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Biomedical subjects

K Takeshita

Publications and source records attributed to K Takeshita.

At least 19 recordsLinked to original sources

Bile salt tauroursodeoxycholic acid modulation of Bax translocation to mitochondria protects the liver from warm ischemia-reperfusion injury in the rat.

BACKGROUND: Tauroursodeoxycholic acid (TUDC) is a hydrophilic bile acid that has a cytoprotective effect in primary biliary cirrhosis and primary sclerosing cholangitis. TUDC also protects hepatocytes from hydrophobic bile acid-induced apoptosis. The aim of this study was to determine whether TUDC ameliorates hepatocyte apoptosis during ischemia-reperfusion injury. METHODS: We used a rat model of hepatic warm ischemia-reperfusion injury to assess the effects of TUDC. Male Sprague-Dawley rats were subjected to 1 or 2 hr of normothermic ischemia followed by 3 or 6 hr of reperfusion. The treatment group received TUDC (50 mg/kg) by bolus intravenous injection 30 min before initiation of ischemia, whereas the control group received saline only. Blood samples for biochemical analysis were obtained after 6 hr of reperfusion. Liver biopsies for histological assessment were obtained 3 and 6 hr after reperfusion. Hepatocyte apoptosis was determined by terminal dUTP nick-end labeling. The pro-apoptotic protein Bax was quantified at the mRNA and protein level. RESULTS: Treatment with TUDC significantly reduced serum transaminase levels. This was associated with a significant amelioration in the levels of hepatocyte apoptosis in the TUDC-treated group compared with control. Furthermore, Western blot analysis of Bax expression in liver tissue indicated that TUDC inhibited the translocation of Bax from the cytosol to the mitochondria. CONCLUSIONS: TUDC significantly reduced hepatic injury in this model. The beneficial effects of TUDC upon hepatocyte apoptosis were related to the modulation of Bax protein translocation.

Animals↗

Effect of highly active antiretroviral therapy on survival in patients with AIDS-associated pulmonary Kaposi's sarcoma treated with chemotherapy.

PURPOSE: Kaposi's sarcoma (KS) is the most common AIDS-related malignancy. Pulmonary involvement by KS (PKS) has carried a poor prognosis with median reported survival ranging from 3 to 10 months. We studied whether the introduction of highly active antiretroviral therapy (HAART; triple antiretroviral therapy including a protease inhibitor and two reverse transcriptase inhibitors) has been associated with improved survival for AIDS patients with PKS. PATIENTS AND METHODS: A retrospective study was performed of 37 consecutive patients with PKS and human immunodeficiency virus infection in the tumor registry at a large municipal hospital in New York City between 1994 to 1997. There were 16 patients from 1994 to 1995 (pre-HAART period) and 21 patients from 1996 to 1997 (post-HAART period). The primary end point was survival, which was defined as time from start of chemotherapy until death from any cause. RESULTS: Patients were analyzed by the date of diagnosis (pre- v post-HAART period) and whether or not they received HAART. Kaplan-Meier analysis showed significantly better survival in patients diagnosed in the post-HAART period (P =.0025). Additional Kaplan-Meier analysis indicated that patients on HAART had substantially better survival (P <.0001). Cox multivariate analyses showed that HAART therapy was associated with a reduced risk of death (hazard ratio = 0.09; 95% confidence interval, 0.03 to 0.69). CONCLUSION: In patients with AIDS-associated PKS and undergoing chemotherapy, administration of HAART was associated with increased survival.

Acquired Immunodeficiency Syndrome↗

Noninvasive detection of hydroxyl radical generation in lung by diesel exhaust particles.

