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Biomedical subjects

A Katz

Publications and source records attributed to A Katz.

At least 199 records · Page 11Linked to original sources

Growth and differentiation of the human megakaryoblastic cell line (ELF-153): a model for early stages of megakaryocytopoiesis.

ELF-153 is a cell line that has been established from a patient with a poorly differentiated acute myeloid leukemia associated with an acute myelofibrosis. A majority of cells had a blast morphology with the phenotype of a myeloid hematopoietic progenitor, ie, CD34+, CD33+, CD13+, HLA-DR+, but CD38-, and the remaining cells (5% to 10%) expressed platelet restricted proteins such as CD41, CD42, CD36, CD61, and von Willebrand factor; some of them were polyploid (up to 32N) and exhibited demarcation membranes and alpha granules. No erythroid or other lineage-specific markers were detected. Proliferation of ELF-153 cells was highly stimulated by interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor and to a lesser extent by stem cell factor and IL-6. In contrast, the cell line did not respond to erythropoietin, leukemia inhibitory factor, IL-7, IL-11, granulocyte colony-stimulating factor, and basic fibroblast growth factor. ELF-153 cells could be separated by flow cytometry into three discrete cell populations (CD34+/CD61-, CD34+/CD61+, and CD34-/CD61+) with different proliferative and endomitotic properties corresponding to distinct stages of the mega karyocyte (MK) differentiation. This MK differentiation, which involved a minority of ELF-153, could be increased in the presence of 5-azacytidine and phorbol ester, but could not be significantly modified by growth factors. By contrast, cytochalasin B dramatically induced polyploidization without differentiation. It is noteworthy that association of 5-azacytidine to cytochalasin B dramatically induced the production of polyploid MK cells. To understand the molecular mechanisms underlying this MK differentiation, the expression of GATA-1 and GATA-2 was investigated in subpopulations of ELF-153. A high level of GATA-1 and GATA-2 mRNA was only present in the CD61+ cells. Therefore, these two transactivating factors may play an important role in the MK differentiation of ELF-153. We conclude that ELF-153 might be an important tool to investigate the mechanisms by which transcription factors control differentiation of MK progenitors.

Acute Disease↗

Utilization of amiloride analogs for characterization and labeling of the plasma membrane Na+/H+ antiporter from Dunaliella salina.

The interactions of amiloride analogs with the Na+/H+ antiporter from plasma membrane of the halotolerant alga Dunaliella salina [Katz et al. (1989) Biochem. Biophys. Acta 983, 9-14] have been investigated. Analogs bearing hydrophobic substitutions at the guanidino moiety of amiloride, such as benzamil, are the most effective inhibitors of Na+ uptake in plasma membrane vesicles, whereas substituents of the 5-amino group are less effective inhibitors than amiloride. This order of specificity is opposite to that found for most Na+/H+ antiporters. The photoaffinity amiloride analog 2'-methoxy-5'-nitrobenzamil (NMBA), a competitive inhibitor with respect to Na+ with Ki = 10 microM, photolabels upon illumination two polypeptides of apparent MW 30 and 50 kDa in purified plasma membrane vesicles. Similar labeling is obtained by immunodetection with antiamiloride antibodies and by incorporation of [125I]NMBA. The specificity of the labeling was ascertained by competition with benzamil. Plasma membrane preparations from high-salt or ammonia-adapted cells, which have higher Na+/H+ antiporter activity [Katz et al. (1992) Plant Physiol. 100, 1224-1229], also show increased incorporation of NMBA into the 30- and 50-kDa polypeptides. It is suggested that: (1) the structure of the Na+ binding site of the D. salina Na+/H+ antiporter differs from that of most Na+/H+ antiporters and (2) the 50- and/or 30-kDa polypeptides are subunits of the plasma membrane antiporter of this alga.

Amiloride↗

Influence of gender in the therapeutic management of patients with acute myocardial infarction in Israel. The Israeli Thrombolytic Survey Group.

