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Biomedical subjects

R Katz

Publications and source records attributed to R Katz.

At least 145 records · Page 8Linked to original sources
PubMed1991

Fine-needle aspiration evaluation of lymphoproliferative lesions in human immunodeficiency virus-positive patients. A multiparameter approach.

Forty-six fine-needle aspirates of lymphoproliferative lesions from 31 human immunodeficiency virus (HIV)-positive patients were reviewed using cytomorphologic, immunocytochemical, flow cytometric (FCM), cytogenetic, and molecular studies. There were 29 lymphomas (15 small non-cleaved cell [SNCL], 11 large cell [LCL], one small lymphocytic, and two Hodgkin's), 14 reactive hyperplasias, and three "atypical lymphoid proliferations." The reactive hyperplasias were characteristically polymorphic and polyclonal lymphoid populations; six of seven were diploid on FCM, the seventh was hypodiploid. Higher proliferative indices (mean, 11.6%) and higher RNA indices (mean, 1.2) characterized this subgroup compared with published reactive lymphoid hyperplasias from patients without HIV positivity. Aspirates of SNCL showed monotonous populations of intermediate-sized cells except in one patient where a giant cell syncytial variant occurred. Nine of 13 SNCL aspirates showed light chain restriction. JH rearrangement revealed B-cell lineage in one aspirate in which immunocytochemical study was negative for Kappa, lambda, B1, and Leu-4. Nine of 12 SNCL were diploid; the mean proliferative index was 25.6% and the mean RNA index 2.3. Chromosomal translocations involving the c-myc locus were demonstrated in five of seven SNCL aspirates karyotyped. Five of eight LCL showed light chain restriction the remaining three showed null cell phenotype. Large cell lymphomas were diploid on tetraploid with the mean proliferative index of 22.0% and mean RNA index of 2.2. One of two LCL aspirates karyotyped demonstrated c-myc translocation. Despite the multiparameter approach, a definitive diagnosis could not be reached in three aspirates.

Adult↗
PubMed1991

Elevated plasma levels of hyaluronate in patients with osteoarthritis and rheumatoid arthritis.

Plasma levels of hyaluronate (HA) in patients with rheumatoid arthritis (RA) and patients with osteoarthritis (OA), measured by enzyme-linked immunosorbent assay, were compared with levels in a healthy, age-matched non-arthritic control group, in a retrospective study. Compared with the controls, the mean level of plasma HA was sevenfold higher in the RA group and twofold higher in the OA group. There was no statistically significant correlation between HA levels and 7 other clinical and biochemical parameters in patients with RA. In the OA group, however, plasma HA levels were found to correlate with an objective functional capacity score and with an articular index based on the total amount of cartilage in involved joints. In a retrospective longitudinal study of 6 patients with RA, plasma levels of HA did not show a significant correlation with plasma levels of elastase or with the erythrocyte sedimentation rate. These data support in part the contention that plasma HA may be unique as a marker, in that it may be a reflection of synovial involvement and inflammation, rather than only of inflammation, in arthritis.

Adult↗
PubMed1991

Radial distribution of dose.

The radial distribution of dose about the path of a heavy ion, principally from delta rays, is one of the central contributions of atomic physics to the systematization of high LET radiation effects in condensed matter, whether the detection arises in chemical, physical, or biological systems. In addition to the radial distribution of dose, we require knowledge of the response of the system to X-rays or gamma-rays or to beams of energetic electrons such that the electron slowing-down spectra from these radiations can approximate the slowing-down spectra from delta rays even at different radial distances from the ion's path. A combination of these data enables us to calculate the action cross sections ion bombardments in all detectors for which this information is available. These cross sections are indispensable for the evaluation of effects caused by high LET radiations. In this paper we focus attention principally on the calculation and measurement of the radial distribution of dose and on their limitations.

Enzymes↗
PubMed1991

6-Mercaptopurine and spermatogenesis in the young rat.

