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Biomedical subjects

J Kato

Publications and source records attributed to J Kato.

At least 217 records · Page 12Linked to original sources

Utility of hepatitis C virus RNA levels for predicting the therapeutic efficacy of interferon.

We studied the levels of serum hepatitis C virus (HCV)-RNA, the HCV genotype before interferon therapy, and the kinetics of serum HCV-RNA at the initial stages of therapy to determine their utility in predicting the therapeutic efficacy of interferon in 44 patients with chronic hepatitis C infection. We also looked at the efficacy of repeated interferon treatment in relation to the kinetics of serum HCV-RNA. The level of serum HCV-RNA determined by a branched DNA probe assay before interferon treatment and that by a reverse transcription nested polymerase chain reaction assay during the initial stages of interferon administration were useful for predicting the efficacy of treatment. Furthermore, detection of serum HCV-RNA by the reverse transcription nested polymerase chain reaction assay after the completion of interferon therapy indicated relapse at its earliest stage. In patients who experience relapse, repeated treatment with an appropriate dose of interferon before an increase in viral levels may increase the proportion of complete responses.

Adult↗

Hypotensive effect of chronically infused adrenomedullin in conscious Wistar-Kyoto and spontaneously hypertensive rats.

1. The hypotensive effect of chronically infused human adrenomedullin (hAM), a potent vasodilator peptide that has been reported to have a natriuretic action, was examined in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). 2. Conscious WKY rats and SHR were infused with 200 ng/h synthetic hAM for 14 days by means of osmotic minipumps. Control groups were infused at the same schedule with 0.9% saline. Systolic blood pressure (SBP) and daily urinary excretion of Na+ and K+ were measured before and during the infusion period. In addition, plasma renin activity (PRA), aldosterone and hAM concentrations were measured on day 14 of infusion. 3. A significant reduction in SBP was observed in hAM-treated SHR at day 2 and SBP remained significantly lower throughout the experiment compared with control SHR. Similarly, SBP in the hAM-treated WKY rats was found to be significantly lower than in control WKY rats during infusion. However, the hypotensive effect was not accompanied by any significant increase in urinary volume or Na+ excretion in hAM-treated rats of either strain. Chronic infusion with hAM significantly suppressed PRA and lowered the concentration of plasma aldosterone in WKY rats but not in SHR. The plasma aldosterone in WKY rats and SHR were 0.9 +/- 0.4 and 0.6 +/- 0.2 fmol/mL, respectively. 4. These findings demonstrate that chronically infused hAM has a hypotensive effect in both WKY rats and SHR without an increase in urinary volume or Na+ excretion at a plasma AM concentration within the physiological limit.

Adrenomedullin↗

Effect of oocyte retrieval from a small leading follicle in fixed-schedule in vitro fertilization program.

OBJECTIVE: To evaluate the propriety of oocyte retrieval (OR) form a small leading follicle during a fixed-schedule in vitro fertilization (IVF) program. METHODS: OR was fixed only to take place on Wednesdays. Gonadotropin-releasing hormone agonist treatment was initiated on the first day of the cycle, human menopausal gonadotrophin was given for 7 days starting on the next Monday, and human chorionic gonadotrophin (hCG) was given on the Tuesday before the OR. Patients were divided into 2 groups according to the follicular size observed before the day of hCG administration: Group 1 (141 cycles), with follicles > 16 mm in mean diameter; and Group 2 (38 cycles) with follicles of 10 to 16 mm in mean diameter. RESULTS: Fertilization rates and the incidence of mature oocytes were higher in Group 1 than in Group 2. However, the mean number of oocytes recovered and pregnancy rates were similar in the 2 groups. CONCLUSION: It is worthwhile to retrieve the oocyte from a small leading follicle in a fixed-schedule IVF program.

Adult↗

The behavior of endometrial hyperplasia: a prospective study. Endometrial Hyperplasia Study Group.

OBJECTIVE: To clarify the behavior of endometrial hyperplasia in a prospective study. METHOD: Fifty-one patients with endometrial hyperplasia were followed up for 6 months. Samples of endometrial tissues were taken by uterine endometrial biopsy every 4 weeks during the first 3 months and at the end of follow-up. RESULTS: In 69% (35/51) of the patients histological picture of the endometrium became normal during the observation period. The lesions persisted in 17% (6/35) of the patients with simple hyperplasia, in 25% (1/4) of those with complex hyperplasia, in 14% (1/7) of those with simple atypical hyperplasia, and in 80% (4/5) of the patients with complex atypical hyperplasia. In the remaining 3 patients with simple hyperplasia, the lesions progressed to complex atypical hyperplasia by the end of follow-up, after showing a normal endometrium. CONCLUSION: Most cases of endometrial hyperplasia, except for complex atypical hyperplasia, disappeared spontaneously within a short period of time.