Diesel exhaust particles (DEP) induce pulmonary tumors, asthma-like symptoms, and the like in experimental animals. The involvement of reactive oxygen species (ROS) is suggested in the injuries induced by DEP, though the generation of ROS has not been proven. The present study provided the first direct evidence of *OH generation in the lungs of living mice after intratracheal instillation of DEP, using noninvasive L-band ESR spectroscopy and a membrane-impermeable nitroxyl probe. *OH generation is confirmed with the enhancement of in vivo ESR signal decay rate of the probe. The decay rate at mid-thorax was significantly enhanced in DEP-treated mice compared to that in vehicle-treated mice. The enhancement was completely suppressed by the administration of either *OH scavengers, catalase, or desferrioxamine, while the administration of SOD further increased the rate. The administration of Fenton's reagents into the lung also enhanced the decay rate of the probe at mid-thorax of mice. These results clearly provided evidence that the intratracheal exposure to DEP in mice produced *OH in the lung through an iron-catalyzed reaction of superoxide/H(2)O(2). This first direct evidence of *OH generation in DEP-treated mice lung may be utilized to determine treatments for DEP-induced lung injury.

Animals↗

Long-term results of double-door laminoplasty for cervical stenotic myelopathy.

STUDY DESIGN: A retrospective study of the long-term results from double-door laminoplasty (Kurokawa's method) for patients with myelopathy caused by ossification of the posterior longitudinal ligament and cervical spondylosis was performed. OBJECTIVE: To know whether the short-term results from double-door laminoplasty were maintained over a 10-year period and, if not, the cause of late deterioration. SUMMARY OF BACKGROUND DATA: There are few long-term follow-up studies on the outcome of laminoplasty for cervical stenotic myelopathy. METHODS: In this study, 35 patients with cervical myelopathy caused by ossification of the posterior longitudinal ligament in the cervical spine and 25 patients with cervical spondylotic myelopathy, including 5 patients with athetoid cerebral palsy, underwent double-door laminoplasty from 1980 through 1988 and were followed over the next 10 years. The average follow-up period was 153 months (range, 120-200 months) in patients with ossification of the posterior longitudinal ligament and 156 months (range, 121-218 months) in patients with cervical spondylotic myelopathy. Neurologic deficits before and after surgery were assessed using a scoring system proposed by the Japanese Orthopedic Association (JOA score). Patients who showed late deterioration received further examination including computed tomography scan and magnetic resonance imaging of the cervical spine. RESULTS: In 32 of the patients with ossification of the posterior longitudinal ligament and 23 of the patients with cervical spondylotic myelopathy, myelopathy improved after surgery. The improvement of Japanese Orthopedic Association scores was maintained up to the final follow-up assessment in 26 of the patients with ossification of the posterior longitudinal ligament and 21 of the patients with cervical spondylotic myelopathy. Late neurologic deterioration occurred in 10 of the patients with ossification of the posterior longitudinal ligament an average of 8 years after surgery, and in 4 of the patients with cervical spondylotic myelopathy, including the 3 patients with athetoid cerebral palsy, an average of 11 years after surgery. The main causes of deterioration in patients with ossification of the posterior longitudinal ligament were a minor trauma in patients with residual cervical cord compression caused by ossification of the posterior longitudinal ligament and thoracic myelopathy resulting from ossification of the yellow ligament in the thoracic spine. CONCLUSIONS: The short-term results of laminoplasty for cervical stenotic myelopathy were maintained over 10years in 78% of the patients with ossification of the posterior longitudinal ligament, and in most of the patients with cervical spondylotic myelopathy, except those with athetoid cerebral palsy. Double-door laminoplasty is a reliable procedure for individuals with cervical stenotic myelopathy.

Adult↗

Adequate endoscopic mucosal resection for early gastric cancer obtained from the dissecting microscopic features of the resected specimens.

