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T Kondo

Publications and source records attributed to T Kondo.

At least 451 records · Page 25Linked to original sources
PubMed1998

The development of a new mouse model of global ischemia: focus on the relationships between ischemia duration, anesthesia, cerebral vasculature, and neuronal injury following global ischemia in mice.

A new model for mouse global ischemia is presented, and the relationship of ischemia duration, cerebral vasculature, and ischemic neuronal injury has been determined. CD-1 mice anesthetized by chloral hydrate were subjected to global ischemia by bilateral common carotid artery occlusion under controlled ventilation for 3, 5, and 10 min. After evaluating the patency of the posterior communicating artery (PcomA) as hypoplastic or normoplastic, neuronal injury was independently determined in the striatum, cortex, and hippocampus in each hemisphere. Ischemic injury was strongly correlated with not only ischemia duration, but also with the patency of the PcomAs. Furthermore, neuronal injury developed in a delayed fashion after 3-min ischemia, while it was maximized at 24 h after 10-min ischemia. Physiological studies showed the induction of slight hypotension as compared with inhalation anesthesia, and improvement of blood gas data relative to spontaneous respiration. These data demonstrate the usefulness of this method to induce selective vulnerability and delayed neuronal cell death in mice, and to provide a useful model to study the detailed mechanism of global ischemia using transgenic or knockout mutant mice.

Anesthesia↗
PubMed1998

Metalloproteinase inhibitor prevents hepatic injury in endotoxemic mice.

This study was conducted to examine of [4-(N-hydroxyamino)-2R-isobutyl-3S-(phenylthiomethyl)-succinyl]-L- phenylalanine-N-methylamide (GI 129471), a matrix metalloproteinase inhibitor, for its effects on increase of serum pro-inflammatory cytokine levels as well as hepatic injury in D-galactosamine plus lipopolysaccharide-injected mice. In vitro experiments showed that GI 129471 was able to inhibit the elevation of tumor necrosis factor-alpha (TNF-alpha) in LPS-stimulated human and mouse whole blood with IC50 values of 370 nM and 260 nM, respectively. When administrated i.p. at 40 mg/kg, GI 129471 significantly reduced serum TNF-alpha level but not other pro-inflammatory cytokines in D-galactosamine plus lipopolysaccharide-injected mice. Treatment of mice with GI 129471 also reduced biochemical indices of hepatic injury to the normal level. Histopathological findings indicated that GI 129471 treatment can prevent severe centrilobular necrosis in liver. These results suggest that release of TNF-alpha from lipopolysaccharide-stimulated cells is the critical step leading to hepatic injury in endotoxemia and that a matrix metalloproteinase inhibitor with an inhibitory action on this step may be a promising drug for the clinical treatment of endotoxemia accompanied by hepatic injury.

Animals↗
PubMed1998

Mitochondrial susceptibility to oxidative stress exacerbates cerebral infarction that follows permanent focal cerebral ischemia in mutant mice with manganese superoxide dismutase deficiency.

Mitochondrial injury has been implicated in ischemic neuronal injury. Mitochondria, producing adenosine triphosphate by virtue of electron flow, have been shown to be both the sites of superoxide anion (O2-) production and the target of free radical attacks. We evaluated these mechanisms in an in vivo cerebral ischemia model, using mutant mice with a heterozygous knock-out gene (Sod2 -/+) encoding mitochondrial manganese superoxide dismutase (Mn-SOD). Sod2 -/+ mice demonstrated a prominent increase in O2- production under normal physiological conditions and in ischemia, as evidenced by specific oxidation of a fluorescent probe, hydroethidine, reflecting decreased activity of Mn-SOD. A mitochondrial viability assay that used rhodamine 123, which is accumulated by transmembrane potential of viable mitochondria, demonstrated accelerated development of mitochondrial injury. This rapid progress of ischemic injury resulted in exacerbation of infarct size and hemisphere enlargement, causing advanced neurological deficits but without altering DNA fragmentation induction. The present study suggests that O2- overproduced in a mitochondrial compartment, when uncoupled from antioxidant defenses, induces impairment of mitochondrial function and causes exacerbation of cerebral infarction after ischemia.

Animals↗
PubMed1998

Carbohydrate malabsorption following acarbose administration.

