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Biomedical subjects

H Goldberg

Publications and source records attributed to H Goldberg.

At least 19 recordsLinked to original sources
PubMed1992

Tissue-specific expression of the mouse alpha 2(I) collagen promoter. Studies in transgenic mice and in tissue culture cells.

We sought to determine the cis-acting elements responsible for the pattern of tissue specific expression of the mouse alpha 2(I) collagen gene. Using an RNase protection assay we first verified that expression of the alpha 2(I) collagen gene is mainly confined to tendons, bone, and skin in mice. Both transgenic mice and DNA transfection of tissue culture cells were used as experimental approaches. Transgenic mice lines were generated harboring chloramphenicol acetyltransferase (CAT) chimeric genes that contained either (a) 2000 base pairs (bp) of 5'-flanking sequences of the mouse alpha 2(I) collagen gene plus additional sequences between +418 and +1524 of the first intron of this gene or (b) the same promoter sequences without intron sequences or (c) the 350-bp proximal promoter sequences. Transgenic mice containing both types of 2000-bp promoters showed a pattern of CAT expression that was tissue specific. The presence of sequences of the first intron in the transgene did not increase the level of promoter activity. Transgenic mice harboring the 350-bp alpha 2(I) collagen promoter also showed a pattern that was tissue-specific except that high level expression also occurred in the brain. This suggests that negative regulation is an important component of tissue-specific expression. In order to analyze the first 350 bases in detail, we performed transient expression experiments, using promoter fragments attached to the luciferase reporter gene. Fibroblasts, which show a high level expression of the endogenous alpha 2(I) collagen gene, and B cells, in which the gene is silent, were transfected with a series of deletions and substitution mutations within the proximal 350-bp promoter. These experiments were unable to define unique cell-specific cis-acting elements. However, when the sequence between -315 and -284 was tandemly repeated upstream of a minimal alpha 2(I) collagen promoter (-41 to +54), the activity of this construction was considerably higher in fibroblasts than in B cells when compared with the minimal promoter itself. In gel retardation assays, the levels of complexes that bind to this sequence were higher in fibroblast nuclear extracts than in myeloma nuclear extracts. Our results are consistent with the hypothesis that the -315 to -284 DNA sequence participates in the cell-specific control of the alpha 2(I) collagen gene in fibroblasts.

Animals↗
PubMed1992

Health of the public. The academic response. Health of the Public Mission Statement Working Group.

Aging of the population, increasing prevalence of chronic and disabling illnesses with multiple social and behavioral risk factors, concern about quality of care, and escalating costs of medical care require fundamental changes in the way that academic health centers discharge their mission. This article describes a newly developed "Mission Statement" for academic health centers that wish to contribute positively to the health of the populations that they serve. A shift toward addressing the needs of the public may produce increasing institutional strength, long-run stability, and enhanced productivity, as well as higher quality, more cost-effective care for patients. Seventeen centers in the Health of the Public Program are currently conducting activities that implement the described mission elements. The goals and objectives described herein create a foundation for change, with more balanced institutional goals, and could turn an emerging confrontation between academe and its public into an opportunity for both.

Academic Medical Centers↗
PubMed1992

Aphasia in multiple sclerosis: clinical and radiologic correlations.

Aphasia is not commonly reported in multiple sclerosis (MS). We report on two clinically definite MS patients, with a remitting-relapsing course, who presented with acute onset of aphasia. MRI demonstrated giant plaques in the left frontal region in one and in the left centrum semiovale in the other. These lesions were not evident in MRI performed several months previously, and may account for the aphasia. In both patients, language functions markedly improved within several weeks. In one patient, follow-up MRI 3 months later revealed a moderate reduction in the size of the plaque.

Adult↗
PubMed1991

Interactions of [3H]amphetamine with rat brain synaptosomes. I. Saturable sequestration.

