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Biomedical subjects

E Schwartz

Publications and source records attributed to E Schwartz.

At least 271 records · Page 15Linked to original sources
PubMed1986

Renal sonography in American Burkitt lymphoma.

Renal involvement is a common finding at necropsy in patients with American Burkitt lymphoma, but its in vivo sonographic features have received little attention in the literature. Of 29 patients with American Burkitt lymphoma who underwent sonography, 10 were found to have renal involvement. The 10 patients demonstrated a range of abnormalities, notably renomegaly (nine patients), diffuse increase in cortical echogenicity (six), and focal renal masses (three). The focal infiltrations were, unexplicably, hypoechoic in two patients and hyperechoic in one. Hydronephrosis was seen in five patients. One patient had evidence of calcium phosphate renal stones. Response to therapy can be assessed by changes in renal size and cortical echogenicity, as well as disappearance of focal lesions.

Adolescent↗
PubMed1986

Sleep, sleepiness, and circadian rhythmicity in aircrews operating on transatlantic routes.

This study was performed on B-747 aircrews operating on regular passenger flights between Frankfurt and the U.S. west coast (9 h time difference). In an initial phase, sleep behavior was surveyed by daily logs in 38 crewmembers. The results for the layover period indicate congruent sleep patterns with shifts in sleep onset distinctly less than 9 h. In comparison with preflight control data, sleep duration was significantly prolonged and, on average, no sleep deficits were experienced before commencing the return flight. The main part of the study consisted of polygraphic sleep recordings and multiple sleep latency tests (MSLT) applied to four complete cockpit crews (12 members total) in a baseline period, during layover, and after return to homebase. In addition, body temperature and ECG were continuously recorded. During layover, mean bed times were shifted by 4.5 h at maximum. Sleep was disturbed by early and prolonged awakenings which led to a reduction of sleep efficiency. In contrast, no sleep deficits nor increases in daytime sleepiness occurred. Night duty associated with the return flight caused sleep deprivation which conversely resulted in good sleep during the first night back in Germany. However, during the second night after return, impaired sleep was observed, at least in part caused by the rhythm disturbances. As predicted by our resynchronization model, ECG and rectal temperature recordings gave evidence for a desynchronization of the circadian system and an internal dissociation of different body functions.

Adult↗
PubMed1986

Expression of GD2 ganglioside by untreated primary human neuroblastomas.

Primary neuroblastomas obtained before therapy from 36 patients were studied to determine the frequency of tumors expressing a specific glycosphingolipid, GD2 ganglioside. Total tissue gangliosides were purified by a new partition method, quantitated, and analyzed by high-performance thin-layer chromatography. All 36 neuroblastoma tumors, representing all clinical stages, contained GD2 ganglioside. The mean relative and absolute concentrations of GD2 were substantial (12% of the total tissue gangliosides and 50 nmol/g of tissue) and were independent of the clinical stage of the tumor. In contrast, 6 samples of related but more differentiated tumors (ganglioneuroblastoma and ganglioneuroma) had little or no detectable GD2 (less than or equal to 1.5% of total gangliosides and less than or equal to 4 nmol/g of tissue). These results suggest that GD2 is a sensitive marker for neuroblastoma tissue and may be an excellent target antigen for immunotherapy of this tumor.

Cell Differentiation↗
PubMed1986

Albuterol protects against exercise-induced asthma longer than metaproterenol sulfate.

Both metaproterenol sulfate and albuterol are inhaled medications commonly used to prevent exercise-induced bronchospasm. Their efficacy and duration of action in controlling exercise-induced bronchospasm were compared with placebo in 18 asthmatic children (age range: 12 to 17 years) in a single-blind randomized crossover study. Standardized treadmill exercise challenges were repeated every two hours for up to six hours following the initial exercise test. With the initial exercise challenge, both active medications blocked exercise-induced bronchospasm with equal efficacy. On the other hand, when the duration of action of the medications was compared: albuterol blocked exercise-induced bronchospasm longer than metaproterenol sulfate in eight subjects, the reverse was true in only one patient, and the medications blocked for equal duration in nine subjects. Thus, although both active agents were equally efficacious in blocking exercise-induced bronchospasm initially, the duration of action of albuterol was significantly (P less than .05) longer on serial testing than that of metaproterenol sulfate. Both medications were significantly better than placebo in efficacy and duration of action.

Adolescent↗
PubMed1985

Functional analysis of a beta-globin gene containing a TATA box mutation from a Kurdish Jew with beta thalassemia.

