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Biomedical subjects

Y Kuroda

Publications and source records attributed to Y Kuroda.

At least 235 records · Page 13Linked to original sources

Apoptotic cell death of renal tubules in experimental severe acute pancreatitis.

BACKGROUND: Recently renal cell apoptosis has been reported in various disorders that result in renal failure. Thus we hypothesized that renal cell injury resulting from apoptosis is involved in renal failure with severe acute pancreatitis. METHODS: Renal cell apoptosis in kidneys harvested from rats with necrotizing pancreatitis was evaluated by in situ nick-end labeling. Ascitic fluid that had been collected 6 hours after development of pancreatitis was injected into the peritoneal cavities of healthy rats, and renal apoptosis was also evaluated. The apoptosis-inducing activity of the ascitic fluid was estimated in vitro with use of isolated rat renal tubules and the normal rat kidney cell line NRK52E by nuclear staining, cell cycle analysis, and DNA electrophoresis. RESULTS: Apoptosis was detected by in situ nick-end labeling on the renal tubules 6 hours after induction of pancreatitis in vivo. Similar tubular apoptosis was detected in the rats that had intraperitoneal injection of the ascitic fluid. In in vitro analyses the ascitic fluid induced nuclear and DNA fragmentation on the isolated renal tubules and promoted apoptosis on NRK52E cells in a time-dependent manner. CONCLUSIONS: Apoptotic cell death of renal tubules occurs in severe acute pancreatitis within several hours and is possibly involved in the mechanism of renal failure through undefined substance(s) in the ascitic fluid associated with pancreatitis.

Animals↗

Clinical implications of telomerase activity in resected hepatocellular carcinoma.

This study investigated the relationship of telomerase activity to its clinical implications in hepatocellular carcinoma (HCC). Telomerase activity was quantatively examined by a non-radioisotope quantitative system based on a TRAP-eze (ONCOR) in 42 HCC nodules and 40 non-cancerous liver tissue adjacent to the HCC nodules, obtained by surgical resection. Telomerase activity was confirmed in 37 HCC nodules (88.1%), being more statistically intense in de-differentiated tumors (p<0.01). Telomerase activity was positive in 9 cases (22.5%) of non-cancerous liver tissue and its activation was closely associated with the biologically malignant potential of the tumor itself such as the histological grade, portal vascular invasion, and intrahepatic metastasis (p<0. 05). The disease-free survival rate with its activity was also statistically lower than that without its activity of the non-cancerous tissue (p<0.01). These results indicate that telomerase may be a useful marker of biological characteristics in HCC and may lead to more effective surgical procedures.

Alanine Transaminase↗

[A case of multiple hepatocellular carcinoma complicated with N3 regional lymph node metastases preventing tumor progression by gradual introduction of lymph node excision and high-dose chemotherapy using percutaneous isolated hepatic perfusion].

We experienced a case of multiple hepatocellular carcinoma (HCC) complicated with N3 regional lymph node metastases. The gradual introduction of lymph node excision and high-dose chemotherapy using percutaneous isolated hepatic perfusion (PIHP) was effective in preventing progress of the tumor. The patient was a 63-year-old male who underwent a thorough medical examination because of elevated AFP at a local hospital. He was referred to our hospital. The preoperative laboratory results showed the elevation of AFP (729 ng/ml) and PIVKA-II (2,110 mAU/ml). CT scan of the liver revealed tumors in segment 4, 5 and 6, and lymph node metastases from the pancreas to the hepato-duodenal ligament. The enlarged lymph nodes were excised and the tumor in segment 5 was resected for pathological examination. Adriamycin was administered in doses of 100 mg/m2 and 80 mg/m2 using PIHP two and three months after the operation. According to the results of laboratory studies conducted 14 months after the operation, AFP was 12 ng/ml and PIVKA-II was within the normal range. CT scan of the liver showed the liquefaction degeneration of the remaining HCC. Although surgery is not generally indicated in a patient with multiple HCC complicated with N3 regional lymph node metastases, it should be considered in combination with PIHP in those with resectable extrahepatic lesion.

