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Biomedical subjects

T Kurosawa

Publications and source records attributed to T Kurosawa.

At least 19 recordsLinked to original sources

Loss of ions in cavity ionization chambers.

Ion losses due to initial recombination, volume recombination, and back diffusion were each determined by measurements and calculations for different size cylindrical ionization chambers and spherical ionization chambers. By measuring signal currents from these ionization chambers irradiated with (60)Co gamma rays, two groups of ion losses were obtained. (Group 1) Ion loss due to initial recombination and diffusion, which changes proportionally to the inverse of the voltage applied to the ionization chambers; (and group 2) ion loss due to volume recombination, which changes proportionally to the inverse of the square of the applied voltage. The diffusion loss was obtained separately by computing electric field distributions in the ionization chambers. It was found that diffusion loss is larger than initial recombination loss for the cylindrical ionization chambers and vise versa for the spherical ionization chambers.

Journal Article↗

The effect of angiotensin receptor blockade ARB on the regression of left ventricular hypertrophy in hemodialysis patients: comparison between patients with D allele and non-D allele ACE gene polymorphism.

OBJECTIVE: It is revealed that LVH is one of risk factors for the development of cardiac complications in long-term HD patients. Therefore, maneuvers to reduce hypertrophy of cardium are very important for improving life prognosis. Angiotensin II receptor blockade (ARB) could reduce LVH in general populations without renal failure. However, no conclusive data has been available regarding the clinical consequences of ARB administration on the regression of LVH in HD patients. Furthermore, it has not clearly determined if ACE gene polymorphism has a possible influential effect on it. This study is conducted to clarify these issues. SUBJECTS AND METHOD: 32 hypertensive patients on regular HD (male/female: 21/11, mean age: 60.5 years, mean duration of HD: 52.8 months) were studied. Patients were classified into two groups according to the different type of ACE gene polymorphism: cases with D allele (DD/ID; D group: n = 13) and those without (II; non-D group: n = 19). All patients were administered ARB (losartan 50 - 100 mg/day) and echocardiography (UCG) was performed at 6-month-interval regularly until the end of observation (24 months). RESULTS: Before the commencement of ARB, no differences were found between the two groups, neither in mean blood pressure (MBP: D group/non-D group: 120 +/- 13 vs. 115 +/- 14 mmHg) nor in left ventricular mass index (LVMI: D/non-D: 172 +/- 41 vs. 165 +/- 41 g/m2). During the 24r-month follow-up, there were significant and similar reductions in MBP in both groups. In respect to LVMI, a significant reduction of LVMI was found in the D group after six months (p < 0.01 vs. basal) with a final reduction rate (FRR) -26 +/- 13%, whereas in the non-D group it was found at 24 months (p < 0.01 vs. basal) with FRR -11 +/- 16% (p < 0.01 vs. D group). There were significant differences between the two groups at all points (p < 0.05 at 6, 18 and 24 months, p < 0.005 at 12 months, respectively). CONCLUSION: It is indicated that ARB could insert a regression effect on LVH predominantly in patients with D allele ACE polymorphism, due partly to factor (s) independent of its anti-hypertensive effect.

Alleles↗

Metabolic profiles and bile acid extraction rate in the liver of cows with fasting-induced hepatic lipidosis.