Carbohydrate absorption was assessed during acarbose administration to investigate the actions of this drug. In 7 healthy volunteers, breath hydrogen concentration was measured at 15-min intervals after administration of 6 g of lactulose, and continued until 4 h after the breath hydrogen level exceeded its pretreatment value by > or =10 ppm, then the amount of undigested carbohydrate was calculated following administration of various doses of acarbose and Ensure Liquid. Breath hydrogen data were also obtained before and after administration of acarbose to 8 patients with Type 2 diabetes mellitus for 2 and 4 months. After administration of 50 mg of acarbose with 250 ml or 500 ml of Ensure, the mean amount of unabsorbed carbohydrate was 5.3 g and 7.7 g, respectively, while unabsorbed carbohydrate increased to 10.8 g after 100 mg of acarbose with 500 ml of Ensure. In the diabetic patients, breath hydrogen excretion decreased to 31.6% of baseline after 2 months of acarbose administration, indicating decreased carbohydrate malabsorption. Despite this, the haemoglobin A1c level remained stable after 5 months. In conclusion, the extent of carbohydrate malabsorption depended on the acarbose dose and the carbohydrate load. Although carbohydrate malabsorption decreased with continued acarbose administration, the improvement of glycaemic control was maintained.

Acarbose↗
PubMed1998

Molecular genetic analysis of a novel Parkin gene in Japanese families with autosomal recessive juvenile parkinsonism: evidence for variable homozygous deletions in the Parkin gene in affected individuals.

Autosomal recessive juvenile parkinsonism (AR-JP) is a distinct clinical and genetic entity characterized by selective degeneration of nigral dopaminergic neurons and young-onset parkinsonism with remarkable response to levodopa. Recently, we mapped the gene locus for AR-JP to chromosome 6q25.2-q27 by linkage analysis and we identified a novel large gene, Parkin, consisting of 12 exons from this region; mutations of this gene were found to be the cause of AR-JP in two families. Now we report results of extensive molecular analysis on 34 affected individuals from 18 unrelated families with AR-JP. We found four different homozygous intragenic deletional mutations, involving exons 3 to 4, exon 3, exon 4, and exon 5 in 10 families (17 affected individuals). In addition to the exonic deletions, we identified a novel one-base deletion involving exon 5 in two families (2 affected individuals). All mutations so far found were deletional types in which large exonic deletion accounted for 50% (17 of 34) and the one-base deletion accounted for 6% (2/34); in the remaining, no homozygous mutations were found in the coding regions. Our findings indicate that loss of function of the Parkin protein results in the clinical phenotype of AR-JP and that subregions between introns 2 and 5 of the Parkin gene are mutational hot spots.

Amino Acid Sequence↗
PubMed1998

Mitochondrial dysfunction in Parkinson's disease.

This review discusses the etiology and pathogenesis of Parkinson's disease (PD). Mitochondrial respiratory failure and oxidative stress appear to be two major contributors to nigral neuronal death in PD. Complex I deficiency has been reported by several groups and appears to be one of the basic abnormalities responsible for mitochondrial failure. The principal question is whether or not complex I deficiency is primary or secondary. The second question is whether or not complex I deficiency is localized in the nigrostriatal system or is systemically present. It is our impression that complex I deficiency is not the primary cause but that its deficiency appears to be systemic. The primary cause may be the combination of genetic background and potential nigral neurotoxins. Exposure of nigral neurons to a high risk for oxidative damage because of its high dopamine content may be the reason for more pronounced nigral complex I deficiency compared to systemic organs. Oxidative stress and mitochondrial failure produce a vicious cycle in nigral neurons. To explore the genetic risk factors of sporadic PD, studies on familial PD and parkinsonism are important. Recently, an autosomal dominant form of familial PD was found to be caused by point mutations of the alpha-synuclein gene, and an autosomal recessive familial parkinsonism was mapped to the long arm of chromosome 6 near the Mn-SOD gene locus. Information obtained in these familial cases will contribute to the research on sporadic PD.

Cell Nucleus↗
PubMed1998

Relationship between Joint National Committee-VI classification of hypertension and ambulatory blood pressure in patients with hypertension diagnosed by casual blood pressure.