A national study was performed in early 1992 in the 25 operating coronary care units in Israel, which enabled the assessment of whether the therapeutic management of patients with acute myocardial infarction was affected by patient gender. During a 2-month period, 1,014 consecutive patients with acute myocardial infarction were hospitalized. Thrombolytic therapy was given to 47% of men (362 of 769), and 43% of women (106 of 245) (p = NS). After adjustment for age, no gender differences in the administration of thrombolytic therapy were noted (odds ratio 0.95; 95% confidence interval 0.73-1.23). Coronary angiography was more frequently performed in men (22%) than in women (16%) (p < 0.05). However, no gender differences in the use of angioplasty or coronary bypass surgery performed during the index hospitalization were found (10% in men, and 8% in women). The main reasons for ineligibility for thrombolytic therapy were: late hospital arrival, absence of qualifying ST-T changes on admission electrocardiogram, and contraindications to thrombolytic therapy. Hospital death was significantly lower in patients receiving thrombolytic therapy (37 of 456; 8%) than in those excluded from thrombolysis (70 of 540;13%) (p < 0.01). This difference was significant for men, but not for women. The 1-year postdischarge mortality was 4% in patients treated compared with 12% in those ineligible for thrombolysis (p < 0.01). This significant difference persisted among men and women.

Aged↗

Apical seal using the GPII method in straight canals compared with lateral condensation, with or without sealer.

The purpose of this study was to test the apical seal provided by a recently introduced low-fusing gutta-percha, GPII, compared with lateral condensation, with or without a sealer. For this study, 84 roots with straight circular canals separated from extracted teeth were prepared to K-file size 45. A standardized gutta-percha master cone was fitted to 80 of these roots. The roots were then randomly separated into four groups of 20 each and filled with GPII or laterally condensed gutta-percha, with or without AH26 sealer. The roots were immersed in India ink, subjected to vaccuum for 2 hours and kept in the marker for 4 days for the study of apical leakage. Four unfilled roots served as an experimental control. The teeth were demineralized, cleared in methyl salicylate and examined with a stereomicroscope. When no sealer was used, 12 roots filled with GPII leaked from 0 to 2.5 mm and in the lateral condensation group ink penetrated from 0 to 6 mm in 14 roots (difference not significant at the 0.05 level). None of the specimens in which sealer was used showed any penetration of ink beyond the end of the preparation of the canal regardless of the filling technique.

Bismuth↗

Treatment of sickle cell trait hematuria with oral urea.

Unilateral hematuria is a vaso-occlusive complication of the sickle syndromes, especially the sickle cell trait. Treatment is usually ineffective, and the duration is variable, often prolonged and subject to recurrences. In sickle cell trait hematuria is usually the only consequence of sickling, possibly because the unique renal countercurrent mechanism may result in a milieu more prone to sickling in the medullary circulation than in the vasculature of other organs. Urea in vitro inhibits gelation of deoxygenated sickle hemoglobin. In 2 previously reported cases of sickle cell trait hematuria ceased within 3 days with oral urea therapy. We describe another such patient in whom hematuria also ceased by day 3 with oral urea. Although clinical trails with intravenous urea were ineffective in shortening the course of sickle crisis, urea may have an enhanced effectiveness in the renal medulla where the propensity for sickling may be much greater than in other organs. If these observations are confirmed in a controlled study, oral urea therapy would emerge as an effective, relatively innocuous and inexpensive treatment for this frustrating condition.

Administration, Oral↗

Chronic nephrotoxicity in psoriatic patients treated with low-dose cyclosporine.

Chronic nephrotoxicity is a major complication in high-dose cyclosporine treatment. We examined the glomerular filtration rate, renal plasma flow, and kidney biopsies of 15 psoriatic patients treated with low-dose cyclosporine (< or = 5 mg/kg/d) for 30 months (25 to 35 months) 1 month after drug withdrawal. The mean (95% confidence interval) age of the patients in the study was 44 years (38 to 50 years). Their serum creatinine levels pretreatment and at the time of the study were 0.94 mg/dL (0.85 to 1.0 mg/dL) and 1.2 mg/dL (1.1 to 1.3 mg/dL). Seven patients had a decreased glomerular filtration rate and four of them also had a reduced renal plasma flow, below the 2.5 percentile of normal. Four patients had moderate tubulointerstitial scarring and arteriolopathy, while the remaining patients had mild structural abnormalities. The severity of acute nephrotoxicity during treatment and chronic structural injury were highly correlated (r = 0.81; P < 0.0003). Recurrent episodes of severe acute nephrotoxicity (defined as reversible increase of serum creatinine > 90% of baseline value) was a marker for moderate chronic nephrotoxicity. No correlation was found between chronic structural injury and patient age, sex, pretreatment creatinine level, blood pressure (pretreatment or during treatment), cyclosporine dose and treatment duration, and cyclosporine blood levels. In seven patients continued on cyclosporine for another 12 months (10 to 14 months), repeat studies showed no interval changes. Despite 40 months (30 to 51 months) of treatment, all but one of these seven patients (with previous hypertension and atherosclerotic vascular disease) had mild functional and structural abnormalities. None had any severe acute nephrotoxicity at any time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Laparoscopic-assisted vaginal hysterectomy: a case control comparative study with total abdominal hysterectomy.

