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Biomedical subjects

D Singer

Publications and source records attributed to D Singer.

At least 73 records · Page 4Linked to original sources

Metabolic reduction in hypothermia: pathophysiological problems and natural examples--Part 1.

Following a description of the protective effects of hypothermia, the limitations resulting from "cold swelling" of the brain, caused by a progressive discrepancy between active and passive cellular transport processes, are discussed. The observation that the tolerable limits of metabolic reduction lie well below the normal turnover rates leads to a short survey of the evolution of energy metabolism. The gradual development of the latter from anaerobiosis to aerobiosis and from poikilothermy to homeothermy apparently provides the background for transient reductions to lower rates which spontaneously occur even in higher vertebrates. As an impressive example of such a natural strategy, the anaerobic survival of diving turtles is outlined which essentially depends on an efficient buffering. This dependence bears analogy to cardioplegia, where an increase in buffering capacity can greatly retard the fall of energy turnover, thus leading, as is shown by microcalorimetry, to an intermediate plateau of anaerobic metabolism.

Adaptation, Physiological↗

Metabolic reduction in hypothermia: pathophysiological problems and natural examples--Part 2.

As an example of spontaneous cooling in homeothermic organisms, hibernation of mammals is described. Based on the fact that all hibernators, at their regulated minimal body temperature, display a uniform turnover rate, related to body weight, the hypothesis is developed that cold tolerance of mammals is generally limited by a common specific minimal metabolic rate, which larger organisms, because of their lower basal metabolism, already attain in less profound hypothermia. The observation that there is, in natural lethargic states, a certain independence between metabolic rate and body temperature, subsequently leads to considerations on the presumable modulating influence exerted by the acid-base balance. Finally, referring to the time limitations of such adaptation strategies, the cold-induced disintegration of metabolic processes with differing temperature dependence is illustrated which, however, will be more pronounced in the intermediate temperature range than in lower cooling. Thus, despite a limited cold tolerance, an extremely profound hypothermia of short duration seems not altogether impossible even for large homeotherms, provided some adequate conditions of rewarming are observed.

Acid-Base Equilibrium↗

Evidence for the existence of a cardiac specific isoform of the alpha 1 subunit of the voltage dependent calcium channel.

Biochemical, pharmacological and electrophysiological evidence implies the existence of tissue specific isoforms of the L-type VDCC. The alpha 1 and alpha 2 subunits of the skeletal muscle calcium channel have been previously cloned and their amino acid sequence deduced. Here we report the isolation and sequencing of a partial cDNA that encodes a heart specific isoform of the alpha 1 subunit. The amino acid sequence deduced from this part cDNA clone shows 64.7% similarity with the skeletal muscle alpha 1 subunit. Northern analysis reveals 2 hybridizing bands, 8.5 and 13 kb, in contrast to one 6.5 kb band in the skeletal muscle. Selective inhibition of mRNA expression in Xenopus oocytes by complementary oligodeoxy-nucleotides derived from the heart clone provides further evidence that the cDNA corresponds to an essential component of the VDCC. These data further support the existence of tissue-specific isoforms of the L-type VDCC.

Amino Acid Sequence↗

Endolymphatic stromal myosis (endometrial low-grade stromal sarcoma) presenting with hematuria: a diagnostic challenge.

In this case of a 41-year-old white woman who presented with hematuria, the diagnosis of metastatic endolymphatic stromal myosis (ESM) in the urinary bladder was reached on the basis of the histologic pattern and with the aid of intermediate filament typing. In the hysterectomy specimen the tumor foci of ESM were of minute size. To the best of our knowledge, this is the first report of such an unusual clinical presentation of this lesion.

Adult↗

Comparative study of the use of prefabricated bone tendon grafts and conventional tendon grafts in flexor tendon reconstruction.

In tendon grafting the weakest area is the junction between the grafted tendon and bone. In dogs a strong union between tendon and bone can be produced by threading the flexor carpi radialis tendon through a hole drilled in the radius. In experimental repair of canine flexor tendons, 3 weeks after operation the strength of the union between a composite bone-tendon graft prepared in this way is double that of the bone-tendon junction of a conventional graft. Use of prefabricated bone-tendon grafts should permit earlier postoperative movement and limit formation of adhesions between a tendon graft and its bed.

Animals↗

Restriction fragment length polymorphism analysis with a cross-reactive HLA class II DR-beta gene probe for the detection of engraftment of MHC-mismatched marrow in the rhesus monkey.

Our interest in MHC-mismatched allogeneic bone marrow transplantation (BMT) in the rhesus monkey prompted us to investigate restriction fragment length polymorphism analysis as a means for detecting lymphohematopoietic chimerism in the primate. A human MHC (HLA) class II DR beta gene cDNA probe was tested on rhesus peripheral blood mononuclear cell DNA digested with any of three restriction enzymes. We found that (1) the human DR beta probe hybridized to as many as 15 restriction fragments per rhesus DNA sample, suggesting cross-hybridization at more than one locus of rhesus MHC class II beta genes; (2) restriction fragment length polymorphisms were common among outbred monkeys as a result of class II beta gene polymorphisms and would be sufficient for chimerism detection in the majority of random pairs of outbred monkeys utilizing only a single restriction enzyme (Bgl II); and (3) sensitivity (5-10% chimerism) was comparable to that reported for restriction fragment length polymorphism assays utilizing non-MHC probes in clinical HLA-identical BMT. Utility of the assay was demonstrated in a preliminary series of experiments in rhesus monkeys conditioned with mixed T cell-depleted MHC-mismatched allogeneic plus T cell-depleted autologous BMT with or without cardiac allograft implantation.

Animals↗

Infants of azotemic mothers: a report of three live births.