Adult↗

Echographic detection of latent severe thrombotic stenosis of the superior vena cava and innominate vein in patients with a pacemaker: integrated diagnosis using sonography, pulse Doppler, and color flow.

Thrombosis of the innominate vein and SVC is a serious complication in patients with pacemakers, inducing pulmonary embolism or SVC syndrome. Venography is the definitive method for its diagnosis; however, it is too invasive for related studies. The purpose of this study was to validate sonography, pulse Doppler, and color flow in detecting noninvasively innominate vein or SVC thrombosis in patients with pacemakers. In 53 patients with pacemakers, the 1 severe SVC stenosis and 18 severe innominate vein stenoses due to thrombosis were diagnosed by digital subtraction angiography. Sonography accurately showed the severe SVC stenosis due to thrombosis, but had limitations on the innominate vein thrombosis. Color flow demonstrated mosaic flow, indicating poststenotic turbulence due to stenosis of the innominate vein and SVC caused by thrombosis in 15 of 16 patients, and pulse Doppler disclosed absence of flow due to complete occlusion of the innominate vein in 2 of 2 patients. Sensitivity and specificity for detecting severe innominate vein stenosis due to thrombosis using combined color flow and pulse Doppler was 94% and 100%, respectively. In conclusion, sonography, pulse Doppler, and color flow allow accurate detection of severe innominate vein or SVC stenosis due to thrombosis, and are therefore useful for the follow-up of patients with a pacemaker.

Aged↗

Fis is required for illegitimate recombination during formation of lambda bio transducing phage.

Specialized transducing particles of phage lambda are formed by illegitimate recombination during prophage induction. We examined the effects of an Esherichia coli int, xis, himA, himD, or fis mutation on illegitimate recombination during formation of lambda Spi- phage, a class of lambda bio transducing phage. This type of phage is distinguishable from the docL and docR particles, which contain one cohesive end and are formed by cutting of the cos site, by plaque formation of lambda bio on Escherichia coli P2 lysogens. The yields of lambda Spi- phage in the int, xis, int-xis deletion, and b2 deletion mutants were about 50- to 200-fold higher than that of the wild-type prophage when bacteria were irradiated with UV light. This result indicates that Int and Xis functions, and the att site, are not required for illegitimate recombination. The yield of lambda Spi- phage in the himA, himD, or fis mutant carrying lambda delta int-xis prophage was 2.6-, 3.3-, or 17-fold lower, respectively, than that in the wild-type bacteria under UV irradiation. Analysis of the nucleotide sequences of the junctions of the transducing phages indicates that recombination at the hotspots, as well as at non-hotspots, takes place between short homologous sequences. Because the growth of infecting phages was not suppressed by the himA, himD, or fis mutation, we conclude that Fis is required, but IHF is only partially required, for short-homology-dependent illegitimate recombination during the formation of lambda bio transducing phage.

Bacterial Proteins↗

Isolation and characterization of Enterobacter cloacae mutants which are defective in chemotaxis toward inorganic phosphate.

Enterobacter cloacae IFO3320 is attracted to Pi when cells are starved for Pi. Two Tn1737KH-induced mutants, which were constitutive for alkaline phosphatase, failed to exhibit Pi taxis even under conditions of Pi limitation. Both of the mutant strains exhibited normal chemotactic responses to peptone, suggesting that they are specifically defective in Pi taxis. Cloning and sequence analysis showed that the TN1737KH insertions were located in either the pstA or pstB genes which encode the channel-forming proteins of the Pi-specific transport (Pst) system in E. cloacae. These results suggest that the E. cloacae Pst system is required for Pi chemoreception.

ATP-Binding Cassette Transporters↗

Prethrombotic state due to hypercoagulability in patients with permanent transvenous pacemakers.

