesterified fatty acid accumulation by intact, freshly isolated proximal tubules on Ca2+, pH, and the cytoprotective amino acid, glycine, during injury induced by hypoxia, antimycin, or antimycin plus ionomycin. In the absence of glycine, similarly high levels of fatty acid accumulation were seen during all three injury conditions irrespective of whether tubules were incubated in normal 1.25 mM Ca2+ medium or in medium where Ca2+ was buffered to 0.1 microM, a maneuver which prevented injury-associated increase of cytosolic-free Ca2+ as measured with fura 2. In the presence of glycine, which strongly suppressed development of lethal membrane damage for at least 60 min and did not have any apparent direct effects on fatty acid accumulation, both Ca(2+)-independent and Ca(2+)-dependent components of fatty acid accumulation were discernible. The Ca(2+)-independent component accounted for approximately 2/3 of fatty acid accumulation and did not vary as Ca2+ ranged from 10 nM to 1 microM. Unequivocal Ca(2+)-dependent accumulation occurred when Ca2+ exceeded 10 microM. Lowering pH to 6.9 had a moderate, generalized suppressive effect on fatty acid accumulation, including the major Ca(2+)-independent component, irrespective of the presence of glycine. These data emphasize the role of Ca(2+)-independent fatty acid accumulation during proximal tubule cell injury, clarify the modulatory actions of the potent, intrinsic cytoprotective factors, glycine and reduced pH, and provide insight into the relationship between fatty acid accumulation and lethal membrane damage.

Acidosis↗

Low back pain hospitalization in Washington State: recent trends and geographic variations.

For several years, interest in clinical practice patterns has increased due to concerns about the costs and quality of health care. Our objectives were to examine recent trends and geographic variations in low back pain hospitalization. We analyzed data from a Washington State automated database for 1987-1992. Low back surgery rates in Washington changed little during the study years. In contrast, nonsurgical hospitalization rates fell from 15.5 to 5.1 per 10,000. The proportion of operations involving fusion decreased from 15.8% in 1987 to 11.7% in 1990, and then remained stable. During 1990, important county-to-county variations were observed in surgery rates, nonsurgical hospitalization rates, the proportion of operations involving fusion, and the percentage of surgical patients undergoing reoperation within 3 years. Wide county variations suggest that there may be overutilization or underutilization of low back pain treatments in some geographic areas. A more consistent approach to the management of back problems may benefit patients.

Adult↗

Cytosolic phospholipase A2 gene expression in rat mesangial cells is regulated post-transcriptionally.

Cytosolic phospholipase A2 (cPLA2) is thought to be the rate-limiting enzyme in the arachidonic acid/eicosanoid cascade. The ability of various agonists to increase steady-state cPLA2 mRNA levels has previously been reported. The current study delineates the contributions of transcriptional and post-transcriptional processes to the regulation of cPLA2 gene expression in response to a variety of agonists in cultured rat glomerular mesangial cells. Epidermal growth factor, platelet-derived growth factor, serum and phorbol myristate acetate all increase the half-life of cPLA2 mRNA transcripts, indicating a role for post-transcriptional modulation of gene expression. The presence of three ATTTA motifs in the 3' untranslated region (3'UTR) of the rat cPLA2 cDNA is ascertained. Heterologous expression of chimeric constructs with different 3'UTRs ligated into the 3' end of the luciferase coding region reveals that the presence of the cPLA2 3'UTR results in reduced luciferase activity compared with constructs without the cPLA2 3'UTR. Furthermore, the luciferase activity in the constructs with the cPLA2 3'UTR is increased in response to the same agonists which stabilize endogenous cPLA2 mRNA. A negligible effect of these agonists on transcriptional control of cPLA2 is evident using promoter-reporter constructs expressed in transient and stable transfectants. Taken together, these results indicate predominant post-transcriptional regulation of cPLA2 mRNA levels.

Animals↗

Isolation of promoter for cytosolic phospholipase A2 (cPLA2).

Cytosolic phospholipase A2 (cPLA2) releases arachidonic acid from membrane phospholipids and is believed to be the rate-limiting enzyme in the arachidonic acid pathway. We report herein the isolation of a 3 kb fragment of rodent genomic DNA containing part of the first intron, the first exon and 5'-flanking sequence. The start site of transcription was mapped by 5'-rapid amplification of cDNA ends and corroborated by ribonuclease protection assay. The gene has a TATAless promoter with no classical Sp1 binding sites or initiator element. A microsatellite series of CA repeats was noted in the 5'-flanking region of both the rodent and human promoters. Deletion constructs have been analysed for luciferase activity and confirmed promoter activity.

Amino Acid Sequence↗