Previous studies have identified a saturable site of d-[3H]amphetamine sequestration (AMSEQ) in rat brain synaptosomes. The present study characterized AMSEQ with respect to its subcellular, neuronal and regional distributions, ontogenetic development, pharmacological specificity and factors required for its maintenance. Although AMSEQ was reduced when assays were performed in Krebs' buffer incubated at 37 degrees C as compared to assays performed in isotonic Tris-sucrose buffer incubated at room temperature, the pharmacological profiles of AMSEQ were virtually identical under both conditions. AMSEQ was negligible in tissues outside the central nervous system, enriched in synaptosomes and partially reduced by striatal kainic acid lesion, indicating neuronal localization. The distribution of AMSEQ in the central nervous system was heterogenous. Highest levels were present in hypothalamus with progressively lower levels noted in parietal cortex, frontal cortex, striatum, thalamus, hippocampus, midbrain, cerebellum, pons-medulla and spinal cord. With regard to its ontogeny, AMSEQ increased early in neonatal life, reaching adult levels by postnatal day 14. Although the effects of amphetamine to abolish the transynaptosomal pH gradient suggest a possible role for this gradient in the maintenance of AMSEQ, the pharmacological profile of AMSEQ indicates that other factors are involved. An interaction with an intrasynaptosomal acid, such as N-acetylaspartate, may account for AMSEQ maintenance. AMSEQ did not possess a stereospecific preference for either d-(IC50 = 177 microM) or I-amphetamine (IC50 = 173 microM). However, the pharmacological profile of AMSEQ indicated structural specificity with antidepressants being relatively potent inhibitors. The saturation analysis and pharmacological characteristics of AMSEQ (i.e., low affinity and lack of stereospecificity) suggest that AMSEQ may be related to high dose, nonstereospecific effects of amphetamine, such as stereotypy in rats and psychosis in humans. The relative high potency of antidepressants in inhibiting AMSEQ suggests the importance of this phenomenon in the therapeutic effects of these drugs. Furthermore, the link between antidepressants and AMSEQ may provide insight into the comorbidity of major depression and drug abuse.

Amphetamines↗
PubMed1990

Survey of exposure to genotoxic agents in primary myelodysplastic syndrome: correlation with chromosome patterns and data on patients without hematological disease.

Exposure to genotoxic agents such as insecticides, pesticides, and solvents correlated with abnormal karyotypes and development of acute nonlymphocytic leukemia (ANLL) similar to, but to a lesser degree compared to, patients exposed to irradiation and alkylating drugs in several reports. Because of the natural progression of myelodysplastic syndrome (MDS) to ANLL, we investigated the relationship of exposure to these carcinogens in patients with primary MDS by having 52 such patients diagnosed and referred to our center answer an occupational/environmental questionnaire. We excluded all secondary MDS patients with exposure to previous chemotherapy and radiation for a previous malignancy. In addition, we prospectively gave the same questionnaire to a similar number of age- and sex-matched comparable control patients from the same socioeconomic group based on their residence, health insurance coverage, and occupation. We found a 46% exposure rate to implicated genotoxic agents in our patients with MDS. Patients with MDS who were exposed had 75% incidence of a poor prognosis French-American-British classification compared to 57% in the nonexposed group but the difference was not significant (P = 0.089). However, the karyotypic abnormalities that were associated with exposure in ANLL were found equally in both exposed (55%) and nonexposed groups (50%) of our MDS patients and our control group had a similarly high exposure rate at 40% to genotoxins. Implicating a relationship between exposure to pesticides and solvents in ANLL and MDS is difficult. All the previous studies indicating such a relationship did not use a control group of patients. Our findings indicate the pitfalls of historical data without investigating the bias of obtaining an exposure history. However, our findings that the majority of our MDS patients came from the middle socioeconomic group which has a high exposure rate as shown by our control group indicate a relationship and that prospective follow-up of the exposed cohort of control patients should be done to determine if ANLL and MDS will increase after a latent period compared to the nonexposed controls.

Adult↗
PubMed1989

Urine citrate and renal stone disease.

Calcium stone disease is attributable to supersaturation of the urine with calcium and other salts, the presence of substances that promote crystallization and a deficiency of inhibitors of crystallization. Citrate is a potent inhibitor of calcium oxalate and calcium phosphate stone formation whose excretion is diminished in some patients with stone disease owing to idiopathic causes or secondary factors such as bowel disease and use of thiazides. The pH within the proximal tubule cells is an important determinant of citrate excretion. Multivariate analysis has shown that the urine concentrations of calcium and citrate are the most important factors in stone formation. In uncontrolled studies potassium citrate, which increases urinary citrate excretion, appears to be promising as a therapeutic agent for patients with stone disease and hypocitraturia refractory to other treatment. On the other hand, there are potential drawbacks to sodium alkali therapy, such as the precipitation of calcium phosphates.

