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Biomedical subjects

D Cohen

Publications and source records attributed to D Cohen.

At least 541 records · Page 30Linked to original sources

Food-borne outbreak of group G streptococcal sore throat in an Israeli military base.

A food-borne outbreak of sore throat caused by Lancefield group G beta-haemolytic streptococci and involving 50 persons occurred in May 1983 in an Israeli military camp. All of the patients available for clinical examination had sore throat and difficulty in swallowing. Exudative tonsillitis occurred in 46% of the patients and the body temperature was above 37.5 degrees C in 81%. The pattern of attack was uniform over the base and 37 became ill during the night and morning of the 5 May. Thirty-two (84%) of the throat cultures taken from 37 patients grew group G beta-haemolytic streptococci. Eight of 29 contacts were positive for group G beta-haemolytic streptococci and 6 of the 28 foodhandlers examined had positive cultures of the same group. The organism was also isolated from one food sample. The epidemiological and laboratory investigations indicated that a food handler, a convalescent carrier of group G streptococci, might have been the source of infection. Assumptions on the potential of non-group A streptococci to cause epidemics are discussed.

Acute Disease↗

Isolation of a human major histocompatibility complex class I gene encoding a nonubiquitous molecule expressed on activated lymphocytes.

The human major histocompatibility complex is a multigene family containing at least 20 class I genes. Included within this family are the loci encoding the highly polymorphic HLA-A, -B, and -C antigens present at the surface of most nucleated cells. The large number of genes detected with class I probes by Southern blot analysis and the existence of serological reagents defining nonubiquitous, non-HLA-A,B,C class I antigens suggest that products other than HLA-A,B,C antigens are encoded within the class I gene family. These products might be the human counterparts of the murine Qa and TL antigens. In order to identify non-HLA-A,B,C genes, we have developed a probe, JF11, located in noncoding regions flanking the HLA-A locus. This probe detects only a limited number of class I genes and does not detect HLA-A,B,C-associated restriction fragments on Southern blots. This probe was used to screen a human cosmid library. Some of the cosmids isolated with this probe were then transferred into mouse fibroblasts expressing human beta 2-microglobulin. One of the transfectants specifically reacts with one alloantiserum (HA2) that detects HLA class I molecules specific to HLA-A2-positive, phytohemagglutinin-activated T cells and not found on resting T or B cells. Data presented in this paper provide evidence for the isolation and expression of a class I gene encoding a nonubiquitous class I antigen that could be a human analogue of the murine Qa antigens.

Animals↗

Interstitial radiobrachytherapy of malignant cerebral neoplasms: rationale, methodology, prospects.

The local use of radionuclides in the management of neoplastic processes was initially considered over 80 yr ago and has enjoyed increasing enthusiasm in the treatment of somatic and central nervous system tumours during the past 30 yr. The marriage of complex neuroimaging techniques and modern stereotactic devices has markedly enhanced the technical precision of interstitial radiobrachytherapy of malignant cerebral neoplasms. In applying these techniques, it is imperative to achieve an optimal placement of radionuclide sources in order to develop a geometrically homogenous, controlled distribution of radiation. Critical considerations include determination of tumour volume and contour, and development of a homogenous dose rate (dependent upon multiple sources at varying intensity) that will not only effect tumour cell kill but do this without excessive production of radionecrosis which necessitates craniotomy because of mass. Using the Brown-Roberts-Wells (BRW) stereotactic guidance system and an image-defined, volumetrically determined target, implants of multiple iridium 192(192Ir) sources were used to establish appropriate isodose envelopes. A methodology for achieving the described objectives is detailed as it applies to a variety of malignant intracerebral neoplasms (glioblastoma multiforme, malignant astrocytoma, malignant mixed glioma, primary cerebral lymphoma, metastatic carcinoma and malignant pineal region tumours). Technical realization of precision implantation relying upon imaging data may be acheived with this method with satisfactory responses that are dependent upon histological tumour type and the morphology of the tumour distribution as related to the image. Early and late complications related to the surgical technique and radionuclide applications were less than 5%. Although encouraging, these techniques require further definition and greater data accrual before uniform application outside major medical centres can be justified. It is anticipated that improvement in results with intrinsic gliomas and other invasive neoplasms will be realized with further definition of tumour boundaries by tract biopsy techniques and concurrent utilization of hyperthermia and brain protective methods.