In recent years, 6-MP treatment has been beneficial in the treatment of inflammatory bowel disease (IBD). Since 6-MP and its metabolites interfere with various steps in nucleic acid biosynthesis, chronic use of 6-MP could theoretically alter normal cell turnover, including spermatogenesis. Therefore, we have investigated the effect of daily 6-MP administration on spermatogenesis in the young rat. 6-Mercaptopurine was administered in clinically relevant doses 24 and 40 mg/m2. Testicular weights of rats treated with 24 mg/m2 for 75 days or 40 mg/m2 for 25 days were not significantly different among 6-MP, pair-fed, or ad libitum chow-fed groups. Quantitation of the stages of seminiferous tubules or the number of homogenization-resistant, mature spermatids per testis were not affected by 6-MP treatment. In addition, 6-MP had no effect on serum testosterone or on HCG-stimulated testosterone release by the testes. These results suggest that chronic low-dose 6-MP therapy, as used in the treatment of IBD, may not carry as great a risk for suppression of spermatogenesis as theorized. Our study in animals indicates that evaluation of 6-MP and spermatogenesis in man is warranted.

Animals↗
PubMed1991

Nature, nurture and depression: a twin study.

We studied a series of twins systematically ascertained through 214 probands (84 monozygotic, 130 dizygotic) who had had one or more episodes of hospital-treated major depression. A variety of definitions of depression were applied to the co-twins all of which resulted in (a) markedly higher rates of disorder than are found in the general population, (b) significantly higher monozygotic than dizygotic concordance. The results of applying a simple additive model in which depression is considered as a threshold trait suggested that both genetic factors and shared family environment make substantial and significant contributions to the familiality of depression.

Adult↗
PubMed1991

RBE vs. dose for low doses of high-let radiations.

According to track theory, the relative biological effectiveness (RBE) of high linear energy transfer (LET) radiations varies with cellular radiosensitivity parameters and the radiation environment. Of special interest is that the RBE varies as the dose of high-LET radiation to the power (1/m - 1) where m is the "target number" parameter, which varies from 2-4 in different cell lines. This applies to neutrons as well as to heavy ions at sufficiently low doses such that cells are not activated in the gamma-kill mode; that is, the tracks of single heavy ions are sufficiently far apart so that there are few cases of inter-track inactivation.

Cell Survival↗
PubMed1991

Reciprocal Ia inhibition between elbow flexors and extensors in the human.

1. Reciprocal inhibition between elbow flexor and extensor muscles (biceps and triceps brachii) has been investigated in nine healthy subjects. Two techniques were used to assess changes in motoneurone excitability after stimulation of antagonist muscle afferents: (1) monosynaptic reflexes elicited by a mechanical stimulation of the distal muscle tendon (tendon tap); (2) post-stimulus time histograms (PSTH) of voluntarily activated motor units. 2. Electrical stimulation of the antagonist muscle nerve produced a short-latency and short-lasting inhibition of the flexor and extensor motoneurones. The amount of this inhibition was found to be similar in both motor nuclei. 3. The inhibition could be evoked with conditioning electrical stimuli as low as 0.7 x motor threshold (MT) or by very weak tendon taps applied to the antagonist tendon. In the former case the threshold of this inhibition was found to be consistently increased after raising the threshold of Ia afferent fibres by a long-lasting muscle vibration. Since a contribution from cutaneous afferent fibres was ruled out, it is concluded that this inhibition was Ia in origin. 4. Post-stimulus time histograms of voluntarily activated triceps and biceps motor units were made following electrical stimulation of homonymous and antagonist muscle afferents. This enabled an estimate of the central synaptic delay of the inhibitory process. An average central delay of 0.94 ms in excess of that of monosynaptic facilitation was found, thus suggesting that the inhibitory process could be mediated by only one interneurone. 5. A conditioning reflex discharge elicited in the antagonist muscle by a tendon tap depressed or suppressed this inhibition. This depression was maximal when the reflex discharge was elicited 10-20 ms before the conditioning stimulus for the inhibition and never lasted more than 30 ms. It is argued that the only mechanism compatible with such a depression is the inhibitory activity of Renshaw cells acting on the pathway mediating reciprocal inhibition. 6. We conclude that group Ia afferent fibres from elbow extensor and flexor muscles project monosynaptically onto Ia inhibitory interneurones to mediate disynaptic reciprocal inhibition of antagonist motoneurones.