Citrates↗
PubMed1989

Identification of P-glycoprotein in renal brush border membranes.

A monoclonal antibody (C219) that recognizes the P-glycoprotein (Mr = 170,000) in plasma membranes of multidrug-resistant Chinese hamster ovary (CHO) cell lines was used to assay renal brush border membrane (BBM) and basolateral membrane (BLM) fractions for the presence of a cross-reactive polypeptide. The C219 antibody bound to a 155,000 dalton protein in immunoblots of rat BBM but not BLM proteins resolved by sodium dodecyl sulfate gel electrophoresis. The corresponding human kidney BBM and dog kidney BBM proteins had molecular weights of 170,000 and 160,000 respectively. The glycoprotein nature of the renal protein was shown by its sensitivity to N-glycanase treatment which reduced the apparent molecular weight of the dog protein to 120,000. In addition, dog P-glycoprotein could be bound to and eluted from immobilized wheat germ agglutinin. The molecular weight, antibody crossreactivity, glycosidase sensitivity and lectin binding show that this protein is a normal kidney analogue of the P-glycoprotein induced in multidrug resistant cell lines.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Long-term results of amiodarone therapy in patients with recurrent sustained ventricular tachycardia or ventricular fibrillation.

Four hundred sixty-two patients, all with either documented spontaneous sustained ventricular tachycardia or cardiac arrest unresponsive to other antiarrhythmic drugs (2.6/patient), were treated with amiodarone. Thirty-five patients (7.6%) failed to respond or died during the initial oral or intravenous loading phase. The remaining 427 patients were discharged on treatment with oral amiodarone and followed up for up to 98 months. Recurrence of ventricular tachycardia or sudden cardiac death at 1, 3 and 5 years by life-table analysis was 19%, 33% and 43%, respectively, for patients discharged on amiodarone therapy. The sudden cardiac death rate was 9%, 15% and 21%, respectively, at 1, 3 and 5 years. Side effects were reported by 45% of patients after 1 year, by 61% after 2 years and by 86% after 5 years. Amiodarone was discontinued because of side effects in 14%, 26% and 37% of patients after 1, 3 and 5 years, respectively. Incidence rates of recurrence of arrhythmia, sudden cardiac death and side effects were highest in the early months and then decreased. By multivariate analysis, advanced age, low ejection fraction and a history of cardiac arrest were independent risk factors for sudden cardiac death during amiodarone therapy.

Aged↗
PubMed1989

Percutaneous needle biopsy of the transplanted kidney: technique and complications.

Over 11 1/2 years, 420 percutaneous needle biopsies were obtained from the transplanted kidneys of 205 patients at one institution. The procedure was performed by one nephrologist and 55 nephrology trainees. No limit was placed on the number of biopsies performed on one kidney, and the highest number was seven. The complications were macroscopic hematuria in 28 biopsies, prolonged hematuria (greater than 24 hours) in eight, transient anuria in five, and prolonged anuria requiring surgical intervention in one. Perinephric hematoma occurred in three patients; retroperitoneal hematoma led to compression of the iliac vein in one. None of these complications led to loss of the transplant. It is suggested that the freedom from serious complication is related to the safety of the technique and the precautions applied to preparation of the patient. These are described in detail.

Adolescent↗
PubMed1989

Mesenteric thrombosis following sclerotherapy during vasopressin infusion: mechanism and therapeutic implications.

In a series of 602 consecutive sclerotherapies, two cirrhotic patients who had received successful sclerotherapy for control of variceal bleeding while on vasopressin infusions developed mesenteric thrombosis. We found no other cases (in our institution or in literature review) where sclerotherapy or vasopressin infusion alone precipitated mesenteric thrombosis. During vasopressin infusion, there is portal stasis and an increased caudad flow of sclerosant. We suggest that mesenteric thrombosis is a consequence of the combination of these two effects. Direct injection of gastric varices is difficult because of increased postsclerotherapy bleeding, but sclerosis of esophageal varices often leads to their obliteration by the caudad flow of sclerosant. We propose, therefore, that vasopressin infusion during esophageal sclerotherapy may be beneficial in the obliteration of gastric varices. We conclude that (a) in patients without gastric varices, vasopressin infusion increases the incidence of mesenteric thrombosis, and (b) vasopressin infusion during sclerotherapy may enhance the sclerosis of gastric varices.

