Long-term outcome of kidney transplantation in children with oxalosis.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to A Katz.
Explore the source record for details and available documents.
Identification and characterization of cells in glomerular tissue culture has been an ongoing concern of experimental renal biologists. We examined the immunocytochemical staining profiles of primary and passaged rat glomerular cultures using a battery of commercially available antisera. In all culture systems examined, two distinct cell populations could be distinguished. One cell type stained positively for desmin and had ultrastructurally smooth muscle features typical of contractile mesangial cells. The second cell type proliferated in a manner classically described for "epithelial" cells but, intriguingly, did not express any of the numerous epithelial markers tested. The second cell population may represent an undifferentiated reserve cell type. Immunocytochemical methods offer an independent modality to the evaluation of cells which proliferate in glomerular cell culture.
We review the data of 141 patients who underwent mitral valve replacement between 1964 and 1986. In the majority of patients, a tilting disk or a Cage ball prosthesis was implanted. Overall operative mortality was 14.8%, and 120 patients who were followed for a mean period of 4.5 +/- 2 years (540 patient years) showed a late mortality (greater than 30 days postoperatively) of 20.8%. The actuarial survival was 84% at 5 years and 44% at 20 years. Most of the late deaths were cardiac related, with sudden death as the leading cause. The incidence of prosthetic valve-related complications--thromboembolism, bacterial endocarditis and warfarin-related hemorrhage--were higher than in other series; however, long-term survival was comparable. Delay in advising mitral valve surgery is the probable cause of some of the results observed in this series.
Between May 1964 and November 1986, 70 patients underwent aortic valve replacement with (20%) or without (80%) additional surgical procedures. Most of the prosthetic devices were Starr-Edwards models and Björk-Shiley and Sorin tilting disks. Long-term follow-up (305 patient years) was assessed in 65 patients who survived the operation. Actuarial survival was 85 +/- 2% at 5 years and 72 +/- 6% at 20 years. The linearized rate of deaths occurring greater than 30 days postoperatively was 3.6% per patient year; sudden death was the most frequent cause of death. Preoperative functional capacity class significantly influenced the immediate outcome of surgery. Although the incidence of prosthetic valve-related complications was higher than in previous studies, survival rates were comparable.
We identified 13 patients who contracted acquired immunodeficiency syndrome or human immunodeficiency virus-related disease after a cardiothoracic operation. The operations were performed between January 1981 and November 1984, and the diagnosis of human immunodeficiency virus-related disease was established from 26 to 54 months after operation. The survival time from diagnosis ranged from 8 days to 14 months in the 10 patients who have died. A clinical illness developed in three of the patients immediately postoperatively that was consistent with primary human immunodeficiency virus mononucleosis. The clinical features included a wide variety of opportunistic infections, but an abnormally high percentage of the patients first showed symptoms of dementia or neoplastic disease. In many patients, the diagnosis was not suspected for a prolonged period of time. On the basis of the prolonged incubation period, the incidence of this disease is likely to increase for several more years.
Prothrombin possesses two high affinity and four low affinity gamma-carboxyglutamic acid (Gla)-dependent gadolinium binding sites. Earlier work (Price, P. A., Williamson, M. K., and Epstein, D. J. (1981) J. Biol. Chem. 256, 1172-1176) has shown that tritium can be specifically incorporated at the gamma-carbon of Gla in proteins at pH 5. In the present work we show that inclusion of saturating concentrations of Ca2+ in nondenaturing buffer systems ranging from pH 5.5 to 8.5 prevents the exchange of tritium into all 10 Gla residues of prothrombin. Similarly, saturating concentrations of Gd3+ prevent tritium incorporation into Gla at pH 5.5. Positive cooperativity was observed for the binding of Gd3+ to human prothrombin (at pH 5.5) for the two high affinity sites (Kd congruent to 35 nM). The four low affinity sites bind Gd3+ with a Kd congruent to 5 microM. Incubation of prothrombin ranging in concentrations from 10 to 40 microM with 2 eq of Gd3+ at pH 5.5 prevents 5.7 (average of seven determinations) Gla residues from tritium incorporation. Sedimentation velocity experiments conducted at pH 5.5 indicate that prothrombin in the presence of saturating concentrations of Gd3+ polymerizes, most likely, to a trimer. Further, in the presence of 2 eq of Gd3+, calculated percent weight average concentration of monomer prothrombin is congruent to 100% at 10 microM, approximately equal to 95% at 20 microM, and congruento to 80% at 40 microM protein concentration. Thus, it appears that under conditions in which prothrombin primarily exists as a monomer, occupancy of the initial two metal binding sites by Gd3+ involves six Gla residues.
