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Biomedical subjects

S Kubo

Publications and source records attributed to S Kubo.

At least 163 records · Page 9Linked to original sources

Methylmethacrylate casting model of temporal bone: a simple technique for skull base research and education.

Methylmethacrylate casting model of the temporal bone simulating the translabyrinthine approach from the bone surface down to the internal auditory canal was developed in order to help to understand the complex anatomy that is often encountered during skull base surgery. Using a cadaver temporal bone and applying dental impression technique, fine structures, such as semicircular canals and facial nerve, were precisely reproduced in a life-size resin casting model. This simple cost-effective modeling method would facilitate both anatomical research and medical education by improving our understanding of the complex anatomy of the temporal bone.

Journal Article↗

Suppressive effect of the angiogenesis inhibitor TNP-470 on the development of carcinogen-induced hepatic nodules in rats.

Tumor metastasis can be prevented by inhibiting angiogenesis. In the present study, we have demonstrated that the angiogenesis inhibitor TNP-470 also suppresses the development of primary hepatic nodules. Hepatocarcinogenesis was performed by the feeding of 2-acetylaminofluorene to hepatectomized rats during 8-14 weeks of age. Predominantly arterial-to-portal circulation and sinusoidal capillarization were determined by the staining of nodules with arterially infused ink and immunostaining for factor VIII-related antigen, respectively. Intraperitoneal administration of 30 mg/kg b.w. of TNP-470 twice a week significantly reduced the number of hepatic nodules. Among the nodules, hyperplastic nodules stained with ink, atypical hyperplastic nodules and hepatocellular carcinoma, all of which possess structurally altered sinusoidal endothelial cells or capillary-type endothelial cells, were dramatically decreased in number. Suppression was observed equally in nodules of all sizes. TNP-470 was more effective when administered during 8-20 weeks than during 14-26 weeks. In contrast, ink-non-stained hyperplastic nodules, which have normal sinusoidal endothelial cells, were not affected at all. The present results indicate that TNP-470 suppresses the development of primary hepatic nodules whose microvessels are capillaries or transitional forms from sinusoids to capillaries.

2-Acetylaminofluorene↗

Clinicopathological criteria for multicentricity of hepatocellular carcinoma and risk factors for such carcinogenesis.

Multicentric occurrence is an important characteristic of hepatocellular carcinoma. We evaluated clinicopathological criteria for multicentric hepatocellular carcinoma and identified risk factors for such carcinogenesis. Subjects were 251 consecutive patients undergoing liver resection for hepatocellular carcinoma. One kind of multicentric hepatocellular carcinoma had at least one tumor consisting of well-differentiated hepatocellular carcinoma, together with moderately or poorly differentiated hepatocellular carcinoma located in a separate region. The other kind had an area of well-differentiated component around hepatocellular carcinoma with less differentiation in all occurrences. The outcome of patients with tumors classified in this way was studied. Univariate and multivariate analyses were done to identify risk factors for multicentric hepatocellular carcinoma. The cumulative survival rate was significantly higher in patients with multicentric hepatocellular carcinoma than in patients with hepatocellular carcinoma associated with intrahepatic metastasis. Analysis by Cox's proportional hazard model showed that multicentricity was not a factor in the outcome. The risk of multicentric occurrence increases with progression of chronic liver disease. Univariate analysis showed hepatitis C virus marker and hepatitis B core antibody to be risk factors. By multivariate analysis, the odds ratio for multicentric occurrence in patients infected with hepatitis C virus and with serum hepatitis B virus core antibody compared with patients without either hepatitis C virus or hepatitis B virus was 10.86. This ratio in patients with hepatitis C virus alone was 4.30. These criteria for multicentric hepatocellular carcinoma seem to be clinically useful. Hepatitis C virus infection with or without former infection by hepatitis B virus is a strong risk factor for multicentric hepatocarcinogenesis.

Aged↗

Congenital megalourethra: a case report.

We describe a case of a male infant with a scaphoid megalourethra. A physical examination showed a large, flabby phallus with bilateral undescended testes. The corpus spongiosum was absent with normal corpora cavernosa. Urethrography showed a crescent-shaped dilatation of the anterior urethra. Further examination revealed an association with concomitant urogenital anomalies, right renal hypoplasia-dysplasia, bilateral vesicoureteral reflux and the prune-belly syndrome. A urethroplasty with resection of the excess urethral tissue and reconstruction of the urethra was performed. There was a satisfactory surgical result and the patient now voids without difficulty.