Venous thrombosis is a relatively usual but serious complication of permanent transvenous pacing. However, the pathogenesis has not been defined. To clarify underlying abnormalities in the coagulation-fibrinolysis system in patients with permanent transvenous pacemakers, we measured serum levels of fibrinopeptide A (FPA), thrombin-antithrombin III complexes (TATs), plasmin-alpha 2 plasmin inhibitor complexes (PICs), D-dimer (D-D), beta-thromboglobulin (beta-TG), and platelet factor 4 (PF4) in 53 patients with permanent transvenous pacemakers and 10 control subjects. The patients were divided into two groups, as follows, according to the presence of mural thrombus documented along the pacing lead(s) by digital subtraction angiography and transesophageal echocardiography: Group Th (-), patients without venous route thrombus; and Group Th (+), patients with venous route thrombus. FPA and TAT levels increased significantly even in Group Th (-), and further increased in Group Th (+) compared with control subjects (FPA: 7.5 +/- 4.9, 15.3 +/- 8.8 vs 3.0 +/- 1.4 ng/mL, respectively, P < 0.05; TAT: 2.9 +/- 1.3, 4.8 +/- 2.3 vs 1.7 +/- 0.6 ng/mL, respectively, P < 0.05). There were no differences in levels of D-D, PIG, beta-TG, and PF4 among control subjects, Group Th (-), and Group Th (+). These findings suggest that the hypercoagulable state appears in patients with permanent transvenous pacemakers, even without apparent venous thrombosis. The patients with permanent transvenous pacemakers are thought to be in the prethrombotic state even if they have no venous route thrombosis.

Adult↗

Acyl amino acid derivatives as novel inhibitors of influenza neuraminidase.

We searched our chemical collection to identify non-N-acetylneuraminate (NeuAC) inhibitors of influenza neuraminidase (NA). Of the 62 acyl derivatives tested, several acyl amino acids, but not acyl alkanolamine derivatives, were effective and inhibited the NA activity in a dose-dependent manner. N-3-Hydroxymyristoyl D-cysteine and N-myristoyl-O-caproyl-D-serine were the more potent compounds and inhibited the enzyme in a noncompetitive manner (Ki = 102 and 125 microM, respectively) without respect to the substrate. An important consideration for the choice of inhibitor is the selectivity of the inhibition. These compounds were selective inhibitors of viral NA and effective for any variant enzyme, but the enzymes from V. cholerae and human placenta were insensitive. Accordingly, the acyl amino acid derivatives may be expected to be inhibitors without cellular toxicity and may serve as lead compounds for anti-influenza agents.

Acylation↗

Changes in cardiac adrenomedullin concentration in renovascular hypertensive rats.

We assessed changes in tissue and plasma adrenomedullin levels in two-kidney, one-clip renovascular hypertensive rats. Four weeks after clipping, adrenomedullin concentrations were significantly higher in the cardiac ventricles and lower in the left atrium than the respective values in sham-operated rats. The left ventricular adrenomedullin concentration significantly correlated with systolic blood pressure and the degree of cardiac hypertrophy. No difference was noted in the adrenomedullin concentrations of the adrenal gland, aorta, lung, kidneys, or plasma between the two groups. These findings indicate possible involvement of cardiac adrenomedullin in this model of hypertension.

Adrenomedullin↗

Determinants of circadian blood pressure variation: a community-based study in Ohasama.

We investigated factors affecting the nocturnal decline in blood pressure (BP). A cross sectional study was done in 706 community-based untreated subjects > or = 20 years of age. Screening and ambulatory BPs were measured and the effects of age and the ambulatory BP on the nocturnal decline were examined. Bivariate analysis demonstrated that the magnitude of the decline and the percent decline in the nocturnal BP increased with increase in daytime ambulatory BP and decreased with increase in nighttime ambulatory BP. Although the magnitude of the nocturnal decline in BP increased with increasing daytime BP, the nocturnal BP in hypertensives was still higher than those in normotensives. The magnitude decreased with increasing age in men but not in women, while the percent decline decreased with increasing age in both men and women. Since bivariate analysis demonstrated that the daytime BP, nighttime BP, and standard deviation of the 24-hour BP strongly correlated with the magnitude of the nocturnal decline, these parameters were excluded as independent variables from the multivariate analysis. In the multivariate analysis the nighttime pulse pressure was negatively and daytime pulse pressure was positively associated with the magnitude of the decline and the percent decline in the nocturnal BP. A non-dipping circadian variation was frequently observed in elderly normotensive men but the rate of nondipper was rather low in hypertensive individuals in the general population. A marked dipping pattern was frequently observed in hypertensive women > or = 70 years of age. The nocturnal BP levels in subjects with daytime hypertension are higher than those in subjects with daytime normotension. Therefore, BP must ideally be lowered over 24-hour period in hypertensive subjects. The diminished magnitude of the decline and the decrease in the percent decline in the nocturnal BP in the elderly may be mediated by the disturbed baroreflex function due to the decrease in compliance of large elastic artery. However, in some elderly hypertensive women, excess nocturnal decline in BP is observed. In such subjects, we should take care of the nocturnal BP levels during treatment.