BACKGROUND: White-coat hypertension has been diagnosed arbitrarily based on different criteria. In 1997, the Joint National Committee-VI (JNC-VI) reported a new classification of hypertension and strongly emphasized the importance of ambulatory blood pressure (ABP) monitoring. The report pronounced normal ABP values for the first time. HYPOTHESIS: The study's aim was to clarify the relationship between casual blood pressure (BP) and ABP of patients with essential hypertension in each stage of JNC-VI classification, and the prevalence of white-coat hypertension diagnosed by using JNC-VI normal ABP criteria. METHODS: Ambulatory blood pressure was monitored non-invasively in 232 patients with essential hypertension whose casual BP was > or = 140/90 mmHg. The patients were classified according to JNC-VI classification, and their casual BP was compared with ABP. The criterion of white-coat hypertension was defined as casual BP > or = 140/90 mmHg with normal ABP according to JNC-VI criteria (< 135/85 during daytime and < 120/75 during nighttime). RESULTS: Mean ABP increased as the stage advanced, and the differences between casual BP and ABP also increased. There were considerable overlaps in the distribution of ABP among stages. The prevalence of white-coat hypertension was 13% overall: 30% of the patients with isolated systolic hypertension, 19% of those in stage 1, 10% in stage 2, and 4% in stage 3. CONCLUSIONS: Classification of hypertension based on casual BP may not always correspond in severity to that based on ABP. Ambulatory blood pressure monitoring recommended by JNC-VI is very useful for the evaluation of hypertension to differentiate white-coat hypertension from true hypertension.

Adult↗
PubMed1998

Two-dimensional gel electrophoretic analysis of the changes after immortalization of human cells: decrease of intracellular alpha-2-macroglobulin fragment.

To study the mechanisms of immortalization of human cells, an early step in cancer development, we compared the cellular proteins of normal and immortalized human fibroblasts. Two-dimensional gel electrophoresis showed that one spot with a molecular mass 20 kDa and an isoelectric point of 6.0, became significantly smaller after immortalization of human cells. Further, the spot was rarely observed in four human liver cancer cell lines. Investigation of the N-terminal amino acids revealed that the spot was a fragment of alpha-2-macroglobulin. Although the 20 kDa fragment contains methionine, the spot was not labeled with [35S]methionine. Thus we concluded that the spot might be derived from the culture medium. These results indicated that intracellular metabolism of a-2-macroglobulin, which is a multifunctional protease inhibitor, changed after the cells were transformed.

Cell Line↗
PubMed1998

Effects of various factors including the CYP2D6 genotype and coadministration of flunitrazepam on the steady-state plasma concentrations of bromperidol and its reduced metabolite.

The effects of various factors, including the cytochrome P450 (CYP) 2D6 genotype and the coadministration of flunitrazepam, on the steady-state plasma concentrations (Css) of bromperidol and its reduced metabolite were studied in 62 schizophrenic inpatients receiving bromperidol 12 mg/day. By use of allele-specific PCR analysis, the wild type allele (CYP2D6*1A) and four mutated alleles causing either absent (CYP2D6*3, CYP2D6*4 and CYP2D6*5) or decreased (CYP2D6*10) CYP2D6 activity were identified. The means (ranges) of the Css of bromperidol and reduced bromperidol corrected to the median body weight were 7.2 (1.3-17.4) and 2.2 (0.4-8.9) ng/ml, respectively. Neither the Css of bromperidol nor that of reduced bromperidol significantly differed among the patients with no (n = 28), one (n = 30) and two mutated alleles (n = 4). The patients coadministered with flunitrazepam (n = 52) had significantly (P < 0.05) higher Css of bromperidol, but not reduced bromperidol, than those not (n = 10). Age, sex and smoking had no significant effects on the Css of these compounds. The present study thus suggests that the polymorphic CYP2D6 is not involved in the metabolism of bromperidol and reduced bromperidol to a major extent. The coadministration of flunitrazepam inhibits the metabolism of bromperidol, but age, sex and smoking do not affect it.

Adolescent↗
PubMed1998

Effect of itraconazole on the single oral dose pharmacokinetics and pharmacodynamics of alprazolam.