Cystoscopy↗

Astemizole-induced torsades de pointes in a patient with vasospastic angina.

Astemizole (Hismanal), an antihistamine agent, has been reported to be associated with ventricular arrhythmias. In this paper we present a case of QT prolongation and torsades de pointes (TdP) in a 77-year-old woman who had been taking astemizole (10 mg/day) for 6 months because of allergic skin disease. At the time of admission, the serum concentration of astemizole and its metabolites was markedly elevated at 15.85 ng/ml, approximately 3 times the normal level. The patient was also taking cimetidine, a known inhibitor of cytochrome P-450 enzymatic activity, and during her admission was diagnosed as having vasospastic angina. To the best of our knowledge, this is the first report of astemizole-induced QT prolongation and TdP in Japan.

Aged↗

Serous cystadenoma of the pancreas with atypical cells. Case report.

CONCLUSION: Serous cystadenomas of the pancreas may have the biologic ability to undergo malignant transformation. BACKGROUND: It is generally recognized that: serous cystadenomas of the pancreas are benign and that their malignant potential is low. METHODS: A serous cystadenoma of the pancreas was resected from a 53-yr-old woman. In the central portion of the tumor, papillary structures were found on the cyst wall. Immunohistologic studies using antibodies to carbohydrate antigen 19-9, carcinoembryonic antigen, and proliferating cell nuclear antigen were performed to determine the malignant potential of this tumor. RESULTS: On histology, most tumor cells were positive for periodic acid-Schiff but were negative for periodic acid-Schiff after diastase digestion and Alcian blue, a staining pattern typical of serous cystadenomas. The cells found in the papillary structure of the cyst wall were mildly atypical. These cells were stained with antibodies to carbohydrate antigen 19-9, carcinoembryonic antigen, and proliferating cell nuclear antigen, indicating that the cells comprising the papillary structure were proliferating more rapidly than cells in other parts of the tumor and strongly suggesting that the cells are premalignant.

CA-19-9 Antigen↗

Effect of urine component on leukocyte chemiluminescence response.

In the urine, the function of polymorphonuclear leukocytes (PMNs) is thought to be impaired because of the high osmolality and low pH along with a high concentration of inorganic salts. We investigated the effect of the properties of urine and its components on the chemiluminescence (CL) response of PMNs. This was helped by using an artificial urine. The CL response was measured by automatic luminometer following stimulation of phorbol myristate acetate. We found the CL response of PMNs to be significantly suppressed at a pH of 6 or 5, but not suppressed at a pH of 7 or 8. The CL response was significantly reduced when the osmolality was increased to 580 or 800 mOsm/kg H2O by the addition of urea as compared to the response in the standard artificial urine at an osmolality of 425 mOsm/kg H2O. A change in the osmolality by the addition of mannitol only minimally influenced the CL responses. In addition, the CL response was significantly impaired by both low and high concentrations of sodium at 12 and 300 mEq/L as compared to 77.5 mEq/L in the standard artificial urine. Potassium significantly reduced the CL response in a concentration-dependent manner in the range of from 4 to 31 mEq/L as compared to 52.3 mEq/L in the standard artificial urine. A high concentration of calcium at 8.1 or 9.9 mg/dL reduced CL response as compared to 3.9 mg/dL, whereas CL response was not reduced by the change in the concentration of magnesium. A high concentration of creatinine significantly reduced the CL response as compared to the standard artificial urine. We conclude that the function of PMNs in urine is reduced mainly by urine pH, concentration of urea, sodium, potassium, and creatinine. We suggest that reversal of these change in urine may restore functions of PMNs to clear bacteria in patients with urinary tract infections.

Bacteriuria↗

[Immunohistochemical studies on neuronal changes in brain stem nucleus of forensic autopsied cases. I. Various cases of asphyxia and respiratory disorder].