BACKGROUND: We have employed endoscopic mucosal resection (EMR), using a cap-fitted panendoscope (EMRC), for early gastric cancer since 1992. The presence of an adequate surgical margin is a requirement because of the radicality of EMR, and dissecting microscopic examination is useful in regard to the diagnosis of spread of the disease. METHODS: To devise an adequate method of EMR that allows no lateral residue, we examined gastric mucosal specimens obtained by EMRC. One hundred and sixty-seven specimens from 97 lesions in 85 patients treated by EMRC were examined in regard to characteristic features, the recovery of marks made around the lesion, and the frequency of residue, and comparisons were made between the dissecting microscopic and histopathological findings. RESULTS: The first specimen obtained with a large cap under full suction was a circular shape measuring 21 x 19mm. The second specimen from fractionated resection was a half-moon or crescent shape, and the third specimen had a ginkgo leaflike or irregular shape. In the elevated lesions, coincidence regarding the spread, as determined by dissecting microscopy and histopathology, was present in 62 (93%) of the 67 lesions. In 16 (53%) of 30 flat or depressed lesions, there was a difference of 2 to 5 mm between the spread determined by these two examinations. CONCLUSION: It is important to place an adequate number of marks around the lesion and recover all marks by resection. When an elevated lesion measures 15mm or more, and a flat or depressed lesion is not clearly demarcated, aggressive use of planned fractionated resection seems to be the best way to prevent a lateral residue in EMR.

Aged↗

Relationship between cervical curvature index (Ishihara) and cervical spine angle (C2--7).

The purpose of this study was to determine the relationship between the cervical curvature index (Ishihara) and the cervical spine angle (C2--7) from both cervical lateral radiographs and a geometrical model. The cervical lateral radiographs of 295 outpatients with no cervical symptoms were reviewed to measure the cervical curvature index (Ishihara) and the cervical spine angle (C2--7). The average cervical curvature index (Ishihara) was 10.9 (SD, 15.3) and the average cervical spine angle (C2--7) was 20.3 (SD, 14.3). A highly significant correlation (0.95; 95% confidence interval [CI], 0.94--0.96) was found between the cervical curvature index (Ishihara) and the cervical spine angle (C2--7). Their linear correlation was also validated in the geometrical model. Their correlation diminished, however, in subjects with an S-shaped cervical spine. The cervical curvature index (Ishihara) and the cervical spine angle (C2--7) were interchangeable, but this interchangeability was lost in the S-shaped cervical spines.

Adolescent↗

Diagnosis of Japanese patients with HHH syndrome by molecular genetic analysis: a common mutation, R179X.

Patients with mitochondrial ornithine transporter deficiency (or HHH syndrome) present with various neurological symptoms, including mental retardation, spastic paraparesis with pyramidal signs, cerebellar ataxia, and episodic disturbance of consciousness or coma due to hyperammonemia. We previously described three novel mutations in the ORNT1 gene in Japanese patients with HHH syndrome. In this article, we report a new patient with HHH syndrome, a 52-year-old woman, who had the typical clinical features, except for an absence of mental retardation. When we screened this patient, as well as a previously described Japanese patient, for mutations in the ORNT1 gene, we found that both were homozygous for a nonsense mutation (R179X). Furthermore, reverse transcription (RT)-polymerase chain reaction (PCR) of fibroblast RNA from one patient showed exon 4 skipping, as had been observed in a previously reported patient with R179X. These results, together with the findings in our previous report, show that, in three of our five reported Japanese HHH patients (six of ten alleles), R179X is present, suggesting that this is a common mutation in Japanese patients with HHH syndrome.

Amino Acid Metabolism, Inborn Errors↗

Adsorption mechanism of hexavalent chromium by redox within condensed-tannin gel.

We have proposed a new recovery system of hexavalent chromium Cr(VI) that is of great toxicity utilizing condensed-tannin gels derived from a natural polymer with many polyhydroxyphenyl groups. The adsorption mechanism of Cr(VI) to the tannin molecules was clarified. The adsorption mechanism consists of four reaction steps; the esterification of chromate with tannin molecules, the reduction of Cr(VI) to trivalent chromium Cr(III), the formation of carboxyl group by the oxidation of tannin molecules and the ion exchange of the reduced Cr(III) with the carboxyl and hydroxyl groups. It was found in this recovery system that a large amount of proton was consumed accompanied with the reduction of Cr(VI) so that the acidic solution containing Cr(VI) was transferred automatically to neutral one by choosing an appropriate initial pH. The carboxyl group which was created by the oxidation of tannin molecules parallel to the reduction of Cr(VI) to Cr(III) contributed to an increase in the ion-exchange sites of the reduced Cr(III). The maximum adsorption capacity of Cr(VI) reached 287 mg Cr/g dry tannin gel under the conditions of 0.77 water content of tannin gel and the initial pH = 2. This adsorption capacity was five to ten times higher than that obtained by the ion exchange between ordinary Cr(III) and tannin molecules for the tannin gels prepared under similar conditions. The system proposed here will provide an important information on a zero-emission-oriented process because it has such advantages as higher adsorption capacity of chromium and lower volume of secondary wastes compared with conventional process.