Adult↗
PubMed1991

Comparison of CATEGO-derived ICD-8 and DSM-III classifications using the composite international diagnostic interview in severely ill subjects.

Two classifications, DSM-III and CATEGO4-derived ICD-8, included in the CIDI, are compared in 63 in-patients and out-patients with a broad range of psychiatric illness. Agreement for main diagnosis between these classifications was statistically significant for two time frames, the present state and lifetime. However, while diagnostic assignment by CATEGO4 remained fairly constant between time frames, there was a marked shift in DSM-III-assigned diagnosis, with cases changing from anxiety state diagnosis (present state) to affective disorder (lifetime). Thirty-nine subjects were assigned a DSM-III diagnosis of affective disorder for lifetime illness compared with 21 assigned to this diagnostic group by CATEGO4.

Adolescent↗
PubMed1991

Biological effectiveness of high-energy protons: target fragmentation.

High-energy protons traversing tissue produce local sources of high-linear-energy-transfer (LET) ions through nuclear fragmentation. We examine the contribution of these target fragments to the biological effectiveness of high-energy protons using the cellular track model. The effects of secondary ions are treated in terms of the production collision density using energy-dependent parameters from a high-energy fragmentation model. Calculations for mammalian cell cultures show that at high dose, at which intertrack effects become important, protons deliver damage similar to that produced by gamma rays, and with fragmentation the relative biological effectiveness (RBE) of protons increases moderately from unity. At low dose, where sublethal damage is unimportant, the contribution from target fragments dominates, causing the proton effectiveness to be very different from that of gamma rays with a strongly fluence-dependent RBE. At high energies, the nuclear fragmentation cross sections become independent of energy. This leads to a plateau in the proton single-particle-action cross section, below 1 keV/micron, since the target fragments dominate.

Cell Survival↗
PubMed1991

Activation of MAP-2 kinase activity by the CD2 receptor in Jurkat T cells can be reversed by CD45 phosphatase.

We have recently characterized a serine kinase in T lymphocytes which phosphorylates microtubule-associated protein-2 (MAP-2) in vitro. This kinase is activated in a rapidly reversible fashion during ligation of CD3/Ti by a process which involves tyrosine phosphorylation of the enzyme itself. We show that the stimulatory anti-CD2 mAb combination, anti-(T11(2) + T11(3), stimulates MAP-2K activity in Jurkat cells with kinetics that are more prolonged than during anti-CD3 treatment. The principal difference is not in the rate of response induction, but in the decline of the response beyond the peak, to which end anti-CD2 stimulation resembles the sustained phytohaemagglutin (PHA) response. Parallel immunoblotting, utilizing anti-phosphotyrosine antibodies, also revealed differences in the rate at which tyrosine phosphorylation of pp43 (MAP-2K) disappears after induction. In spite of these differences, CD2 was absolutely dependent on the presence of CD3 for inducing a MAP-2K response in Jurkat cells. These results indicate that, even though CD2 and CD3 are using a common signalling pathway in Jurkat cells, additional differences such as the involvement of a tyrosine phosphatase may have to be considered in response generation. We also demonstrate that the common CD45 isoform, when cross-linked to CD2 by mAb, could inhibit the MAP-2K response during both induction as well as the disappearing phase of the response.

Antibodies, Monoclonal↗
PubMed1990

CD-3-mediated activation of MAP-2 kinase can be modified by ligation of the CD4 receptor. Evidence for tyrosine phosphorylation during activation of this kinase.