We recently reported a TATA box mutation (ATAAAA to ATACAA) in a cloned beta-globin gene from a Kurdish Jew with homozygous beta thalassemia (Poncz, M., Ballantine, M., Solowiejczyk, D., Barak, I., Schwartz, E., and Surrey, S. (1982) J. Biol. Chem. 257, 5994-5996). We have now introduced this gene into HeLa cells after CaPO4 precipitation of the DNA and studied expression by analyzing globin-gene transcripts with a novel S1 nuclease mapping assay. Quantitative and qualitative comparison with the normal beta-globin gene revealed a promoter-down phenotype in the TATA box mutant, with normal RNA processing, and a normal start site for initiation of the primary transcript. Decreased transcriptional efficiency was confirmed directly by analysis of run-off transcripts using assays in vitro. The patient's phenotype of beta thalassemia major is probably the result of two different mutations since haplotype analysis of the beta-like globin gene clusters in genomic DNA from this patient shows heterozygosity for the Mediterranean-type haplotypes I and VII, with the TATA box mutation on a haplotype I chromosomal background.

Base Sequence↗
PubMed1985

Comparative ototoxicity of netilmicin, gentamicin, and tobramycin in cats.

Netilmicin, a semisynthetic aminoglycoside antibiotic, is less ototoxic in a variety of species than other aminoglycosides currently in therapeutic use. In this study, mixed-breed cats (four/group) were given daily sc injections of netilmicin (20, 40, and 80 mg/kg), gentamicin (20 and 40 mg/kg), or tobramycin (20, 40, and 80 mg/kg) for up to 30 weeks or until ototoxicity was observed. The animals were examined throughout the study for effects on cochlear and vestibular function. Hematologic, serum chemical, and drug-serum (24-hr postdose) assays were performed at approximate monthly intervals during the dosing period. The cochleae, kidneys, and liver were examined microscopically. The mean number of dose days required to produce vestibulotoxic effects, demonstrated by impaired righting reflex or locomotor ataxia, was from 41 to 61 in cats dosed with tobramycin (40 and 80 mg/kg) or gentamicin. No vestibular dysfunction was observed in any of the netilmicin 20-mg/kg-dosed cats, in two cats each of the tobramycin 20-mg/kg and netilmicin 40-mg/kg groups, and in one netilmicin 80-mg/kg-dosed animal. Histologic examination of the cochleae revealed degeneration of the hair cells and supporting sensory structures in the majority of cats dosed with gentamicin at 20 and 40 mg/kg and tobramycin at 40 and 80 mg/kg. Less than 50% of the tissues from cats of the tobramycin 20-mg/kg and netilmicin 40- and 80-mg/kg-dosed groups had similar degenerative cochlear changes. No cochlear damage was noted in any of the cats given netilmicin at 20 mg/kg. Results of the clinical laboratory determinations were generally unremarkable. Proximal tubular degeneration was the principal finding observed in the kidneys of the animals. Under the conditions of this study, at least a twofold (vestibular) to fourfold (cochlear) relative safety margin for ototoxicity was established in favor of netilmicin over tobramycin and gentamicin.

Animals↗
PubMed1985

Ascorbate-generated endogenous extracellular matrix affects cell protein synthesis in calf aortic smooth muscle cells.

Ascorbate supplementation of cultured fetal calf aortic smooth muscle cells leads to increased deposition of extracellular matrix proteins and stimulation of cellular protein synthesis (E. Schwartz et al., J cell biol 92 (1983) 462) [7]. In the present study, we have investigated this phenomenon at the level of gene expression. Cells were grown for three weeks on tissue culture plastic with or without ascorbate (50 micrograms/ml). When compared to controls, cells grown in presence of ascorbate had twice as much poly(A+) RNA per microgram of total RNA, and ascorbate led to a 50% increase in [35S]methionine incorporation when the total RNA was translated in the reticulocyte lysate system. SDS-PAGE revealed no change in the protein pattern under the two conditions. "Northern" hybridization revealed a two- to fivefold increase in the sequence content of beta-actin, alpha-tubulin and type I pro alpha 1-collagen in total RNA of ascorbate-supplemented cells, but no difference was observed in the mRNA sequence content for the three specific proteins when equal amounts of poly(A+) RNA from ascorbate and control cells were hybridized with the three cloned cDNAs. To evaluate the effect of an exogenous matrix, cells were also plated on collagen gels. RNA isolated from cells grown on collagen without added ascorbate exhibited translational activity and mRNA sequence content similar to cells grown with ascorbate on tissue culture plastic. In contrast, no differences from controls were found in cells grown for one week in the presence of ascorbate, at which time no significant deposition of collagen occurs in the extracellular matrix. These results suggest that the stimulation in protein synthesis in fetal calf smooth muscle cells supplemented with ascorbate is associated with an increase in the proportion of poly(A+) RNA in the total RNA pool, and that the production of an endogenous collagen-rich matrix in the presence of ascorbate may be the basis for these pretranslational changes.

