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Biomedical subjects

K Nosaka

Publications and source records attributed to K Nosaka.

At least 91 records · Page 5Linked to original sources

Effect of thiamin on cordycepin sensitivity in Saccharomyces cerevisiae.

The sensitivity of Saccharomyces cerevisiae to the antibiotic cordycepin (3'-deoxyadenosine) was found to be decreased by the addition of thiamin to the growth medium. A thiamin transport mutant of S. cerevisiae was also found to be resistant to the growth inhibitory effect of cordycepin. Not only the thiamin uptake but also adenosine uptake by this mutant cell was markedly reduced compared to those by the parent yeast cells. This strongly suggested that cordycepin, an analog of adenosine, is virtually taken up by the thiamin transport system of growing yeast cells; thus the drug sensitivity is decreased by the presence of thiamin in the growth medium.

Adenosine↗

Upstream activation element of the PH03 gene encoding for thiamine-repressible acid phosphatase in Saccharomyces cerevisiae.

The PH03 gene of Saccharomyces cerevisiae encodes thiamine-repressible acid phosphatase and requires the positively acting regulatory protein THI2 for its expression. Deletion analysis of the 5'-flanking region of PH03 gene revealed that an activating region located at nucleotide position -234 to -215 relative to the translation initiation codon is required for the expression and sensitivity to thiamine. A chemically synthesized DNA fragment covering -234 to -215 showed a significant level of expression when inserted in front of the PH03 promoter lacking the activating region. Electrophoretic mobility shift assay demonstrated the presence of proteins that bound to the above DNA fragment in the nuclear extract from cells grown in thiamine-free medium. These findings suggested that this region between -234 and -215 acts as an upstream activation element of the PH03 gene that can interact with regulatory proteins.

Acid Phosphatase↗

Cloning and characteristics of a positive regulatory gene, THI2 (PHO6), of thiamin biosynthesis in Saccharomyces cerevisiae.

A thi2(pho6) mutant of Saccharomyces cerevisiae, defective in the expression of structural genes for thiamin-repressible acid phosphatase and enzymes involved in thiamin biosynthesis, was found to retain sufficient thiamin transport activity. The transport activity was repressed by thiamin in growth medium. We isolated from a S. cerevisiae genomic library two hybrid plasmids, pTSR1 and pTSR2, containing 10.2- and 12.0-kilobase (kb) DNA fragments, respectively, which complement the thi2(pho6) mutation of S. cerevisiae. This gene was localized on a 6.0-kb ClaI-ClaI fragment in the subclone pTSR3. Complementation of the enzyme activities for thiamin metabolism in the thi2(pho6) mutant transformed by some plasmids with the TH12(PHO6) gene was also examined.

Cloning, Molecular↗

Acute tubulointerstitial nephritis with uveitis syndrome presenting as multiple tubular dysfunction including Fanconi's syndrome.

We describe an 11-year-old male patient with acute tubulointerstitial nephritis with uveitis (TINU) syndrome. He presented with easy fatigability, pallor, nocturia and weight loss. Laboratory examination disclosed anaemia, polyclonal hypergammaglobulinaemia, low molecular weight proteinuria, glycosuria, aminoaciduria, proximal and distal renal tubular acidosis, a urine concentration defect and decreased creatinine clearance. The multiple renal tubular dysfunction and slight glomerular dysfunction subsided spontaneously. Bilateral anterior uveitis was manifested 7 months after the onset of the disease. This is the first reported case of TINU syndrome with multiple proximal and distal tubular dysfunction including a complete type of Fanconi's syndrome.

Acidosis, Renal Tubular↗

Cisplatin-induced alterations in renal structure, ammoniagenesis and gluconeogenesis of rats.

Cisplatin [cis-diamminedichloroplatinum (II): CDDP] is a widely used cancer chemotherapeutic agent which has been shown to cause dose-related acute renal failure. The kidney damage is histologically characterized by widespread tubular necrosis, predominantly found in the third segments (S3) of the proximal tubules. To identify the intranephron targets of CDDP more precisely, we examined alterations in ammoniagenesis (AMG) and gluconeogenesis (GLG) using rat kidney slices (for AMG and GLG), tubule suspensions (for GLG), and microdissected nephron segments (for AMG). Ultramicroassay of AMG was carried out using the enzymatic cycling method, and GLG was measured by the HK/G6PHD method. GLG obtained from kidney slices and tubule suspensions on day 3 and day 7 following CDDP treatment did not change significantly from levels in control rats. In contrast, AMG increased on day 3 in the first and third kidney slices cut from the surface inward and decreased significantly on day 7 in the third and fourth slices. Microdissected nephron segments examined on day 7 showed decreased AMG in the second segments (S2; 20.3 +/- 7.7 pmol/mm/15 min vs. 78.7 +/- 9.7 for control, P less than 0.005) and the third segments (S3; 26.3 +/- 14.4 pmol/mm/15 min vs. 79.2 +/- 7.8 for control, P less than 0.005) of the proximal tubules. Additionally, we observed morphological changes under light microscopy to examine the relationship between metabolism and morphology. On day 3 following the CDDP treatment, typical acute tubular necrosis was seen primarily localized in the outer stripe of the outer medulla, while on day 7 the lesion appeared to be recovering. Our data imply a prominent dissociation between renal metabolic and morphologic changes induced by CDDP.

