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Biomedical subjects

Y Kuroda

Publications and source records attributed to Y Kuroda.

At least 415 records · Page 23Linked to original sources

Elevated cerebrospinal fluid lactate/pyruvate ratio in Machado-Joseph disease.

To identify the metabolic alterations related to mitochondrial functions in Machado-Joseph disease (MJD), we analyzed the cerebrospinal fluid (CSF) levels of lactate, pyruvate, and citric acid cycle intermediates by high performance liquid chromatography (HPLC) in 7 Japanese patients with that disease and then measured some mitochondrial enzymes. Their mean age was 46 years. Diseased controls were matched by age to the patients studied. The CSF level of lactate was significantly elevated, pyruvate was significantly decreased, and the lactate/pyruvate (L/P) ratio was significantly elevated in the patients with MJD. There were no significant differences of citric acid cycle intermediates of the CSF between the patients and the controls. We measured the native and dichloroacetate (DCA)-activated pyruvate dehydrogenase complex (PDHC) activities, and mitochondrial electron transport activities in 3 patients with MJD, and found these activities to be normal. Therefore, the increased CSF lactate, increased lactate/pyruvate ratio, and decreased pyruvate may reflect the decreased regional cerebral blood flow rather than metabolic derangement of the mitochondria.

Adult↗

Reconstructed three-dimensional images of flow-sorted nuclei hybridized with chromosome-specific probes.

We demonstrated that the three-dimensional (3-D) locational and morphological differences of chromosome 17 are dependent on each cell cycle phase in the clinical materials. Cell suspensions prepared from hypertrophied tonsil were hybridized with chromosome 17 whole painting probe or its centromeric probe and the probes were detected with fluorescein isothiocyanate. Then the cells were sorted from G(0+1), S-, and G(2+M)-phase fractions by flow cytometry and observed by confocal laser scanning microscopy to obtain the serial optical sections. The 3-D images were obtained by assembling these sections using a computerized image analysis device. The distribution of centromeric copies was analyzed statistically, and the data values were not a population of random distribution within a sphere. The copies were observed in the periphery of the nuclei in G(0+1)- and S-phase. The 3-D images revealed that chromosome 17 was oval in shape in the G(0+1)-phase nucleus, and was changing into a flame shape in the S-phase, with arms stretching out along the nuclear membrane, and looked bush shaped in G2-phase. The eccentric distribution of chromosome 17 in G(0+1)- and S-phase nuclei may reflect the optimal efficiency of incorporating and/or releasing essential materials and products.

Biomarkers↗

Interferon-alpha is effective in HTLV-I-associated myelopathy: a multicenter, randomized, double-blind, controlled trial.

A double-blind, multi-center study was performed on patients with HTLV-I-associated myelopathy (HAM) to evaluate the therapeutic effect of treatment with natural interferon-alpha (HLBI). Forty-eight HAM patients were enrolled and treated with either 0.3 MU (n = 15), 1.0 MU (n = 17), or 3.0 MU (n = 16) of HLBI for 28 days. Clinical evaluation included motor dysfunction, urinary disturbances, and changes of neurologic signs. The frequency of therapeutic response judged as excellent to good 4 weeks after starting therapy and 4 weeks after completion of therapy were 7.1% (1 of 14) and 8.3% (1 of 12) in the 0.3-MU group, 23.5% (4 of 17) and 26.7% (4 of 15) for the 1.0-MU group, and 66.7% (10 of 15) and 61.5% (8 of 13) for the 3.0-MU group. The therapeutic benefit in the 3.0-MU group was significantly higher than in the 0.3-MU group. There was no significant difference in the incidence of symptomatic side effects between groups. Abnormal laboratory data were obtained for some patients in the 1.0-MU and 3.0-MU groups; however, the treatment schedule could be continued in most patients. These results suggest that HAM patients may be safely treated with HLBI 3.0 MU every day for 4 weeks with favorable clinical effects.

Adult↗

[Immunohistological study on proliferative activities and expression of c-erbB-2 oncoprotein in salivary gland tumors].

