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Biomedical subjects

Yasuo Katayama

Publications and source records attributed to Yasuo Katayama.

46 records · Page 3Linked to original sources

The effect of ozagrel sodium on photochemical thrombosis in rat: therapeutic window and combined therapy with heparin sodium.

The therapeutic efficacy of ozagrel sodium (ozagrel), alone and in combination with heparin, and its therapeutic time window were studied in a photochemically induced thrombotic cerebral infarction rat model. Cerebral artery thrombosis was induced by irradiating the brain with green light through intact skull using rose bengal as the photosensitizing dye. One set of animals was treated immediately after thrombosis with (1) vehicle, (2) 10 mg/kg ozagrel in saline, intravenously (i.v.), (3) 150 U/kg unfractioned heparin, subcutaneously (s.c.), or (4) ozagrel, i.v. plus heparin, s.c. Infarct volume was significantly smaller and edema was reduced in the ozagrel-treated groups compared to the vehicle-treated group; heparin did not convey additional benefit. In another set of animals, rats were given either vehicle or 10 mg/kg ozagrel in saline, i.v., 60 min or 120 min after induction of thrombosis. Ozagrel reduced infarct volume, but its effect diminished with delayed administration. The therapeutic window was determined to be less than 60 minutes after induction of thrombosis.

Animals↗

Homeostatic regulation of intestinal villous epithelia by B lymphocytes.

The epithelial cell of the small intestine is one of the most rapidly regenerating cells in the body. However, the cellular mechanism and biological significance underlying this rapid regeneration remain elusive. In this study we examined the intestinal epithelia of mutant mice that lack B and/or T cells and those of normal littermates. The absence of B cells in Ig mu-chain mutant mice or B and T cells in recombination-activating gene (RAG)-2(-/-) as well as SCID mutant mice was associated with a marked acceleration of epithelial cell turnover and an up-regulation of the expression of MHC class II molecules. No such effects were observed in T cell-deficient TCR-delta and -beta double-mutant mice. As far as the goblet cells of villous epithelium are concerned, absolute numbers of them remained the same among these mutant mice that have no B and/or T cells. Alymphoplasia (aly/aly) mutant mice that lacked Peyer's patches and Ig-producing cells in the lamina propria, but harbored a large number of intestinal mucosal T cells, also displayed a significant acceleration of epithelial cell turnover and, to some extent, up-regulated expression of MHC class II molecules. Notably, the accelerated epithelial cell turnover was not observed and returned to normalcy in the Ig mu-chain mutant mice that had been given antibiotic-containing water. These findings indicate that B cells down-regulate the generation and differentiation of intestinal epithelial cells in the normal wild-type condition and suggest that enteric microorganisms are implicated in the accelerated generation of epithelial cells in mice that have no B cells.

Ampicillin↗

Interaction between the LDL-receptor gene bearing a novel mutation and a variant in the apolipoprotein A-II promoter: molecular study in a 1135-member familial hypercholesterolemia kindred.

Lipid and lipoprotein concentrations in plasma generally reflect complex influences of multiple genetic loci. Even an autosomal dominant disorder, familial hypercholesterolemia (FH), is characterized by phenotypic heterogeneity, as low-density lipoprotein (LDL) levels vary widely within the same pedigree. Molecular screening for LDL receptor ( LDLR) mutations among 75 patients with clinically apparent FH led to identification of a novel splice-site mutation (IVS14+1 G>A) shared by 14 patients. Genealogical research confirmed that all 14 carriers were part of the same 1135-member pedigree with a common ancestor. The mutation resulted in an abruptly truncated LDLR protein, reducing functional LDLR activity by half in heterozygous carriers of the mutant allele. Of the 208 members of the kindred who were screened for the presence of this LDLR mutation, we identified 94 carriers and 114 noncarriers. Nine principal apolipoprotein genes that might affect LDL cholesterol differentially according to LDL-receptor status were examined in this pedigree. Strikingly lower total cholesterol and LDL-cholesterol values were observed among the majority of the LDLR mutation carriers who were simultaneously homozygous for the -265C variant of apoA-II (total cholesterol: 324 +/- 8 vs 244 +/- 19 mg/dl, P = 0.0015; LDL-cholesterol: 237 +/- 8 vs 155 +/- 18 mg/dl, P = 0.0008). In vitro transfection assays showed that transcriptional activity of the apoA-II promoter was reduced by 30% in the -265C variant as compared with the -265T variant. We thus concluded that one variant of the apoA-II gene was associated with reduced plasma LDL cholesterol only in FH patients.