We compared laparoscopic-assisted vaginal hysterectomy (LAVH) with total abdominal hysterectomy (TAH) in a case control study that evaluated length of operation, blood loss, length of hospital stay, drug requirements for pain, and postoperative pain and activity levels. Of 81 women who underwent nonradical hysterectomy for a primary diagnosis of pelvic pain between June 1 and December 31, 1992, 19 who underwent each procedure were chosen for inclusion in the study. Patients were matched in a case control manner with age, weight, diagnosis, and uterine weight. All 38 hysterectomies were completed without incident. When indicated, unilateral or bilateral oophorectomies were performed. The average surgery time for LAVH was 144 minutes and for TAH 98 minutes, a significant difference (p <0. 005). There were no significant differences between estimated blood loss and change in hemoglobin from preoperative levels to postoperative day 1 levels between the groups. Women having TAH reported significantly more pain after their release from the hospital. There was no significant difference in pain during hospitalization apparently because patients who had TAH self-medicated to maintain acceptable levels. That group in fact used an average of 436 mg meperidine during their hospital stay, significantly more than the 197 mg used by the LAVH group (p <0.005). The length of stay was 2.125 days for LAVH and 3.542 days for TAH (p <0.001). On a scale of 1 to 10 (10 being complete normal activity) the activity level of women undergoing LAVH was 9.2 by day 14 compared with 6.4 for those having TAH (p <0.005). By the sixth postoperative week the latter group reported an activity level of only 8.5, indicating that the ability to function is much more severely limited after TAH than LAVH.

Adult↗

Laparoscopic-Assisted Vaginal Hysterectomy: A Case Control Comparative Study with Abdominal Hysterectomy

A case control study of the operative time, blood loss, time for return to work, pain levels, and medications was conducted comparing laparoscopic-assisted vaginal hysterectomies (LAVH) with total abdominal hysterectomy (TAH). The average operating time for LAVH was 151 minutes whereas for TAH it was 99 minutes (P<.01). The average length of stay for the LAVH was 2.5 days and for the abdominal hysterectomy it was 3.5 days (P<.01). During hospitalization the LAVH group required an average of 180 mg of meperidine while the TAH group required 414 mg of meperidine (P<.01). Patients undergoing LAVH reported activity levels of 9.2 on a scale of 1 to 10, with 10 being unlimited activity, by day 14. Abdominal hysterectomy patients' activity was reported as only 6.4 on the same scale (P<.005). The LAVH group, although requiring more operating time, made a more rapid recovery, and less pain medication, and required shorter hospitalization than the TAH group.

Journal Article↗

Direct measurement of extracellular lactate in the human hippocampus during spontaneous seizures.

The effect of clinical, spontaneous-onset seizures on extracellular fluid lactate was investigated by the method of lactography, the in vivo on-line measurement of lactate levels using microdialysis. Studies of experimental animals have suggested that generation of extracellular lactate as measured by microdialysis is an index of local glucose utilization and is dependent on the activity of neurons under physiological conditions. Patients with medically refractory complex partial epilepsy underwent stereotactic implantation of combination depth electrode/microdialysis probes into both hippocampi for 7-16 days. During spontaneous complex partial seizures with secondary generalization, extracellular lactate levels rose by 91 +/- 32%. Moreover, this increase persisted for 60-90 min. During a unilateral hippocampal seizure that did not propagate to the contralateral hippocampus, the increase in lactate content was restricted to the side of seizure activity. Between seizures, extracellular lactate levels correlated with the frequency of interictal spikes. In summary, these data suggest that brief clinical seizures increase nonoxidative glucose metabolism significantly as measured by the generation of extracellular lactate. Furthermore, the increase in extracellular lactate levels is limited to the site of seizure activity. Lactate is transported extracellularly via a lactate/proton cotransporter, therefore, the rise in extracellular lactate level may mediate the drop in pH0 associated with seizure activity. As acidification of the extracellular compartment has an inhibitory effect on neuronal excitability, the rise in extracellular lactate content may be a mechanism of seizure arrest and postictal refractoriness. Moreover, extracellular lactate may also mediate the decreased seizure susceptibility associated with frequent interictal spikes.