This study was designed to monitor lipid profile in the portal and hepatic blood of cows with fasting-induced hepatic lipidosis, and to compare the results with those in the jugular blood. The work was also carried out to investigate bile acid (BA) in these vessels, and further to investigate BA extraction rate in the liver. Five cows were equipped with catheters in the portal, hepatic and jugular veins (day 0), fasted for 4 days (day 1-day 4) and then refed (day 5-day 11). Before morning feeding, blood was sampled before, during and after fasting from the catheterized vessels. In the portal blood, the concentration of non-esterified fatty acids (NEFA) showed a progressive increase and at day 5 there was an approximate twofold rise. Increased NEFA concentrations were also found similarly in the other two veins. At day 5, beta-hydroxybutyrate (BHBA) in the portal, hepatic and jugular blood rose to 197, 190 and 186% of the pre-fasting value, respectively. However, the concentrations of NEFA and BHBA in the three veins gradually returned to pre-fasting concentration during the refeeding period. Compared with the pre-fasting value at day 0, the content of liver triglyceride (TG) increased significantly at day 5 (P < 0.01). In the liver, the hepatic extraction rate of BA dropped from 3.1 times pre-fasting to 2.2 times during fasting. There were no significant differences in the concentrations of glucose, TG, total cholesterol, cholesterol esters, free cholesterol and phospholipids. The results of the current study show that metabolic alterations occur in the portal, hepatic and jugular veins during induction of hepatic lipidosis in cows, and mostly metabolites, with exception of BA concentration, run parallel. The decreased BA extraction rate in the liver of fasted cows was considered to reflect hepatic cell impairment caused by TG accumulation. Hopefully, the findings, at least in part, contribute to the explanation of the pathophysiology of hepatic lipidosis in dairy cows.

Animals↗

Ultrasonographic imaging of experimentally induced pancreatitis in cattle.

This study was conducted to determine the ultrasonographic patterns of pancreatitis evoked in cattle, with reference to laboratory and pathological findings. Using ultrasonographic guidance, acute necrotizing pancreatitis was induced in six cows by injecting chloroform into the pancreatic tissue. Ultrasonographic examination was then performed once daily for nine days. Pancreatic lesions were visible 24h after induction of pancreatitis, as represented by a uniform increase in echogenicity and by intralobular and subcapsular fluid accumulation. As the experiment progressed, patchy hypoechogenic foci appeared within the gland parenchyma. Amylase and lipase activities showed rapid increases. Post mortem examination revealed gross and microscopic necrotic and haemorrhagic lesions in the body and right lobe of the pancreas, accompanied by oedema and fibrosis. Ultrasonography was found to be extremely useful for the detection and characterization of experimentally induced pancreatitis and to monitor its progression in the cow. These findings are of potential value as a reference for the diagnostic workup of bovine pancreatitis, and ultrasonography is seen as a promising non-invasive technique for the diagnosis of suspected pancreatitis in cattle.

Animals↗

Transcutaneous ultrasound-guided pancreatic biopsy in cattle and its safety: a preliminary report.

This study describes a free-hand technique for percutaneous pancreatic biopsy in cattle with ultrasound-guidance using a 14G spinal biopsy needle. Its safety was evaluated based on 36 consecutive procedures. To assess the immediate effects of pancreatic biopsy, 31 cows were necropsied shortly after the procedure and examined. The remaining five cows were examined daily for eight days and then necropsied and examined. No life-threatening complications nor clinically detectable abnormalities were observed. Changes indicative of inflammation were not apparent in total and differential WBC counts or in total protein and fibrinogen concentrations. A small increase of amylase activity was detected in only one cow kept for the eight-day observation period. Serum lipase activity increased significantly on day four after biopsy. Urea nitrogen, creatinine, glucose and the activities of aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltransferase remained within reference ranges. Changes in the peritoneum and pancreas observed at necropsy were negligible. We conclude that percutaneous ultrasound-guided pancreatic biopsy did not appear to influence the cow's condition adversely and the procedure provided an excellent method of obtaining a pancreatic specimen for histological examination. The procedure was considered safe, fast, cost-effective, and practical when performed properly. We believe that the technique can be used in cows with suspected pancreatic disease for making an ante mortem diagnosis.

Animals↗

Angle dependence of signal currents from cylindrical ionisation chambers.