Women with severe renal failure rarely conceive, and when they do become pregnant these women often deliver prematurely. The clinical course of mothers with renal failure has been described, but little attention has been given to the offspring. In this report, we provide data on three infants born prematurely to mothers either on dialysis or with severe renal failure. The infants were the appropriate size for gestational age and demonstrated no obvious physical abnormalities. Laboratory data, including renal function, was also within normal limits. Renal size in the two infants studied by ultrasound was near or above the 95th percentile when corrected for gestational age. The premature birth appeared to be a function of maternal complications rather than a primary in utero growth disturbance.

Adolescent↗

Local microwave hyperthermia in the treatment of carcinoma of the prostate.

The clinical electromagnetic hyperthermia system has been in use at the Kaplan Hospital since 1980, for treating patients with hyperthermia combined with radio- or chemotherapy. For prostatic tumors, hyperthermia at 43 degrees C is achieved in the prostatic mass using microwaves of 2.45 GHz, with simultaneous cooling of the rectal mucosa and the rectal wall. Thirty-two patients with carcinoma of the prostate have been treated: 4 with heat alone, 20 with hyperthermia combined with radiotherapy, and 8 with hyperthermia combined with hormonal therapy. Follow-up was carried out up to 34 months. Objective local tumor regression was achieved in 3 out of 4 patients treated by heat alone, but the patients relapsed after 6 months. All the 20 patients treated with combined hyperthermia and radiotherapy responded to treatment. Patients treated with combined hyperthermia and hormone therapy responded locally to treatment but died of their metastatic disease, or of unrelated diseases with a follow-up period up to 31 months. Hyperthermia did not increase morbidity beyond that expected for radiation therapy.

Aged↗

Localized deep microwave hyperthermia in the treatment of poor operative risk patients with benign prostatic hyperplasia.

Non-invasive localized deep microwave hyperthermia was applied as an alternative treatment to surgery in 29 patients with contraindications for prostatectomy. Patients were treated twice weekly, on Mondays and Thursdays, for 1 hour, without sedation on an outpatient basis. All patients tolerated treatment well without secondary effects. The results indicate that localized deep microwave hyperthermia applied by this method is safe and effective in the treatment of benign prostatic hyperplasia.

Aged↗

Generation of primary murine CTL specific for allogeneic and xenogeneic MHC determinants upon stimulation with murine L cells transfected with class I genes.

This communication describes in vitro culture conditions that permit the use of MHC gene-transfected L cells as stimulators of primary CTL responses. The use of L cells as stimulators usually results in the generation of "nonspecific" anti-L cell cytotoxicity too great to permit visualization of antigen-specific CTL responses. This study demonstrates that the generation of such anti-L cell cytotoxicity can be abrogated by strategies that prevent the in vitro activation of self-Ia-restricted TH cells. These maneuvers allowed the use of L cell transfectants as stimulators of allospecific and xenospecific CTL precursors in primary in vitro mixed lymphocyte reaction cultures.

Animals↗

Influence of hypocholesterolemic drugs on aortic cholesterol esterase in rabbits.

We have studied the influence of three hypocholesterolemic drugs (Fenofibrate, Pirinixil and Probucol) on aortic cholesterol esterase (E.C.3.1.1.13) activity in cholesterol-fed rabbits. After three weeks, cholesterol-fed controls exhibited a 28% increase in cholesteryl ester synthetase activity (S) and a 13% decrease in cholesteryl ester hydrolase activity (H) giving a 47% increase in S/H ratio. None of the drugs influenced cholesterol-induced synthetase activity, but fenofibrate treatment increased hydrolase activity resulting in a fall in the S/H ratio to the level observed in rabbits fed corn oil but no cholesterol. The other two hypocholesterolemic agents did not affect the aortic S/H ratio.

Animals↗

Liver-spleen studies with the rotating gamma camera. I: Utility of the rotating display.

The clinical utility of a computer-generated dynamic cine display (rotating display) of the unprocessed projection images of the liver and spleen obtained with rotating gamma-camera tomography was prospectively compared with that of the standard multi-view static scintigram display. Two hundred cases were independently and blindly analyzed by three observers. Each study was coded from 1-5, indicating the certainty of normality or abnormality present. When abnormality was noted, the study was assessed for the presence of metastatic disease, inhomogeneous uptake, hepatosplenomegaly, and colloid distribution shift. ROC analysis was then performed on the initial coding for certainty of abnormality, and the causes for discrepancies were evaluated from the assessment of the type of abnormality present. No significant interdisplay differences could be demonstrated. In the small percentage of cases where interdisplay disagreement occurred, this was usually accompanied by marked interobserver variation and was most commonly due to differing assessment of organ size. It is concluded that the static and rotating display formats can be used interchangeably in the evaluation of technetium-99m-labeled sulfur colloid liver studies.

Data Display↗

Liver-spleen studies with the rotating gamma camera. II: Utility of tomography.

A prospective comparison of conventional scintigrams and single-photon emission computed tomography (SPECT) studies of the liver and spleen was carried out. Care was taken to insure high-quality, artifact-free studies. Two hundred patients were imaged by both methods. A definitive diagnosis of normal was established in 86 cases, abnormal in 107 cases, and seven cases were indeterminate. All studies were read by two observers and graded as to degree and type of abnormality seen. ROC curves were constructed and errors of interpretation studied to identify problems. One observer showed no difference in performance between the two methods. The other showed a small improvement with SPECT. Image artifacts apparently contributed to errors of interpretation in 24 of 54 cases using SPECT. SPECT appears comparable with conventional scintigraphy and may improve specificity. Improvements are needed in SPECT imaging equipment and image display capability to realize fully the potential of SPECT.

Humans↗