Adsorption↗

A Japanese girl with leukoencephalopathy with vanishing white matter.

A Japanese girl with peculiar leukoencephalopathy was reported. Following normal development until 1 year of age, she showed progressive neurological deterioration with ataxia, epilepsy, pyramidal tract signs and choreic movement. Serial brain computed tomographies (CTs) revealed markedly low density and progressive volume loss in whole white matter. In extensive laboratory investigations, the level of glycine in the urine was elevated. She died at the age of 4 years, and the neuropathological findings were comprised of severe extensive changes in cerebral and cerebellar white matter, such as marked rarefaction or cystic degeneration with axonal loss. The pontine central tegmental tracts were also affected. Neuronal loss was seen in the cerebellar cortex. These features were compatible with leukoencephalopathy with vanishing white matter, which was recently established as a clinical entity. To our knowledge, this is the first report of a non-Caucasian patient with this new type of leukoencephalopathy.

Brain↗

Varicella-associated acute necrotizing encephalopathy with a good prognosis.

A patient with acute necrotizing encephalophathy (ANE) following varicella infection with a good prognosis is reported. A somatosensory evoked magnetic field (SEF) study using a 37-channel-magnetoencephalography system demonstrated normal latency and strength of the first component (N20m) elicited by median nerve stimulation, despite bilateral symmetrical thalamic lesions on MRI. The normal SEF findings and the good prognosis suggested a reversible breakdown of the blood-brain barrier, and an edematous process as the brain pathology. Furthermore, our results support the idea of distinct generators for the three earliest cortical SEF components (N20m, P30m, N45m).

Chickenpox↗

A functional magnetic resonance imaging study during sentence reading in Japanese dyslexic children.

A functional magnetic resonance imaging (fMRI) study during Japanese 'kana' readings was performed on Japanese dyslexic children. Five dyslexic children (aged 9-12 years) and five healthy children (aged 9-11 years) were investigated. The fMRI examination was performed by getting these children to read sentences constructed from Japanese phonograms, 'kana', compared with staring at meaningless figures as a control task. All control subjects showed activation of the left middle temporal gyrus. In the dyslexic children, the activation of the middle temporal gyrus was rather vague. However, other distinctively activated regions were detected as follows: the bilateral occipital cortex in two dyslexics, the inferior part of the frontal regions in two other dyslexics, and both the bilateral occipital cortex and the inferior part of precentral gyrus in the remaining one. These results indicate compensatory management processes for the unskilled reading ability of dyslexic children. The present results were similar to previous ones for adult dyslexia with the Roman alphabet, and suggest that brain malfunction in dyslexia during the task of reading must be common despite differences in languages.

Cerebral Cortex↗

Effects of KE-758; an active metabolite of the new anti-rheumatic drug KE-298, D-penicillamine, bucillamine and auranofin on the proliferation of murine lymphocytes, and the production of nitric oxide by murine macrophages.

