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Biomedical subjects

A Katz

Publications and source records attributed to A Katz.

At least 271 records · Page 15Linked to original sources
PubMed1991

In vitro effects of hematopoietic growth factors on the proliferation, endoreplication, and maturation of human megakaryocytes.

A liquid culture technique was used to study regulation of human megakaryocytopoiesis in vitro. Low-density cells from adult bone marrow were cultured in the presence of normal plasma, plasma from patients with aplastic marrows (AP), recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and interleukin-3 (IL-3). Megakaryocytes (MK) were studied at day 10 of culture by a two-color staining technique using a pool of monoclonal antibodies for their identification and propidium iodide to label DNA. Their ploidy distribution was analyzed by flow cytometry. In some experiments cytoplasmic maturation was also studied by ultrastructural techniques. Normal plasma provides a low number of MK with a ploidy distribution including 8 N and 16 N MK. AP promoted in a dose-dependent manner proliferation of MK and some batches favored endoreplication. This effect was clearly demonstrated when ploidy distribution was compared between normal plasma and AP on parallel marrow cultures. However, ploidy distribution was shifted toward low values compared with uncultured MK. rhGM-CSF had no significant effect on these two parameters. In contrast, rhIL-3 from 0.1 U/mL to 100 U/mL had a proliferative effect but was unable to induce endoreplication. Furthermore, when associated with AP it totally abrogated the effect of AP on endoreplication because in most experiments more than 90% of MK were 2 N and 4 N. This effect was also observed when rhIL-3 was added after 7 days of culture (when it has little proliferative effects). Studies of the maturation of MK grown with rhIL-3 indicate that the majority were small mature cells synthesizing alpha-granules and demarcation membranes. The effect of AP on MK proliferation and endoreplication was not related to IL-6 because its IL-6 content was identical to that of normal plasma and its neutralization did not modify these parameters. In conclusion, this study indicates that liquid culture technique in association with flow cytometry could be a powerful tool in identifying the humoral regulators of human megakaryocytopoiesis.

Anemia, Aplastic↗
PubMed1991

Variations in blood supply to the anterior interventricular septum: incidence and possible clinical importance.

The variations of the blood supply to the anterior interventricular septum in a series of 1,089 patients are described. Special attention has been given to variations and frequency of occurrence of the septal perforators originating from the left anterior descending artery. These variations may have clinical significance in this era of coronary angioplasty and coronary bypass surgery.

Coronary Angiography↗
PubMed1991

Does interictal spiking change prior to seizures?

We studied 10 patients with intractable epilepsy being evaluated for epilepsy surgery for preictal changes in spiking. All patients were implanted with intracranial electrodes and underwent continuous EEG/audiovisual monitoring. Interictal spikes were detected and recorded continuously by a dedicated computerized system. Edited spikes were counted during 0-5, 5-10, and 0-60 min epochs before each seizure, during epochs of unvarying state of arousal (awake or sleep stage II). When comparing by repeated measures, 1-way ANOVA, total spiking (in all recording channels) did not differ among the different preictal epochs (0-5, 5-10, 0-60 min) in 45 seizures (F = 0.88, P = 0.40, using the Geisser-Greenhouse adjustment--GGA). Likewise, no significant differences were obtained during those same epochs when comparing spiking originating from the channel of seizure onset in 5 patients with 28 seizures of localized onset (F = 1.19, P = 0.38 using the GGA). Our findings indicate that in patients with intractable epilepsy, no changes in spiking occur in the 5 min prior to seizures, when compared to more distant preictal epochs.

Action Potentials↗
PubMed1991

Tooth length determination: a review.

Tooth length determination is a crucial step in endodontic treatment. Until the late 1970s, tooth length determination was based mainly on radiographic interpretation. The advent of apex locators, which identify the difference in the electrical resistance between the root canal and the periodontal membrane, ushered in a new era for measuring tooth length. However, the accuracy of these devices has been questioned. Pertinent literature is discussed with the aim of providing information on the development of the concept, techniques, and devices for tooth length determination.

Dental Pulp Cavity↗
PubMed1991

Transesophageal electrocardiography using a temporary pacing balloon-tipped electrode in acute cardiac care.