Antineoplastic Agents↗

[Trigeminal neuralgia with the offending artery transfixing the trigeminal nerve: a case report].

We report a rare case of a patient manifesting trigeminal neuralgia with the offending artery transfixing the trigeminal nerve. A 67-year-old woman was admitted with typical episodes of trigeminal neuralgia on the right side. Magnetic resonance angiograms revealed the right superior cerebellar artery (SCA) compressing the nerve. Through a retromastoid suboccipital craniotomy on the right side, the right SCA was found to compress the root entry zone (REZ) and then penetrate the portio major of the trigeminal nerve. The nerve was dissected parallel to the axis, 7 mm distally from the transfixing point to facilitate transposition of the SCA. In addition to anchoring the distal portion of the SCA to the tentrium, a prosthesis was interposed between the proximal portion and the pons to secure the decompression. The pain was completely relieved immediately after operation with no neurological deficit. Procedures, such as the longitudinal rhizotomy employed in this case, must be carried out for microcompression, in response to individual anatomical variations in neurovascular structures.

Aged↗

[Optimal thoracic irradiation for stage IV lung cancer].

To investigate optimal thoracic irradiation (TI) for stage IV lung cancer, we retrospectively reviewed 150 patients. In all, 101 patients underwent radiotherapy for the primary lesion, and 130 had radiotherapy for metastasized sites. TI fields were basically divided into two groups; whole thoracic lesion irradiation (WTLI) and partial thoracic lesion irradiation (PTLI). Overall survival rates at 6 months, 1 year and 2 years were 58%, 27% and 11%, respectively, and MST was 7.1 months. There was no difference in survival according to histological type. On univariate analysis, the factors of good prognosis included good PS, free of bone metastasis, metastasis limited to a single organ, TI, chemotherapy, age (less than or equal to 75 years), and TN factors (T0-2 and N0-1). Multivariate analysis showed PS was the predominant factor. Among the patients treated with TI, survival rates of patients with PS 0-1 were superior to those of patients with PS 2-4. Radiation pneumonitis was more frequent in WTLI than in PTLI. The rates of thoracic failure death were 31.7% in patients treated with TI and 63.3% without TI. However, the size of the thoracic radiation field did not affect the rates of thoracic failure death. We concluded that TI for stage IV patients could reduce thoracic symptoms and increase the survival rate in the subgroup with good PS. Furthermore, we considered PTLI was worth while in the subgroup with poor PS.

Aged↗

The effect of a newly developed ointment containing eicosapentaenoic acid and docosahexaenoic acid in the treatment of atopic dermatitis.

While various therapeutic modalities have been tried for atopic dermatitis (AD), numerous obstinate cases exist in which sufficient effects cannot be obtained. Therefore, we developed and prepared an ointment containing docosahexaenoic acid and eicosapentaenoic acid as a topical therapeutics for AD. We applied this ointment to 64 patients with AD (aged between 2 months and 29 years) who showed poor responses to conventional therapies and obtained satisfactory results. This ointment is considered a new topical preparation for AD.

Adolescent↗

Molecular genetic analysis of pyridoxine-nonresponsive homocystinuric siblings with different blood methionine levels during the neonatal period.

Two mutations in the cystathionine beta-synthase (CBS) gene were found in two Japanese siblings with pyridoxine non-responsive homocystinuria who had different methionine levels in their blood during the neonatal period. Both patients were compound heterozygotes of two mutant alleles: one had an A-to-G transition at nucleotide 194 (A194 G) that caused a histidine-to-arginine substitution at position 65 of the protein (H65R), while the other had a G-to-A transition at nucleotide 346 (G346A) which resulted in a glycine-to-arginine substitution at position 116 of the protein (G116R). The two mutant proteins were separately expressed in Escherichia coli, and they completely lacked catalytic activity. Despite their identical genotypes and almost equal protein intake, these siblings showed different levels of blood methionine during the neonatal period, suggesting that the level of methionine in blood is determined not only by the defect in the CBS gene and protein intake, but also by the activity of other enzymes involved in methionine and homocysteine metabolism, especially during the neonatal period. Therefore, high-risk newborns who have siblings with homocystinuria, even if the level of methionine in their blood is normal in a neonatal mass screening, should be followed up and diagnosed by an assay of enzyme activity or a gene analysis so that treatment can be begun as soon as possible to prevent the development of clinical symptoms. In addition, a new, more sensitive method for the mass screening of CBS deficiency in neonates should be developed.