Actins↗
PubMed1985

Extracellular matrix microfibrils are composed of core proteins coated with fibronectin.

Extracellular proteins of cultured calf aortic smooth muscle cells consist predominantly of microfibrils 10-20 nm in diameter typical of "elastin-associated" microfibrils described in many tissues. Chemical and immunochemical evidence is presented that microfibrils consist of at least two proteins: core protein and fibronectin. Insoluble proteins of the microfibrils were obtained in the form of a pellet and antibodies raised in rabbits against these components. The antisera reacted with the insoluble microfibrillar proteins and with soluble fibronectin in enzyme-linked immunosorbent assay, and immunostained the extracellular microfibrils in cultured cells. An immunoglobulin (Ig) fraction was prepared and absorbed with fibronectin. The absorbed IgG retained its reactivity with the microfibrillar proteins but was no longer reactive with soluble fibronectin. Immunofluorescence studies were carried out using the absorbed IgG and IgG to soluble fibronectin. Both antibodies showed immunoreactive microfibrils in the extracellular matrix of cells in log phase. However, with increasing time in culture, as the cells reached confluence, the immunofluorescence of microfibrils reacting with the absorbed IgG became less intense, whereas that of microfibrils reacting with IgG to fibronectin increased; in confluent cells, essentially no staining was detected with the absorbed IgG, and a dense network of intensely stained microfibrils was seen with IgG to fibronectin. Treatment of these cultures with urea led to partial dissociation of the fibronectin and increased visualization of the microfibrils with the absorbed IgG; double-label immunofluorescence showed that both proteins occurred on the same microfibrils. The localization of immunoreactive sites to the extracellular microfibrils was confirmed by immunoelectron microscopy. Nearly quantitative cleavage with CNBr failed to dissociate the antigenically active fragments of fibronectin from the CNBr fragments of the core proteins of the microfibrils. It was concluded that microfibrils contain core proteins and fibronectin that are codistributed in insoluble, possibly covalently cross-linked, aggregates. The core proteins are first deposited by the cell and, as a function of time in culture, fibronectin gradually coats their surface.

Animals↗
PubMed1985

Oxygen binding and stability properties of Hb Santa Ana (beta 88 Leu----Pro).

Hb Santa Ana (beta 88 Leu----Pro) was found at a level of 30% of total hemoglobin in red cells from a patient with congenital hemolytic anemia. Since no detailed functional studies of this hemoglobin have been done previously, we determined oxygen equilibrium curves of red cell suspensions, hemolysates, and isolated Hb Santa Ana. The P50 values obtained were 22.5 mm Hg (37 degrees C, pH 7.4) for red cell suspensions (normal mean = 27.0 mm Hg), 10.0 mm Hg (25 degrees C, pH 7.0) for hemolysate (normal = 13.5 mm Hg), and 1.3 mm Hg (25 degrees C, pH 7.0) for isolated Hb Santa Ana. Measurements of mechanical stability of Hb Santa Ana showed that the oxy-form of this hemoglobin was 10 times more unstable than that of Hb S and 100 times more unstable than that of Hb A. The deoxy-form of Hb Santa Ana was as unstable as its oxy-form, indicating that no stabilization (R----T conversion) takes place upon the deoxygenation of Hb Santa Ana.

Anemia, Hemolytic, Congenital↗
PubMed1985

Amodiaquine-induced agranulocytosis: drug inhibition of myeloid colonies in the presence of patient's serum.

We report a patient who developed agranulocytosis following exposure to three drugs: amodiaquine, pyrimethamine and dipyrone. The combination of amodiaquine with the patient's serum, obtained during the agranulocytosis, inhibited in vitro granulocyte-monocyte colony-forming unit (CFU-GM) growth of autologous and allogeneic marrow. These results support the view that amodiaquine-induced agranulocytosis is immune in nature. This in vitro approach may be used to study the mechanism of drug-induced agranulocytosis, especially when patients are exposed to multiple drugs.

Agranulocytosis↗
PubMed1985

Skin and mucous membrane ulceration in beagle dogs following oral dosing with an experimental aminoglycoside antibiotic.