STUDY OBJECTIVE: The study was undertaken to determine the feasibility of obtaining esophageal ECGs using resterilized 3F temporary pacing balloon-inflated electrodes in place of the more expensive pill-electrode and its associated expensive preamplifier. SETTING: Tests were conducted in the emergency department and ICU. TYPE OF PARTICIPANTS: Subjects were 12 acutely ill patients for whom standard 12-lead surface ECGs were insufficient to afford accurate, immediate arrhythmia diagnosis. INTERVENTIONS: Reasonable quality esophageal ECGs were obtained by use of the electrodes, generally with minimal patient discomfort. The test never required more than ten minutes. Of the 12 patients who participated in this preliminary study, esophageal ECGs enabled definitive diagnoses to be made in ten cases. CONCLUSION: The use of resterilized temporary pacing balloon-inflated electrodes enables esophageal ECGs to be obtained in an acute care setting.

Arrhythmias, Cardiac↗
PubMed1991

Renal entactin (nidogen): isolation, characterization and tissue distribution.

Entactin/nidogen (E/N) was isolated from bovine renal tubular basement membrane. Apparent molecular weight, amino acid composition, and molecular configuration by electron microscopy rotary shadowing were similar to that of nidogen from EHS mouse tumor. The identity of bovine E/N was confirmed using a thrombin derived peptide, the sequence of which corresponded to a region within mouse and human E/N. Monoclonal and polyclonal anti-E/N antibodies were used to determine the distribution of E/N in human kidney by immunofluorescent and immunoelectron microscopy. E/N was present in all renal basement membranes and was distributed through the full width of the glomerular basement membrane (GBM) with accentuation along its epithelial aspects. E/N distribution was similar to that of novel collagen chain alpha 3(IV) NC domain in the GBM. In the mesangium, E/N was distributed mainly in the peripheral mesangial region that is bounded by the GBM, while classical collagen chain alpha 1(IV) NC as present diffusely throughout the mesangium. In the developing nephron, E/N was present in basement membranes of the ureteric bud, primitive vesicle and S-form. In all instances, E/N co-localized with laminin B2 chain. Prominent E/N detection within the mesangium was observed in diseases where mesangial expansion was present. This process was also seen in early diabetic nephropathy, but disappeared with disease progression. However, all thickened diabetic renal basement membranes showed an increase in E/N which was also present in Kimmelstiel-Wilson lesions. E/N was observed in the GBM "spikes" of membranous glomerulonephritis and in epithelial crescents associated with various disorders. The association between E/N, laminin and type IV collagen chains observed in the normal kidney were maintained in disorders with altered E/N distribution. We could not detect any changes in the distribution of E/N in other acquired and hereditary kidney diseases. These observations reflect the involvement of E/N in the structure and disease alteration of renal basement membranes and mesangial matrix.

Amino Acid Sequence↗
PubMed1991

Distribution of tubulointerstitial nephritis antigen and evidence for multiple forms.

A monoclonal antibody (A8) to a basement membrane component (TIN antigen), which is associated with autoimmune tubulointerstitial nephritis, was developed and utilized to characterize tissue distribution and properties of TIN antigen by immunofluorescence microscopy and immunoblotting. Results were confirmed with polyclonal goat anti-rabbit and human autoantibodies. TIN antigen was found in basement membranes of kidney cortex, small intestines, skin, and cornea, but was not detected in the renal medulla. Within the kidney cortex proximal tubular basement membrane (TBM) showed the strongest staining. TIN antigen was also detected in Bowman's capsule, distal TBM, peritubular capillaries, and focally in the interstitium, but not in glomerular basement membrane or mesangial matrix. Immunoblotting of SDS-extracted human, rabbit, mouse, and Brown Norway rat TBM with A8 revealed predominantly a 58 kD TIN antigen; however, other reactive components were detected in minor quantities. Bovine TBM contained components of 52 kD, 45 kD and 35 kD in varying concentrations. Immunoblotting of isolated rabbit TIN antigen revealed the major 58 kD component that was characterized previously, and minor components of 300 kD, 175 kD, 160 kD and 50 kD. TIN antigen was not detected in Lewis rat TBM by immunofluorescence or immunoblotting. These studies suggest the following: 1) TIN antigen may be synthesized as a high molecular weight glycoprotein that is processed to smaller forms; 2) it may be covalently associated with other basement membrane components; 3) the antibody reactive epitope may be present on multiple TBM components; and 4) high molecular weight forms may represent aggregates of TIN antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Phase II trial of etoposide (V), adriamycin (A), and cisplatinum (P) in patients with metastatic gastric cancer.