Adult↗

Inhibition of octapeptide N-myristoylation by acyl amino acids and acyl alkanolamines.

Several acyl amino acids and acyl alkanolamines were prepared and screened for their inhibition of octapeptide N-myristoylation and HIV-1 replication in MT-4 cells. Of the 62 acyl derivatives tested, N-myristoyl-O-caproyl-L-serine, N-myristoyl-O-caproyl-D-serine and N-decanoyl-O-myristoyl-L-serine were found to be uncompetitive inhibitors of N-myristoylation, but did not prevent HIV-induced cytopathicity in MT-4 cells. However, other acyl derivatives such as N-3-hydroxymyristoyl ethanolamine, N-3-hydroxymyristoyl-D-serine and N-myristoyl-L-cysteine, which did not inhibit N-myristoylation, suppressed the cytopathicity in the infected cells. The acyl derivatives described here may serve as lead compounds for antiviral agents.

Acylation↗

[Cdk inhibiting proteins].

Mammalian cell growth is governed by a number of extracellular signals, among which anti-proliferative stimuli arrest cells in G1 phase of the cell cycle by increasing the activity of a group of polypeptides called cdk inhibitors (cdk inhibiting proteins). So far seven members of cdk inhibiting proteins have been isolated and characterized. They mostly locate in the nucleus and inhibit G1 cyclin/cdk activities by directly binding to them, thereby interfering with phosphorylation of key substrates to exit G1 including retinoblastoma proteins among them. Some of the cdk inhibiting protein genes are frequently deleted or mutated in tumor cells, and certain oncoproteins encoded by transforming viruses target cdk inhibiting proteins, suggesting that cdk inhibiting proteins function as tumor suppressors. It is important to investigate signaling pathways and regulatory mechanisms involving cdk inhibiting proteins not only to better understand cellular proliferation, cell cycle regulation, or cancer development, but also to search for new target molecules for chemotherapy.

Animals↗

Structure of aromatase mRNA in the rat brain.

In order to elucidate the mechanism of the region-specific expression of rat brain aromatase, we investigated the multiple promoter systems in the brain. Total RNA extracted from the amygdala (AMY) was subjected to a reverse transcription-polymerase chain reaction (RT-PCR) with the primers for mouse brain-specific exon I (exon I-f). The nucleotide sequence of the RT-PCR product had 89.4% homology to the corresponding region of exon I-f of the human aromatase cDNA. It was first demonstrated that aromatase mRNA with exon I-f was expressed in the rat brain. This type message was expressed in the hypothalamus-preoptic area (HPOA) but not in the cerebral cortex (CC). Furthermore, total RNAs from the HPOA, AMY and CC of the rat brain were analysed by RT-PCR with the primers for rat ovarian type message-specific exon II. Significant levels of the products were generated in the HPOA and AMY with no signals in the CC. Cortical aromatase mRNA seemed to be unique in that the tissue had no exon I-f and ovarian type mRNAs. We thus analysed the 5'-region of aromatase mRNA in the rat CC by 5'-rapid amplification of cDNA ends (RACE) with antisense primers for exon V. The upstream sequence from the 5'-end of exon IV of the aromatase RACE clones was completely different from that of the aromatase mRNA which encoded the full-translated region. These results indicated that the aromatase gene in the rat brain contained at least three promoters: hypothalamus type (exon I-f), ovarian type and cortical type, and that the region-specific expression of the brain aromatase seemed to be regulated, at least in part, by differential promoter usage.

Animals↗

[Modification of the surgical strategy based on intraoperative echographic findings of atherosclerotic ascending aorta].