To assess the effect of itraconazole, a potent inhibitor of cytochrome P450 (CYP) 3A4, on the single oral dose pharmacokinetics and pharmacodynamics of alprazolam, the study was conducted in a double-blind randomized crossover manner with two phases of treatment with itraconazole-placebo or placebo-itraconazole. Ten healthy male subjects receiving itraconazole 200 mg/day or matched placebo orally for 6 days took an oral 0.8 mg dose of alprazolam on day 4 of each treatment phase. Plasma concentration of alprazolam was measured up to 48 h after alprazolam dosing, together with the assessment of psychomotor function by the Digit Symbol Substitution Test, Visual Analog Scale and Udvalg for kliniske undersøgelser side effect rating scale. Itraconazole significantly (P < 0.01) increased the area under the concentration-time curves from 0 h to infinity (252 +/- 47 versus 671 +/- 205 ng h/ml), decreased the apparent oral clearance (0.89 +/- 0.21 versus 0.35+/-0.10 ml/min per kg) and prolonged the elimination half-life (15.7 +/- 4.1 versus 40.3 +/- 13.5 h) of alprazolam. The test performed during itraconazole treatment showed significantly depressed psychomotor function. It is suggested that itraconazole, a potent CYP3A4 inhibitor, increases plasma concentration of alprazolam via its inhibitory effects on alprazolam metabolism. Thus, this study supports previous studies suggesting that CYP3A4 is the major enzyme catalyzing the metabolism of alprazolam. Enhanced side effects of alprazolam by itraconazole coadministration were probably reflected by these pharmacokinetic changes.

Administration, Oral↗
PubMed1998

Impact of ischemia-reperfusion injury on dimensional changes of hepatic microvessels.

Dimensional alteration of hepatic microvessels was demonstrated during reperfusion after normothermic hepatic ischemia. Using a specially designed cover glass, it was possible to relocate selected sites of observation and microvessels repeatedly throughout the whole reperfusion time. Twenty minutes of hepatic ischemia resulted in a decrease of sinusoidal diameter (mean +/- SEM; 10.0 +/- 0.3 microns at baseline, 8.2 +/- 0.2 microns after ischemia) and diameter of postsinusoidal venules (26.4 +/- 1.2 at baseline, 23.0 +/- 1.0 after ischemia). In the control group (no ischemia induced) no changes of these parameters were observed. Thus, the reduction of hepatic microvascular cross section was present during the early phase of reperfusion. Hepatic dysfunction was characterized by increased serum activity of liver enzymes and reduction of bile flow in the ischemia-exposed animals. It has been suggested that postischemic dimensional microvascular changes are involved in postischemic liver dysfunction.

Animals↗
PubMed1998

Circadian rhythm of breath hydrogen in young women.

Breath hydrogen levels, which reflect colonic fermentation of undigested starches, are usually low in the fasted state. Fasting levels of breath hydrogen are important for estimation of oro-cecal transit time and diagnosis of lactase deficiency. In young women, however, fasting levels of breath hydrogen are high. To clarify the reason for this, we studied the circadian pattern of breath hydrogen and the effect of alpha-D-galactosidase on fasting breath hydrogen in one study, and the effect of sleep deprivation on fasting breath hydrogen in another study, in 13 women students aged 21-23 years. In the first study, two breath samples were collected, one in the evening and the other the next morning. On another occasion, alpha-D-galactosidase was given before dinner and breath samples were collected the next morning. In the second study, the circadian rhythm of breath hydrogen was assessed for 3 days and the subjects were deprived of sleep on the second night. Breath samples were collected every 30 min, except during the second night when samples were collected at 1-h intervals. Fasting breath hydrogen was 24 +/- 3.9 ppm (mean +/- SE), which did not differ from the value for the previous night. Alpha-D-galactosidase significantly decreased fasting breath hydrogen levels, to 17 +/- 2.4 ppm (P < 0.05). There was a clear circadian pattern of breath hydrogen, high in the morning and decreasing to the nadir by 16:00. After dinner, the level increased again and stayed high during the night. Sleep deprivation did not affect fasting levels of breath hydrogen. High fasting breath hydrogen levels in young women followed a circadian pattern and this may have been due, in part, to an high intake of dietary fiber on the previous day.