2-Mercaptomethyl-4-(4-methylphenyl)-4-oxobutanoic acid (KE-758), which is the active metabolite of 2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid (KE-298), is a novel sulphydryl anti-rheumatic drug. In this study we analyzed the effect of KE-758 on the proliferation of murine lymphocytes, and on the production of nitric oxide (NO) by RAW264.7 murine macrophage cells. We compared its effect with other sulphydryl drugs such as D-penicillamine, bucillamine and auranofin. The proliferation of lymphocytes was measured by 3H-thymidine incorporation assay. Nitrite was measured using Griess Reagent. In the absence of copper ions, KE-758, D-penicillamine and bucillamine rarely affected the proliferation of concanavarin A (ConA) activated murine splenocytes. However, in the presence of copper, pharmacological concentrations of KE-758 but not D-penicillamine and bucillamine suppressed the proliferation of murine splenocytes through a hydrogen peroxide-dependent mechanism. Auranofin markedly suppressed the proliferation regardless of the presence of copper ions by reducing the cellular viability. Furthermore, only KE-758 markedly suppressed the proliferation of phorbol myristate acetate (PMA) plus ionomycin activated murine whole blood lymphocytes (WBL) even in the absence of exogenous copper ions by a hydrogen peroxide-independent mechanism. Meanwhile, lipopolysaccharide (LPS) or LPS plus interferon-gamma (IFN-gamma) induced NO production by RAW264.7 cells were suppressed by KE-758 and auranofin but not by D-penicillamine and bucillamine. In conclusion, KE-758 is a novel immunosuppressive drug, which inhibits both lymphocyte and macrophage functions and its unique anti-rheumatic profile is distinct from that of D-penicillamine, bucillamine and auranofin.

Animals↗

Dietary D-psicose, a C-3 epimer of D-fructose, suppresses the activity of hepatic lipogenic enzymes in rats.

D-Psicose (D-ribo-2-hexulose), a C-3 epimer of D-fructose, is present in small quantities in commercial carbohydrate complexes or agricultural products. Wistar male rats were fed experimental diets which consisted of 5% D-psicose, cellulose, D-fructose or D-glucose for 28 days. Abdominal adipose tissue weight was significantly lower (P < 0.05) in rats fed the D-psicose diet than in rats fed a D-fructose and D-glucose diets, even though the four dietary groups were offered the same amount throughout the experimental period. Fatty acid synthase and glucose 6-phosphate dehydrogenase activities in the liver were significantly lower (P < 0.05) in rats fed the D-psicose diet than in rats fed the D-fructose and D-glucose diets. However, lipoprotein lipase activities in the heart, soleus muscle and perirenal adipose tissue were the same. These results suggest that a supplement of D-psicose in the diet suppresses hepatic lipogenic enzyme activities. The lower abdominal fat accumulation in rats fed a D-psicose diet might result from lower lipogenesis in the liver.

Abdomen↗

Early gastric carcinoma: evaluation with high-spatial-resolution MR imaging in vitro.

PURPOSE: To determine signal intensity characteristics of the gastric wall layers and to assess the accuracy of the evaluation of early gastric carcinomas in vitro by using resected specimens studied with high-spatial-resolution magnetic resonance (MR) imaging. MATERIALS AND METHODS: Fifteen gastric specimens obtained from patients suspected of having early gastric carcinoma were studied with a 1.5-T MR system with a 4-cm-diameter loop coil. High-spatial-resolution spin-echo MR images were obtained with a field of view of 50 mm, a matrix of 256 x 256, and a section thickness of 2 mm, resulting in a voxel size of 0.08 mm(3). Findings from MR images were compared with histopathologic findings. RESULTS: T1- and T2-weighted MR images clearly depicted the normal gastric wall as consisting of four and six layers, respectively, which corresponded well to the histologic layers. In 14 (93%) of 15 gastric carcinomas, the depth of mural invasion visualized with MR imaging correlated well with the histopathologic stage. The stage determined with MR imaging, however, was lower in one instance (7%) than the histopathologic stage. MR imaging also depicted the gross features of the tumor, presence of ulceration, and adjacent lymph node swelling. CONCLUSION: High-spatial-resolution MR imaging has a high diagnostic accuracy in the evaluation of the mural invasion of early gastric carcinoma in vitro and thus potentially enables preoperative histopathologic staging.

Adenocarcinoma↗

Effects of hypercapnia and hypocapnia on [Ca2+]i mobilization in human pulmonary artery endothelial cells.