Brachytherapy↗

A method for combining MEG and EEG to determine the sources.

A three-step method is presented which combines an MEG and EEG map over the head to solve the inverse problem (to determine the sources). This method uses the feature that the MEG does not see a radial source, but only a tangential source, while the EEG sees both. A first test is also made of the method, using computer simulation, and the results presented. The purpose of the test is to see if the method is valid with noisy MEG and EEG data, and when some modelling errors are present; a single dipole source was used in a spherical head. It was found that the method works well when the RMS noise at each map location is 5% of the maximum MEG and EEG (readily attained in practice), but breaks down when the noise is 10% (quite noisy data). The modelling errors involved grid size, head radius and distance to the MEG coil, and were studied only through the first step of the method; with errors in a reasonable range, this limited test again worked well.

Brain↗

Molecular genetic analysis of the major histocompatibility complex in an ELA typed horse family.

Restriction fragment length polymorphism was studied in an ELA typed horse family which included a stallion, a mare with two full-sibs, another mare with three full-sibs and, in addition, three paternal half-sibs. DNA samples from all individuals were investigated by Southern blot analysis using three restriction enzymes (EcoRI, HindIII or TaqI) and human cDNA class I, class II (DR beta) and class III (C4) probes. In addition, a genomic class II DQ alpha probe was used. Fragments hybridized with the various probes revealed the existence of DNA sequences homologous to HLA class I, DR beta, DQ alpha and C4 genes in the horse. Polymorphic fragments were found when DNA was hybridized with class I and class II probes irrespective of the enzyme used; but hybridization with the C4 probe did not reveal variability. All polymorphic fragments segregated according to the ELA serological specificities, thus indicating a close linkage between the different revealed subregions. Banding patterns suggest that the horse possesses about 20-30 class I genes, probably more than one DR beta and DQ alpha genes and possibly only one C4 gene. The high degree of polymorphism observed suggests that molecular DNA typing may represent a potentially powerful aid to decision in parentage control determination.

Animals↗

Hereditary cystatin C (gamma-trace) amyloid angiopathy of the CNS causing cerebral hemorrhage.

Hereditary CNS amyloid angiopathy occurring in Icelanders is the first human disorder known to be caused by deposition of cystatin C amyloid fibrils in the walls of the brain arteries leading to single or or multiple strokes with fatal outcome. One or more affected members have been verified by histological examination in 8 families containing 127 affected. These originated from the same geographic area. Abnormally low value of cystatin C found in the cerebrospinal fluid of those affected can be used to support or make diagnosis of this disease, also in asymptomatic relatives. By amino acid sequence analysis the amyloid fibrils in the patients are found to be a variant of cystatin C (gamma-trace), a major cysteine proteinase inhibitor. The variant protein has an amino acid substitution (glutamine for leucine) at position 58 in the amyloid molecule. It is postulated that a point mutation has occurred leading to production of amyloidogenic protein causing the disorder.

Amyloid↗

Determination of 18O by prompt nuclear reaction analysis: application for measurement of microsamples.

A method is described for the routine determination of 18O concentrations in microsamples of biological fluids. The method utilizes the prompt nuclear reaction 18O(p, alpha o)15N, and 846-keV protons from a 3-MeV Van de Graaff Accelerator are focused on approximately 2,000-A-thick Ta2O5 targets prepared by anodic oxidation from 50-microliter samples of water distilled from blood or other biological fluids. The broad cross section of the resonance peak for this nuclear reaction (47 keV) ensures high yields, especially at small reaction angles, and the high-energy alpha particles produced by the reaction (4 MeV) are readily separated from scattered protons by the use of an aluminized Mylar foil of suitable thickness. Background levels of 18O (0.204 atom%) can be detected with run times of approximately 5-8 min, and the sensitivity of the method is of the order of 0.05 atom %. Experimental error due to sample preparation was found to be 1.7%, and counting errors were close to theoretical limits so that total error was of the order of 2.5%. Duplicate samples were analyzed by use of the 18O(p, alpha o)15N reaction at Lucas Heights, Australia, and the 18O(p,n)18F reaction by the method of Wood et al. (Anal. Chem. 47: 646-650, 1975) at the University of California, Los Angeles, and the agreement was excellent (y = 1.0123x - 0.0123, r = 0.991, P less than 0.001). The theoretical limitations and the general applicability of the method in biological studies designed to estimate the rate of metabolism of free-ranging animals are discussed.