The CD4R has been shown to exert variable effects on T cell activation responses. Depending on the manner of ligation, the CD4R has been demonstrated to have positive as well as negative effects on the generation of [Ca2+]i flux by the CD3R. Coaggregation of CD3 with CD4 enhanced Ca2+ flux while their independent ligation and aggregation diminished this response. To further elucidate these paradoxical CD4 effects, we studied induction of a microtubule-associated protein 2 kinase (MAP-2K) activity during ligation of the CD3R. Lymphoid MAP-2K activation by CD3 is an evanescent event that is dependent on phosphorylation of 43-kDa MAP-2K via a pathway that involves protein kinase C. Coaggregation of CD4 and CD3 with cross-linking antibodies and avidin enhanced the CD3-mediated MAP-2K response almost twofold. In contrast, independent ligation and cross-linking of CD4 reduced the CD3-induced MAP-2K response by approximately 50%. An important requirement for this inhibitory effect was that CD4 be ligated before stimulation with anti-CD3. The negative effect of anti-CD4 mAb was specific as other mAb failed to simulate this event. The PMA-induced MAP-2K response was not inhibited by anti-CD4. Intact 32P-labeled Jurkat and normal human T cells demonstrated the appearance of a single 43-kDa tyrosine phosphoprotein during stimulation with PMA and anti-CD3. When these crude cellular extracts were extensively fractionated across DEAE- and hydrophobic columns, MAP-2K was resolved into two peaks of activity, each containing a single tyrosine phosphoprotein around 43 kDa. In addition to tyrosine-specific labeling, mitogenic stimulation of normal human T cells also induced threonine-specific labeling of MAP-2K. These results imply that activation of lymphoid MAP-2K is a dual process requiring at least two independent kinases for optimal activity. Inasmuch as CD3 activates protein kinase C and CD4 is associated with a tyrosine kinase, pp56lck, we suggest that their coaggregation may create the conditions whereby MAP-2K may be activated by dual phosphorylation. Independent aggregation of these receptors may lead to physical separation and breakdown of this interactive mechanism.

Adult↗
PubMed1990

Stimulation of MAP-2 kinase activity in T lymphocytes by anti-CD3 or anti-Ti monoclonal antibody is partially dependent on protein kinase C.

Signaling via the alpha-beta T cell Ag receptor (Ti)-CD3 complex is a complicated event that implicates several protein kinases, most notably protein kinase C (PKC). We have recently identified a serine kinase in T lymphocytes with the following characteristics: molecular mass 43 kDa, in vitro substrate affinity for microtubule associated protein 2 (MAP-2) with a preference for Mn2+ during the catalytic reaction, and elution from DEAE resin over a salt range 100 to 200 mM NaCl. This kinase is activated in a rapidly reversible fashion during ligation of CD3/Ti by a process which involves prior phosphorylation; in vitro exposure of activated 43-kDa MAP-2 kinase (MAP-K) to an immobilized phosphatase abrogated its kinase activity. We now show that a MAP-2K response could also be obtained during treatment with mAb to Ti and the specific PKC agonist, PMA. Although the kinetics of the former response was rapidly reversible, PMA elicited a more prolonged response. The dose responsiveness for PMA was similar to the requirements for PKC activation in intact lymphocytes. Moreover, as with PKC, we found that the CD3-induced MAP-2K response could be further enhanced by using a second layer cross-linking antibody. The specificity of CD3/Ti in the Jurkat cell response is demonstrated by the fact that OKT-11(CD2) and anti-CD4 mAb did not stimulate a MAP-2K response. It was also not possible to elicit a response in a Jurkat cell mutant that lacks surface expression of CD3 and Ti. The specificity of PKC in these events was further explored with the cell permeant diacylglycerol, 1-oleoyl-2-acetylglycerol, and the nonagonist phorbol ester, 4 alpha-phorbol 12,13-didecanoate: whereas the former was an effective inducer of the MAP-2K response, the latter failed to yield any stimulation. Prior exposure of Jurkat cells to 100 mM PMA for 24 h eliminated greater than 60% of the MAP-2K response during anti-CD3 treatment. This response could also be inhibited in dose-dependent fashion by prior treatment of Jurkat cells with the potent PKC inhibitor 1-(5-isoquinolinesulfonyl) 2-methylpiperazine dihydrochloride. Although a Ca2(+)-ionophore failed to synergize with PMA at inducing a MAP-2K response, depletion of extracellular Ca2+ by EGTA abrogated anti-CD3 responsiveness. The events culminating in MAP-2K activation were slightly inhibited in the presence of cholera toxin but not pertussis toxin.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗
PubMed1990

Does intensive medical therapy influence the outcome in unstable angina?