The efficacy and toxicity of a combination of etoposide (100 mg/m2 i.v. on days 1 to 3), Adriamycin (20 mg/m2 i.v. on days 1 and 8) and cisplatinum (40 mg/m2 i.v. on days 2 and 8) repeated every 4 weeks as an outpatient regimen were assessed in 29 consecutive patients with metastatic gastric cancer with measurable disease. Five of these patients were refractory to 5-Fluorouracil, Adriamycin, and Mitomycin C. Three of these previously treated patients responded to the etoposide. Adriamycin, cisplatinum (VAP) therapy. An overall objective response rate of 72.5% was achieved, including 14% that were complete responses. The median duration of response was 6.0 months; median overall survival was 7.2 months, overall one-year survival was 34.4%. Hematologic toxicity was intense, particularly among patients with lower performance status. Three patients died as a consequence of nadir sepsis episodes.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

In Vivo pH Regulation by a Na/H Antiporter in the Halotolerant Alga Dunaliella salina.

Na(+)/H(+) exchange activity in whole cells of the halotolerant alga Dunaliella salina can be elicited by intracellular acidification due to addition of weak acids at appropriate external pH. The changes in both intracellular pH and Na(+) were followed. Following a mild intracellular acidification, intracellular Na(+) content increased dramatically and then decreased. We interpret the phase of Na(+) influx as due to the activation of the plasma membrane Na(+)/H(+) antiporter and the phase of Na(+) efflux as due to an active Na(+) extrusion process. The following observations are in agreement with this interpretation: (a) the Na(+) influx phase was sensitive to Li(+), which is an inhibitor of the Na(+)/H(+) antiporter, did not require energy, and was insensitive to vanadate; (b) the Na(+) efflux phase is energy-dependent and sensitive to the plasma membrane ATPase inhibitor, vanadate. Following intracellular acidification, a drastic decrease in the intracellular ATP content is observed that is reversed when the cells regain their neutral pH value. We suggest that the intracellular acidification-induced change in the internal Na(+) concentration is due to a combination of Na(+) uptake via the Na(+)/H(+) antiporter and an active, ATPase-dependent, Na(+) extrusion. The Na(+)/H(+) antiporter seems, therefore, to play a principal role in internal pH regulation in Dunaliella.

Journal Article↗
PubMed1991

Carbohydrate supplementation attenuates IMP accumulation in human muscle during prolonged exercise.

The effect of carbohydrate (CHO) ingestion on metabolic responses to exercise has been investigated. Subjects cycled at approximately 70% of maximal oxygen uptake to fatigue [135 +/- 17 (+/- SE) min] on the first occasion (control, CON) and at the same work load and duration on the second occasion but with addition of ingestion of CHO during the exercise. Biopsies were taken from the quadriceps femoris muscle before and after exercise. The sum of the hexose monophosphates (HMP), as well as lactate and alanine, in muscle was higher after CHO exercise (P less than or equal to 0.05, P less than or equal to 0.05, and P less than or equal to 0.01, respectively). Acetylcarnitine increased during exercise but was not significantly different between treatments after exercise (CON, 6.6 +/- 1.7; CHO, 10.0 +/- 1.2 mmol/kg dry wt; P = NS). The sum of the tricarboxylic acid cycle intermediates (TCAI; citrate + malate + fumarate) was increased during exercise and was higher after CHO exercise (2.34 +/- 0.32 vs. 1.68 +/- 0.17 mmol/kg dry wt; P less than or equal to 0.05). IMP was less than 0.1 mmol/kg dry wt at rest and increased to 0.77 +/- 0.26 (CON) and 0.29 +/- 0.11 mmol/kg dry wt (CHO) (P less than or equal to 0.05) during exercise. It was recently found that during prolonged exercise there is initially a rapid and large expansion of TCAI and glycogenolytic intermediates in human muscle followed by a continuous decline in TCAI and glycogenolytic intermediates [K. Sahlin, A. Katz, and S. Broberg. Am. J. Physiol. 259 (Cell Physiol. 28): C834-C841, 1990].(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Regulation of glucose utilization in human skeletal muscle during moderate dynamic exercise.

