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Biomedical subjects

E Schwartz

Publications and source records attributed to E Schwartz.

At least 217 records · Page 12Linked to original sources

Characterization of a dermal derived malignant mesenchymal tumor arising in ultraviolet irradiated mice.

Skh/hr-1 hairless albino mice were irradiated with photocarcinogenic dosages of ultraviolet light for periods of 30 weeks or longer. A high proportion of mice developed pleomorphic spindle cell tumors and epidermal neoplasms of various types. These spindle cell tumors were studied by immunofluorescence and immunoperoxidase techniques and by electron microscopy. Freshly isolated tumor cells were grown in tissue culture. Immunocytochemical analysis showed varying expression of markers of mesenchymal differentiation: vimentin, procollagens I and III, type I collagen, and lysozyme. Electron microscopy showed spindled and cuboidal cells with abundant endoplasmic reticulum, filopodia, and lysosomes, but no intercellular connections. The cells grown in vitro were cuboidal and stellate and also showed mesenchymal differentiation by electron microscopy. These results are perhaps similar to those described for a human actinically produced fibrohistiocytic neoplasm, atypical fibroxanthoma, and this system may provide a useful model of ultraviolet-induced dermal neoplasia.

Animals↗

A large deletion encompassing the entire alpha-like globin gene cluster in a family of northern European extraction.

We describe a new deletional form of alpha thalassemia segregating in three generations of a family of northern European origin. A full-term female girl had hypochromic, microcytic anemia since early infancy associated with delayed language development, slow growth and weight gain. Hematologic studies suggested the presence of alpha thalassemia. Gene-blotting studies showed no abnormal alpha-like globin gene fragments; however, studies of inheritance of informative polymorphic restriction fragments using zeta, alpha and 3'-alpha-hypervariable region (3'-HVR) probes showed evidence for an extensive deletion encompassing the entire alpha-like globin gene cluster. The 3' breakpoint of this deletion maps beyond the 3'-HVR, a region implicated as a hot spot for the generation of other large deletional events within the alpha-like cluster. The 5' breakpoint maps at least 10 kilobases (kb) 5' to the zeta-globin gene. The minimum size estimate for this deletion is greater than 47 kilobases.

Child, Preschool↗

Booster irradiation to the spleen following total body irradiation. A new immunosuppressive approach for allogeneic bone marrow transplantation.

Graft rejection presents a major obstacle for transplantation of T cell-depleted bone marrow in HLA-mismatched patients. In a primate model, after conditioning exactly as for leukemia patients, it was shown that over 99% of the residual host clonable T cells are concentrated in the spleen on day 5 after completion of cytoreduction. We have now corroborated these findings in a mouse model. After 9-Gy total body irradiation (TBI), the total number of Thy-1.2+ cells in the spleen reaches a peak between days 3 and 4 after TBI. The T cell population is composed of both L3T4 (helper) and Lyt-2 (suppressor) T cells, the former being the major subpopulation. Specific booster irradiation to the spleen (5 Gy twice) on days 2 and 4 after TBI greatly enhances production of donor-type chimera after transplantation of T cell-depleted allogeneic bone marrow. Similar enhancement can be achieved by splenectomy on day 3 or 4 after TBI but not if splenectomy is performed 1 day before TBI or 1 day after TBI, strengthening the hypothesis that, after lethal TBI in mice, the remaining host T cells migrate from the periphery to the spleen. These results suggest that a delayed booster irradiation to the spleen may be beneficial as an additional immunosuppressive agent in the conditioning of leukemia patients, in order to reduce the incidence of bone marrow allograft rejection.

Animals↗

IS150: distribution, nucleotide sequence and phylogenetic relationships of a new E. coli insertion element.

Recently we identified the new insertion (IS) sequence IS150 in various strains of Escherichia coli K-12. We have screened other strains of E. coli and Salmonella typhimurium for the presence of homologous sequences. The strains of E. coli K-12 and W tested contain one or more copies of homology to IS150. We have also determined the complete nucleotide sequence of a copy of IS150 inserted into IS1. Comparison of nucleotide and deduced amino acid sequences of IS150, IS2, IS3, IS51, IS600 and IS629 reveals significant homologies suggesting that these elements are members of a family of phylogenetically related insertion sequences.

Amino Acid Sequence↗

Ectopic insulin production by a primary ovarian carcinoid.

An insulin-containing ovarian carcinoid was found at the autopsy of a 63-year-old woman with a 12-year history of episodic hyperinsulinemic hypoglycemia. In terms of histology, the carcinoid displayed both insular and trabecular patterns and contained a small focus of mucinous cystadenoma. Beta secretory granules were demonstrated by electron microscopy, and immunoreactivity for insulin was demonstrated in tumor cell cytoplasm by immunohistochemistry. Additional autopsy findings included a solitary parathyroid adenoma and a microscopic focus of pituitary hyperplasia. This is the first recorded case of insulin production by a primary ovarian neoplasm. The patient's constellation of endocrine findings may represent a variant of the syndrome of type I multiple endocrine neoplasia.