Adolescent↗

Volatile anesthetic effects on sarcoplasmic reticulum Ca content and sarcolemmal Ca flux in isolated rat cardiac cell suspensions.

BACKGROUND: Cardiac cellular Ca metabolism is central to the control of the inotropic state of the heart and is altered in various ways by the volatile anesthetics halothane, enflurane and isoflurane. Specifically, differences among the agents regarding their effect on the uptake and release of Ca from the sarcoplasmic reticulum (SR) have been found, but the nature of such differences is not yet certain. At the sarcolemma, the effects of the anesthetics on the peak Ca current generally are believed to be similar among the three agents, but their impact on other aspects of sarcolemmal Ca transport is less understood. The authors sought to measure the direct action of these agents on SR Ca content and, in the same preparation, to provide a measure of Ca transfer across the sarcolemma during sustained depolarizations. METHODS: In stirred suspensions of quiescent rat cardiac cells, the effects were measured of halothane, enflurane, and isoflurane on changes in quin2Ca fluorescence produced by the addition of caffeine (10 mM) and by depolarization with increased extracellular K+. The peak of the fluorescence response to caffeine, which is due to a sudden release of Ca from the SR into the cytoplasm, was used as an index of SR Ca content. Analysis of the fluorescence increase that occurred after increasing extracellular K+ from 5 mM to 30 mM in the presence of caffeine provided a measure of net Ca influx across the sarcolemma during sustained depolarizations. RESULTS: The Ca channel blocker nitrendipine maximally inhibited 77% of the initial net Ca influx during 30 mM K+ depolarization, indicating that most of this influx involves L-type Ca channels. Of the volatile anesthetics, isoflurane (2.6 vol% or 0.57 mM) and enflurane (4.3 vol% or 1.25 mM) inhibited initial net Ca influx during K depolarization significantly more than halothane (1.7 vol% or 0.50 mM), which had no apparent effect. Isoflurane caused no transient change in cytoplasmic Ca concentration and had no effect on the SR Ca content of these quiescent cells. Enflurane (4.3 vol%) caused a significant reduction in SR Ca content. CONCLUSIONS: As previously reported, halothane depleted the SR of Ca in quiescent rat cardiac cells, and the present results indicate that enflurane had a similar effect. However, isoflurane did not produce any SR Ca depletion and thus must not significantly alter the balance between SR Ca efflux and uptake in these quiescent cells. The different effects of the three volatile anesthetics on a Ca influx largely carried by L-type Ca channels stand in contrast to the reported findings of similar inhibition of peak L-channel current among the three agents. This result may indicate a differential action (at least in the case of halothane) on peak and steady-state Ca currents.

Animals↗

Clinical evaluation of a new single pass lead VDD pacing system.

UNLABELLED: Twenty-five patients with second- to third-degree AV block and normal sinus function (16 males, mean age 60 +/- 18; range 15-78 years) underwent implantation of VVD pacemakers (THERA VDD, Medtronic, Inc.) with a single pass (SP) lead. RESULTS: During implantation the mean amplitude of the atrial (A) signal was 3.9 +/- 1.4 mV (range 2.0-7.8 mV). Stable, acceptable A-signals during implantation were usually observed in the mid- or lower part of the right atrium. The lead tip electrical parameters were not compromised in any patient in order to obtain an acceptable A-signal. To verify VDD device function, patients underwent pacing system analysis on the second day and again 1, 3, and 6 months after implantation. Acute and chronic electrical measurements in the ventricle were similar to those with regular steroid leads. During follow-up tests, stable atrial sensing (A > or = 0.7 mV) was found in all but one patient (in whom A was 0.25-0.5 mV and an intermittent loss of atrial sensing occurred). There was no difference between serial measurements of A-signal amplitudes on the second day or 1, 3, and 6 months after implantation: 1.9 +/- 1.3 mV, 1.5 +/- 0.6 mV, 1.3 +/- 0.8 mV, and 1.5 +/- 1.1 mV, respectively. The mean implantation time was 54.0 +/- 17 minutes and the mean fluoroscopy time was 3.2 +/- 1.3 minutes. CONCLUSIONS: SP lead VDD pacing is reliable and easy to manage with dependable atrial sensing and ventricular pacing.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Initial experience with a new algorithm for automatic mode switching from DDDR to DDIR mode.

