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Biomedical subjects

K Wakabayashi

Publications and source records attributed to K Wakabayashi.

At least 73 records · Page 4Linked to original sources
PubMed2001

Gravitational force regulates elongation growth of Arabidopsis hypocotyls by modifying xyloglucan metabolism.

Growth of dark-grown Arabidopsis hypocotyls was suppressed under hypergravity conditions (300 g), or was stimulated under microgravity conditions in space (Space Shuttle STS-95). The mechanical extensibility of cell walls decreased and increased under hypergravity and microgravity conditions, respectively. The amounts of cell wall polysaccharides (pectin, hemicellulose-I, hemicellulose-II and cellulose) per unit length of hypocotyls increased under hypergravity conditions, and decreased under microgravity conditions. The amount and the molecular mass of xyloglucans also increased under the hypergravity conditions, while those decreased under microgravity conditions. The activity of xyloglucan-degrading enzymes extracted from hypocotyl cell walls decreased and increased under hypergravity and microgravity conditions, respectively. These results indicate that the amount and the molecular mass of xyloglucans are affected by the magnitude of gravity and that such changes are caused by changes in xyloglucan-degrading activity. Modifications of xyloglucan metabolism as well as the thickness of cell walls by gravity stimulus may be the primary event determining the cell wall extensibility, thereby regulating the growth rate of Arabidopsis hypocotyls.

Arabidopsis↗
PubMed2001

Coffee consumption and serum aminotransferases in middle-aged Japanese men.

We investigated the relation between coffee drinking and serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations among 7313 Japanese men receiving a health examination, excluding former alcohol drinkers and men with a history of chronic liver disease. Serum AST > 40 and/or ALT > 40 U/L was defined as liver inflammation. Adjustment was made for alcohol use, smoking, body mass index, serum marker for hepatitis virus infection, and other possible confounders. Adjusted odds ratios of liver inflammation were 1.00 (reference), 0.80, 0.69, and 0.61 for men drinking < 1, 1-2, 3-4, and > or = 5 cups of coffee daily, respectively. Among 6898 men without liver inflammation, serum AST and ALT were inversely associated with coffee consumption, and alcohol-related rise in AST was attenuated with coffee drinking. These findings suggest coffee may have an effect of suppressing the rise of serum aminotransferase, partly by inhibiting the alcohol-related elevation. Studies regarding biological mechanism are warranted.

Alanine Transaminase↗
PubMed2001

Interferon-associated retinopathy in a uniform regimen of natural interferon-alpha therapy for chronic hepatitis C.

BACKGROUND/AIMS: The development of retinal lesions induced by a uniform regimen of interferon-alpha therapy for chronic hepatitis C was prospectively investigated. METHODS: Eighty-one patients received 6 mega units of natural interferon-alpha intramuscularly daily for 2 weeks and then 3 times a week for 22 weeks. The total dose of interferon-alpha administered was uniformly 478 mega units per patient. Two expert ophthalmologists prospectively examined the patients for retinal lesions before, during and after the therapy. RESULTS: Retinopathy was not found in comparison groups or any of the patients before treatment. In total 34.6% (28/81) of the patients showed cotton-wool spots or minor retinal hemorrhage, or both lesions, during therapy, but these lesions were reversed during or after interferon therapy. The occurrence rates of cotton-wool spots alone, retinal hemorrhage alone and both lesions were 13.6% (11/81), 6.2% (5/81), and 14.8% (12/81), respectively. The appearance of retinopathy did not correlate with patients' background including viral loads and response to the therapy, but was more frequently found in older patients and patients with hypertension and/or diabetes mellitus; disappearance of retinopathy was more prolonged than in patients without these complications. Almost all the lesions appeared 2-4 months after the start of the therapy, and the severity of the lesions did not differ between patients with and without hypertension and/or diabetes mellitus. CONCLUSION: Although it is not clear if interferon-associated retinopathy occurs in a dose-dependent manner, the present study shows a standard pattern of the occurrence of retinopathy in patients with chronic hepatitis C receiving a uniform dosage of natural interferon-alpha.