The proliferative activity of tumors and the expression of c-erbB-2 oncoprotein were investigated in 86 salivary neoplasms (54 pleomorphic adenomas and 32 malignant tumors), and in 17 normal salivary glands. Numbers of cells that stained positive to anti-proliferating cell nuclear antigen (PCNA) antibody and the nucleolar organizer region associated protein (AgNOR) were used as an index of the proliferative activity. The results obtained in this study were as follows: 1) PCNA-positive and AgNOR-positive cells were elevated in malignant tumors relative to pleomorphic adenomas and normal salivary glands. 2) Salivary gland tissue around the pleomorphic adenoma with high proliferative activity demonstrated higher activity than normal gland tissue. 3) The proliferation of pleomorphic adenoma was not affected by the age or size of the tumors. 4) Expression of c-erbB-2 oncoprotein was not observed in pleomorphic adenoma and normal gland but was observed in malignant tumors. 5) In one case of a carcinoma in pleomorphic adenoma, the pleomorphic adenoma region also revealed c-erbB-2 positive cells.

Adenoma, Pleomorphic↗

[Squamous cell carcinoma of the parotid gland in children].

A five-year-old boy with squamous cell carcinoma of the parotid gland is presented. The patient had a painless mass in his left parotid region with left facial palsy. Squamous cell carcinoma of the parotid gland shows high grade malignancy and is extremely rare in children, especially under five years old. After neo-adjuvant chemotherapy, he was given a total parotidectomy and radical neck dissection. The left facial nerve could not be preserved. Radiotherapy was also administered postoperatively. There was no evidence of local recurrence or distant metastasis 18 months after the surgery. Careful long-term follow-up is mandatory for this patient.

Carcinoma, Squamous Cell↗

Pancreas transplantation using non-suture cuff technique in the neck.

To get a successful pancreas transplantation in a rat model, we performed heterotopic pancreas transplantation with non-suture cuff technique to neck vessels. As the graft was placed in the neck, we could avoid the clamping of systemic circulation which is essential but detriment to the rat during vascular anastomosis in intraabdominal grafting. The diameter of the portal vein was enlarged to prevent outflow block after transplantation. The cuff was fixed by fat clay during anastomosis to perform vascular anastomosis easily. As a result the success rates was 16/20, 80%. 16 rats survived more than 30 days and maintained serum glucose level within 200 mg/dl throughout the experiment. The heterotopic pancreas transplantation using non-suture cuff technique to the neck vessels is safe, reliable and recommended as the experimental model using the rat.

Animals↗

[Administration method and recurrence-preventing effect of medroxyprogesterone acetate (MPA) as a postoperative adjuvant endocrine therapy for stage III breast cancer. Kitakyushu Collaborative Study Group for Breast Cancer].

By a collaborative study undertaken by 11 medical institutions in the Kita-Kyushu area, we evaluated the clinical efficacy of the combination of medroxyprogesterone acetate (MPA) and Tamoxifen (TAM) as a postoperative adjuvant endocrine therapy for Stage III breast cancer. First, 1 course of CAF therapy was administered; then, in combination with the basic therapy of 5-FU 200 mg/day p. o. for 3 years, ER (+) patients were treated with either 2-week sequential therapy of TAM (30 mg/day) and MPA (800 mg/day) or TAM (30 mg/day), and ER (-) patients received either MPA (800 mg/day) or 5-FU alone. Neither survival nor disease-free rates of the 92 analyzable patients were different between these treatment groups. Furthermore, the blood levels of MPA and cortisol had no correlation with survival and disease-free periods. We studied the effect of MPA on the natural inhibitors of blood coagulation, but found no difference from the result in healthy adults. It was, however, shown that MPA had a bone marrow-protecting effect.

Adult↗

Detection of hepatitis C virus core protein in the glomeruli of patients with membranous glomerulonephritis.

Two Japanese patients suffered from membranous glomerulonephritis associated with hepatitis C virus (HCV) infection. Renal histologic changes were characterized by granular deposits of IgG and C3 along the capillary wall and numerous subepithelial deposits in glomeruli. Hypocomplementemia was present in one patient, but both cryoglobulins and rheumatoid factors were absent. HCV RNA was detected in both their sera by RT-PCR, both free and in the form of circulating immune complexes. The HCV core protein was found in the glomeruli from both patients by indirect immunofluorescence. These results suggest that in some patients chronic HCV infection causes membranous glomerulonephritis through immune complex deposition involving HCV proteins.