Animals↗

Low-energy transvenous ablation of the canine atrioventricular conduction system with a suction electrode catheter.

A single suction electrode catheter was used for His bundle electrogram recording. His bundle pacing, and low-energy (20 or 30 J) His bundle ablation in seven dogs. The suction electrode catheter was actively fixed to the atrial endocardium at the His bundle level. Electrophysiologic studies were performed in the control state, immediately after, and late (greater than 40 days) after His bundle ablation and results were correlated with histologic findings in the conduction system. Unipolar His bundle recording and pacing were successfully performed in all dogs with the suction electrode catheter before and after ablation. Complete heart block developed after a single 20 J shock delivered via the suction electrode catheter in all dogs immediately, but reverted to 1:1 atrioventricular conduction with first-degree atrioventricular block in two dogs in which one or two additional shocks (20 or 30 J) produced complete heart block. Mean ablation energy per shock was 22 +/- 4 J. The mean total delivered energy per dog was 31 +/- 20 J. Late electrophysiologic study in all dogs showed persistent complete heart block in five dogs and paroxysmal second-degree or third-degree atrioventricular block in two dogs. Gross examination of the ablation site showed a white plaque above the medial tricuspid leaflet (1.4 to 2.0 cm long and 0.4 to 0.6 cm wide). Microscopically, fibrosis of the penetrating and branching His bundle was seen in all dogs, with minimal atrioventricular node and atrial involvement. Significant proximal right bundle branch fibrosis was observed in the two dogs receiving one or two additional shocks. We conclude that the suction electrode catheter permits repeated His bundle recording, pacing, and ablation with a single catheter. Permanent and safe low-energy ablation of the canine His bundle is feasible. Focal injury localized to the target area in the conduction system can be obtained.

Animals↗

Computed imaging stereotaxy: experience and perspective related to 500 procedures applied to brain masses.

The evolution of more sophisticated imaging techniques has initiated a renewed interest in stereotactic devices, methods, and applications. The Brown-Roberts-Wells instrument was available to us early in its prototype stage, and this report reviews the first 500 cases using the system at the University of Southern California Medical Center Hospitals. Procedures were undertaken after recognition of apparent structural alterations on imaging studies, with objectives being both diagnostic and therapeutic. Target locations were predominantly within the cerebral centrum-basal ganglia (284 cases) and diencephalic-mesencephalic regions (129 cases). Operative objectives included: histological and microbiological assay, cyst and abscess aspiration, installation of temporary or permanent drainage conduits, point source and colloid base brachytherapy, cerebroscopy and ventriculoscopy with biopsy, aspiration, and excision, and intraoperative vascular localization. Using multiple instrumentation at the target point (741 point placements), we realized procedural objectives in 95.6% of the cases. The mortality was 0.2% and the morbidity was 1%: hematoma, 2 cases; infection, 1 case; increased deficit, 1 case; intraprocedural seizure, 1 case. A specific diagnosis was not obtained in 4.4% (necrosis, 10 cases; inflammatory response, 9 cases; granuloma, 1 case; gliosis, 1 case; diagnostic error, 1 case). Individual guidelines for case selection, technique, institutional requirements, and applications of the method are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Demonstration of new class I antigens in man].

