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Biomedical subjects

T Kondo

Publications and source records attributed to T Kondo.

At least 271 records · Page 15Linked to original sources
PubMed2000

Therapeutic spectrum of nemonapride and its relationship with plasma concentrations of the drug and prolactin.

The therapeutic spectrum of nemonapride, a new substituted benzamide, and its relationship with plasma concentrations of the drug and prolactin were investigated by a fixed-dose study (18 mg/day for 3 weeks) in 31 patients with acutely exacerbated schizophrenia. Of 31 patients, 25 (80.6%) were responders who showed a reduction in symptoms (percentage of improvement) of 50% or more after 3 weeks. The mean values of percentage of improvement in scores on the total Brief Psychiatric Rating Scale (BPRS) and the five subscale symptoms were 71.5% for total, 73.2% for Positive, 86.0% for Excitement, 53.9% for Negative, 84.2% for Cognitive, and 67.5% for Anxiety-Depression. Responders had higher percentage of improvement in positive (84.6 +/- 17.0% vs. 25.9 +/- 15.7%; p < 0.001) and anxiety-depression (76.9 +/- 18.8% vs. 28.5 +/- 39.9%; p < 0.005) symptoms than did nonresponders after 3 weeks. The percentage of improvement in total BPRS after 2 weeks was well correlated with that after 3 weeks (Spearman rank correlation coefficient: r(s) = 0.711; p < 0.01). There was an inverted U-shaped relationship between plasma drug concentrations (nemonapride plus desmethylnemonapride) and percentage of improvement in total BPRS symptoms after a 3-week treatment (y = 46.9 + 73.9x - 44.2x2; p < 0.001). These findings suggest that nemonapride has a broad therapeutic spectrum in the treatment of acute schizophrenia. The improvements in scores for the Positive and Anxiety-Depression subscale symptoms are regarded as determinant factors for total response to nemonapride. An assessment of clinical status after 2 weeks and plasma drug monitoring may be useful for the prediction of the final outcome for patients.

Adolescent↗
PubMed2000

Effect of a genetic polymorphism of CYP1A2 inducibility on the steady state plasma concentrations of haloperidol and reduced haloperidol in Japanese patients with schizophrenia.

The effect of a genetic polymorphism of inducibility of cytochrome P450 (CYP) 1A2 on the steady state plasma concentrations (Css) of haloperidol and reduced haloperidol was studied to clarify if these Css are dependent on the CYP1A2 activity. The subjects were 101 Japanese schizophrenic inpatients receiving oral haloperidol 12 mg/d. The Css of haloperidol and reduced haloperidol were measured in duplicate by high performance liquid chromatographic method, and were corrected to the mean body weight. A point mutation from guanine (wild-type) to adenine (mutated-type) at position -2964 in the 5'-flanking region of CYP1A2 gene was identified by polymerase chain reaction (PCR)-fragment length polymorphism method. Based on the present results, i.e., significant effects of CYP2D6 genotypes on the Css of haloperidol and reduced haloperidol, analyses were separately performed in two groups, i.e., patients with 0 mutated allele of the CYP2D6 (41 cases) and those with 1 or 2 mutated alleles (60 cases). Subjects in each CYP2D6 genotype group consisted of 4 subgroups according to smoking habit and the presence of the mutated allele of the CYP1A2. Neither the Css of haloperidol nor that of reduced haloperidol significantly differed among the 4 subgroups in either CYP2D6 genotype group. The present study thus suggests that the CYP1A2 activity does not play an important role in controlling the Css of haloperidol or reduced haloperidol.

Alleles↗
PubMed2000

The relationship between dopamine D2 receptor polymorphism at the Taq1 A locus and therapeutic response to nemonapride, a selective dopamine antagonist, in schizophrenic patients.

Previous studies have demonstrated that subjects with one or two A1 alleles of dopamine D2 receptor (DRD2) polymorphism at the Taq1 A locus have lower DRD2 density than those with no A1 allele. The present study aimed to examine whether the Taq1 A DRD2 genotypes are related to therapeutic response to nemonapride, a selective dopamine antagonist, in schizophrenic patients. The subjects were 25 acutely exacerbated schizophrenic inpatients who had received no medication for at least 1 month before the study. The fixed dose (18 mg/day) of nemonapride was administered to each patient for 3 weeks. The clinical status was prospectively monitored by the Brief Psychiatric Rating Scale (BPRS) before, and 3 weeks after, the treatment. The Taq1 A genotypes (A1 and A2 alleles) were determined by the polymerase chain reaction method. Three patients were homozygous for the A1 allele, 11 were heterozygous for the A1 and A2 alleles, and 11 were homozygous for the A2 allele. The patients with one or two A1 alleles (n = 14) showed significantly higher percentage improvement in total BPRS and positive symptoms than those with no A1 allele (n = 11) after 3-week treatment while the percentage improvement in other subgrouped symptoms (negative, anxiety-depression, excitement and cognitive symptoms) was similar between the two genotype groups. The present results suggest that the Taq1 A DRD2 polymorphism is related to early therapeutic response to nemonapride in schizophrenic patients, possibly by modifying the efficiency of DRD2 antagonism of the drug in the central nervous system.