Age Distribution↗
PubMed2001

The cellular pathology of Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disorder of unknown cause that occurs in adults. The presence of Lewy bodies (LB) in association with nerve cell loss in the substantia nigra and various other regions of the nervous system is a diagnostic hallmark of the disease. In 1997, a mutation was identified in the alpha-synuclein gene in families with autosomal dominant PD. Subsequent immunohistochemical studies have revealed that all of the LB in familial and sporadic PD contain the gene product alpha-synuclein: abnormal filaments that constitute LB were clearly recognized by antibodies against alpha-synuclein. Moreover, it was shown that the glial cells, both astrocytes and oligodendrocytes, are also affected by alpha-synuclein pathology. Recently, a novel protein, synphilin-1, has been identified that interacts with alpha-synuclein. Interestingly, synphilin-1 immunohistochemistry has demonstrated that this protein is present in the central core of classical (brainstem) LB, which are composed mainly of densely packed vesicular structures. The role of both alpha-synuclein and synphilin-1 in normal conditions has yet to be clarified.

Animals↗
PubMed2001

Chemopreventive effects of ONO-8711, a selective prostaglandin E receptor EP(1) antagonist, on breast cancer development.

Levels of prostaglandin E(2) (PGE(2)) in human and rodent breast cancers are higher than surrounding normal tissues. PGE(2) exhibits biological activity through binding to membrane receptors, EP(1-4). The present study was designed to investigate the effects of ONO-8711, a newly synthesized selective PGE receptor EP(1) antagonist, on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced breast cancer development. Starting at 7 weeks of age, female Sprague-Dawley (SD) rats were given PhIP (85 mg/kg body weight) by gavage four times weekly for two weeks. Dietary administration of ONO-8711 at 400 or 800 p.p.m. delayed occurrence of breast tumors for 2 or 4 weeks, respectively. At 20 weeks after the last dosing of PhIP, all animals were killed and complete autopsy was made. All breast tumors were diagnosed as invasive ductal adenocarcinomas histopathologically. Administration of ONO-8711 at 800 p.p.m. significantly decreased PhIP-induced breast cancer incidence, multiplicity and volume compared with those of rats fed the control diet (56% versus 79%, P < 0.05, 1.2 versus 2.5, P < 0.05, 0.7 versus 1.4 cm(3), P < 0.01, respectively). Apoptosis was significantly increased in breast cancer cells by feeding of ONO-8711 at 800 p.p.m. of 158% (P < 0.05). EP(1) receptor was detected by reverse transcription-polymerase chain reaction (RT-PCR) in breast cancers, not in normal tissues. These results suggest that EP(1) receptor is associated with breast cancer development and selective PGE receptor EP(1) antagonists may possess chemopreventive effects through the induction of apoptosis without any side effects.

Animals↗
PubMed2001

Experimentally induced leptomeningeal glioneuronal heterotopia and underlying cortical dysplasia of the lateral limbic area in rats treated transplacentally with methylmercury.

Leptomeningeal glioneuronal heterotopia (LGH) is a developmental anomaly sometimes observed at the surface of human brains with severe malformations. We experimentally induced LGH in brains of rat pups by transplacental exposure to methylmercury. Histopathological profiles of the induced LGH, including the spatio-temporal predominance of the manifestation, suggest some aspects of the histogenesis of this malformation. Pregnant rats on embryonic day 8 (E8), E11, E13, E16, E18 or E21 were treated orally with a single administration of 20 mg/kg methylmercury chloride, and the brains of their delivered offspring were examined on postnatal day 7 (P7) and P28. The incidence of LOH varied significantly according to the treatment day: it was almost exclusively restricted to individuals treated on E13. Furthermore, all the induced LGH was confined to the subarachnoid space dorsal to the rhinal fissure, unilaterally or bilaterally. A part of the nest was connected to the underlying cortical surface of the lateral limbic area, where glia limitans and basal lamina were disrupted. Narrow stripes of disarrangement of cortical neurons underlying the bridges were observed. The P7 LGHs consisted mainly of neurons, some of which were GABA-immunolabeled. and a small number of astrocytes as well as endogenous blood vessels and fibroblasts. LGHs in P28 brains consisted mainly of GFAP-positive astrocyte processes. An additional experiment with double administrations of 5-bromo-2-deoxyuridine (BrdU) and methylmercury on E13 disclosed an abnormally widespread distribution of labeled neurons throughout all cortical layers underlying the LGH in P28 brains. Thus, cerebral LGH would be induced if a developing brain were insulted at the early stage of neurogenesis. accompanied by cortical dysplasia.