The hypothesis of new class I antigens has been postulated in man, and several antigen systems have been proposed: HT (Gazit), TC (TCA, TCB) (Van Leeuwen). The present study describes a new class I antigenic marker system, expressed selectively on PHA-activated T lymphocytes and on lymphoblastoid B cell lines. These markers correlated at the cellular activation stage, have been called: human activation or HA markers. 7% of the sera from multiparous women present anti-HA antibodies. The definition of class I molecule (dimer 41K - 12K) has been established by a structural analysis of the molecule; the responsible gene, located on the 6th chromosome could be close to the HLA-A gene. The equivalence with the mouse Qa markers is postulated, but remains to be totally demonstrated.

B-Lymphocytes↗

[Alpha genes of the T cell receptor: a possible implication in genetic susceptibility to multiple sclerosis].

Multiple sclerosis (MS) is a neurological disease in which 60% of patients are DR2 (versus 20% in controls). Restriction fragment length polymorphism (RFLP) associated with T cell receptor alpha-chain and beta-chain genes have been analysed in a sample of 46 MS patients and compared with those of 142 controls. The alpha-chain gene polymorphism is localized to the V-J region and consists of 3 Bgl II alleles (alpha a = 3.2 kb; alpha b = 2.9 kb; alpha c = 2.8 kb). A significant difference was found in the distribution of these three alleles since 97% of DR2 patients versus 60% in DR2 non-MS individuals were found to be homozygotes alpha a/alpha a. These results suggest the influence of T cell antigen receptor germ line repertoire on the etiopathology of this disease.

Alleles↗

Surface glycoconjugates on rat photoreceptor cilium. Effect of neuraminidase digestion.

In retinal photoreceptors the connecting cilium constitutes a boundary between the inner and outer segments. In previous studies we demonstrated that, while opsin could be localized in abundance in the distal ciliary membrane, very little opsin was detected in the proximal ciliary plasma membrane. In the present study we extended our view of molecular specialization on the ciliary membrane with respect to glycoconjugates. Saccharide moieties of ciliary glycoconjugates were studied in immature and mature rat photoreceptors. Surface saccharides were detected and localized by means of ferritin-labeled lectins and electron microscopy. Dense labeling of the ciliary membrane surface with wheat germ agglutinin (WGA) was observed. In immature photoreceptors the labeling was restricted to the proximal ciliary membrane, in a region where opsin molecules could not be detected. Neuraminidase digestion abolished WGA binding to the proximal ciliary membrane surface, indicating that sialic acids mediate WGA binding to this domain. Peanut agglutinin (PNA) did not label the ciliary surface, nor did it bind to the surface of other photoreceptor domains. Neuraminidase digestion exposed numerous PNA binding sites on the ciliary membrane surface. In view of the carbohydrate specificity of PNA, we suggest that a terminal trisaccharide sequence, sialic acid-galactose-(beta 1----3)-N-acetyl galactosamine, is present in high density on the proximal ciliary membrane surface.

Animals↗

Arhinia revisited.

Arhinia is a rare anomaly in which a total absence of the nose and parts of the olfactory system occurs. It is frequently associated with various multiple central nervous system (CNS) and somatic anomalies of different degrees of severity, with high mortality rate. Twelve cases that have been reported in the literature are analyzed according to multiple criteria. The anomalies that have been found to be associated with arhinia are: lack of olfactory bulbs and nerves, missing paranasal sinuses, high arched or cleft palate, various eye anomalies, low set ears - all in a very high incidence. Various degrees of CNS malformations have been found in part of the cases. Somatic anomalies have been reported in 50% of the cases. In two cases chromosome 9 anomalies have been reported. A classification is suggested in which arhinia is classified into arhinia (total absence of the nose and rhinencephalon) and partial arhinia (partial absence of the nose), each may or may not be associated with other malformations (facial, CNS and somatic).

Abnormalities, Multiple↗

Common origin of transmissible venereal tumors (TVT) in dogs.

We determined the sequence of the 1.5-kb insert upstream to c-myc in the transmissible venereal tumor (TVT) of dogs. The sequence is highly homologous to the 3' region of the mammalian repetitive LINE element. The insert is bound by a 10-bp repeat indicating DNA transposition by a mechanism involving reverse transcriptase. We analyzed DNA of four TVT tumors from various geographical locations as well as normal canine DNA for the presence of the LINE insert. The results indicate that in all TVT tumors, but not in normal tissues, the same LINE insert was present upstream to c-myc. This result suggests that TVT tumors in various dogs may have a common cellular origin.