Adolescent↗

The effect of the two-layer cold storage method on islet isolation from ischemically damaged pancreas.

Previous studies have shown that the two-layer cold storage method (TL) resuscitates the function of warm ischemically (WI) damaged pancreas when transplanted as a segmental graft in a dog model. In this study, we evaluated the effect of TL on yield and viability of islets isolated from WI damaged pancreas. In group 1 (n = 10), dog pancreases were processed into islets immediately after total pancreatectomy. In group 2 (n = 5), excised pancreases were left in the abdominal cavity for 60 minutes as WI then processed. In group 3 (n = 5), WI damaged pancreases were preserved in TL at 4 degrees C for 24 hours before islet isolation. Islets were isolated by the digestion methods described by Ricordi, et al. And purified on Euro-Ficoll discontinuous gradients. We compared three groups in terms of islet yields before and after purification, expressed as islet equivalents (IEQ, diameter standardizing to 150 microns) per pancreas weight (IEQ/g pancreas). Viability of islets was assessed with in vitro static incubation test. Islet yields after purification were 2500 +/- 1100 (mean +/- SD) in group 1, 1200 +/- 800 in group 2, (p = 0.04 vs. group 1, p = 0.03 vs. group 3), and 2200 +/- 300 in group 3 (p = 0.38 vs. group 1). Static incubation test revealed that islets in group 1 and 3 showed sufficient insulin release in response to glucose stimuli. These data clearly demonstrated that TL can regain islet yield from WI damaged pancreas up to similar level to that from fresh pancreas. Viability of those islets was well maintained. Thus temporary TL applied before islet isolation may allow to use islets from non-heartbeating cadavers in the clinical setting.

Animals↗

[KMO1].

Explore the source record for details and available documents.

Antigens, Tumor-Associated, Carbohydrate↗

Experimental study on paratumoral injection of cisplatin-loaded microspheres for gastric cancer.

Microspheres from glycolide-L-lactide copolymers incorporating cisplatin (CDDP-MS) were prepared to evaluate the sustained release and anticancer effect by paratumoral injection on the gastric cancer with regional lymphnode metastases induced by VX2 tumor in rabbits. In the first set of experiment, the rabbits were divided into three groups subjected to treatment and compared the tissue cisplatin distribution. In the first group (CDDP-MS pt group), 1 mg/kg of cisplatin was administered by the method of paratumoral injection in the form of CDDP-MS. In the second group (CDDP solution pt group), the same dose was given in the form of CDDP aqueous solution in the same way and in the third group (CDDP solution i.v. group), the same dose was intravenously administered. In the second set of experiment, after twice of each therapy the anticancer effects were compared between CDDP-MS pt and CDDP solution i.v. groups. In results, the platinum concentrations of the tumor and regional lymphnodes were 3.14 +/- 6.22, 0.65 +/- 0.79 micrograms/g in the first group, 0.43 +/- 0.39, 0.16 +/- 0.16 microgram/g in the second group and 0.03 +/- 0.01, 0.07 +/- 0.05 microgram/g in the third group, respectively.

Animals↗

A nationwide follow-up system is essential for a neonatal screening program.

A long-term follow-up study gives many benefits to patients detected by neonatal screening, their families, and all members who are involved in neonatal screening program. However, the follow-up system is not functioning satisfactorily enough in Japan. A nationwide long-term follow-up system needs to be established immediately to make the neonatal screening system complete in Japan.

Child Health Services↗

In vitro changes of the nuclear AgNORs pattern induced by RNA inhibitors and 5-fluorouracil in human breast cancer cells, MCF-7 and HBC-4.