Several nuclei in brain stem are well known to play an important role in supporting human life. However, the connection between neural changes of brain stem and the cause of death is not yet fully understood. To investigate the correlation of brain stem damage with various cause of respiratory disorders, neural changes of the arcuate nucleus (ARC), the hypoglossal nucleus (HN) and the inferior olivary nucleus (IO) were examined using immunohistochemical technique. Based on the cause of death, the forensic autopsy cases were divided into 5 groups as follows. Group I: hanging, ligature strangulation and manual strangulation, Group II: smothering and choking, Group III: drowning, Group IV: respiratory failure, control group: heat stroke and sun stroke. Brain was fixed with phosphate-buffer formalin, and the brain stem was horizontally dissected at the level of apex, then embedded in paraffin. The sections were stained with the antibodies against microtubule-associated protein 2 (MAP2), muscalinic acetylcholine receptor (mAChR), c-fos gene product (c-Fos) and 72 kD heat-shock protein (HSP70). Three nuclei showed no obvious morphological changes in all examined groups. However, in case of asphyxia (Group I to III), neurons in HN were positively stained with both HSP70 and c-Fos antibodies. This may indicate that the occlusion of upper airway results in the neuronal damage of HN without their morphological changes. Positive staining of HSP70 and c-Fos in IO was more frequently observed in Group III than other 4 groups. Since IO is involved in maintaining body balance which is often disturbed by drowning, it seems possible that neuronal damage in IO observed in drowning may be related to the disturbance of body balance. These observations indicate that immunohistochemical study on the damage to neurons in brain stem nuclei can provide useful information for determining the cause of death.

Arcuate Nucleus of Hypothalamus↗

[Immunohistochemical studies on neuronal changes in brain stem nucleus of forensic autopsied cases. II. Sudden infant death syndrome].

Several nuclei in brain stem are well known to play an important role in supporting human life. However, the connection between neural changes of brain stem and the cause of death is not yet fully understood. Previously, in sudden infant death syndrome (SIDS) it has been suggested that impaired cardioventilatory control might contribute to cause of death. So, to investigate the brain stem damage in SIDS, neural changes of the arcuate nucleus (ARC), the hypoglossal nucleus (HN) and the inferior olivary nucleus (IO) was examined using immunohistochemical technique. Brain was fixed with phosphate-buffer formalin, and the brain stem was horizontally dissected at the level of apex, then embedded in paraffin. The sections were stained with the antibodies against microtubule-associated protein 2 (MAP2), muscalinic acetylcholine receptor (mAChR), c-fos gene product (c-Fos) and 72 kD heat-shock protein (HSP70). Morphological changes of neurons in three nuclei were not evident. Moreover, because MAP2 degeneration and expression of HSP70 and c-Fos were not observed, neuronal damage in those nuclei was not suspected. However, although there was no abnormality of mAChR immunostaining in HN and IO, the rate of mAChR-immunopositive neurons in ARC was less than that in control. These observations indicate that immunohistochemical study on the neuronal changes in ARC can provide useful information for diagnosing SIDS.

Arcuate Nucleus of Hypothalamus↗

Effect of alcohol abuse on polyamine metabolism in hepatocellular carcinoma and noncancerous hepatic tissue.

BACKGROUND: Alcohol abuse is a risk factor for hepatocellular carcinoma (HCC) and the recurrence of HCC after resection. We therefore investigated polyamine metabolism, which is important in cell proliferation, HCC tissue, and noncancerous hepatic tissue. METHODS: In 30 patients who underwent liver resection for HCC, 13 patients had drunk 86 gm or more ethanol per day for at least 10 years (group 1), whereas the remaining 17 patients were nondrinkers or occasional drinkers (group 2). The control subjects were five patients who did not have liver disease or abuse alcohol. Tissue ornithine decarboxylase (ODC) activity and polyamine concentrations were measured. RESULTS: ODC activity in the HCC tissue was significantly higher in group 1 than in group 2. ODC activity in noncancerous tissue was significantly higher in group 1 than in group 2 and the control group. The ratio of spermidine/spermine in the HCC tissue was significantly higher in group 1 than in group 2. The ratio in noncancerous tissue was significantly higher in groups 1 and 2 than in the control group. CONCLUSIONS: Alcohol abuse affects polyamine metabolism, which influences the grade of malignancy of HCC. Hepatic tissue has greater potential for carcinogenesis in patients with chronic liver disease and alcohol abuse than in patients without them.

Aged↗

Immunohistochemical diagnosis and significance of forensic neuropathological changes.