Apolipoproteins↗

Monteplase reduces infarct volume and hemorrhagic transformation in rat model of embolic stroke.

Monteplase, a modified recombinant tissue plasminogen activator (rt-PA), has a long half-life and reduces binding to plasminogen activator inhibitor. In this study we investigated whether its systemic administration reduces infarct volume without increasing the risk of intra-cerebral hemorrhage. The effect of the drug was tested on an embolic stroke rat model that uses white clots. Thirty minutes after clot embolization, rats were infused with 2.2 mg kg(-1) of monteplase or the same amount of saline, over 60 min. Relative regional cerebral blood flow had recovered 60 min after monteplase administration and infarct volume was significantly smaller 24 h after clot embolization in the monteplase-treated rats (47.0 mm3) than in the saline-treated rats (130.4 mm3). Also, the hemorrhagic transformation area was significantly smaller in monteplase-treated rats (0.8 mm2 vs. 18.0 mm2, respectively). These results indicate monteplase can be a promising thrombolytic agent for treatment of the acute stage of cerebral ischemia.

Animals↗

Plasma immunoadsorption therapy for Guillain-Barré syndrome: critical day for initiation.

Immunoadsorption plasmapheresis (IAPP) is a method of removing circulating immune factors that is used to treat Guillain-Barré syndrome (GBS). We retrospectively analyzed the data on our GBS patients. In 21 patients treated with IAPP, linear regression analysis showed that the time from the onset of symptoms to the initiation of IAPP was correlated with the time required for improvement by one Hughes functional grade. We investigated the critical day for initiating treatment, which we defined as the day when initiation of IAPP was significantly more likely to improve function by at least one Hughes grade when compared with the outcome in patients receiving supportive therapy (non-IAPP group). The critical day was found to be day 6 after the onset of GBS.

Adolescent↗

Decreased cerebral blood flow in renal transplant recipients.

OBJECTIVE: We performed single-photon emission computed tomography (SPECT) to investigate the influence of renal transplantation on cerebral blood flow (CBF). PATIENTS AND METHODS: Fifteen renal transplant recipients and twelve normal subjects underwent cerebral SPECT with N-isopropyl-p -[123I] iodoamphetamine (123I-IMP). All transplant recipients received prednisolone and cyclosporine (CyA). Regional CBF (rCBF) was measured by defining regions of interest in the cerebral cortex, deep white matter, striatum, thalamus, and cerebellum. In transplant recipients, correlations to the mean overall cortical CBF were assessed using the interval from transplantation to measurement of SPECT, as well as the serum creatinine concentration. Moreover, to investigate the influence of CyA on CBF, the correlation between mean overall cortical CBF and CyA trough concentrations was assessed. RESULTS: In all regions, CBF in renal transplant recipients was significantly lower than in normal subjects. No significant correlation was seen between serum creatinine, interval from transplantation, or CyA trough concentrations and mean overall cortical CBF. CONCLUSION: Renal transplant recipients demonstrated a decrease in CBF, that can have an associated secondary pathology. Therefore, renal transplant recipients may benefit from post-operative MRI or CT.

Adult↗

[An autopsy case with subacute spinal cord disease showing progressive paraplegia].