Mouse ornithine decarboxylase (ODC) genomic clones were isolated from a bacteriophage lambda genomic library representing mouse myeloma 653-1 cells which over-produce ODC due to amplification of an active ODC gene. Sequence analysis of the amplified ODC gene revealed that ODC mRNA is encoded by 12 exons, 10 of which (exons 3 to 12) code for the ODC protein. Exon 12 also corresponds to the 3' noncoding region of the two species of ODC mRNA which are formed by alternative utilization of two polyadenylation signals separated from each other by 422 nucleotides. The transcription initiation site was mapped by S1 nuclease protection and by primer extension analysis. The 5' flanking region is extremely rich in G + C and contains typical promoter motifs such as the TATA box and SP1 transcription factor binding sites. Joining the 5' flanking region to the Escherichia coli chloramphenicol acetyltransferase structural gene and its introduction into mouse cells resulted in the expression of a high level of chloramphenicol acetyltransferase activity. Comparing the sequence of the ODC gene to our previously published sequence of ODC cDNA revealed a disagreement between the sequences located 5' to the AvaI site and demonstrated that this region of our previously reported cDNA represents a cloning artifact. The portion of the correct 5' noncoding region encoded by exon 1 is extremely rich in G + C and includes potential secondary structures which may be involved in translational regulation of ODC mRNA.
Explore the source record for details and available documents.
The effect of dynamic exercise on the NADH content of human type I (slow-twitch) and II (fast-twitch) muscle fibres was investigated. Muscle biopsy samples were obtained from the quadriceps femoris of seven healthy subjects at rest and after bicycle exercise at 40, 75 and 100% of the maximal oxygen uptake [VO2(max.)]. At rest and after exercise at 100% VO2(max.), muscle NADH content was significantly higher (P less than 0.05) in type I than in type II fibres. After exercise at 40% VO2(max.), muscle NADH decreased in type I fibres (P less than 0.01), but was not significantly changed in type II fibres. After exercise at 75 and 100% VO2(max.), muscle NADH increased above the value at rest in both type I and II fibres (P less than 0.05). Muscle lactate was unchanged at 40% VO2(max.), but increased 20- and 60-fold after exercise at 75 and 100% VO2(max.) respectively. The finding that NADH decreased only in type I fibres at 40% VO2(max.) supports the idea that type I is the fibre type predominantly recruited during low-intensity exercise. The increase of NADH in both fibre types after exercise at 75% and 100% VO2(max.) suggests that the availability of oxygen relative to the demand is decreased in both fibre types at high exercise intensities.
The response of plasma arginine vasopressin (AVP) to nicotine administered by chewing gum (Nicorette, 2 mg) was examined in nine healthy volunteers. Heart rate, mean arterial pressure, serum osmolality, plasma AVP level, and plasma nicotine level were measured at baseline (control) and at 30, 45, and 60 minutes after initial administration of the gum. There were small increases in heart rate (72 +/- 6.3 to 82 +/- 5.1 beats/min, p less than 0.05) and mean arterial pressure (88 +/- 8.2 to 93 +/- 10 mm Hg, p = NS), while the plasma nicotine level increased to a maximum of 16 +/- 2.0 ng/ml (p less than 0.001). No changes were seen in either osmolality (283 +/- 3.4 mOsm/kg) or AVP level (4.3 +/- 2.0 pg/ml) in eight of the nine subjects who remained asymptomatic. In one subject whose hemodynamic and plasma nicotine responses were similar to the others but who became nauseated, the plasma AVP level increased from 4.2 to 26 pg/ml. These data suggest that nicotine at the plasma concentrations achieved in this study is not associated with stimulation of plasma AVP secretion in normal man. Other factors in association with nicotine use, in this case nausea, may be required for AVP stimulation to occur.