UNLABELLED: Implantation of dual chamber devices in patients with paroxysmal atrial tachyarrhythmias who require permanent pacemakers may lead to significant complications due to an inappropriately triggered ventricular response. VVI/VVIR units cause loss of AV synchrony in the presence of sinus activity. A new DDDR device (THERA DR, model 7940), with an automatic mode switching (AMS) algorithm, was evaluated. When the mean atrial rate is > 182 beats/min, atrial tachyarrhythmia is detected, and AMS is activated. Twenty-three patients (12 males, mean age 71 +/- 7 years) underwent implantation of a THERA DDDR device with the AMS algorithm. Seventeen patients had AV block and/or sick sinus syndrome (SSS) and atrial arrhythmias, and 6 patients (2 with hypertrophic obstructive cardiomyopathy) had SSS and paroxysmal atrial fibrillation (PAF). The follow-up period was from 1-9 months. During follow-up, Holter monitoring and treadmill tests were performed. RESULTS: Eighty-seven episodes of AMS were recorded. Telemetered AMS recordings demonstrated episodes in which the DDDR mode switched to the DDIR mode in the presence of PAF, and reverted to DDDR when sinus rhythm returned. Paroxysmal supraventricular arrhythmias with a heart rate < 182 beats/min did not activate the mode switch. CONCLUSIONS: This early, short-term clinical experience with a DDDR device capable of AMS from DDDR to DDIR demonstrated appropriate clinical function and response to PAF. These preliminary results suggest that DDDR pacemakers with AMS to DDIR may significantly extend the current indications for dual chamber pacing.

Aged↗

Hexokinase kinetics in human skeletal muscle after hyperinsulinaemia, hyperglycaemia and hyperepinephrinaemia.

The effects of 120 min of euglycaemic hyperinsulinaemia (UH, approximately 5 mM; 40 mU m-2 min-1), UH plus adrenaline infusion (0.05 microgram kg-1 min-1), and hyperglycaemic normoinsulinaemia (26 mM) on hexokinase kinetics in human skeletal muscle were examined. Biopsies were obtained from the quadriceps femoris muscle before and after each clamp. Total muscle hexokinase activity (HKt) (measured on a 2500 g supernatant) at a saturating level of the substrate glucose (1 mM) averaged 13 mmol kg dry wt-1 min-1 in the basal state and did not change significantly under any condition. Soluble hexokinase activity (HKs) (16,000 g supernatant) accounted for approximately 65% of HKt in the basal state, and this percentage was not significantly affected by any condition, suggesting that there was no major transfer of HK between cytosol and mitochondria. The activity of HKt and HKs was inhibited by glucose 1,6-bisphosphate (G-1,6-P2) in a concentration dependent manner in the basal state, and the sensitivity to G1,6-P2 inhibition was not altered by any condition. The activity of HKt and HKs in the presence of a subsaturating level of glucose (0.1 mM) accounted for approximately 70% of the activity at 1 mM glucose, and this percentage was not altered by any condition. These data suggest that under the present conditions alterations in the rates of whole body glucose disposal cannot be associated with alterations in HK distribution between cellular compartments nor its measured kinetics properties.

Epinephrine↗

Antimitochondrial antibody negative primary biliary cirrhosis: a distinct syndrome of autoimmune cholangitis.