Aged↗

[Evaluation of concomitant use of cyclosporin and percutaneous isolated liver perfusion under complete venous isolation and charcoal hemoperfusion].

It is difficult to administer an effective dose of cyclosporin A (CsA), a potent inhibitor of P-glycoprotein, to prevent multiple drug resistance due to its side effect. We herein evaluated the efficacy of concomitant use of this agent and complete hepatic venous isolation and charcoal hemoperfusion (HVI.CHP). Dogs were divided into two groups; group I (n = 4), intraarterial infusion of only adriamycin (ADM) and group II (n = 4), intraarterial infusion of CsA and ADM. In both groups, ADM was intraarterially administered for 10 minutes under HVI.CHP. In addition, in group II, CsA infusion (0.3 mg/min.kg) was initiated 20 min prior to the start of ADM infusion and maintained for 30 min. The AUC (micrograms.min/ml) of ADM were 21.2 +/- 8.6 (mean +/- SD) and 28.4 +/- 10.3 in groups I and II, respectively, at prefilter (hepatic venous level) and 8.1 +/- 4.6 and 4.8 +/- 3.8, respectively, at postfilter, showing an effective drug elimination in both groups. The Cmax (micrograms/ml) were 14.1 +/- 2.2 at prefilter, 2.4 +/- 0.5 at postfilter, and 3.4 +/- 1.2 in systemic level. These results indicated that HVI.CHP allowed the high-dose CsA infusion required for P-gp inhibition in the liver and could reduce extraregional CsA leakage.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[The effect of high-dose intraarterial chemotherapy with percutaneous hepatic venous isolation and charcoal hemoperfusion (HVI.CHP) for unresectable multiple hepatocellular carcinoma--comparison with other therapeutic modalities].

We evaluated the therapeutic effect of HVI.CHP in 11 patients with Stage III and IVA multiple hepatocellular carcinoma (group H) in comparison with conventional intraarterial chemotherapy (group S, 12 patients) and transarterial embolization (TAE; group T, 15 patients). The patients in each group had the same background as group H in terms of liver function tests. The Vp3 positive rates in group H (37%) and group S (47%) were significantly higher than group T (0%). One-year survival rates of groups H, S and T were 63. 6%, 8.3% and 46.7%, respectively, and 2-year survival rates were 63.6%, 0% and 20%, respectively. A significant difference was seen between the survival curves of groups H and S (p < 0.01), whereas no significant differences were detected between those of groups H and T. The survival rates for stage IVA patients in groups H, S and T were 55.6%, 10% and 40%, respectively, for 1 year and 55.6%, 0% and 10%, respectively, for 2 years. The difference of survival curves between Stage IVA patients of each group was analogous to those between overall patients of each group. Although 4 patients with Vp3 were included in group H but none in group T, the survival rates of group H were rather higher than in group T at 2 years. These data suggest that HVI.CHP could be the treatment of choice for unresectable multiple hepatocellular carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗

[Evaluation of a single catheter technique for percutaneous isolated liver perfusion].

We have established a single catheter technique of percutaneous isolated liver perfusion using a 4-lumen-2-balloon (4L - 2B) catheter for treatment of unresectable malignant liver tumors. Herein reported are the technique, safety and pharmacokinetics of the system in comparison with the original double-balloon technique. This study included 19 patients with malignant liver tumors treated by adriamycin at a dose of 100 mg/m2. Seven patients had the double-balloon technique (group D), in which filtered hepatic effluent and the rest of the inferior vena caval blood were separately drawn and returned to the left axillary vein. The other 12 patients had single catheter technique (group S). In group S, hepatic effluent was solely isolated and directed to CHP filters. All patients except for one in group S showed good hemodynamic stability. The hepatic venous flow rate of group S was significantly higher than in group D (p < 0.05). Although the mean area under the time concentration curve at systemic serum was significantly lower in group S compared to group D, the rate of side effects was similar in both groups. A 4L. 2B single catheter allowed safe and repeated percutaneous isolated liver perfusion for technical simplification of the treatment.