Animals↗
PubMed2001

Detection and cloning of a protein recognized by anti-human prostate-specific antigen (PSA) antibody in the rat ventral prostate.

Prostate-specific antigen (PSA), a 33 kDa glycoprotein produced in the epithelium of the human prostate, has become established as a useful tumor marker for prostate cancer in man. Since reports of homologous proteins in animals other than primates have been lacking, the present investigation was carried out to identify any PSA-like protein in rats. Immunoblot analysis using a specific monoclonal anti-human PSA antibody detected a 32 kDa immunoreactive protein in the ventral lobe of the rat prostate, but not in other lobes or in other tissues. Positive immunostaining was observed only for the luminal surface of the glandular epithelium and the intraductal fluid in the ventral prostate. Sequence analysis of a cDNA for the rat PSA-like protein, cloned by immunoscreening of an expression cDNA library prepared from the ventral lobe, revealed identity to the rat submaxillary gland S3 kallikrein. Human PSA also belongs to the kallikrein family. Thus, this protein produced in the rat ventral prostate was suggested to be a possible counterpart of human PSA.

Amino Acid Sequence↗
PubMed2001

Effect of the molar ratio of branched-chain to aromatic amino acids on growth and albumin mRNA expression of human liver cancer cell lines in a serum-free medium.

Supplementation of branched-chain amino acids (BCAAs) is often used for the treatment of hepatic encephalopathy and low albuminemia in Japan. In this scenario, although many cases are complicated with hepatocellular carcinoma in chronic viral infection, the effect of BCAA levels on hepatocellular carcinoma cells remains unclear. We investigated the effect of the molar ratios of BCAAs to aromatic amino acids (AAAs) on the growth and albumin mRNA expression of cultured human liver cancer cell lines, HCC-M, HCC-T, PLC/PRF/5, and Hep G2. To exclude the effect of fetal serum in culture media on modification of the growth and albumin transcription of cell lines, we used a synthetic serum-free medium. We found that an increase in the molar ratio of BCAAs to AAAs reduced the growth of Hep G2 cells, and it increased albumin mRNA expression in this cell line at a molar ratio of 0.1-10. These results suggest that the molar ratio of BCAAs to AAAs affect the growth and mRNA expression of some liver cancer cells, and supplementation of BCAAs may at least be beneficial to patients with cirrhosis, even complicated with liver cancer.

Albumins↗
PubMed2001

[Complement activity among individuals at a ground self-defense force base].

OBJECTIVE: This study aims to examine the distribution of hemolytic complement activity, the prevalence of hypocomplementemia and the disorders causing hypocomplementemia among individuals taking part in a mass screening program. METHODS: The subjects consisted of 1340 male Japanese participating in a mass screening program at a Ground Self-Defense Force base in Asaka. We measured the hemolytic complement activity (CH50) after overnight fasting. The CH50 levels for hypercomplementemia and hypocomplementemia were defined as those outside the range of mean +/- 2 SD, respectively. We next measured the concentration of complement components: CIq, C4, B, C3, C5, C9, and C1-inhibitor for men with hypocomplementemia. Rheumatoid factor, ANA, HBsAg, HbsAb, and HCVAb were also measured. RESULTS: The mean +/- SD of age was 43.7 +/- 5.7. The CH50 levels ranged from 7.2 to 66.4 U/ml (mean +/- SD = 37.1 +/- 4.0 U/ml). Twenty-one and 37 men were classified as having hypocomplementemia (CH50 < 29.1 U/ml) and hypercomplementemia (CH50 > 45.1 U/ml), respectively. The age of the individuals with hypocomplementemia was 43.9 +/- 5.6 (Mean +/- SD) years. Three men with C9 deficiencies, 2 men with C5 deficiencies and 7 men with cold activation were identified among the 21 hypocomplementemic men. Three hepatitis C and 2 hepatitis B patients were also found among the 21 hypocomplementemic men. Other disorders found among the hypocomplementemic men were 3 glomerulonephritides and 1 possible SLE. CONCLUSION: We examined the distribution of CH50 levels in 1340 adult male Japanese. We identified 21 men with hypocomplementemia, and also found 5 cases of complement component deficiencies among 21 hypocomplementemic men. In addition the measurement of the complement activity may have also helped detect the presence of hepatitis, hypocomplementemic glomerulonephritis and collagen disease at an early stage.