Adult↗
PubMed2000

Rfc5, in cooperation with rad24, controls DNA damage checkpoints throughout the cell cycle in Saccharomyces cerevisiae.

RAD24 and RFC5 are required for DNA damage checkpoint control in the budding yeast Saccharomyces cerevisiae. Rad24 is structurally related to replication factor C (RFC) subunits and associates with RFC subunits Rfc2, Rfc3, Rfc4, and Rfc5. rad24Delta mutants are defective in all the G(1)-, S-, and G(2)/M-phase DNA damage checkpoints, whereas the rfc5-1 mutant is impaired only in the S-phase DNA damage checkpoint. Both the RFC subunits and Rad24 contain a consensus sequence for nucleoside triphosphate (NTP) binding. To determine whether the NTP-binding motif is important for Rad24 function, we mutated the conserved lysine(115) residue in this motif. The rad24-K115E mutation, which changes lysine to glutamate, confers a complete loss-of-function phenotype, while the rad24-K115R mutation, which changes lysine to arginine, shows no apparent phenotype. Although neither rfc5-1 nor rad24-K115R single mutants are defective in the G(1)- and G(2)/M-phase DNA damage checkpoints, rfc5-1 rad24-K115R double mutants become defective in these checkpoints. Coimmunoprecipitation experiments revealed that Rad24(K115R) fails to interact with the RFC proteins in rfc5-1 mutants. Together, these results indicate that RFC5, like RAD24, functions in all the G(1)-, S- and G(2)/M-phase DNA damage checkpoints and suggest that the interaction of Rad24 with the RFC proteins is essential for DNA damage checkpoint control.

Cell Cycle↗
PubMed2000

Respiratory-related bronchial rhythmic constrictions in the dog with extracorporeal circulation.

Respiratory-related bronchial rhythmic contraction was quantitatively analyzed in eight paralyzed dogs. The caliber of the fifth-generation bronchus was continuously measured as the pressure (Pbr) of a balloon-tipped catheter under the condition of complete immobilization due to extracorporeal oxygenation. Pbr changed rhythmically in synchrony with phrenic nerve activity (PNA) bursts. Rhythmic bronchial constriction started at 1.4 +/- 0.49 (SD) s after onset of PNA, reached a maximum level at 2.8 +/- 1.6 s after termination of PNA, and then decreased exponentially with a time constant of 6.9 +/- 2.5 s. When the respiratory rate of dogs increased at hypercapnia, the various bronchial contractions fused to behave like a tonic contraction. The rhythmic component of this contraction was separated and quantitatively analyzed. Each rhythmic Pbr amplitude linearly increased with increases in PNA amplitude, whereas the end-expiratory Pbr level was not significantly changed. Bilateral efferent nerve transection did not decrease the end-expiratory Pbr level. In response to electric stimulation of efferent nerve fibers, the bronchus did not maintain tonic contraction. We concluded that vagally mediated commands contract bronchial smooth muscle only intermittently and that most of bronchial resting tension may thus be attributed to the summation of rhythmic contractions.

Animals↗
PubMed2000

Difference in the effects of low temperatures on the tension of human pulmonary artery and vein ring segments.

BACKGROUND: Although limited data suggest that pulmonary flushing with organ preservation solutions should not be performed at too low temperatures, the influence of temperature on pulmonary vascular tone is unclear. OBJECTIVE: The purpose of this study was to examine the effect of low temperatures of the tension of human pulmonary artery and vein ring segments and the vascular resistance of perfused rat lungs. METHODS: 5 sets of human pulmonary artery and vein ring segments were suspended from a force displacement transducer at 37, 24 and 8 degrees C, and the effect of 30 mM K(+) on the tension was monitored. The effect of 30 mM K(+) on vascular resistance was also examined at low temperatures in 5 perfused rat lungs. RESULTS: Pulmonary artery segments dilated at 24 degrees C, and more significant vasodilatation was observed at 8 degrees C. In contrast, there was a significant constriction of pulmonary veins at 8 degrees C. Vasoconstriction induced by 30 mM K(+) at 37 degrees C was significantly inhibited at low temperatures in both pulmonary arteries and veins. In rat lungs, perfusion at 8 degrees C caused a significant increase in pulmonary vascular resistance, even though no further increase was observed in the presence of 30 mM K(+). CONCLUSIONS: Our data indicate that pulmonary arteries dilate and the veins constrict at 8 degrees C and may increase pulmonary vascular resistance. We conclude that the different effect of low temperatures between pulmonary arteries and veins may explain why pulmonary vascular flushing with organ preservation solutions at room temperature is more satisfactory.