The effect of bicycle exercise (75% of maximal oxygen uptake) on glucose uptake by the inferior limb (LGU) and glycolysis in human skeletal muscle has been investigated. Biopsies were obtained from the quadriceps femoris muscle before exercise, after 5 and 40 min of exercise, and at fatigue [74.9 +/- 4.7 (SE) min]. LGU was 0.05 +/- 0.02 mmol/min at rest, increased approximately sevenfold after 5 min of exercise, and continued to increase linearly during the first 40 min of exercise. Thereafter LGU stabilized at approximately 1.4 mmol/min until fatigue. Intracellular glucose was low at rest but increased sixfold after 5 min of exercise (P less than 0.01 vs. rest); thereafter, intracellular glucose decreased and was not significantly different from the value at rest after 40 min or at fatigue (P greater than 0.05). D-Glucose 6-phosphate (G-6-P) and alpha-D-glucose 1,6-bisphosphate (G-1,6-P2) (inhibitors of hexokinase) increased significantly after 5 min of exercise (approximately 300% G-6-P; approximately 25% G-1,6-P2) and then decreased continuously. The muscle glycolytic rate (glycogenolysis + glucose uptake) averaged 7.7 mmol.kg dry wt-1.min-1 during the first 40 min of exercise and 3.7 mmol.kg dry wt-1.min-1 during the last 35 min of exercise. The contribution of extracellular glucose to muscle glycolysis was estimated to be only 5 and 19% during the initial and latter phases of exercise, respectively. It is concluded that, during the initial phase of exercise, glucose utilization is limited by phosphorylation, probably due to G-6-P-dependent inhibition of hexokinase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Epinephrine inhibits insulin-mediated glycogenesis but enhances glycolysis in human skeletal muscle.

The effect of epinephrine (E) infusion on insulin-mediated glucose metabolism in humans has been studied. Eight glucose-tolerant men were studied on two separate occasions: 1) during 120 min of euglycemic hyperinsulinemia (UH, approximately 5 mM; 40 mU.m-2.min-1); and 2) during UH while E was infused (UHE, 0.05 microgram.kg-1.min-1). Biopsies were taken from the quadriceps femoris muscle before and after each clamp. Glucose disposal, correcting for endogenous glucose production, was 36 +/- 3 and 18 +/- 2 (SE) mumol.kg fat-free mass (FFM)-1.min-1 during the last 40 min of UH and UHE, respectively (P less than 0.001). Nonoxidative glucose disposal (presumably glycogenesis) averaged 23.0 +/- 3.0 and 4.0 +/- 1.1 (P less than 0.001), whereas carbohydrate oxidation (which is proportional to glycolysis) averaged 13.1 +/- 1.4 and 15.3 +/- 1.1 mumol.kg FFM-1.min-1 (P less than 0.05) during UH and UHE, respectively. UHE resulted in significantly higher contents of UDP-glucose, hexose monophosphates, postphosphofructokinase intermediates, and glucose 1,6-bisphosphate (G-1,6-P2) in muscle (P less than 0.05-0.001), but there were no significant differences in high-energy phosphates or fructose 2,6-bisphosphate (F-2,6-P2) between treatments. Fractional activities of phosphorylase increased (P less than 0.01), and glycogen synthase decreased (P less than 0.001) during UHE. It is concluded that E inhibits insulin-mediated glycogenesis because of an inactivation of glycogen synthase and an activation of glycogenolysis. E also appears to inhibit insulin-mediated glucose utilization, at least partly, because of an increase in G-6-phosphate (which inhibits hexokinase) and enhances glycolysis by G-1,6-P2-, fructose 6-phosphate-, and F-1,6-P2-mediated activation of PFK.

Adult↗
PubMed1991

Epinephrine increases tricarboxylic acid cycle intermediates in human skeletal muscle.