Isosorbide-5-mononitrate was administered in a continuous intravenous infusion, according to the haemodynamic response, to 19 patients with left heart failure of ischaemic aetiology; 12 with acute heart failure complicating an acute myocardial infarction and 7 with chronic ischaemic failure. In both groups, the following statistically significant haemodynamic changes were observed: a decrease in PCWP from 25.4 +/- 4.6 to 17.2 +/- 4.6 mmHg; an increase in SWI from 19.1 +/- 10 to 23.6 +/- 13.1 gm m-2; a slight increase in cardiac index with no change in arterial pressure and only minimal decrease in vascular resistance. There were two major differences in the haemodynamic response between the patients with acute heart failure and those with chronic disease: (a) the duration of the effect of isosorbide-5-mononitrate on the PCWP was longer in the first group (mean, 8 hours, compared to 1.5 hours in the chronic group), and (b) the effect on afterload was more pronounced in the group with chronic ischaemic failure than in the first group. Thus, isosorbide-5-mononitrate administered by intravenous infusion under careful monitoring appears to have a beneficial role in the treatment of acute as well as chronic ischaemic heart failure.
Explore the source record for details and available documents.
Two patients had trichothiodystrophy but did not exhibit the commonly associated findings such as mental retardation, increased sensitivity to sunlight, ichthyosis, decreased fertility in males, and short stature. One of the patients had a transient combined immunodeficiency syndrome in early childhood lasting four years, but has remained in good health untreated for four years. The association of these two rare findings in this patient should alert us to the possibility that others with trichothiodystrophy may exhibit immunodeficiency.
Explore the source record for details and available documents.
The effect of circulatory occlusion on the content of glucose 1,6-bisphosphate (G-1,6-P2), glycogenolytic intermediates, and high-energy phosphates in the quadriceps femoris muscles of eight men was investigated. Needle biopsies were obtained at rest, after 30 min of circulatory occlusion, and 15 min after the occlusion was released. G-1,6-P2 averaged 75 +/- 8 (SE) mumol/kg dry wt at rest and did not change significantly after occlusion (82 +/- 10; P greater than 0.05) but was slightly elevated after 15 min recovery (88 +/- 12; P less than 0.05 vs. rest). Phosphocreatine (PCr) decreased in all subjects after occlusion (from 80.4 +/- 2.6 to 66.2 +/- 4.7 mmol/kg dry wt; P less than 0.001) and was completely resynthesized after recovery (80.9 +/- 2.4). Fructose 1,6-bisphosphate (F-1,6-P2) was doubled after occlusion (P less than 0.05). During occlusion, the average glycolytic and anaerobic ATP turnover rates were 0.08 +/- 0.02 mmol.kg dry wt-1.min-1 (approximately 4 times the calculated rate at rest) and 0.7 +/- 0.2 mmol.kg dry wt-1.min-1 (less than 20% of the calculated rate at rest), respectively. Total glycolysis was strongly related to the calculated increase in inorganic phosphate (Pi, r = 0.93; P less than 0.01), the decrease in PCr/Cr (reflects an increase in free ADP and AMP) (r = 0.92; P less than 0.01), and the increase in hexosemonophosphates (r = 0.77; P less than 0.05). It is concluded that short-term ischemia in human skeletal muscle results in no change in the content of G-1,6-P2.(ABSTRACT TRUNCATED AT 250 WORDS)
The content of glucose 1,6-bisphosphate (G-1,6-P2), an in vitro activator of phosphofructokinase (a rate-limiting enzyme for glycolysis), and the glycolytic rate in skeletal muscle during isometric contraction have been determined. Subjects contracted the knee extensor muscles at two-thirds maximal voluntary force to fatigue. Biopsies from the quadriceps femoris muscle were obtained before and immediately after contraction. G-1,6-P2 increased in all subjects from a mean of 101 +/- 15 (SE) mumol/kg dry wt at rest to 128 +/- 24 at fatigue (P less than 0.05). Muscle glucose did not change significantly, whereas hexosemonophosphates were significantly increased after contraction. The glycogenolytic and glycolytic rate averaged 70.0 +/- 13.8 and 47.3 +/- 6.7 mmol.kg dry wt-1.min-1, respectively, and the glycolytic rate was positively correlated with the accumulation rates of fructose 6-phosphate (F-6-P) (r = 0.95, P less than 0.01) and G-6-P (r = 0.96, P less than 0.01). Phosphocreatine and ATP decreased by 87 and 17%, respectively, whereas ADP increased by 31% after contraction. These data demonstrate that intense, short-term isometric contraction results in an elevation of the muscle content of G-1,6-P2. The increase in G-1,6-P2 could not be accounted for by the side reactions of phosphoglucomutase or phosphofructokinase. It remains to be determined whether the observed increase in G-1,6-P2 is sufficient to account for the high glycolytic rate during intense exercise. The lack of increase in muscle glucose while G-6-P increased (which will inhibit hexokinase) suggests that the debranching enzyme complex was not active during contraction.