Animals↗

Ventricular fluid interleukin-1 activity in patients with head injury.

Patients with severe head injury are hypermetabolic and hypercatabolic, and manifest several components of the acute phase response. Interleukin-1 (IL-1) is a cytokine that mediates many aspects of the acute phase response, and rats with experimental head injury produce IL-1 of brain origin. IL-1 administered intracerebroventricularly to experimental animals has disproportionately greater systemic biologic effects compared with IL-1 injected intravenously. In this study, patients with severe head injury were evaluated to determine whether IL-1 activity in the ventricular fluid was increased and whether IL-1 levels correlated with some of the altered metabolic responses. Twelve hospitalized patients with head injury (24-hour peak admission Glasgow Coma Scale scores of 4 to 10) were evaluated on admission and longitudinally for 21 days after injury. IL-1 activity in ventricular fluid from patients with head injury was significantly elevated whereas IL-1 activity in cerebrospinal fluid from age- and sex-matched patients undergoing lumbar puncture for myelograms was not detectable (P less than 0.005). The patients with head injury had clinical and biochemical indicators of IL-1 activity such as fever, hypozincemia, and increased C-reactive protein levels that improved during the period of hospitalization. It is speculated that the elevated IL-1 activity may play a role in the altered metabolic response of patients with severe head injury.

Adolescent↗

T cell rearranging gene gamma: diversity and mRNA expression in fresh cells from T cell acute lymphoblastic leukemia.

Rearrangement and in most cases expression of the T cell rearranging genes gamma (TRG gamma) and T cell antigen receptor beta chain (TCR beta) genes were studied in 19 cases of T cell acute malignancies where the surface phenotype is representative of the different stages of thymic maturation. TCR alpha gene transcription was also studied. TRG gamma and TCR beta genes were found to be rearranged in all but one case. The TRG gamma rearrangement pattern seen in most cases is compatible with biallelic rearrangement by loop excision involving the J gamma 2 regions. The sizes of all but two rearranged bands were identical to those of the rearranged bands seen in polyclonal T lymphocytes also studied in this work. One identical-sized band was found in 11 of the 18 rearranged cases. The expression of TRG gamma mRNA (transcripts of 1.6 kilobases [kb]) was highly variable from case to case and did not correlate with the stage of differentiation of the malignant cells, the expression of the molecules CD4 and CD8, the expression and size of the transcripts of the TCR beta genes, and the transcription of TCR alpha genes. In one CD3 + case, strong expression of the TRG gamma transcripts coexisted with the exclusive presence of TCR beta mRNA of 1.0 kb. The cells from this case did not react with anti-Ti antibody and exhibited no natural killer activity. These findings are suggestive of a malignancy that may express the recently isolated CD3-TRG gamma complex.

Acute Disease↗

Cytochemical characterization of sialoglycoconjugates on rat photoreceptor cell surface.

Terminal saccharide sequences in rat photoreceptor cell surface glycoconjugates were characterized. Lectin cytochemistry and electron microscopy were used for preembedding cytochemical localization of surface carbohydrates. Neuraminidase digestion was employed for the exposure of penultimate saccharides in sialoglycoconjugates. Isolated rat retinas were incubated with ferritin-labeled wheat germ agglutinin (WGA), peanut agglutinin (PNA), and soybean agglutinin (SBA) prior to and after neuraminidase digestion. PNA and SBA did not label untreated photoreceptors. WGA densely labeled the photoreceptor surface and interphotoreceptor matrix (IPM) components. Following neuraminidase treatment, PNA, but not SBA, labeled the photoreceptor surface and the IPM. WGA labeling of the IPM was abolished, and the labeling of the photoreceptor surface was reduced. Based on the lectin specificity, it was concluded that photoreceptor surface glycoconjugates in the rat retina contain a terminal trisaccharide: sialic acid-D-galactose-(beta 1----3)-N-acetyl-D-galactosamine.

Acetylgalactosamine↗