Ammonia↗

Relationship between post-exercise plasma CK elevation and muscle mass involved in the exercise.

The purpose of this study was to investigate whether a larger post-exercise increase in plasma creatine kinase (CK) activity would be produced when a larger amount of muscle is damaged by eccentric exercise. Twenty-two non-weight trained females were placed into two groups; Group A (n = 12) and Group B (n = 10). Both groups performed 24 maximal eccentric actions of the forearm flexors on each bout. The right and left arm were exercised on the same day for Group A (24 eccentric actions per arm, a total of 48 actions). In contrast, Group B performed 24 actions with either the right or the left arm on the first bout and performed 24 eccentric actions with the opposite arm on the second bout 3-5 weeks later. Blood samples were taken before and for 5 days after each exercise and plasma CK activity was determined. Forearm flexion isometric force (ISO), range of motion evaluated by relaxed elbow joint angle (RANG) and flexed elbow joint angle (FANG), and perceived muscle soreness (SOR) were also examined to indirectly assess muscle damage. All of the muscle damage indicators changed significantly over time (p < 0.01) for both groups, but changes were not significantly different between arms or between groups. Because it seemed that both arms were equally "damaged" for each group, it was expected that Group A (two arms were exercised on the same day) should show an approximate two-fold increase in plasma CK compared to Group B when one arm was exercised on each bout.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Splenic metastasis of hepatocellular carcinoma. Accumulation of Tc-99m HDP.

Considerable accumulation of Tc-99m HMDP was noted in a huge splenic mass in a 62-year-old man with hepatocellular carcinoma. An autopsy revealed a massive hemorrhage within the splenic metastasis. The splenic uptake of the radionuclide corresponded to the marked deposition of hemosiderin.

Carcinoma, Hepatocellular↗

Changes in plasma zinc following high force eccentric exercise.

This study was done to determine whether eccentric exercise that causes muscle damage will produce an increase in plasma levels of zinc. Changes in total plasma zinc concentration (Zn) were examined following an eccentric and concentric exercise of the forearm flexors. Eight female subjects performed 24 maximal concentric actions (CON) with one arm and 10-14 days later performed 24 maximal eccentric actions (ECC) with the other arm. Maximal isometric force, elbow joint angles at a relaxed (RANG) and flexed position (FANG), muscle soreness, and plasma creatine kinase activity (CK) were measured as indicators of muscle damage. Zn levels were determined at the same time as CK. Maximal isometric force, RANG, FANG, and muscle soreness showed large changes after ECC but little if any change after CON. CK increased significantly after ECC but did not change after CON. Neither ECC nor CON showed significant changes in Zn following exercise. It is concluded that exercise-induced muscle damage does not appear to produce an increase in plasma zinc levels.

Adult↗

A positive regulatory gene, THI3, is required for thiamine metabolism in Saccharomyces cerevisiae.

We have isolated a thiamine auxotrophic mutant carrying a recessive mutation which lacks the positive regulatory gene, THI3, which differs in the regulation of thiamine transport from the THI2 (PHO6) gene described previously (Y. Kawasaki, K. Nosaka, Y. Kaneko, H. Nishimura, and A. Iwashima, J. Bacteriol. 172:6145-6147, 1990) for expression of thiamine metabolism in Saccharomyces cerevisiae. The mutant (thi3) had a markedly reduced thiamine transport system as well as reduced activity of thiamine-repressible acid phosphatase and of several enzymes for thiamine synthesis from 2-methyl-4-amino-5-hydroxymethylpyrimidine and 4-methyl-5-beta-hydroxyethylthiazole. These results suggest that thiamine metabolism in S. cerevisiae is subject to two positive regulatory genes, THI2 (PHO6) and THI3. We have also isolated a hybrid plasmid, pTTR1, containing a 6.2-kb DNA fragment from an S. cerevisiae genomic library which complements thiamine auxotrophy in the thi3 mutant. This gene was localized on a 3.0-kb ClaI-BglII fragment in the subclone pTTR5. Complementation of the activities for thiamine metabolism in the thi3 mutant transformed by some plasmids with the THI3 gene was also examined.