Carcinoid Tumor↗

Sinus arrest associated with clonidine therapy.

A 65-year-old male with diabetes, hypertension, and mild renal failure developed dizziness and syncope one week after starting clonidine 0.45 mg/day. A continuous ECG recording revealed sinus bradycardia, nodal rhythm, and multiple episodes of sinus arrest lasting up to 4.5 seconds. Upon discontinuation of clonidine, serial continuous ECG recordings revealed gradual decrease in the number and duration of the sinus arrest episodes, until their complete disappearance shortly after the third day off clonidine. This report shows that clonidine may cause a concentration-dependent sinus node dysfunction in addition to the atrioventricular (AV) node abnormalities previously ascribed to it.

Aged↗

Second-element turn-on of gene expression in an IS1 insertion mutant.

To learn more about the ways in which genes silenced by insertion mutations can be reactivated, we have undertaken a systematic investigation of Gal+ revertants of the polar mutant galOP-306::IS1 in Escherichia coli K12. The selective conditions used excluded reversion to wild type by precise excision of IS1. In this system (which resided on a multi-copy plasmid) reversion to the Gal+ phenotype occurred with a frequency of about 10(-7) per cell and per generation. Analysis of the revertants revealed that - with the single exception of the previously published chromosomal mutant sis1 - alterations in the structure of IS1 lead to reactivation of gal operon expression. These events fall into four classes: (I) insertion of IS2 at position 327 in IS1, insertion of IS2 at position 687 in IS1, (III) insertion of a hitherto undetected mobile element, IS150, at position 387, (IV) a 16-bp deletion encompassing IS1 coordinates 553-568. Of some 200 independent reversion events studied, all but one were of types I-III i.e. they involved the intervention of a second mobile element.

Base Sequence↗

Early and long-term effects of acute caloric deprivation in obese diabetic patients.

PURPOSE: It is generally assumed that diet therapy can ameliorate the metabolic derangements experienced by obese type 2 diabetic patients, thereby leading to discontinuation of insulin or oral sulfonylurea drug therapy. We decided to retrospectively investigate which clinical and biochemical parameters affect therapeutic responses. PATIENTS AND METHODS: Sixty-four poorly controlled obese diabetic patients were hospitalized and placed on a precisely defined, hypocaloric diet. Known duration of diabetes, type of pharmacologic therapy, body weight, weight loss, fasting plasma glucose concentrations, C-peptide levels, hemoglobin A1C, and plasma lipid levels were assessed, as were nitrogen and electrolyte balances. RESULTS: Average weight loss was 13 pounds in a mean of 23 days. During hospitalization, the mean fasting plasma glucose value for the group fell from 221 +/- 10 to 122 +/- 5 mg/dl. In 45 patients (73 percent), the final fasting plasma glucose level was less than 125 mg/dl (mean: 102 +/- 2 mg/dl). Oral glucose tolerance even in those patients in whom fasting plasma glucose levels normalized was still grossly diabetic at the end of the hospital stay, deteriorating further after three days of liberalized caloric intake. In part this may have been due to decreased insulin secretory reserve as reflected by blunted plasma C-peptide response. Forty of 42 patients who entered the study taking insulin were able to discontinue the drug within one to seven days of hospitalization. After a mean follow-up period of 19 months, only 10 of 50 patients continued to maintain fasting euglycemia; five were on diet alone, and five were receiving oral hypoglycemic agents. Thirteen patients were receiving insulin therapy. CONCLUSION: Diet therapy in these patients resulted in short-term improvement of glycemic control and, in the majority, normalization of fasting plasma glucose levels. However, long-term outpatient follow-up revealed that relapse occurred in most patients.

Blood Glucose↗

The mortality, morbidity, and economic costs of alcohol abuse in New Hampshire.