Adult↗
PubMed1989

Diagnosis and management of subclavian vein thrombosis occurring in association with subclavian cannulation for hemodialysis.

With the aim of improving the diagnosis and treatment of subclavian vein thrombosis, associated with subclavian cannulation for hemodialysis, we performed Doppler examination of the subclavian vein and clinical inspection of the ipsilateral arm at every dialysis in 50 consecutive patients who received subclavian hemodialysis catheters over 1 year. Edema of the arm and disappearance of the subclavian vein bruit correctly detected 3 cases of subclavian vein obstruction which were confirmed by X-ray venograms. All 3 cases failed to respond to systemic heparin, but were successfully recanalized within 36 h with continuous local streptokinase infusion at a rate of 10,000 U in 1 ml/h. In 4 other cases of edema of the arm, Doppler examination correctly predicted patency of the vein, also confirmed radiologically. In 2 cases of thrombosis, there was an underlying stenosis of the left innominate vein close to its union with the superior vena cava. These were dilated by balloon angioplasty; the stenosis recurred in both cases without recurrent thrombosis, and the angioplasty was repeated. Doppler surveillance seems to be a promising aid to the detection of subclavian vein thrombosis from hemodialysis catheters. Local streptokinase infusion is effective in treating thrombosis. Underlying venous stenosis should be looked for because this may be at least partly remediable by balloon angioplasty.

Angioplasty, Balloon↗
PubMed1989

Cavernous lymphohemangioendothelioma of the right atrium--a case report.

The authors report a successful resection of a rare cystic tumor in the right atrium, discovered in an asymptomatic patient with atrial fibrillation. The cystic nature of the tumor was characterized by two-dimensional echocardiogram preoperatively. The site of attachment and movement of the tumor were clearly shown by cine computed tomography preoperatively. The tumor contained numerous endothelium-lined cavernous channels and groups of red blood cells. These features are distinctly different from those of other cystic tumors.

Echocardiography↗
PubMed1988

Reduced cyclosporin accumulation in multidrug-resistant cells.

Cyclosporin accumulation was reduced by 50% or more in multidrug- resistant CHRC5 CHO cells with high levels of P-glycoprotein expression compared to drug sensitive AuxB1 CHO cells. This difference could be overcome by verapamil which is known to interact with P-glycoprotein and reverse multidrug resistance. The difference in cyclosporin accumulation between sensitive and resistant cells decreased with increasing cyclosporin concentrations suggesting that cyclosporine itself regulated its own accumulation through interaction with P-glycoprotein. Indeed, cyclosporin also reversed differences in vinblastine accumulation between resistant and sensitive cell lines. Since P-glycoprotein is highly expressed in the kidney which is also a target for cyclosporin toxicity, the effects of verapamil on cyclosporin accumulation were studied in two renal cell lines, rat mesangial cells and LLCPK1, cells. Verapamil increased cyclosporin accumulation by approximately 70%. These results suggest that cellular cyclosporine accumulation is regulated at least in part by its interaction with P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1988

Selective toxicity of gossypol against epithelial tumors and its detection by magnetic resonance spectroscopy.

The antitumor toxicity of gossypol was measured in 6 human carcinoma cell lines and compared with its toxicity against human bone marrow stem cells. Marrow cells were more resistant than any of the tumor cell lines, and tumor cell sensitivity depended on the content of intracellular LDH-M. [31P]-Magnetic resonance spectroscopy showed decline in tumor ATP levels occurring within 24 hours of treatment, suggesting that this non-invasive technique may serve as an early biochemical monitor of gossypol toxicity.

Animals↗
PubMed1988

Fatal necrotizing fasciitis following suction-assisted lipectomy.

Forty-eight hours following extensive blunt suction lipectomy with 3,000 cc of tissue removed, a 36-year-old woman presented to an emergency room with necrotizing fasciitis of both lower extremities extending over the buttock and to the lower third of the back. Tissue cultures and blood culture grew out a pure culture of beta-hemolytic streptococci. The patient rapidly progressed into a comatose state and, despite extensive debridement and appropriate antibiotic therapy, in addition to hyperbaric oxygen treatments, she died on day 9 of her hospitalization (day 11 following the suction lipectomy). To our knowledge this is the first published mortality reported in the United States following this procedure.

Adipose Tissue↗