Three hundred and forty-six patients of all ages and both sexes were admitted to coronary care with documented unstable angina. Management was conservative, without the routine use of beta-blockers or calcium antagonists. Mortality was 3.2%, and the nonfatal myocardial infarction rate was 10.1% during the first 28 days. After one year, coronary mortality was 10.5% with a nonfatal infarction rate of 13.1%. Twenty-six patients were subjected to coronary artery bypass surgery, eleven during the first 28 days and fifteen subsequently. No patient underwent coronary angioplasty. The factors influencing immediate and long-term prognosis in these patients were studied. Persistence of pain in hospital, previous chronic angina, and age had an adverse effect on outcome. A total of 143 patients complained of persistent pain lasting for 24 hours or more. The use of beta blockers or calcium antagonists in patients with persistent pain exceeding five days did not appear to influence outcome. The current widespread adherence to "intensive medical treatment," including the routine use of beta blockers and calcium antagonists, is questioned.

Adrenergic beta-Antagonists↗
PubMed1990

Personality disorders in anorexia nervosa and bulimia nervosa.

Two self-report questionnaires (MCMI and BSI) designed to measure personality disorder (PD) according to DSM-III (R) criteria were administered to patients with a diagnosis of anorexia nervosa (AN) (n = 19), bulimia nervosa (BN) (n = 16), or both diagnoses (AN + BN) (n = 9), both before and after treatment for the eating disorder. The main finding was that self-reported Personality Disorder (PD) diagnoses are not stable enduring characteristics among this group of eating disorder patients. A high rate of PD diagnoses occurred in all patient groups at admission (93%) and at discharge (79%). Both MCMI and BSI scales were subject to significant change following treatment. A high prevalence of borderline personality disorder was found in patients with BN. Changes in depression and self-esteem scores correlated most strongly with changes in schizoid, schizotypal, histrionic and narcissistic scales. Assessment of PD using self-report measures should be interpreted with caution in acutely symptomatic patients with eating disorders.

Adolescent↗
PubMed1990

Early ribavirin treatment of respiratory syncytial viral infection in high-risk children.

A 3-year prospective, blinded, multicenter study was done to assess the efficacy of early ribavirin intervention in mild respiratory syncytial virus illness in children with bronchopulmonary dysplasia or with congenital heart disease. A cohort of 178 children younger than 36 months of age with bronchopulmonary dysplasia or congenital heart disease were followed. Forty-seven infants whose respiratory syncytial virus infection resulted in mild symptoms of less than or equal to 72 hours' duration received ribavirin (n = 20) or water placebo aerosol (n = 27) either in a hospital or at home. Outcome measures included respiratory and analog score, room air oxygen, saturation, and oxygen flow needed to maintain saturation at greater than or equal to 91%. No difference in age, gender, family size, passive smoking, baseline oxygen saturations in room air, or duration of symptoms before treatment was found between groups. After 3 days of therapy, ribavirin produced a greater rate of improvement of analog scores (p = less than or equal to 0.001), lower oxygen requirements (p = 0.01), and higher oxygen saturation (p = 0.01). Respiratory scores and total hospital days did not differ significantly between the groups. Treatment failure occurred in 2 of 20 children (10%) in the ribavirin group versus 5 of 27 children (18%) in the placebo group, a nonsignificant difference. No child required assisted ventilation or had an adverse reaction. We conclude that early ribavirin therapy may help to reduce morbidity from respiratory syncytial virus infection in high-risk young children.

Bronchopulmonary Dysplasia↗
PubMed1990

The prediction of rehabilitative success after three years. The use of social, symptom and cognitive variables.

A three-year follow-up study of 49 psychiatric patients, representative of those found in long-stay care, tested whether behavioural, symptom and demographic variables as well as response-processing difficulties could predict levels of psychiatric care. The researchers were blind to the criteria for allocating patients to particular forms of care and the staff responsible for care had no access to information collected by the research team. Not only was it possible, using only these few factors, to predict the form of care, but one factor, response processing, was related to whether patients moved to more independent forms of psychiatric care.

Achievement↗