It has been recently suggested that high glucose infusion rates during euglycemic hyperinsulinemia result in accumulation of free glucose in human skeletal muscle (J. Clin. Invest. 76: 357, 1985). To examine this possibility, we performed a euglycemic, hyperinsulinemic clamp together with biopsies from the quadriceps femoris muscle on seven healthy men. Insulin was infused at successive rates of 40 and 400 mU. m-2.min-1, resulting in mean plasma insulin concentrations of 69 +/- 3 and 1,285 +/- 115 (SE) microU/ml, respectively. Glucose infusion rates averaged 7.79 +/- 0.86 and 12.01 +/- 0.77 mg.kg body wt-1.min-1. The total glucose content in muscle averaged 1.72 +/- 0.26, 1.37 +/- 0.21, and 1.65 +/- 0.35 mmol/kg dry wt at rest, and after the low- and high-dose insulin infusions, respectively (P greater than 0.05). Assuming that the plasma glucose concentration reflects the glucose concentration in the extracellular space and that there are 0.3 liters of extracellular water per kilogram dry weight, the intracellular glucose contents are calculated to be 0.15 +/- 0.25, -0.35 +/- 0.21, and -0.06 +/- 0.34 mmol/kg dry wt at rest, and after the low- and high-dose infusions, respectively. None of these values is significantly different from zero. Thus euglycemic hyperinsulinemia does not result in appreciable accumulation of glucose in the muscle of insulin-sensitive men.
Glucose 1,6-bisphosphate (G-1,6-P2) is a potent activator of phosphofructokinase (PFK) and an inhibitor of hexokinase in vitro. It has been suggested that increases in G-1,6-P2 are a main means by which PFK can achieve significant catalytic function in vivo despite falling pH and that increases in G-1,6-P2 will inhibit hexokinase in vivo. The purpose of the present study was to determine whether contraction-induced changes in flux through PFK and hexokinase are associated with changes in G-1,6-P2 in skeletal muscle. Ten men performed bicycle exercise for 10 min at 40 and 75% of maximal O2 uptake (VO2max) and to fatigue [4.8 +/- 0.6 (SE) min] at 100% VO2max. Biopsies were obtained from the quadriceps femoris muscle at rest and after each work load and analyzed for G-1,6-P2. G-1,6-P2 averaged 111 +/- 13 mumol/kg dry wt at rest and 121 +/- 16, 123 +/- 15, and 123 +/- 11 mumol/kg dry wt after the low-, moderate-, and high-intensity exercise bouts, respectively (P less than 0.05 for all means vs. rest). Flux through PFK was estimated to increase exponentially as the exercise intensity increased and muscle pH decreased at the higher work loads, whereas flux through hexokinase was estimated to increase during exercise at 40 and 75% VO2max but decrease sharply at 100% VO2max. These data demonstrate that flux through neither PFK nor hexokinase is mediated by changes in G-1,6-P2 in human skeletal muscle during short-term dynamic exercise.