Immunohistochemistry is very useful when investigating the cause of death. Ischemic cell changes in the hippocampal neurons were not obvious in the brains damaged by hypoxic injury. However, it is suggested that even a moderate hypoxia, which may affect the neuronal proteins and metabolism, induced astrocytosis in the CA3 and CA4 regions, and that in patients with a history of hypoxic attacks neuronal damage may be severe even several hours after ischemic injury. Furthermore, hsp70 expression was found in the CA2, CA3 and CA4 regions of long-term survivors after severe hypoxic/ischemic injury. In forensic practice, detailed information about the duration and extent of a hypoxic/ischemic injury is often unavailable, so that immunohistochemical detection of hsp70 and glial cell staining can be of great value in diagnosing not only the hypoxic/ischemic injury during the process of death but also the victim's past history of hypoxic attacks. In diffuse axonal injury, degeneration of axon and myelin, such as swelling and waving, were observed in survivors of more than 8 hours. Retraction balls appeared in survivors of more than 1 days. In longer term survivors, such as 3 or 5 months, breakdown of myelin and fat-granule cells were observed. In addition, retraction balls were also found. Immunohistochemical staining of 200 kD neurofilament was a very useful method to examine axonal changes, because antisera is specific for degenerative neurofilaments. In our study, all cases which had pathological findings of diffuse axonal injury (DAI) were associated with focal head injuries. From the immunohistochemical staining of neurons in the hippocampus, it was suggested that neurons in the hippocampus were injured by diffuse brain damage. Furthermore, repairing and protective mechanisms occurred especially from CA2 to CA4. It was considered that neuronal damage in diffuse brain injury was elucidated not only morphologically but also functionally. Therefore, in cases of suspected diffuse brain damage, it is recommended to examine the neuronal changes in addition to observing the findings of diffuse axonal injury. Immunohistochemical staining of the carotid body is potentially very useful for necropsy diagnosis, since it provides a method to detect evidence of mechanical asphyxia in suspected cases of manual and/or ligature strangulation.

Biomarkers↗

[Percutaneous transhepatic portal vein embolization for hepatocellular carcinoma].

We report on the significance of percutaneous transhepatic portal vein embolization (PTPE) for hepatocellular carcinoma based on the results in 111 patients who underwent PTPE in our hospital. All patients tolerated the procedure without major complications, although transient elevations in serum transaminase levels were noted. Immediately after PTPE, the portal pressure increased. Portal venous flow at the main portal trunk decreased, but the flow in the nonembolized part of the liver increased. PTPE produced regenerative hypertrophy in the nonembolized part of the liver, which was mainly predicted by the volume of the embolized area and the morphological score of the hepatitis or cirrhosis. PTPE increased the safety of subsequent hepatectomy and expanded the indications for hepatectomy. PTPE is also useful as a type of multiplicative therapy for hepatocellular carcinoma.

Carcinoma, Hepatocellular↗

Delayed hepatic resection for ruptured hepatocellular carcinoma.

BACKGROUND: Although transcatheter arterial embolization is advocated as initial therapy for ruptured hepatocellular carcinoma (HCC), hepatic resection is necessary for cure. The effectiveness of delayed hepatic resection for ruptured HCC was determined. METHODS: The records of 10 patients who underwent delayed hepatic resection for ruptured HCC were reviewed. RESULTS: All patients were men, and the mean age was 63 years. For hemostasis, transcatheter arterial embolization was performed in three patients, whereas in the other patients bleeding stopped without special procedures. Mean interval from rupture to hepatic resection was 74 days. Liver function test results before hepatic resection were almost normal. Trisegmentectomy in one and bisegmentectomy in four patients were performed, whereas minor hepatic resection was performed for four extrahepatic HCCs. There were no operative or hospital deaths. Four patients had cirrhosis. The mean tumor diameter was 7.5 cm. Of seven patients with recurrence, two with dissemination had tumors that ruptured on the inferior aspect of the liver. The 1- and 3-year survival rates were 77% and 48%, respectively. CONCLUSIONS: Because delayed hepatic resection for ruptured HCC was safe and compared similarly with that for other patients who underwent resection for HCC, it should be used. However, when HCC ruptures in an inferior location, recurrence of tumor as dissemination is likely.

Adult↗

Comparative study of MR myelography and conventional myelography in the diagnosis of lumbar spinal diseases.