A signal current from a cylindrical ionisation chamber with an ionisation volume of 62.7 cm3, 40 mm in diameter and 50 mm long, peaked when the chamber was lixed at 0 degrees and at 90 degrees in 137Cs and 60Co gamma ray fields for source-chamber distances of 1 m and 2 m. A smaller ionisation chamber showed a small peak at 0 degrees in both fields but not at 90 degrees. However, calculations indicated that the signal current from the smaller chamber would also show a peak at 90 degrees in a 137Cs point-source gamma ray field. Peaks occur because gamma rays attenuate along the cylindrical side wall or along the end walls when a chamber is tilted slightly from 0 degrees or 90 degrees and the direction of the gamma ray beam agrees with the plane of one of these walls. These facts suggest the need for care in the common practice of measuring and calculating responses for cylindrical ionisation chambers fixed perpendicular to gamma ray beams.

Cesium Radioisotopes↗

Modulatory effect of cAMP on fungal ergosterol level and inhibitory activity of azole drugs.

The functions and biosynthesis of sterols have been effective targets for fungal control in different areas, including pharmaceutical and agricultural applications. Fungi are among the organisms that synthesize sterols, principally ergosterol. In this paper, the effect of dibutyryl-cAMP (db-cAMP) on ergosterol level and the interaction of drugs that would change the concentration of cAMP with antifungal drugs have been investigated. Sterols were extracted from Candida albicans, and ergosterol was measured using the gas chromatography method. The interaction of different agents was measured by the broth dilution method. It was found that phosphodiesterase inhibitors reverse the inhibitory activity of azole antifungal drugs. Evaluating the ergosterol level of C. albicans incubated with db-cAMP revealed that it increased ergosterol level. Further experiments provided evidence attributing the observed interaction between azoles and phosphodiesterase inhibitors to the relationship between ergosterol and cAMP. The possible significance of this interaction includes potentiation of antifungal activity of drugs by manipulating the cAMP level.

Amphotericin B↗

Bile acid extraction rate in the liver of cows fed high-fat diet and lipid profiles in the portal and hepatic veins.

The purposes of this study are to assess the responses of increased supplemental dietary fat in the cow, without upsetting rumen fermentation, on the bile acid (BA) extraction rate in the liver and to determine whether this diet would affect the postprandial lipid profiles in the portal and hepatic venous blood. Six Holstein cows were equipped with catheters fitted in the portal and hepatic veins. Two cows each were assigned randomly to a sequence of three dietary treatments of 21-day period. The methodology of this study was based on the supplementation of the basal concentrate diet with 0 (control), 5, or 10% calcium salts of fatty acids (CSFA). The total bile acids were significantly increased in the portal and hepatic veins with the 5% CSFA diet, whereas no increase occurred with the 10% CSFA diet. Data obtained in this study showed that 10% CSFA diet failed to stimulate BA secretion to exceed the values obtained with 5% CSFA-diet. Moreover, there was no change in the hepatic extraction rate of BA in animals fed either the 0 or 5% CSFA diets which ranged from 2.4 to 6.5-fold and 3.1 to 7.3-fold, respectively. However, the extraction rate increased sharply with the 10% CSFA diet (27-fold). The median portal and hepatic concentrations of total lipids, triglycerides, total cholesterol, phospholipids and non-esterified fatty acids did not show any significant increase during feeding of the control diet. Moreover, feeding either the 5 or 10% CSFA diet did not significantly increase these values in either vein.

Animals↗

Advanced glomerulosclerosis is reversible in nephrotic mice.

Advanced glomerulosclerosis, a common hallmark of chronic renal diseases (CRD) is believed to be irreversible, and it is thought that glomerular hyperfiltration and hypertrophy may participate in its pathogenesis. We demonstrate here that glomerulosclerosis is "reversible" in an animal model. We used nephrotic ICGN (nep/nep) mice which showed a rapid progression of glomerulosclerosis, accompanied by histological findings for glomerular hyperfiltration. It is known that ureter ligation reduces glomerular filtration in ligated kidneys. When ureter ligation was applied to our model, glomerulosclerosis (characterized by myofibroblast hyperplasia and over-accumulated matrix protein) weakened in conjunction with suppressed glomerular hypertrophy. During this process, glomerular myofibroblasts showed apoptotic cell death after unilateral ureter ligation (UUO) treatment. Our results suggest that inhibition of glomerular filtration in sclerotic tufts may cause glomerular remodeling through the modulation of molecular and cellular sclerogenesis.