The morphological changes of argyrophilic nucleolar organizer regions (AgNORs) were studied in two human breast cancer cell lines, MCF-7 and HBC-4. Treatment with an RNA polymerase inhibitor (actinomycin D) reduced the size of AgNORs and increased the number of AgNORs. Messenger RNA polymerase inhibitor (alpha-amanitin) also increased the number of AgNORs. However, translational blocking agents closely related to ribosomal RNA (cycloheximide and anisomycin) caused a decrease in the number of AgNORs, which seemed to fuse to an aggregate around the nucleolus and formed a single large spherical AgNOR in the final stage. These changes were observed typically when cells were treated with 5-fluorouracil or 5-fluorouridine. These morphological changes in the AgNORs pattern, AgNORs aggregation, might reflect certain damage in ribosomal RNA.

Antimetabolites, Antineoplastic↗

Marginal benefit/disadvantage of granulocyte colony-stimulating factor therapy after autologous blood stem cell transplantation in children: results of a prospective randomized trial. The Japanese Cooperative Study Group of PBSCT.

In this prospective trial, a total of 74 children who were scheduled to undergo high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) were prospectively randomized at diagnosis to evaluate the effectiveness of exogenous granulocyte colony-stimulating factor (G-CSF) treatment in accelerating hematopoietic recovery after PBSCT. The diagnosis included acute lymphoblastic leukemia (ALL) (n = 27), neuroblastoma (n = 29), and miscellaneous solid tumors (n = 18). Eligibility criteria included (1) primary PBSCT, (2) chemotherapy-responsive disease, and (3) collected cell number >1 x 10(5) colony-forming unit-granulocyte-macrophage (CFU-GM)/kg and >1 x 10(6) CD34(+) cells/kg patient's body weight. After applying the above criteria, 11 patients were excluded due to disease progression before PBSCT (n = 6) or a low number of harvested cells (n = 5), leaving 63 patients for analysis; 32 patients in the treatment group (300 microg/m2 of G-CSF intravenously over 1 hour from day 1 of PBSCT) and 31 in the control group without treatment. Two distinct disease-oriented high-dose regimens without total body irradiation consisted of the MCVAC regimen using ranimustine (MCNU, 450 mg/m2), cytosine arabinoside (16 g/m2), etoposide (1.6 g/m2), and cyclophosphamide (100 mg/kg) for patients with ALL, and the Hi-MEC regimen using melphalan (180 mg/m2), etoposide (1.6 g/m2), and carboplatinum (1.6 g/m2) for those with solid tumors. Five patients (two in the treatment group and three in the control group) were subsequently removed due to protocol violations. All patients survived PBSCT. The median numbers of transfused mononuclear cells (MNC), CD34(+) cells, and CFU-GM were, respectively, 4.5 (range, 1 to 19) x 10(8)/kg, 8.0 (1.1 to 25) x 10(6)/kg, and 3.7 (1.2 to 23) x 10(5)/kg in the treatment group (n = 30) and 2.9 (0.8 to 21) x 10(8)/kg, 6.3 (1.1 to 34) x 10(6)/kg, and 5.5 (1.3 to 37) x 10(5)/kg, respectively, in the control group (n = 28), with no significant difference. After PBSCT, the time to achieve an absolute neutrophil count (ANC) of >0.5 x 10(9)/L in the treatment group was less than that in the control group (median, 11 v 12 days; the log-rank test, P =.046), although the last day of red blood cell (RBC) transfusion (day 11 v day 10) and the duration of febrile days (>38 degrees C) after PBSCT (4 v 4 days) were identical in both groups. However, platelet recovery to >20 x 10(9)/L was significantly longer in treatment group than control group (26 v 16 days; P =.009) and >50 x 10(9)/L tended to take longer in the treatment group (29 v 26 days; P =.126), with significantly more platelet transfusion-dependent days (27 v 13 days; t-test, P =.037). When patients were divided into two different disease cohorts, ALL patients showed no difference in engraftment kinetics between the G-CSF treatment and control groups, while differences were seen in those with solid tumors. We concluded that the marginal clinical benefit of 1 day earlier recovery of granulocytes could be offset by the delayed recovery of platelets. We recommend that the routine application of costly G-CSF therapy in children undergoing PBSCT should be seriously reconsidered.

Adolescent↗