To prevent the atheroembolic complications such as brain infarction due to the manipulation of atherosclerotic ascending aorta during cardiac surgery, the ascending aorta of 55 patients including 6 emergencies (mean age: 67.7 +/- 6.9 years, valvular disease: n = 12, ischemic heart disease only or combined with valvular disease: n = 43) were evaluated with intraoperative echography as a routine, to enable a proper placement of the cannulae, clamp etc. Irregular elevated lesions into the aortic lumen from the intima were identified in 7 patients (13%, mean age: 71.0 +/- 6.9 years) of ischemic heart disease, which included 2 emergent cases. Arch cannulation was employed in 3 patients with wide-spread lesions on the posterior wall and femoral cannulation was done in 1 patient with wide-spread lesions on the anterior wall. Two of these patients received CABG with in situ arterial conduits under ventricular fibrillation, and the other 2 patients received CABG with aortic cross clamping at the lesion-free site during proximal anastomosis of vein grafts (single clamp technique). Two patients with localized lesion were done CABG with partial aortic clamping and one of them had cerebral infarction during the operation. We recognized that manipulation of the ascending aorta has to be done with a meticulous care and well away from the diseased site. In another patient with localized lesion, the arch cannulation and the single clamp technique were used 2 cm away from that lesion. The brain infarcted patient completely recovered without any sequelae and the others also had no atheroembolic complications. Although calcified lesions on CT were correlated with atheromatous lesions on echogram (p = 0.004), these atheromatous plaques were not detected by enhanced CT, except in only one patient. For screening of the atherosclerosis of ascending aorta, the CT examination was not so effective and the intraoperative echography was the most sensitive and could be easily accomplished. In conclusion, in order to prevent the atheroembolism that might occur due to the improper manipulation of the diseased ascending aorta during usual procedures, surgical strategies have to be modified according to the position, extent and quality of the atherosclerotic lesions, diagnosed by intraoperative echoscanning of the aorta.

Aged↗

[Current status of management of omphalocele and gastroschisis].

Forty-five cases of gastroschisis and 85 of omphalocele were reviewed. The survival of gastroschisis has dramatically improved over the past 20 years, however, that of omphalocele still remained in the lower value, because the size of the defect and the presence of associated anomalies are prognostic factors. The primary fascial closure was first employed for the patients with gastroschisis and a silo chimney was used for limited cases. On the other hand, for the patients with omphalocele, primary closure was possible in 34 cases, silo chimney was used in 17, and 45 cases had nonoperative management with epithelialization. Among them, nonoperative management using painting was the most reliable therapeutic for omphalocele.

Abdominal Muscles↗

Plasma adrenomedullin in cerebrovascular disease: a possible indicator of endothelial injury.

BACKGROUND: Cultured vascular endothelial and smooth muscle cells actively produce adrenomedullin, a novel vasodilator peptide discovered in human pheochromocytoma tissue. This present study was designed to determine whether the plasma level of adrenomedullin is a useful indicator for estimating the degree of endothelial injury in patients with atherosclerotic disease. METHODS: We used a radioimmunoassay to measure plasma adrenomedullin concentrations in 51 patients with chronic cerebrovascular disease (34 infarctions and 17 haemorrhages) and in 10 subjects without symptomatic cerebrovascular disease. We also measured the plasma concentrations of thrombomodulin and endothelin as markers of endothelial injury. The patients were divided into three groups (A, B, and C) on the basis of the number of risk factors for atherosclerosis: hypertension, hyperlipidemia, smoking, low HDL-cholesterol, diabetes mellitus, and hyperuricaemia. Group A (68.7+/-2.7 years) consisted of patients with 0 or 1 risk factors; B (68.3+/-4.2 years) those with 2 risk factors; and C (69.2+/-3.6 years) those with 3 or more risk factors. RESULTS: The plasma concentration of adrenomedullin in these patients showed a significant positive correlation with age (r=0.33, p<0.05), as well as with the plasma concentrations of thrombomodulin (r=0.54, p<0.001) and endothelin (r=0.53, p<0.001). Moreover, the plasma concentrations of adrenomedullin and thrombomodulin (p<0.005 and p<0.02, respectively) tended to be higher in Group B and to be significantly higher in Group C as compared to Group A. Plasma adrenomedullin concentrations did not, however, significantly differ between the infarction and haemorrhage patients. CONCLUSIONS: These findings suggest that the plasma adrenomedullin concentrations reflect the degree of endothelial injury in patients with atherosclerotic disease.

Adrenomedullin↗