Adult↗
PubMed2000

Superoxide dismutase in alveolar macrophages from patients with diffuse panbronchiolitis.

BACKGROUND: Diffuse panbronchiolitis (DPB) is characterized by chronic neutrophil-mediated inflammation of the airway mediated by oxygen radical production. DPB can be controlled with low-dose and long-term erythromycin therapy based on its anti-inflammatory effect. OBJECTIVE: In this study, the antioxidant levels were analyzed as an anti-inflammatory effect of erythromycin in the patients. METHODS: We investigated the activity and protein level of an antioxidant enzyme, Cu, Zn-superoxide dismutase (SOD) in alveolar macrophages (AMs) of patients with DPB before and after erythromycin therapy. AMs were obtained from bronchoalveolar lavage fluid. RESULTS: There was no significant difference in the activity of Cu, Zn-SOD between normal subjects and untreated patients. Erythromycin therapy (600 mg/day) significantly increased the activity of the enzyme relative to that before therapy and normal subjects [18.2 units/10(6) cells (9.2-26.2) vs. 4.4 units/10(6) cells (1.1-9.3), p < 0.01 and 10.4 units/10(6) cells (2.4-20.6), p < 0.05, respectively]. Furthermore, the protein level of Cu, Zn-SOD in AMs in treated patients was significantly higher than in the other two groups [69.4 ng/10(6) cells (34.2-147.1) vs. 20.1 ng/ 10(6) cells (16.9-39.8) for untreated patients, p < 0.01 and 43.2 ng/10(6) cells (32.6-68.2) for normal subjects, p < 0.01], but the levels in the latter groups were not different. CONCLUSION: Our results suggest that one of the anti-inflammatory effects of erythromycin in DPB may be, in part, mediated by enhancement of antioxidant activity in AMs.

Adult↗
PubMed2000

Basic helix-loop-helix proteins and the timing of oligodendrocyte differentiation.

An intracellular timer in oligodendrocyte precursor cells is thought to help control the timing of their differentiation. We show here that the expression of the Hes5 and Mash1 genes, which encode neural-specific bHLH proteins, decrease and increase, respectively, in these cells with a time course expected if the proteins are part of the timer. We show that enforced expression of Hes5 in purified precursor cells strongly inhibits the normal increase in the thyroid hormone receptor protein TR(&bgr;)1, which is thought to be part of the timing mechanism; it also strongly inhibits the differentiation induced by either mitogen withdrawal or thyroid hormone treatment. Enforced expression of Mash1, by contrast, somewhat accelerates the increase in TR(beta)1 protein. These findings suggest that Hes5 and Mash1 may be part of the cell-intrinsic timer in the precursor cells.

Animals↗
PubMed2000

Gordonan, an acidic polysaccharide with cell aggregation-inducing activity in insect BM-N4 cells, produced by Gordonia sp.

An acidic polysaccharide, termed gordonan, was isolated from the culture medium of Gordonia sp. as an inducer of cell aggregation in an insect cell line, BM-N4. Gordonan had an average molecular weight of 5 x 10(6) and its structure was identified as -->3)-4-O-(1-carboxyethyl)-beta-D-Manp-(1-->4)-beta-D-GlcAp-(1-->4)-beta-D-Glcp-(1--> mainly by acid hydrolysis experiments and NMR analysis. It induces cell aggregation at the concentration of 4 microg/ml. A partially hydrolyzed polysaccharide derived from gordonan with a molecular weight of 5 x 10(5) showed weak activity, while any fragment molecules with lower molecular weights prepared from gordonan showed no activity.

Actinomycetales↗
PubMed2000

Application of a type-specific enzyme-linked immunosorbent assay for equine herpesvirus types 1 and 4 (EHV-1 and -4) to horse populations inoculated with inactivated EHV-1 vaccine.