The hydrogen ion is an important factor in the alteration of vascular tone in pulmonary circulation. Endothelial cells modulate vascular tone by producing vasoactive substances such as prostacyclin (PGI2) through a process depending on intracellular Ca2+ concentration ([Ca2+]i). We studied the influence of CO2-related pH changes on [Ca2+]i and PGI2 production in human pulmonary artery endothelial cells (HPAECs). Hypercapnic acidosis appreciably increased [Ca2+]i from 112 +/- 24 to 157 +/- 38 nmol/l. Intracellular acidification at a normal extracellular pH increased [Ca2+]i comparable to that observed during hypercapnic acidosis. The hypercapnia-induced increase in [Ca2+]i was unchanged by the removal of Ca2+ from the extracellular medium or by the depletion of thapsigargin-sensitive intracellular Ca2+ stores. Hypercapnic acidosis may thus release Ca2+ from pH-sensitive but thapsigargin-insensitive intracellular Ca2+ stores. Hypocapnic alkalosis caused a fivefold increase in [Ca2+]i compared with hypercapnic acidosis. Intracellular alkalinization at a normal extracellular pH did not affect [Ca2+]i. The hypocapnia-evoked increase in [Ca2+]i was decreased from 242 +/- 56 to 50 +/- 32 nmol/l by the removal of extracellular Ca2+. The main mechanism affecting the hypocapnia-dependent [Ca2+]i increase was thought to be the augmented influx of extracellular Ca2+ mediated by extracellular alkalosis. Hypercapnic acidosis caused little change in PGI2 production, but hypocapnic alkalosis increased it markedly. In conclusion, both hypercapnic acidosis and hypocapnic alkalosis increase [Ca2+]i in HPAECs, but the mechanisms and pathophysiological significance of these increases may differ qualitatively.

Acidosis, Respiratory↗

Pneumonitis induced by ou-gon (scullcap).

A 53-year-old Japanese man with recurrent interstitial pneumonia was referred to us. The patient had taken a traditional herb medicine, otsu-ji-to, before the onset of pneumonia. A provocation test for each herbal ingredient contained in otsu-ji-to revealed that the pneumonitis had been induced by ou-gon (scullcap). Lymphocytosis with the CD8+ T-cell subset predominance was found in the bronchoalveolar lavage fluid and lymphocytic alveolitis was noted in the transbronchial lung biopsy specimen after the provocation test. Ou-gon, or scullcap, should be included in the list of drugs with definite causal association with pneumonitis.

Biopsy↗

[A case of relapsed small cell lung cancer recognized by simple metastasis to the duodenum].

We describe a case of relapsed small cell lung cancer (SCLC) recognized by a duodenal tumor, its probable metastasis. A 69-year-old man was admitted to Keio University Hospital complaining of persistent sputum production in September, 1996. A diagnosis of SCLC of the left lung invading the mediastinum was based on a transesophageal biopsy. Chemotherapy consisting of CDDP and VP-16 followed by thoracic irradiation at a total dose of 50 Gy was performed from October 1996 to August 1997, resulting in CR (Complete Response) of the tumor. In April of 1999, a mass surrounding the duodenum was found through an abdominal CT survey for tumor relapse, but no other tumors were detected in a series of CT scans or inbone scintigraphy. Subsequent fiberscopy of the upper gastrointestinal tract revealed an ulcerative tumor extensively invading the mucosa of the duodenal bulb. Biopsy specimens obtained from the duodenal tumor showed small-cell carcinoma with features similar to those of SCLC found in 1996, suggesting that SCLC of the left lung metastasized to the duodenal wall. Chemoradiotherapy with 4 cycles of CDDP and VP-16 followed by abdominal irradiation at a dose of 30 Gy was given again from May to September 1999, producing good PR (Partial Response). Although metastasis of SCLC to the duodenum seldom occurs, this report indicates that its early detection and effective treatment may prevent serious symptoms caused by obstruction of the duodenum or the papilla Vater.

Aged↗