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H Goldberg

Publications and source records attributed to H Goldberg.

At least 55 records · Page 3Linked to original sources

Reduced phospholipase A2 activity is not accompanied by reduced arachidonic acid release.

Arachidonic acid release in cells highly over expressing cytosolic phospholipase A2 has been attributed to mitogen-activated protein kinase phosphorylation of cytosolic phospholipase A2 on serine-505. To investigate the role of cytosolic phospholipase A2 in cellular physiology, we attempted to inhibit cytosolic phospholipase A2 in the intact cell employing an antisense RNA strategy. Swiss 3T3 cells were stably transfected with an antisense cytosolic phospholipase A2 expression vector. A clone of cells with reduced immunodetectable cytosolic phospholipase A2, compared to a vector transfected cell line, was identified by Western blotting and a corresponding decrease in phospholipase A2 activity was confirmed by enzymatic assay in cell free extracts. However, arachidonic acid release from intact cells in response to agonists was not different between antisense and control cell lines. Thus, arachidonic acid release in intact cells with decreased cytosolic phospholipase A2 activity is likely to be modulated by rate limiting factors that are extrinsic to cytosolic phospholipase A2.

3T3 Cells↗

[Cisplatin-based chemotherapy for advanced basal and squamous cell carcinomas].

The majority of basal cell (BCC) and squamous cell (SCC) carcinomas of the skin are curable by surgery and/or radiation. However, additional therapy is required when the tumor is locally advanced, or has metastasized. 4 men and 4 women (mean age 70, range 49-86) with advanced BCC and/or SCC were treated with cisplatin-based chemotherapy. The disease was local in 4, local with regional lymph node involvement in 2, involved regional lymph nodes in 1 and was local with distant metastases in 1 patient. All were treated with a combination of cisplatin and 5'-fluorouracil. 2 were treated in addition with a combination of cyclophosphamide, doxorubicin, and cisplatin (CAP). Complete pathological response was seen in 2/8 and partial response in 4/8 with an overall response rate of 75%. There was tumor progression in 2. Survival of patients who responded was from 3-47 months (mean 12). The 2 who did not respond to chemotherapy died within 1 and 3 months of treatment. Significant side-effects in 6 included myelotoxicity and transient renal toxicity. We conclude that chemotherapy is effective in advanced BCC and SCC of the skin and may have curative potential when combined with local therapy.

Aged↗

Update on nasopharyngeal carcinoma in northern Israel.

PURPOSE: Because Israel is one of the world's intermediate risk areas for nasopharyngeal carcinoma (NPC), we continue to analyze retrospectively all referred cases. PATIENTS AND METHODS: We previously reported our work with 49 NPC patients, and we now extend our analysis to include an additional 26 patients. All our 75 patients were treated between 1968 and 1991 at the Northern Israel Oncology Center in Haifa. They were typical in the preponderance of male sex (74%), Mediterranean origin (80%) and late stage presentation (91%). All patients received a combination of photon and electron radiotherapy to the tumor site, base of skull and neck, with an average dose to the nasopharynx of 6095 cGy. Nearly 40% of the patients received combined modality treatment (CMT), i.e., cisplatin-based chemotherapy prior to radiotherapy. RESULTS: There was an overall complete response (CR) of 88%, with 44% of the patients experiencing recurrence. Serious complications occurred in 5%. We found a 5-year survival rate of 48% and a 10-year survival rate of 44%, with some indication that CMT was advantageous to later-stage patients with non-keratinizing histologies, but not to earlier stages nor to those with keratinizing squamous cell carcinoma (SCC). Pediatric patients had better survival rates. CONCLUSIONS: 1. The somewhat better survival performance of Arabs and Sephardic Jews may reflect their greater tendency to have the non-keratinizing histological variants (lymphoepithelioma and undifferentiated carcinoma). 2. Ethnicity was consistently prognostic, both as risk and survival factors. 3. The role of CMT in advanced non-keratinizing NPC should be explored in future randomized trials.

Adolescent↗

Primary progressive freezing gait.

Freezing gait is an incapacitating symptom often observed in patients with Parkinson's disease. It has been less frequently described in association with multi-infarct state, multisystem atrophies, and normotensive hydrocephalus. In our movement disorder clinic, we have diagnosed (and followed up to 3 years; median, 16 months), 18 patients in whom progressive freezing gait was the sole neurological dysfunction. These 15 men and 3 women (aged 60-82 years; 74 +/- 6) were subjected to an extensive neurological workup that included clinical evaluation, videotaping for grading of gait disability, comprehensive blood and cerebrospinal fluid (CSF) analysis, and brain computed tomography (CT) and magnetic resonance imaging (MRI). Mean disease duration was 2.5 +/- 1.9 years (range, 0.5-6). Neurological examination disclosed freezing gait, often associated with varying degrees of postural instability. The degree of freezing gait ranged from sudden motor blocks only when confronted with obstacles to severe disability with total inability to start walking requiring a walker, massive assistance, or a wheelchair. However, patients could mimic gait movements with absolutely no freezing when seated or lying prone, and most of them could overcome arrests by the "walking-over-lines" maneuver. Otherwise, neurological examination was normal with no signs of bradykinesia, rigidity, or tremor. Blood chemistry and CSF analysis were normal. Brain CT and MRI were normal or showed mild cortical atrophy in 12 and putative lacunes in 6 patients. Therapy with levodopa or dopamine agonists was ineffective. During the follow-up period, a gradual progression of the freezing gait was observed. However, it remained unaccompanied by any other neurological findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Dexfenfluramine, fluoxetine, and weight loss among female carbohydrate cravers.

The consumption of excess calories as carbohydrates (CHO)-rich, protein-poor snacks characterizes the overeating of obese CHO cravers, premenstrual women, patients with Seasonal Affective Disorder, and former smokers. This specific appetite for CHOs may involve brain serotonin, as the synthesis and release of this neurotransmitter can increase following consumption of CHO-rich foods. To examine whether weight loss produced by serotoninergic drugs involves a selective reduction in CHO intake, obese females who consumed at least 30% of their daily calories from CHO-rich snacks were treated with dexfenfluramine ([DF] 15 mg b.i.d.); fluoxetine ([FL] 20 mg t.i.d.); or placebo (PL) for 12 weeks. Weekly weight loss for 25 of 29 PL completers was 0.22 kg +/- 0.06 (mean +/- SEM); for 21 of 28 DF completers, 0.56 +/- 0.08 kg; and for 18 of 30 FL completers, 0.58 +/- 0.09 kg (PL < DF = FL; p = .039). Seven FL subjects, 2 PL subjects, and 1 DF subject withdrew from the study due to side effects; other withdrawals were due to intercurrent illness or personal problems. Prior to treatment, subjects consumed over 40% of their daily CHO intake from snacks. Both of the drugs selectively decreased CHO snack intake (p < 0.05); DF, but not FL, also decreased meal CHO intake (p < .025). These results suggest that weight loss following treatment with serotoninergic drugs may relate to a selective decrease in CHO appetite.

Adult↗

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↗

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↗

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↗