We report a 72-year-old woman who died of respitory failure. History included onset of diabetes mellitus at the age of 67 years and hypertension at the age of 72 years. The patient had been in good health otherwise until 2000, when she had onset of numbness or tingling of the bilateral lower limbs. On December 3, 2000, she was admitted to a hospital in the vicinity of her home because of the above-mentioned complaints. Neurological examinations revealed progressive paraplegia. Symptoms and signs suggested Guillain-Barré syndrome. Examinations of cerebrospinal fluids revealed cell count of 338/3 (mono 72%, poly 18%) and protein value of 100 mg/dl. Later the patient course deteriorated. On December 15, 2000, she was admitted to Hakujikai Memorial Hospital for the second time. Ten days later, MRI examination showed diffuse swelling of the spinal cord from the cervical (C 3/4) level to the thoracic level. Gd-enhanced T 1-weighted MRI performed 22 days later showed a partially enhanced lesion at the thoracic (Th 5/6) level of the spinal cord. The patient was treated with steroid therapy (methylprednisolone 500 mg/dl). She died of respiratory failure on January 6, 2001. The patient was presented in a neurological CPC. Neurological and imaging findings suggested a transverse myelopathy. However, there were several points in this case that were unusual for a typical transverse myelopathy, such as total sensory loss below spinal segments of thoracic level (Th 5) and motor weakness of the upper limbs of upper segment of the same level. A clinical neurologist concluded that the patient had subacute transverse myelopathy with fused multiple pathy pathologic lesions. We discussed whether this case was a transverse myelopathy or multiple sclerosis. Post mortem examination revealed acute necrotic myelopathy affecting the spinal cord from the second cervical to the tenth thoracic vertebrae, with conspicuous infiltration of CD 68-positive macrophages involving both gray and white matter, partially necrotic associated with scattered UCHL-1 dominants lymphocytic infiltration of T cells around vessels. There were relatively older lesions with demyelinating features in the spinal roots that were particularly dominant in the anterior roots. No demyelinated plaques in the optic chiasm, tracts and nerves, or in the cerebero-cerebellar white matter were found. Systemic pathological diagnosis was lung edema with fresh hemorrhage, pancreatic atrophy consistent with diabetes mellitus and choleductlithiasis.

Aged↗

Cerebral blood flow index: dynamic perfusion MRI delivers a simple and good predictor for the outcome of acute-stage ischemic lesion.

OBJECTIVES: To evaluate the feasibility of utilizing cerebral blood flow (CBF) index images, calculated automatically and quickly from dynamic perfusion imaging (DPI), to identify acute cerebral ischemia. We attempted to investigate (1) whether the CBF index has a threshold for assessing tissue outcome, (2) whether CBF index images can predict the resulting infracted area, and if so, (3) whether the predictive capacity of the CBF index image is comparable to the regional CBF (rCBF) image delivered from singular value decomposition (SVD) deconvolution methods, which are regarded as most accurate in predicting the final infarct area. METHODS: Diffusion-weighted images (DWI) and DPI were obtained in 17 patients within 12 hours of stroke onset and follow-up magnetic resonance imaging (MRI). On 3 DPI-delivered images, namely relative regional cerebral blood volume (rrCBV), uncorrected mean transit time (MTTu) and CBF index images, univariate discriminant analysis was done to estimate cut-off values to discriminate between infarcted and noninfarcted areas. Subsequently, correlations between the initial lesion volume of 3 images together with rCBF images delivered with SVD methods and the final infarct volume on follow-up T2-weighted MRI taken at the 8th to 20th day were determined. RESULTS: Among the 3 images, only the CBF index image was able reveal the threshold of the ischemic region. Lesion volume of CBF index images against follow-up infarct volume had the highest correlation (r = 0.995) to a linear fit and the slope was closest to 1.0 (0.91) among the 3 and had identical accuracy to the regression coefficient of rCBF images. CONCLUSIONS: CBF index images can predict final infarct volume. Evaluating CBF index images together with DWI can guide the initial assessment in the acute stage of cerebral ischemia.

Acute Disease↗

The effect of ascorbic acid on the pharmacokinetics of levodopa in elderly patients with Parkinson disease.

Levodopa (LD) is one of the most effective drugs for clinical symptoms in patients with Parkinson disease (PD). Most PD patients are advanced in age and may have trouble with LD absorption because aging influences drug absorption processes. Previous reports have indicated that ascorbic acid (AsA) can reduce LD dosage without losing its effectiveness. The current study sought to determine whether AsA affects LD absorption in elderly PD patients. Sixty-seven elderly PD patients took a tablet orally containing 100 mg LD and 10 mg carbidopa following an overnight fast. Plasma LD concentrations were determined at 6 points up to 3 hours, using high-performance liquid chromatography with electrochemical detection. The area under the curve (AUC), peak drug concentration (Cmax), and time to peak drug concentration (Tmax) were calculated. The pharmacokinetic evaluation was repeatedly performed 1 week later in the same way except for adding 200 mg AsA to the tablet. The changes in AUC, Cmax, and Tmax between the tests were evaluated. Significant changes in these parameters were not observed when analyzed using data from all patients. However, significant increases in AUC and Cmax, and a significant reduction in Tmax by adding AsA were observed in 25 patients with baseline AUC < or =2500 ng.hour/mL. In conclusion, AsA can improve LD absorption in elderly PD patients with poor LD bioavailability. LD therapy in combination with AsA may be one of the strategies for PD treatment.

Aged↗