The effects of epinephrine (E) and insulin infusions on the contents of tricarboxylic acid cycle intermediates (TCAI), adenine nucleotides and their catabolites, and amino acids in skeletal muscle have been investigated. Eight men were studied on two separate occasions: 1) during 120 min of euglycemic hyperinsulinemia (UH, approximately 5 mM; 40 mU.m-2.min-1) and 2) during UH while E was infused (UHE, 0.05 microgram.kg-1.min-1). Biopsies were taken from the quadriceps femoris muscle before and after each clamp. The sum of citrate, malate, and fumarate in muscle did not change significantly during UH (P greater than 0.05) but doubled during UHE (P less than 0.001). There were no significant changes in any of the adenine nucleotides, their catabolites (including inosine monophosphate), or aspartate during UH and UHE (P greater than 0.05); nor were there any significant changes in pyruvate or alanine contents during UH (P greater than 0.05). On the other hand, there were significant increases in pyruvate and alanine contents during UHE (P less than 0.01 and 0.05, respectively), suggesting that there was increased production of 2-oxoglutarate (a TCAI) via the alanine aminotransferase (ALT) reaction. It is concluded that E infusion increases the contents of TCAI in human skeletal muscle, and it is likely that at least part of the increase is attributable to increased flux through the ALT reaction.

Adenine Nucleotides↗
PubMed1991

Role of glycogen in control of glycolysis and IMP formation in human muscle during exercise.

The effect of prior glycogen depletion on glycolysis [flux through phosphofructokinase (PFK)] and inosine monophosphate (IMP) formation in human skeletal muscle has been investigated. Eight subjects cycled at a work load calculated to elicit 95% of maximal O2 uptake on two occasions, the first to fatigue [5.5 +/- 0.3 (SE) min] and the second at the same workload and for the same duration as the first. Before the first experiment, muscle glycogen stores were lowered by a combination of exercise and diet. Before the second experiment, muscle glycogen stores were supercompensated. In the low-glycogen (LG) state muscle glycogen decreased from 201 +/- 31 mmol glucosyl units/kg dry wt at rest to 105 +/- 28 after exercise, and in the high-glycogen (HG) state from 583 +/- 40 to 460 +/- 49. The accumulation of fructose 6-phosphate (F-6-P; activator of PFK) during exercise was markedly attenuated in the LG state (P less than 0.01), whereas lactate accumulation in muscle was similar between treatments, suggesting that muscle pH was also similar. Glycolysis (estimated from glycogenolysis minus accumulation of hexose monophosphates) was not measurably different between treatments (LG = 88 +/- 17, HG = 106 +/- 43 mmol/kg dry wt; P greater than 0.05). IMP was significantly greater in the LG state after exercise (3.63 +/- 0.85 vs. 1.97 +/- 0.44 mmol/kg dry wt; P less than 0.05). It is concluded that decreased glycogen availability does not measurably alter the rate of muscle glycolysis during intense exercise. It is hypothesized that the attenuated increase in F-6-P in the LG state, which should theoretically decrease glycolysis, is compensated for by increases in free ADP and AMP (activators of PFK) at the enzymatic site during the contraction phase. The greater increase in IMP in the LG state is consistent with this hypothesis, since ADP and AMP are also activators of AMP deaminase.

Adenine Nucleotides↗
PubMed1991

Basal and insulin-mediated carbohydrate metabolism in human muscle deficient in phosphofructokinase 1.

Biopsies were obtained from the quadriceps femoris muscle of two male patients deficient in phosphofructokinase (PFK) 1. In the basal state the patients had markedly higher contents of UDP-glucose (approximately 5-fold), hexose monophosphates (approximately 7- to 13-fold), inosine monophosphate (IMP) (approximately 15-fold), and fructose 2,6-bisphosphate (F-2,6-P2; approximately 6-fold) than controls. Fructose 1,6-bisphosphate was not detectable, and phosphocreatine was lower (33 and 54 mmol/kg dry wt) than in controls [72 +/- 4 (SD)]. Patients had normal fasting plasma glucose and insulin levels and basal glucose turnover rates and responded normally to a 75-g oral glucose challenge. Patients were also studied during euglycemic hyperinsulinemia (approximately 95 mg/dl; 40 and 400 mU.m-2.min-1). Whole body glucose disposal rates were normal during both insulin infusion rates. Biopsies taken after the 400 mU insulin infusion showed decreases in acetylcarnitine and citrate and increases in the fractional activity of glycogen synthase. It is suggested that the high basal levels of F-2,6-P2 are, at least partly, a consequence of the high levels of fructose 6-phosphate, which will stimulate flux through PFK-2 and inhibit fructose-2,6-bisphosphatase. The low phosphocreatine and high IMP contents indicate that carbohydrate availability is important for control of high-energy phosphate metabolism, even in the basal state. The insulin-mediated decreases in acetylcarnitine and citrate suggest an activation of the tricarboxylic acid cycle in skeletal muscle but an absence of the normal response to replenish these intermediates.