The purpose of this study was to investigate the usefulness of magnetic resonance (MR) myelography by comparing it with conventional myelography. MR myelography was performed on 40 patients (24 men and 16 women; mean age, 44 years) with lumbar spinal diseases. MR myelography was imaged three-dimensionally by fast spin-echo technique with fat suppression and maximum intensity projection. We assessed both the ability to provide the images of nerve root sheaths and the similarity of the findings to conventional myelography. Satisfactory images of nerve root sheaths in the lumbar region were provided almost equally by MR and conventional myelography. The images obtained by MR myelography were similar in quality to those obtained by conventional myelography. When combined with some other conventional MR imaging techniques, this diagnostic technique of imaging lumbar spinal diseases is further enhanced.

Adolescent↗

Determination of unbound warfarin enantiomers in human plasma and 7-hydroxywarfarin in human urine by chiral stationary-phase liquid chromatography with ultraviolet or fluorescence and on-line circular dichroism detection.

Enantiomers of warfarin and 7-hydroxywarfarin in human plasma and urine, respectively, were determined by high-performance liquid chromatography using a cellulose-derivative column with UV or fluorescent detection, and their absolute configuration was determined simultaneously by a circular dichroism spectropolarimeter connected in series. Enantiomers of warfarin and its major metabolites [i.e., (R)-6-hydroxywarfarin, (S)-7-hydroxywarfarin and (RS)-warfarin alcohol] were well resolved. The method was precise and sensitive: within- and between-day coefficients of variation were <9.6% for warfarin enantiomers in plasma and <7.1% for 7-hydroxywarfarin enantiomers in urine, respectively, and the lower detection limits were 20 ng/ml for (R)-warfarin, 40 ng/ml for (S)-warfarin, 2.5 ng/ml for (R)-7-hydroxywarfarin and 4.5 ng/ml for (S)-7-hydroxywarfarin in 0.5 ml of both plasma and urine. The ultrafiltration technique was used for determining unbound concentrations of warfarin enantiomers in plasma using [14C]warfarin enantiomers resolved by the present HPLC system. Clinical applicability of the method was evaluated by determining unbound concentrations of warfarin enantiomers in five consecutive plasma samples obtained from a patient exhibiting an unstable anticoagulant response to warfarin (4 mg/day, p.o.). Results indicated that the present method would be useful in clarifying factors responsible for a large intra- and inter-patient variability in warfarin effects with regard to unbound plasma enantiomer pharmacokinetics.

Anticoagulants↗

Complete rescue of lethal albino c14CoS mice by null mutation of 4-hydroxyphenylpyruvate dioxygenase and induction of apoptosis of hepatocytes in these mice by in vivo retrieval of the tyrosine catabolic pathway.

Hereditary tyrosinemia 1 (HT1) is characterized by progressive liver damage, from infancy, and by a high risk for hepatocellular carcinoma. HT1 is due to mutations in the fumarylacetoacetate hydrolase gene Fah, encoding the last enzyme in the tyrosine catabolic pathway. Lethal albino deletion c14CoS mice and mice with target-disrupted Fah are models for HT1, but they die in the perinatal period, albeit with a different phenotype from that seen in HT1 in humans. We first asked whether homozygous null mutation of the 4-hydroxyphenylpyruvate dioxygenase gene Hpd could rescue the homozygous c14CoS mice (c14CoS/c14CoS or Fah-/-). The double mutant Fah-/- Hpd-/- mice appeared normal, at least until age 18 months, and there was no evidence of liver disease, findings that facilitated examination of the effect of Fah-/- on mature and unmodified hepatocytes in vivo. The hepatocytes of Fah-/- undergo rapid apoptosis, and acute death follows. Essentially the same phenomena were observed when Fah-/- Hpd-/- mice were administered homogentisate intraperitoneally. These changes in liver pathology in Fah-/- Hpd-/- mice after the administration of homogentisate were associated with massive urinary excretion of succinylacetone. These results suggest that accumulation of fumarylacetoacetate, maleylacetoacetate, or succinylacetone seems to trigger the endogenous process of apoptosis in hepatocytes that lack fumarylacetoacetate hydrolase activity. This apoptosis may be related to the development of hepatocellular carcinomas seen in HT1 patients and pharmaceutically treated fumarylacetoacetate hydrolase-deficient mice.

4-Hydroxyphenylpyruvate Dioxygenase↗