Aged↗

[A case of advanced hepatoma cured by repeated percutaneous isolated liver perfusion using hepatic venous isolation and charcoal hemoperfusion].

We have reported the treatment results of percutaneous isolated liver perfusion using hepatic venous isolation and charcoal hemoperfusion (HVI.CHP) for unresectable liver cancers. This is a case of multiple advanced hepatoma cured completely by repeated per cutaneous isolated liver perfusion. The patient was a 58-year-old woman who was referred to our hospital for a hepatic tumor detected by abdominal computed tomograpy (CT). On admission, she showed HBs antigen positive, mild anemia and liver dysfunction, and elevation of tumor markers. Abdominal CT demonstrated nodular tumors in segment 4. In addition, hepatic angiography additionally revealed multiple bilobar metastases. We treated this case with high-dose intraarterial adriamycin (150 mg/body) using HVI.CHP. There after, the patient received intermittent intraarterial low-dose epirubicin infusions (30 mg/body, 5 times) via an implantable catheter system. Furthermore, she was given a second high-dose of adriamycin (130 mg/body) under HVI.CHP 7 months after the first treatment. Despite repeated high-dose treatments, she had no severe side effects. The levels of tumor markers, including AFP and PIVKA-II, decreased to normal range, and all tumor nodules have disappeared in abdominal CT studies at present, 20 months after the initial treatment. In conclusion, our experience suggests that advanced hepatoma with multiple bilobar lesions, as in this case, would be cured by repeated percutaneous isolated liver perfusion using HVI.CHP.

Antineoplastic Combined Chemotherapy Protocols↗

[A case of advanced cholangiocellular carcinoma treated successfully by percutaneous isolated liver perfusion with cisplatin].

Herein reported is a case with unresectable intrahepatic cholangiocellular carcinoma (CCC) treated successfully with high-dose cisplatin infusion under hepatic venous isolation and charcoal hemoperfusion (HVI.CHP). The patient was a 43-year-old woman, who was investigated for liver dysfunction and subsequently referred to our institution with a diagnosis of unresectable intrahepatic CCC. We gave this patient a total of 2 treatments of percutaneous isolated liver perfusion with HVI.CHP (a total dose of cisplatin, 400 mg and adriamycin 30 mg). Although she had a slight elevation of serum GOT levels, leukopenia and renal dysfunction did not occur throughout the posttreatment course. The level of DUPAN-2 after the first treatment showed a marked reduction to 910 U/ml, from a pretreatment level of 2,700 U/ml. Abdominal CT scan also demonstrated a remarkable regression of liver tumors (PR: volume reduction, 76%). In conclusion, in percutaneous isolated liver perfusion using HVI.CHP, we have safely accomplished a dose intensification of intraarterial cisplatin. The treatment resulted in a marked tumor regression. Therefore, we consider that this method offers an effective therapeutic option for unresectable CCC.

Adult↗

[A case of crescentic glomerulonephritis with extensive hematuria resulting in severe anemia].

A 24-year-old woman was admitted to our hospital because of macroscopic hematuria with clotting. She had been well until two months before admission, when she experienced fever, arthralgia and lethargy and entered another hospital. Laboratory tests showed macroscopic hema-turia, anemia and mild renal dysfunction. Two weeks prior to admission, she had experienced an episode of macroscopic hematuria with clotting followed by severe anemia requiring blood transfusion. Because of the deterioration of her renal function, she was transferred to our hospital. Examinations to determine the source of bleeding from the urinary tract, including a renal arteriogram, were negative. Tests for c-anti-neutrophil cytoplasmic antigen (ANCA) and anti-glomerular basement membrane antibody gave negative results, whereas the test for p-ANCA was positive. Renal biopsy revealed crescentic glomerulonephritis with focal necrosis. Therefore, we diagnosed rapidly progressive glomerulonephritis (RPGN) due to ANCA-associated renal disease. As a result of methypre-dnisolone pulse treatment followed by oral steroid therapy, macroscopic hematuria disappeared with marked improvement of her renal function. We considered this patient to be a rare case of RPGN with blood loss through glomerular lesions resulting in severe anemia.

Adult↗