Animals↗

Synthesis of coenzyme A esters of 3alpha,7alpha,12alpha-trihydroxy- and 3alpha,7alpha-dihydroxy-24-oxo-5beta-cholestan-26-oic acids for the study of beta-oxidation in bile acid biosynthesis.

3alpha,7alpha,12alpha-Trihydroxy- and 3alpha,7alpha-dihydroxy-24-oxo-5beta-cholestan-26-oyl CoAs were chemically synthesized by the conventional method for the study of side chain cleavage in bile acid biosynthesis. 3alpha,7alpha,12alpha-Triformyloxy- and 3alpha,7alpha-diformyloxy-5beta-cholan-24-als were initially subjected to the Reformatsky reaction with methyl alpha-bromopropionate, and the products were then converted into methyl 3alpha,7alpha,12alpha-triformyloxy- and 3alpha,7alpha-diformyloxy-24-oxo-5beta-cholestan-26-oates. Protection by acetalization of the 24-oxo-group of these methyl esters with ethylene glycol, followed by alkaline hydrolysis, gave 3alpha,7alpha,12alpha-trihydroxy- and 3alpha,7alpha-dihydroxy-24,24-ethylenedioxy-5beta-cholestan-26-oic acids. These acids were condensed with coenzyme A by a mixed anhydride method, and the resulting CoA esters were treated with 4M-hydrocholic acid to remove the protecting group to give 24-oxo-5beta-cholestanoic acid CoA esters. The chromatographic behaviors of these CoA esters were also investigated.

Bile Acids and Salts↗

Conjugation reactions catalyzed by bifunctional proteins related to beta-oxidation in bile acid biosynthesis.

The conjugation reactions of hydration and dehydrogenation catalyzed by the dehydratase and dehydrogenase activities of D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein (DBP) and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase bifunctional protein (LBP) in the side chain degradation step of bile acid biosynthesis were investigated using chemically synthesized C27-bile acid CoA esters as substrates. The hydration catalyzed by DBP showed high diastereoselectivity for (24E)-3alpha,7alpha,12alpha-trihydroxy- and (24E)-3alpha,7alpha-dihydroxy-5beta-cholest-24-en-26-oyl CoA to give (24R,25R)-3alpha,7alpha,12alpha,24-tetrahydroxy- and (24R,25R)-3alpha,7alpha,24-trihydroxy-5beta-cholestan-26-oyl CoAs, respectively, and the dehydrogenation catalyzed by DBP also showed high stereospecificity for the above (24R,25R)-isomers to give 3alpha,7alpha,12alpha-trihydroxy- and 3alpha,7alpha-dihydroxy-24-oxo-5beta-cholestan-26-oyl CoAs, respectively. On the other hand, the dehydratase activity of LBP displayed a different diastereoselectivity producing the (24S,25S)-isomer, and dehydrogenase activity of LBP was stereospecific for the (24S,25R)-isomer to give the above 24-oxo-derivative. The hydration and dehydrogenation reactions catalyzed by DBP were effectively conjugated to convert (24E)-5beta-cholestenoyl CoA to 24-oxo-5beta-cholestanoyl CoA. However, the reactions catalyzed by LBP were not conjugated. These results indicate that DBP plays an important role in the biosynthesis of bile acid.

17-Hydroxysteroid Dehydrogenases↗

3beta-hydroxy-delta5 -C27-steroid dehydrogenase deficiency: diagnosis and treatment.