A type-specific enzyme-linked immunosorbent assay (ELISA) using equine herpesvirus types 1 (EHV-1) and 4 (EHV-4) glycoprotein G was applied for sero-epizootiology of EHV infections in Japan. Recently, an inactivated EHV-1 vaccine has been administered to racehorses for prevention of upper respiratory disease. To examine the effect of the vaccination on the result of the ELISA, 6 horses were experimentally inoculated three times intramuscularly or intranasally with inactivated EHV-1 vaccine. Sera collected from these horses were used to the type-specific ELISA and complement-fixation (CF) test. Although the CF test detected a significant increase of antibody elicited by vaccination, the ELISA did not detect any antibody response. Next, sera collected from thirty-eight horses, which were intramuscularly inoculated with inactivated EHV-1 twice at an interval of four weeks, were used in the ELISA and CF test. The results also indicated that CF titers increased by vaccine inoculation, but ELISA titers did not. To examine epizootiology of EHVs serologically in racehorse populations at two Training Centers of the Japan Racing Association, the type-specific ELISA and CF test were carried out using paired sera collected from racehorses before and after the winter season. The results showed that the ELISA could distinguish EHV-1 and EHV-4 infections in vaccinated horses serologically. In conclusion, the type-specific ELISA is considered to be useful for sero-diagnosis and sero-epizootiological research on EHV-1 and EHV-4 infections not only in unvaccinated horses, but also in vaccinated horses in Japan.

Administration, Intranasal↗
PubMed2000

The effect of chronic exercise on the rat pancreas.

BACKGROUND: We recently demonstrated that chronic physical exercise increases pancreatic protein content and basal amylase secretion. It is unknown whether chronic exercise causes hypertrophy or proliferation of pancreatic acinar cells. METHODS: Female F344 rats (age, 6 wk) were divided into control (n = 7) and exercise (n = 6) groups. Food consumption was matched between the 2 groups. Rats in the control group were kept sedentary. Rats in the exercise group were exercised for 60 min, 5 d/wk during the experiment. After 8 wk, the pancreas and hindlimb muscles were rapidly excised and weighed. Protein and DNA content and enzyme activity in pancreatic tissue were measured. Pancreatic tissues from control and exercised rats were also prepared for transmission electron microscopy. RESULTS: Inhibition of growth and hypertrophy of hindlimb muscles were exhibited by the exercise group. In the exercise group, pancreatic wet weight, protein content, and amylase and lipase activities, but not DNA content, were significantly higher than those in the control group. Electron micrographs clearly revealed that acinar cells were hypertrophied and zymogen granules were increased in number in exercised rats. CONCLUSION: Chronic endurance exercise increases pancreatic weight, protein content and enzyme activity through hypertrophy of acinar cells.

Amylases↗
PubMed2000

Comparison of vectorcardiographic and 12-lead electrocardiographic detections of abnormalities in repolarization properties due to preexcitation in patients with Wolff-Parkinson-White syndrome: proposal of a novel concept of a "remodeling gradient".

Repolarization abnormalities after radiofrequency ablation in patients with manifest Wolff-Parkinson-White syndrome (WPW) have been attributed to cardiac memory of pre-existing changes in repolarization properties. We compared spatial ventricular gradient (VG) from vectorcardiograms with QRST values of 12-lead ECG in 41 patients with WPW (group A, manifest WPW due to left-sided accessory pathway (n = 20); group B, manifest WPW due to right-sided accessory pathway (n = 12); group C, concealed WPW (n = 9)) before and after ablation. Group N (n = 607) served as control. In groups A and B, the abnormalities of spatial VG and QRST values of 12-lead ECG that existed before and 1 day after ablation significantly decreased 1 week after ablation. In group C, spatial VG and QRST values of 12-lead ECG showed no significant changes. The diagnostic ability of spatial VG is almost equivalent to that of the QRST value of ECG in detecting repolarization abnormalities in patients with WPW before and after ablation. We propose a new concept of a "remodeling gradient" directing from the preexcited area to the opposite side of the ventricle as a result of preexcitation-induced electrical remodeling.

Adolescent↗
PubMed2000

Applicability of Hyland's Living with Asthma Questionnaire for Japanese asthmatic patients.

OBJECTIVE: To assess the applicability of Hyland's Living with Asthma Questionnaire (LWAQ, 1991), one of the international health-related quality of life scales, for Japanese asthmatic patients with reference to its reproducibility and validity. SUBJECTS AND METHODS: The LWAQ was given to randomly selected asthmatic patients on two occasions separated by a 12-week interval. RESULTS: The mean scale score in the first study (n=304) was 1.83 (range, 1.14-2.77) and logarithmic values of the scores approached normal distribution. The scale scores in the first and second (n=158) studies were well correlated (r=0.81), however, the mean score decreased (0.08) significantly. The questions were further separated into 11 domains. The sex-domain was notable for a low response rate (68%), and scale scores in the sleep-, colds- and sex-domains in the first study varied considerably from those of the other domains. Frequency distributions of scores in the five constructs (Hyland 1996) were not normal and, with the exception of the colds construct, the relations among the remaining four constructs were similar to those previously reported (Hyland 1996). CONCLUSION: Analysis using the mean scale score, domain and construct in the LWAQ is applicable to Japanese asthmatic patients.