Adult↗
PubMed1998

Morphologic changes in long head of biceps brachii in rotator cuff dysfunction.

Morphologic changes in the long head of the biceps brachii (LHB) and bicipital groove associated with cuff tears were studied in 170 cadavers. In specimens with minimum or moderate cuff tears, the primary finding was relative stenosis at the bicipital groove induced by enlargement of the LHB. However, this stenosis was not apparent in specimens with massive cuff tears and in these specimens, the medial wall of the groove exhibited wear and tear, a potential cause of LHB instability. We suggest that the long head of the biceps brachii muscle can potentially compensate for inadequate rotator cuff function. This increasing activity could lead to enlargement of the tendon and cause deterioration of the bicipital gliding mechanism.

Adult↗
PubMed1998

Prognostic assessment of 1310 patients with non-small-cell lung cancer who underwent complete resection from 1980 to 1993.

OBJECTIVE: The TNM staging system of lung cancer is widely used as a guide for estimating prognosis and selecting treatment modality. In 1997, the International Union Against Cancer and the American Joint Committee on Cancer have adopted a revised stage grouping for lung cancer. However, the validity of the new stage grouping has not been fully established. We investigated the prognoses of patients who had resection of non-small-cell lung cancer to confirm the validity of the revised classification. METHODS: A total of 1310 patients with non-small-cell lung cancer underwent complete resection and pathologic staging of the disease in our hospitals from 1980 through 1993. A pulmonary resection was performed with a systematic nodal dissection. The survivals were calculated with the Kaplan-Meier method on the basis of overall deaths, and the survival curves were compared by log rank test. RESULTS: There were significant differences in survival between patients with T1 N0 M0 and T2 N0 M0 disease and between those with T1 N1 M0 and T2 N1 M0 disease. However, there was no significant difference between patients with T2 NO M0 disease and those with T1 N1 M0 disease. No significant difference in survival was observed among patients with T2 N1 M0, T3 NO M0, and T3 N1 M0 cancer. Patients with different invaded organs of T3 subdivision (pleura, chest wall, pericardium, or diaphragm) had a different prognosis. There was no significant difference between patients with T3 N2 M0 disease and those with stage IIIB disease. CONCLUSIONS: We supported most of the revision, such as dividing stage I, dividing stage II, and putting T3 N0 M0 to stage IIB. Furthermore, we found some candidates for a subsequent revision, such as putting T3 N1 M0 to stage IIB, putting T2 N0 M0 and T1 N1 M0 together, regarding diaphragm invasion as T4, and putting T3 N2 M0 to stage IIIB.

Carcinoma, Non-Small-Cell Lung↗
PubMed1998

Correlation between steady-state plasma concentrations (Css) of bromperidol and haloperidol.

1. Bromperidol is a close structural analogue of haloperidol, and its metabolic pathways are similar to those of haloperidol. The authors studied the correlation between the Css of bromperidol and haloperidol. 2. The subjects were 16 schizophrenic inpatients. Fourteen patients received firstly bromperidol 12 mg/day and secondly haloperidol 12 mg/day, while the remaining two patients received the two treatments in the opposite sequence. 3. Blood samplings were performed 2-3 weeks after the initiation of each treatment, and the Css of bromperidol, haloperidol and their reduced metabolites were measured by high-performance liquid chromatography. 4. Neither the correlation between the Css of bromperidol and haloperidol (r = 0.246) nor that between the Css of reduced bromperidol and reduced haloperidol (r = 0.142) was significant. 5. The present study thus suggests that the Css of bromperidol and haloperidol do not correlate well in individuals.

Adult↗
PubMed1998

Familial cortical tremor with epilepsy: an under-recognized familial tremor.

The authors report three Japanese families presenting with cortical tremor and epilepsy. The patients showed either tremulous finger movements or seizures as the initial symptoms between 19 and 30 years of the age without progression. Postural tremor resembled essential tremor and responded to the anticonvulsants such as clonazepam, primidone and sodium valproate. Seizures were infrequent. These patients seem to have the same disorder as what the authors have described as 'familial cortical tremor with epilepsy'. Familial cortical tremor must be more common than previously thought and should be taken into consideration in the patients with 'familial essential tremor' who do not respond well to beta-blockers.

Adult↗