Adult↗
PubMed2001

Effects of seasoning and heating device on mutagenicity and heterocyclic amines in cooked beef.

Pan-roasted beef showed a lower mutagenicity after various degrees of cooking than charcoaled one. The high mutagenicity of charcoaled beef was due to the formation of more heterocyclic amines, especially AalphaC (2-amino-9H-pyrido- [2,3-b]indole) and PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) because of rapid and direct heating on the surface of the meat at a high temperature. Seasoning decreased mutagenicity of pan-roasted beef except the very well done sample with unchanged heterocyclic amine contents, but increased mutagenicity of charcoaled beef with decreased levels of AalphaC and PhIP, probably due to the change of heterocyclic amine precursors or alternatively to the occurrence of other mutagens.

Animals↗
PubMed2001

[Hemorrhages of dorsal root ganglia and sensory disturbance in congenitally hydrocephalic HTX rats].

Recently we reported the frequent occurrence of hemorrhages in the dorsal root ganglia of congenitally hydrocephalic HTX rats, an animal model of human congenital hydrocephalus. Therefore, we hypothesized that sensory disturbance might be present in these rats. In order to evaluate the sensory abnormality quantitatively, we injected 50 microliters of 5% formalin into the footpad of the left hind paw of hydrocephalic (n = 5) and non-hydrocephalic HTX rats (n = 5) and Wistar rats (n = 5) on postnatal days 17-23, and then recorded the licking response time for 60 min after injection. The mean licking time in the early (0-10 min) and late (10-60 min) phases was significantly longer in hydrocephalic HTX rats than in non-hydrocephalic HTX and Wistar rats (P < 0.05). Histologically, hemorrhages in the dorsal root ganglia were found in all five hydrocephalic animals, of which two had shown thalamic degeneration. These findings suggest that lesions in the dorsal root ganglia and thalamus may correspond to the sensory disturbance observed in congenitally hydrocephalic HTX rats.

Animals↗
PubMed2001

A case of generalized Hailey-Hailey disease with fatal liver injury.

We report a case of a 59-year-old man with a severe generalized form of Hailey-Hailey disease that was complicated by fatal liver injury. Erosive lesions were first noted in the axillary and perianal regions at 15 year of age, and Hailey-Hailey disease was diagnosed based on the clinical features and histologic findings in skin biopsy specimens. The patient was treated with at first topical steroids and later a low dose of a corticosteroid, but the skin lesions gradually became generalized. At 45 years of age liver dysfunction was detected after azathioprine and vinblastine treatment for the generalized skin lesions. The liver injury gradually progressed and finally the patient died. The gene responsible for Hailey-Hailey disease was recently identified as ATP2C1, and it encodes a Ca(2+)-transport ATPase with broad expression, including in skin and liver. This finding suggests that mutation of the ATP2C1 gene may give rise to an extracutaneous phenotype, such as the liver dysfunction observed in severe cases, including our own. Further accumulation of cases is necessary to determine whether this is true.

Calcium-Transporting ATPases↗
PubMed2001

[FLEP therapy for advanced and recurrent gastric cancer].