Asthma↗
PubMed2000

Thermal perception threshold testing for the evaluation of small sensory nerve fiber injury in patients with hand-arm vibration syndrome.

The aim of the present study was to investigate whether thermal perception threshold testing is a useful method that could replace pain threshold testing in the evaluation of small sensory nerve fiber injury in vibration-induced neuropathy. Vibration, pain, and thermal (warm and cold) perception thresholds were examined on both middle fingers of 50 patients with hand-arm vibration syndrome and 29 healthy controls of similar age. The patients were divided into three subgroups according to the Stockholm Workshop sensorineural scale. Thermal (warm and cold) thresholds as well as vibration and pain thresholds were significantly more deteriorated among the patients than in the controls. Among the patients, warm thresholds elevated and cold thresholds lowered according to the Stockholm Workshop scale. Thermal thresholds were significantly correlated with pain thresholds, and the sensitivity of the thermal threshold testing tended to be greater than that of the pain threshold testing. The present findings indicate that thermal threshold testing for warm and cold perception can be a useful substitute for pain threshold testing to examine small nerve fiber injury in vibration-induced neuropathy.

Arm↗
PubMed2000

MDM2 expression is associated with progress of disease and WAF1 expression in resected lung cancer.

Although MDM2, p21/WAF1, and p53 are considered as regulating each other based on in vitro studies, the relation in human lung cancer is not fully understood. The expressions of these proteins were examined immunohistochemically in 112 resected non-small cell lung cancer specimens and the correlation between them were analyzed. MDM2 was expressed in 45% of all lung cancers. In advanced stage, MDM2-positive cases were observed more frequently than in early stage, showing significant difference. No significant difference was observed in the prognosis of the patients regardless of the expression of any protein. Although no correlation was observed between MDM2 expression and p53 expression, or between p21/WAF1 expression and p53 expression, MDM2 expression was strongly related with p21/WAF1 expression. Therefore, MDM2 expression may relate to the progress of the stage of lung cancer, and MDM2 expression and p21/WAF1 expression may be associated not through the p53-related pathway.

Adenocarcinoma↗
PubMed2000

[The result of mass screening of 1997 for prostatic cancer in Isesaki City].

PURPOSE: Screening by only prostate specific antigen (PSA) for prostate cancer was started since PSA had been added to mass screening as one of check lists in 1997 in Isesaki city, Gunma pref. We expected PSA screening to be introduced into other areas. We therefore studied how to perform a screening procedure for prostate cancer as well as discussed our result of the screening conducted lately. MATERIALS AND METHODS: 1,382 out of 1,423 Isesaki citizens who took mass screening aged 40 to 64 were chosen. Regardless of age, men with a serum PSA level equal or larger than 4.1 ng/ml (Tandem R) were selected for second screening since we determined it was a cut-off level for further check-up. Of those men, 38 were requested for second screening and actually only 24 took it. All these men took PSA check-up again, furthermore 23 took transrectal examination (TRE) and/or transrectal ultra sonography (TRUS) except for one of them. The next screening was requested for sixteen of them. Prostate biopsy was conducted for all of them. RESULTS: More old men took screening and were diagnosed prostate cancer. The findings derived from such diagnosis showed one of them aged 50 to 59 and six of them aged 60 to 64 had the cancer. Moreover, four out of twenty with PSA level ranging 4.1 to 10.0 ng/ml and all of three with PSA level over 20.0 ng/ml had the cancer. Five out of sixteen with a positive sign for further PSA check-ups had the cancer. All the three suspect of the cancer by TURS and DRE had prostate cancer. Two of seven with PSA negative showed suspicion of prostate cancer and had the cancer. No neo-adjuvant and total prostatectomy was conducted for four with 4.0 to 10.0ng/ml diagnosed T2N0 M0. One of them with PSA equal or over 20.0 ng/ml was diagnosed T3N0M0. After hormone therapy its PSA decreased to that equal or under 0.5 ng/ml. Total prostatectomy was conducted for it. CONCLUSION: It is not proved that only PSA mass screening for prostatic cancer contributes to detect early cancer and better prognosis cure case. For the proof, it will be nessary that PSA mass screening is examined more people in the wide area. We conclude men aged 65 to 69 also should take PSA check-up based on epidemiological feature of prostatic cancer.

Adult↗