Acid Phosphatase↗

Syntheses and antiulcer activities of 2-aminonorbornene derivatives.

2,2,-Disubstituted norbornenes (1, 2), 2,2-Disubstituted norbornane (3), 2,2,3-trisubstituted norbornenes (4, 5), oxanorbornenes (6) and azanorbornenes (7) were synthesized by the Diels-Alder reaction using alpha, beta-dehydroamino acids as a key step, and their antiulcer activities were examined. The oxazolidine derivative (1h) exhibited the most potent activities against several ulcer-models in rat.

Animals↗

Effects of atrial natriuretic peptide on glycerol induced acute renal failure in the rat.

Acute and chronic experiments were performed in rats to examine whether atrial natriuretic peptide (ANP) has any beneficial effects on glycerol-induced acute renal failure (ARF). ANP infusion (Atriopeptin III, 1.0 microgram/kg+0.2 microgram/kg/min) improved the renal blood flow (RBF) and the glomerular filtration rate (GFR), and induced profound natriuresis in the early stage of ARF. By contrast, ANP decreased RBF in the control rats. In addition to these acute hemodynamic effects, long-term beneficial effects of ANP were also observed. A 75-min infusion of ANP significantly lessened the degree of azotemia as well as the extent of renal histologic damage assessed 24 hours after the glycerol injection. These results indicate that ANP can afford partial protection against both acute renal dysfunction and the chronic course of the glycerol-induced ARF, suggesting that ANP may be useful in the treatment of ARF.

Acute Kidney Injury↗

Muscle function after exercise-induced muscle damage and rapid adaptation.

This brief review focuses on the time course of changes in muscle function and other correlates of muscle damage following maximal effort eccentric actions of the forearm flexor muscles. Data on 109 subjects are presented to describe an accurate time course of these changes and attempt to establish relationships among the measures. Peak soreness is experienced 2-3 d postexercise while peak swelling occurs 5 d postexercise. Maximal strength and the ability to fully flex the arm show the greatest decrements immediately after exercise with a linear restoration of these functions over the next 10 d. Blood creatine kinase (CK) levels increase precipitously at 2 d after exercise which is also the time when spontaneous muscle shortening is most pronounced. Whether the similarity in the time courses of some of these responses implies that they are caused by similar factors remains to be determined. Performance of one bout of eccentric exercise produces an adaptation such that the muscle is more resistant to damage from a subsequent bout of exercise. The length of the adaptation differs among the measures such that when the exercise regimens are separated by 6 wk, all measures show a reduction in response on the second, compared with the first, bout. After 10 wk, only CK and muscle shortening show a reduction in response. After 6 months only the CK response is reduced. A combination of cellular factors and neurological factors may be involved in the adaptation process.

Adaptation, Physiological↗

Time course of serum protein changes after strenuous exercise of the forearm flexors.

The time course of changes in serum proteins and other blood constituents after eccentric exercise of the forearm flexors by six nonweight-trained female subjects (age, 19.7 +/- 1.9 years) was investigated. Eccentric muscle actions are those in which the muscle lengthens as it exerts force, as when a person lowers a weight. Serum levels of creatine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, myoglobin, as well as urea nitrogen, uric acid, creatinine, calcium, and phosphorus were examined before and for 6 days after exercise. Creatine kinase increased dramatically (peak value ranged from 6740 to 24,200 U/L) and aspartate aminotransferase, lactate dehydrogenase, alanine aminotransferase, and myoglobin followed the same time course as creatine kinase, but their peak values were lower. These proteins did not increase significantly until 48 hours after exercise and reached peak values 3 to 5 days after exercise. Alkaline phosphatase, gamma-glutamyl transpeptidase, uric acid, urea nitrogen, creatinine, calcium, and phosphorus showed no change. There is either a delay in muscle protein release by damaged muscle fibers, or the proteins are unable to leave the interstitial area for the 24 to 48 hour period after exercise. Because of the long delay, care should be taken when blood protein levels are interpreted in persons who have exercised strenuously (even if only for a short period of intense effort) several days before any diagnostic tests are performed.

Adolescent↗

Time course of muscle adaptation after high force eccentric exercise.