The FLEP regimen (5-FU, LV, ETP and CDDP) is a combination chemotherapy administered regionally and systemically for the control of both local and disseminated disease in intra- and extra-abdominal regions in patients with advanced and recurrent gastric cancer. Sixty-one patients with advanced and recurrent gastric cancer were entered into this study. The treatment regimen consisted of 5-FU at 370 mg/m2 (days 1 to 5, i.v. 24 h); LV at a dose of 30 mg (days 1 to 5, i.v. bolus); and ETP and CDDP each at 70 mg/m2 (days 7 and 21, ia 2 h). This regimen was repeated every four weeks. The overall response rate was 36.1% (22/61) and the 50% and median survival times were 10.23 and 11.80 months, respectively. The adverse events were Grade 3/4 leukocytopenia (18.0%), Grade 3/4 thrombocytopenia (4.9%), Grade 3 nausea and/or vomiting (3.3%) and Grade 3 stomatitis (1.6%). Of the 17 NAC patients, the six curability B patients showed a statistically higher survival rate than the curability C and unresected patients. Based on the encouraging response rate and the improvement in prognosis, we recommend the FLEP regimen for patients with primary gastric cancer. Neoadjuvant chemotherapy using the FLEP regimen should be performed with curative resection as an objective.

Adult↗
PubMed2001

Progress with inactivated poliovirus vaccines derived from the Sabin strains.

To produce a safe and effective inactivated poliovirus vaccine (IPV), we have developed S-IPV using Vero cells infected with the Sabin strains in a semi-production scale. All production steps including virus culture on microcarrier beads were highly reproducible. Mean recovery percents of infectious viruses or D-antigens during all processes for concentration, purification and inactivation were 30-50% in the three types. The S-IPV potency was adjusted for D-antigen content as determined by in-house ELISA and was comparable to WHO reference IPV derived from the virulent strains in immunogenicity tests in rats. Antibody development in more than 30 seronegative infant volunteers after two shots of S-IPV at four-week interval were 100% without notable adverse reactions. The mean antibody titres (log2) to Sabin 1, 2 and 3 viruses were 11.1, 8.3 and 8.9, respectively. The antibodies neutralized the Mahoney, MEF-1, and Saukett virulent strains with slightly inferior titres to those of the Sabin strains. D-antigens for each type of S-IPV were stable at 4 degrees C without any significant decrease over more than two years.

Adult↗
PubMed2001

[Discharge planning for home care].

The department of medical social work and discharge planning was established in the University of Tokyo hospital to ensure that patients would receive proper care at a right place. The discharge planning team consists of a physician, a medical social worker and a home care coordinator. The home care coordinator, who coordinates with the home nursing station and the primary care physician, is effective for advance of home care. The role of the home care coordinator is to relieve patients of their anxiety about home care. As a result, the number of home care patients has gradually increased.

Caregivers↗
PubMed2001

[A case of cavernous sinus syndrome following a mycotic aneurysm of extracranial carotid artery].

A 66-year-old man was admitted to our department with left abducens palsy and pain in the territory of the left trigeminal nerve. He had a history of left mandibular osteomyelitis that had been treated for five years in the dental department. However, the osteomyelitis was resistant to therapy. Two months before this admission, he had an infectious aneurysm of the left extracranial carotid artery with occlusion. On admission, the ESR was 140 mm/hour. P-ANCA and antinuclear antibody were negative. Lumbar puncture revealed elevated cell counts (43% neutrophils) and protein. Microbiological studies were negative. Cranial MR images showed an enhanced lesion in the left cavernous sinus. His condition gradually improved with high dose of penicillin and low dose of corticosteroid. However, he died of pulmonary embolism after 81 days. At autopsy, the left extracranial carotid aneurysm was highly fibrose. The left CCA, ICA, and ECA were occluded from the origin of the left common carotid artery to the ICA in the cavernous sinus. There were also fibrosis, hemosiderin, and macrophages around these arteries, and parts of these arteries were destroyed. The left cavernous sinus lesion was also highly fibrose. These pathological findings indicated that there was old inflammation around the left extracranial carotid aneurysm, left carotid artery, and left cavernous sinus. We believe that the left cavernous sinus syndrome in our patient was caused by left carotid artery vasculitis induced by the left infectious extracranial carotid aneurysm. We also believe that this infectious aneurysm was caused by the left mandibular osteomyelitis.

Abducens Nerve Diseases↗