G-418 is a unique aminoglycoside antibiotic that is structurally related to gentamicin; however, unlike gentamicin, G-418 inhibits growth of both procaryotic and eucaryotic cells. In a preliminary acute oral safety study, adult male and female beagles were given a single oral dose of either 2000, 1000, 500, 200, or 50 mg/kg of G-418. Ulceration of the lip, tongue, and/or gingiva occurred in all G-418-dosed dogs 1 to 9 days after dosing. Ulceration of the glans penis, penis sheath, and scrotum occurred 7 to 14 days after a single oral dose with 1000 and 500 mg/kg G-418, and ulceration of the vaginal mucosa of the 2000-, 1000-, 500-, and 50-mg/kg-dosed female dogs occurred 2 to 8 days after dosing. Ulcers of the lip and vaginal area began at the mucocutaneous border and were more severe at these borders. In some dogs a yellow membrane formed over these lesions. Ulceration of the oral and vaginal mucosa disappeared 10 days after the first occurrence and reoccurred 3-7 days later. All ulcers healed within 30 days after the single oral dose; however, at necropsy hemorhagic areas of the urinary bladder were observed in at least one of two dogs at each dose level. Similar lesions have not been reported in animals treated with any other aminoglycoside antibiotics. The etiology of these lesions is unknown.

Aminoglycosides↗
PubMed1985

Dermatomyositis and Hodgkin's disease. Case report and review of the literature.

The association between dermatomyositis and malignant tumors, especially carcinomas, is well documented. However, lymphoreticular malignancies have rarely been reported. A patient in whom Hodgkin's disease was diagnosed 5.5 years after the onset of dermatomyositis is described. The independent course of the two diseases is discussed and previously reported cases of lymphoma and dermatomyositis are reviewed.

Dermatomyositis↗
PubMed1984

Hemoglobin I mutation encoded at both alpha-globin loci on the same chromosome: concerted evolution in the human genome.

Genetic analysis of an individual expressing an unexpectedly high level of hemoglobin I, an alpha-globin structural mutant, reveals that the mutation is present at both the alpha 1- and the alpha 2-globin gene loci. Kindred analysis confirms that the two affected genes are located in cis. The most likely explanation for this finding is that a recent conversion event occurred within the human alpha-globin gene cluster.

Base Sequence↗
PubMed1984

Frequent occurrence of a zeta-globin-region deletion in American blacks accounts for a previously-described restriction site polymorphism.

We describe an 11.3 kb deletion within the zeta-globin gene region which was found in 2 of 16 American Black neonates. The deletion is consistent with an unequal crossover between the homologous zeta and psi zeta gene regions, resulting in a shortened Eco RI fragment (17.2 kb) containing a single zeta and the psi alpha, alpha 2, and alpha 1 genes. An earlier report of zeta-region crossovers (1) may have overestimated the size of this fragment by 2 kb. This finding led us to re-evaluate another report which concluded that a 17 kb Eco RI fragment found in 10% of the Black population was the result of a restriction site polymorphism (2). Our data do not substantiate this conclusion and we propose that the high frequency of this shortened fragment is due instead to an unequal crossover. Possible clinical consequences of this deletional event are also discussed.

Black People↗
PubMed1984

Relationship between tetramer-dimer assembly and the stability of Hb Malmö (alpha 2 beta 2 97Gln).

The effects of the mutation of the alpha 1 beta 2 contact in Hb Malmö (alpha 2 beta 2 97(FG4)His----Gln) on oxygen-binding properties, ease of dissociation into dimeric hemoglobin and stability were studied. The P50 value of Hb Malmö in the absence of organic phosphates was 1.9 mmHg, in contrast to 8.8 mmHg of Hb A. The n-value of Hb Malmö was 1.6. The overall free energy of interaction of oxygen with Hb Malmö was about 25% that of Hb A. The Adair constant, K1, of Hb Malmö was about 10-times larger than that of Hb A, but the K4 of Hb Malmö was similar to that of Hb A. The liganded form of Hb Malmö was found to dissociate into dimers more readily than Hb A by gel filtration on Sephadex G-100. Dissociation into dimeric hemoglobin was enhanced in dilute solutions. Increased instability during mechanical agitation of diluted samples was greater for Hb Malmö than for Hb A. The denaturation rate constants of tetramers of the oxyform of Hb A and Hb Malmö were about 20-times greater than those of dimers of these hemoglobins. The instability of Hb Malmö depends on a greater alpha 1 beta 2 dissociation constant compared with that of Hb A. These findings allow an examination of the role of the intersubunit contact in determining the functional properties and the stability of the hemoglobin molecule.

Drug Stability↗