The aim of this study was to evaluate the effects of bile acid treatment and to obtain further information about the pathway of bile acid biosynthesis in a patient with 3beta-hydroxy-delta5-C27-steroid dehydrogenase/isomerase (3beta-HSD) deficiency by gas chromatography-mass spectrometry. Results showed that at 2 months of age, 3beta-hydroxy-5-cholen-24-oic acid (3.0 micromol/mmol Cr, 7.9%) was detected in the urine in essentially the same relative amount as 3beta,7alpha-dihydroxy- and 3beta,7alpha,12alpha-trihydroxy-5-cholen-24-oic acids (3.7 micromol/mmol Cr, 9.8%) during ursodeoxycholic acid treatment combined with prednisolone. As a result, diagnosis was delayed until 18 months of age. One month later with substitution of chenodeoxycholic acid treatment, urinary 3beta,7alpha-dihydroxy- and 3beta,7alpha,12alpha-trihydroxy-5-cholen-24-oic acids decreased significantly, and subsequent improvement of liver dysfunction was accelerated. Chenodeoxycholic acid treatment is useful in 3beta-HSD deficiency. However, in the diagnosis of this disease in early life, it should be noted that the acidic pathway may be the major route for bile acid biosynthesis in the neonatal period. Diagnosis of 3beta-HSD deficiency may have been delayed by administration of ursodeoxycholic acid, resulting in prolonged diagnostic investigation in this child with cholestasis. Further, use of prednisolone may have been contraindicated.

3-Hydroxysteroid Dehydrogenases↗

Comparison of intact PTH assay and whole PTH assay in long-term dialysis patients.

Adynamic bone disease has become a major problem in long-term dialysis patients. It has been suggested that higher levels of parathyroid hormone (PTH) are needed to maintain normal bone turnover in uremia. PTH levels currently are evaluated routinely by intact PTH assay, which may detect inactive 7-84 PTH fragments as well as 1-84 PTH. We examined the efficacy of whole PTH assay, which detects 1-84 PTH exclusively, in 99 nondiabetic patients on maintenance dialysis for more than 10 years, without any residual renal function. PTH levels determined by whole PTH assay were lower than those determined by intact PTH assay in all cases. Serum markers of bone metabolism, such as serum activity of bone alkaline phosphatase, correlated well with whole PTH levels. Because 7-84 PTH has been shown to inhibit the effects of 1-84 PTH, the biologic activity of circulating PTH in uremic patients may be much lower than the values assayed by conventional intact PTH assay. Despite an attempt to correlate 1-84 PTH/7-84 PTH ratio with bone histology, we could find only 1 patient out of 99 with 1-84 PTH/7-84 PTH ratio less than 1, which has been suggested to be indicative of low turnover bone. A cutoff value of this ratio should be set in the future for patients with a long hemodialysis history, with various modes of medical therapy.

Alkaline Phosphatase↗

Enzyme immunoassay for conjugated 7alpha-hydroxy-3-oxo-4-cholenoic acid in human urine.

A microplate enzyme immunoassay (EIA) was developed for the measurement of glycine- and taurine-conjugated 7alpha-hydroxy-3-oxo-4-cholenoic acids (CDCA-delta4-3-one) in human urine. The antiserum was prepared by immunizing rabbits with N-(7alpha-hydroxy-3-oxo-4-cholen-24-oyl)-3-aminopropionic acid--bovine serum albumin conjugate. A colorimetric EIA was established using horseradish peroxidase-labeled antigen having a shorter bridge length than that of the immunogen, and 3, 3', 5, 5'-tetramethylbenzidine /hydrogen peroxide for the measurement of the enzyme activity. The reactivities of the antiserum for glycine and taurine conjugates of CDCA-delta4-3-one was almost the same. The specificity of the antiserum was investigated by determining the cross-reactivities of various bile acids and related compounds. An appropriate dose-response curve for conjugated CDCA-delta4-3-one was obtained in the range of 0.05-10 ng/well. This method was used for direct analysis of conjugated CDCA-delta4-3-one in urine of healthy infants and patients with liver diseases.

Chenodeoxycholic Acid↗