Carbohydrate Metabolism↗
PubMed1991

Fasting inhibits insulin-mediated glycolysis and anaplerosis in human skeletal muscle.

Euglycemic (approximately 5.5 mM) hyperinsulinemic (60 mU.m-2.min-1) clamps were performed for 2 h after a 10-h fast and after a prolonged (72-h) fast. Biopsies were obtained from the quadriceps femoris muscle before and after each clamp. The rate of whole body glucose disposal was approximately 50% lower during the clamp after the 72-h fast (P less than or equal to 0.001). The increase in carbohydrate (CHO) oxidation (which is proportional to glycolysis) during the clamp after the 10-h fast (to 13.8 +/- 1.5 mumol.kg fat free mass-1.min-1) was completely abolished during the clamp after the 72-h fast (1.7 +/- 0.6; P less than or equal to 0.001). During the clamp after the 10-h fast, postphosphofructokinase (PFK) intermediates and malate in muscle increased, whereas glutamate decreased (P less than or equal to 0.05-0.001 vs. basal) and citrate did not change. During the clamp after the 72-h fast, there were no significant changes in post-PFK intermediates or glutamate (P greater than 0.05 vs. basal), but there was a decrease in citrate (P less than or equal to 0.01 vs. basal). Euglycemic hyperinsulinemia increased glycogen synthase fractional activity in muscle under both conditions but to a greater extent after the 72-h fast (P less than or equal to 0.01). It is concluded that insulin (after 10-h fast) increases glycolytic flux and the content of malate in muscle, which is probably due to increased anaplerosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Relationship between carbohydrate oxidation and G-1,6-P2 in human skeletal muscle during euglycemic hyperinsulinemia.

Euglycemic (approximately 5.5 mM) hyperinsulinemic clamps were performed on normoglycemic insulin-sensitive (NIS) men and men who were normoglycemic but insulin resistant (NIR) and hyperglycemic and insulin resistant (HIR) (i.e., noninsulin-dependent diabetes mellitus). Insulin was infused at successive rates of 40 and 400 mU.m-2.min-1, and biopsies were obtained from the quadriceps femoris muscles before and after insulin and analyzed for regulators of phosphofructokinase, a rate-limiting enzyme for glycolysis. Glucose disposal and whole body carbohydrate oxidation were markedly lower in NIR and HIR vs. NIS (P less than 0.001 for disposal and oxidation). The alpha-D-glucose 1,6-bisphosphate (G-1,6-P2) content increased almost twofold during the 40-mU insulin infusion (P less than 0.001) without any further change during the 400-mU infusion in NIS men. The increase in G-1,6-P2 in NIR and HIR was only approximately 25 and 50% of the increase observed in NIS during the 40- and 400-mU infusions, respectively. The mean content of G-1,6-P2 was strongly related to the mean rate of carbohydrate oxidation (r = 0.99; P less than 0.001). Because during euglycemic hyperinsulinemia approximately 90% of the glucose utilization is accounted for by skeletal muscle (J. Clin. Invest. 76: 149, 1985), it is likely that whole body carbohydrate oxidation is proportional to carbohydrate oxidation and glycolysis in muscle. The different rates of carbohydrate oxidation between NIS and insulin-resistant men could not be associated with differences in fructose 6-phosphate, fructose 1,6-bisphosphate, fructose 2,6-bisphosphate, Pi, free ADP and free AMP (activators of phosphofructokinase), or ATP and citrate (inhibitors of phosphofructokinase).

Adult↗