Since alcoholism and alcohol abuse are the number one health problem in the United States, community-based estimates of mortality, morbidity, and economic costs associated with alcohol abuse are needed to convey their impact in local areas. In the state of New Hampshire, data were collected on alcohol consumption patterns, alcohol-associated mortality, years of potential life lost, hospital days associated with alcohol-related diagnoses, direct medical care costs, employment levels, and per capita incomes. Alcohol-attributable mortality and morbidity percentages were applied to these data to estimate the effects of alcohol abuse. In 1983, alcohol was associated with 4% of total statewide deaths. These included 37% of the deaths due to injury, 26% of the deaths due to digestive disease, and 3% of the deaths due to cancer. These deaths represented over 6,000 years of potential life lost. Between 4 and 7% of hospital days were attributable to alcohol-related diagnoses. Direct medical care costs attributable to alcohol were over $101 million; 10% of the direct medical costs in the state. Indirect costs (present value of lost earnings due to premature mortality and morbidity associated with alcohol) represented over $142 million. Property damage and insurance costs associated with alcohol were almost $13 million, and alcohol-related arrests added another $17 million. Excess absenteeism due to alcohol abuse cost another $33 million and lost productivity at work cost over $278 million. These economic costs totaled almost $600 million, or 5% of the gross state product. The methodology used to obtain these results is easily applied and is shown in the Appendix.

Alcoholism↗

Nonmutagenicity of maleic acid and its sodium salts in salmonella assays.

Maleic acid (cis-butenedioic acid) and its mono- and disodium salts are shown to be non-mutagenic in the standard Ames Salmonella/mammalian microsome assay in the absence and presence of Aroclor-1254-induced rat liver S9. This lack of activity occurred despite depression of top agar pH in accordance with the degree of protonation of this polybasic acid. These results indicate that when chemical compounds which are maleate salts show activity in this assay, the effect is attributable to the base moiety rather than maleate or pH depression per se.

Hydrogen-Ion Concentration↗

Connective tissue alterations in the skin of ultraviolet irradiated hairless mice.

Connective tissue alterations were induced in hairless mouse skin by ultraviolet (UV) irradiation. Hairless mice were irradiated three times a week for 10 weeks with sunlamps (UVA and UVB) and the skin was examined using immunochemical and biochemical techniques. Indirect immunofluorescence was performed with antibodies directed against elastin, microfibrillar proteins, and fibronectin. Increased fluorescence was observed in the actinically damaged skin for elastin, microfibrillar proteins, and fibronectin. The elastic fiber components, elastin and microfibrillar proteins, were then isolated and quantified. Control skin contained approximately 0.1% by dry weight of elastic fiber components, whereas actinically damaged skin contained 0.2% by dry weight. These data are consistent with previous observations of elastic fiber hyperplasia in UV irradiated mice. In addition, irradiated mouse skin contained 1.12 mg of extracted fibronectin per gram wet weight as compared with 0.59 mg in control skin. Irradiated mouse skin contained increased quantities of hyaluronic acid and chondroitin sulfate (uronic acid content). These studies further support the validity of the UV irradiated hairless mouse as a model of human dermal photoaging.

Animals↗

A proportionate mortality ratio analysis of pulp and paper mill workers in New Hampshire.

A proportionate mortality ratio (PMR) analysis of 1071 deaths in pulp and paper mill workers in New Hampshire during 1975-85 showed an increase in cancers of the digestive tract and lymphopoietic tissues. A similar analysis of deaths for 452 timber cutters and loggers failed to show excess PMRs for cancers of these sites. Despite methodological constraints, these results suggest that one or more of the exposures experienced by pulp and paper mill workers may pose a significant carcinogenic risk. More definitive epidemiological studies are required to determine particular high risk processes or specific aetiological agents.

Adult↗

Structure of platelet glycoprotein IIIa. A common subunit for two different membrane receptors.

The platelet membrane glycoprotein IIb/IIIa complex is a member of a family of alpha/beta heterodimers that function as receptors for adhesive proteins. In this report we describe the structure of the human beta subunit GPIIIa deduced from an analysis of 4.0 kb of overlapping cDNA sequences isolated from a human erythroleukemia (HEL) cell cDNA expression library. A continuous open reading frame encoding all 788 amino acids for GPIIIa was present. The deduced amino acid sequence included a 26-residue amino-terminal signal peptide, a 29-residue transmembrane domain near the carboxy terminus, and four tandemly repeated cysteine-rich domains of 33-38 residues. An exact correspondence of 128 amino acids from seven human platelet GPIIIa fragments with HEL GPIIIa indicates that HEL and platelet GPIIIa are the same gene product. The HEL GPIIIa sequence was compared with the sequences of the beta subunit for the human LFA-1/Mac-1/p150.95 complex and human endothelial cell GPIIIa, revealing a 38% similarity with the former and virtual identity with the latter. Northern blot analysis using RNA from both HEL and endothelial cells revealed two GPIIIa transcripts of 5.9 and 4.1 kb. However, HEL RNA, but not endothelial cell RNA, contained a transcript for GPIIb. This indicates that the GPIIIa-containing heterodimers in platelets and endothelial cells are not identical structures, but are members of a subfamily within the human family of adhesion protein receptors sharing an identical beta subunit.

Amino Acid Sequence↗