The repeated bout effect on changes in muscle damage indicators was examined in two groups of subjects following two bouts of 70 maximal eccentric actions of the forearm flexors. Fourteen college age female subjects were placed into two groups. The two bouts were separated by 6 weeks (n = 6), and 10 weeks (n = 8). The subjects performed the same amount of work for the bouts. The muscle damage indicators were isometric strength (STR), relaxed elbow joint angle (RANG), flexed elbow joint angle (FANG), perceived muscle soreness ratings (SOR), and plasma creatine kinase activity (CK). These measures were obtained pre-exercise and 5 days following each bout. The first bout showed significant changes in all measures over time for both groups (P less than 0.01). For the 6-week group, significantly smaller changes in RANG (P less than 0.01), SOR (P less than 0.05), and CK (P less than 0.01), as well as significantly faster recoveries (P less than 0.05) for STR and FANG were produced in the second bout. For the 10-week group, significantly smaller changes in RANG (P less than 0.05) and CK (P less than 0.01) were demonstrated by the second bout, but not significant difference was found for STR, FANG, and SOR between bouts 1 and 2. Changes in CK were still significantly smaller than that of the first bout when 6 subjects (3 subjects from each group) performed the same exercise 6 months after the second bout, but no difference in other measures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

Muscle soreness and serum enzyme activity following consecutive drop jumps.

The purpose of this study was to evaluate changes in muscle soreness and serum enzyme activity following consecutive drop jumps. Seven male subjects (mean age 30.6 years) performed drop jumps from a 80-cm box height every 7 s until exhaustion (mean = 114 drop jumps). A questionnaire was used to assess muscle soreness (0 = no pain, 7 = unbearable painful) both pre- and post-exercise (0, 12, 24, 36 and 48 h, and 3, 4 and 5 days after the exercise). Blood samples were also taken from three subjects at each of these times. For the other four subjects, blood samples were taken pre-exercise and 0, 12 and 36 h and 5 days post-exercise only. Although there was large inter-subject variability in the development of muscle soreness, all the subjects reported muscle soreness in their lower extremity muscles, especially in the quadriceps femoris. Muscle soreness developed significantly (P less than 0.01) over time, its peak (mean +/- S.E. = 3.7 +/- 0.7) occurring 12-48 h post-exercise. Serum enzyme activity changed significantly over time (P less than 0.05), but the changes were small. Not one subject showed a large increase in creatine kinase, and the average increase was less than 1.3 times as much as the pre-exercise level throughout the period of study. These results suggest that the muscle damage that occurs after drop jumping is not associated with a large release of muscle enzymes into the blood, and muscle soreness is not necessarily related to enzyme elevation following drop jumps.

Adult↗

A constitutive thiamine metabolism mutation, thi80, causing reduced thiamine pyrophosphokinase activity in Saccharomyces cerevisiae.

We identified a strain carrying a recessive constitutive mutation (thi80-1) with an altered thiamine transport system, thiamine-repressible acid phosphatase, and several enzymes of thiamine synthesis from 2-methyl-4-amino-5-hydroxymethylpyrimidine and 4-methyl-5-beta-hydroxyethylthiazole. The mutant shows markedly reduced activity of thiamine pyrophosphokinase (EC 2.7.6.2) and high resistance to oxythiamine, a thiamine antagonist whose potency depends on thiamine pyrophosphokinase activity. The intracellular thiamine pyrophosphate content of the mutant cells grown with exogenous thiamine (2 x 10(-7) M) was found to be about half that of the wild-type strain under the same conditions. These results suggest that the utilization and synthesis of thiamine in Saccharomyces cerevisiae is controlled negatively by the intracellular thiamine pyrophosphate level.

Acid Phosphatase↗

Tubuloglomerular feedback response in rats with antithymocyte serum-induced glomerular lesions.

Glomerular function and tubuloglomerular feedback (TGF) responses were studied in rats treated with antithymocyte rabbit serum (ATS). Microscopic findings revealed extensive mesangial cell loss and injury, enlarged capillary lumen, and decreased tortuosity of glomerular capillaries. Whole kidney GFR and SNGFR were lower in ATS-treated rats than in control rats (1.04 +/- 0.04 vs 0.94 +/- 0.03 ml/min/g kidney weight, 32 +/- 2 vs 27 +/- 1 nl/min, respectively) due to a decrease in Kf (0.017 +/- 0.001 vs 0.021 +/- 0.001 nl/s/mmHg). The magnitude of the TGF responses of SNGFR was less in ATS rats than in control rats (17% +/- 4% vs 34% +/- 5%), but that of SFP was not significantly different (18% +/- 2% vs 23% +/- 1%). These results indicate that the mesangial cells are necessary for full expression of the TGF mechanism and suggest the involvement of changes in Kf in the TGF mechanism.

Animals↗