This study reports on a group of 20 patients with an initial diagnosis of primary biliary cirrhosis (PBC) whose serum tested negative for antimitochondrial antibodies by immunofluorescence. All had a clinical history compatible with primary biliary cirrhosis, and results of biochemical, histological, and radiological investigations were consistent with this diagnosis despite the absence of antimitochondrial antibodies by immunofluorescence. For comparison, these patients were matched for sex and serum bilirubin with 20 antimitochondrial antibody positive (> 1:160) and histologically confirmed primary biliary cirrhosis patients who served as controls. Serum samples from both groups were retested blindly for antimitochondrial antibodies using immunoblotting and for antibodies to the major M2 mitochondrial autoantigens by enzyme linked immunosorbent assay (ELISA). Three antimitochondrial antibody immunofluorescence negative patients had antimitochondrial antibodies by immunoblotting and ELISA; the remaining 17 patients were confirmed negative by all methods. The antimitochondrial antibody immunofluorescence positive controls were verified by immunoblotting or ELISA, or both. All 17 patients negative for antimitochondrial antibodies had antinuclear antibodies, often in high titres, compared with 3/17 of the antimitochondrial antibody positive controls (p = 0.0001). Additionally, the antimitochondrial antibody negative group also had significantly higher smooth muscle antibody titres (p = 0.03) and lower serum IgM (p = 0.01) and aspartate aminotransferase (p = 0.03) activities than the antimitochondrial antibody positive controls. Analysis of clinical findings, histological tests, serum bilirubin, alkaline phosphatase, alanine aminotransferase, and IgG, disclosed no significant differences between the two groups. This paper describes a group of patients with the clinical and histological features of PBC but who do not fulfil the usual criteria necessary to make this diagnosis. Because they also have very high titres of antinuclear antibodies, smooth muscle antibodies, and comparatively low IgM and aspartate aminotransferase activities, we believe they are distinct from PBC and have a syndrome of autoimmune cholangitis.

Adult↗

IgG heavy-chain deposition disease.

A 51-yr-old man presented with renal failure, proteinuria, hematuria, and hypertension. The serum contained two monoclonal protein spikes, an IgG4 lambda and free lambda light chains. Free gamma heavy chains were absent from serum. A bone marrow biopsy did not show evidence of a plasmalymphocytic dyscrasia. Renal biopsy showed a nodular glomerulopathy with linear deposits of gamma 4 heavy chains alone along glomerular, tubular, and vascular basement membranes and in mesangial regions. No light chains were detected in the kidney despite staining with antisera directed against both free and bound light chains and the F(ab')2 fragment of IgG. The term heavy-chain deposition disease is appropriate in view of the above features.

Heavy Chain Disease↗

Entactin/nidogen: synthesis by bovine corneal endothelial cells and distribution in the human cornea.

PURPOSE: The purposes of this study were to determine whether entactin/nidogen (E/N) is synthesized and secreted by corneal endothelial cells and to characterize the distribution of E/N in the human cornea. METHODS: Cultured bovine corneal endothelial cells were metabolically labeled with [35S]methionine. Newly synthesized E/N was detected in cell lysates and culture medium by immunoprecipitation, using monoclonal anti-E/N antibodies, polyacrylamide gel electrophoresis, and autoradiography. The presence of E/N in the subendothelial extracellular matrix was demonstrated by Western blot analysis of solubilized extracellular matrix proteins. The distribution of E/N in normal human corneas was studied by indirect immunofluorescent staining of frozen sections, using monospecific anti-E/N antibodies. RESULTS: E/N was detected in the basement membrane (BM)-like extracellular matrix deposited by corneal endothelial cells, as well as in cell lysates and culture medium. Immunofluorescence studies revealed the presence of E/N in both the epithelial and endothelial BM and to a much lower extent in the stroma. E/N was detected throughout the thickness of the epithelial BM, but its staining decreased in intensity toward the central part of the cornea. In the endothelial BM (Descemet's membrane), E/N fluorescence was limited to its most posterior portion, produced postnatally. CONCLUSIONS: Corneal endothelial cells synthesize and secrete E/N, E/N was found in both the epithelial and endothelial basement membranes but was primarily localized to the posterior portion of Descemet's membrane and the periphery of the epithelial BM. The authors suggest that E/N may be important in healing processes of corneal injuries and in the pathogenesis of diseases involving the postnatal region of Descemet's membrane.

Animals↗