Schizophrenia associated with psoriasis vulgaris: three case reports.
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Biomedical subjects
Publications and source records attributed to T Ohno.
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A seroepidemiological study of HBV infection was carried out to investigate the seroprevalence of hepatitis B surface antigen (HBsAg) and the transmission routes of hepatitis B virus (HBV) infection among residents of a nursing home for the elderly. HBV serum markers were examined in 119 residents and 71 healthcare workers in the institution, as also in 1330 healthy subjects from the same geographical area, as the control group. HBsAg was detected in 6 (5%), 0 and 20 (1.5%) residents, healthcare workers and healthy subjects, respectively. Four residents (A-D) who had HBV-DNA in the serum were studied by molecular evolutionary analysis. The strains derived from residents A, B and D were clustered together within a close range of evolutionary distances. Residents B and D, who were not positive for HBsAg at the time of admission to the institution, subsequently became HBsAg-positive asymptomatic carriers. These results suggested intrainstitutional transmission of HBV in the nursing home for the elderly, and confirmed that the source of transmission of HBV to residents B and D was resident A who was positive for HBsAg. Residents in a nursing home for the elderly should be considered as being a high-risk group for HBV infection, and vaccination against HBV of these groups is recommended.
As basic studies to apply an intestinal pressure-controlled colon delivery capsule (PCDC) for glycyrrhizin (GZ), the characteristics of intestinal absorption and disposition of GZ were investigated in mice. In the in vivo study, after intravenous (iv) administration of GZ, 10 mg/kg dose, plasma GZ disappeared from the systemic circulation with t(1/2(alpha)) of 0.0063 h, thereafter, it slowly declined with t(1/2(beta)) of 15.23 h. The area under the plasma drug concentration versus time curve (AUC) values of iv (10 mg/kg), intracolonic (50 mg/kg) and intraduodenum (50 mg/kg) administrations were 115.1, 16.7 and 2.7 microgh/mL, respectively. The AUC values of plasma glycyrrhetic acid (GA), a degradation product after intracolonic and intraduodenum administrations were 2.8 and 8.4 microgh/mL, respectively. In the in situ closed loop study, the concentrations of GZ in plasma and liver after intracolonic administration were significantly increased (p<0.05) in comparison with those after intrajejunum or intraileum administration, while the concentration of GA in plasma and liver after intracolonic administration had trends to increase. These observations clearly suggest that the intracolonic administration is a useful way to improve the oral bioavailability of GZ and to enhance its pharmacological efficacy. These pharmacokinetic results of GZ suggest that GZ is a subject drug to be applied for the PCDC system we previously developed. The PCDCs formulation of GZ will enable us to carry GZ to the colon and enhance the oral bioavailability of GZ.
The inducibility of cytotoxic T lymphocytes (CTL) that react with carcinoembryonic antigen (CEA) was tested in cancer patients with elevated (more than 5 ng/ml) serum CEA levels when antigen presentation was carried out with paraformaldehyde-fixed adhesive peripheral blood mononuclear cells (PBMC) from the patient that had been pre-loaded with CEA652(9), an HLA-A2402-restricted tumor antigenic peptide derived from CEA. By culturing fresh autologous PBMC on the fixed cell layer in medium containing interleukin-1, -2, -4 and -6. three out of eight patients developed CTL. The CTL from two of these patients killed CEA-protein-producing gastric cancer cells carrying HLA-A2402 and the cells from the remaining patient killed CEA-non-producing stomach cancer cells pre-loaded with CEA652(9). The results suggest that a single antigenic peptide on the fixed adhesive cells will allow the ex vivo induction of peptide-reactive CTL that are easier to handle and allow antigen presentation without tedious preculture of the "professional" antigen-presenting dendritic-cells.
OBJECTIVE: To report four cases of rice bodies (RBs) showing remarkable size variations and discuss their pathogenesis. DESIGN AND PATIENTS: Based on analysis of the clinical data, we speculate on the pathogenesis of RBs using immunohistochemical and ultrastructural methods. The patients comprised three men and one woman, three with RBs in the subacromial bursae and one in the wrist synovial sheath, aged 28 (woman), 44, 50 and 81 (wrist) years, respectively. RESULTS: There were no particular differences in clinical data among the patients. T2-weighted MR imaging was very useful for diagnosis of the RBs, allowing their clear delineation from the bursal fluid. The RBs consisted of a layered protein- aceous substance with vague targetoid cut surfaces. Much fibrin and a lesser amount of collagen fibers were recognized together with various mononuclear cells, which were few in number and predominantly T cells. The bursae and synovial sheath had multiple fibrinoid spheroids at the luminal surface. CONCLUSION: Fibrinoid nodular deposits probably became detached, forming the nuclei of RBs and growing to a giant RB 65 mm in diameter.
UNLABELLED: We investigated serum vascular endothelial growth factor (SVEGF) levels in Kawasaki disease and determined whether these levels had any association with the development of coronary artery lesions. We measured SVEGF levels in 66 patients with Kawasaki disease, 18 patients with active infections and 18 afebrile controls. SVEGF levels of patients in the acute phase of Kawasaki disease (0.0-2003.6 pg/ml, median 59.87 pg/ml) were significantly higher than those of patients with active infections (0.0-45.2 pg/ml, median 8.10 pg/ml; P < 0.05) or afebrile controls (0.0-49.8 pg/ml, median 7.75 pg/ml; P < 0.05) and decreased to undetectable or low levels in the recovery phase (n = 31, acute phase: 0.0-2003.6 pg/ml, median 62.50 pg/ml versus recovery phase: 0.0-146.5 pg/ml, median 26.90 pg/ml; P = 0.0007) of the disease. There existed a positive correlation between SVEGF levels and serum C-reactive protein concentrations in the acute phase of Kawasaki disease (rs = 0.347, P = 0.0051). In addition, SVEGF level and duration of fever were found to be major risk factors for the occurrence of coronary artery lesions by univariate (P = 0.012 and P = 0.003, respectively) and multivariate (P = 0.037, OR 6.16 and P = 0.0059, OR 7.59, respectively) analyses. CONCLUSION: Serum vascular endothelial growth factor level, in combination with persistence of fever, could be a powerful predictor for the development of coronary aneurysms.
BACKGROUND: A fragment of cytokeratin 19, referred to as CYFRA 21-1, is abundant in the serum of many patients with malignant tumors and is recognized as one of the established tumor markers, especially for non-small-cell lung cancer. In this study, the clinical usefulness of CYFRA 21-1 was investigated in cervical cancer patients treated with radiation therapy with reference to squamous-cell-carcinoma-related antigen (SCC-Ag), a common tumor marker of cervical squamous cell carcinoma. MATERIALS AND METHODS: The serum levels of CYFRA 21-1 and SCC-Ag of 50 patients with squamous cell carcinoma of the uterine cervix were measured before and after radiation therapy. RESULTS: CYFRA 21-1 was positive in 52% of the patients. The incidence increased with the stage of the cancer, and post-treatment increases were a sign of disease progression. During radiation, serum levels of CYFRA 21-1 decreased significantly and reflected the radiation effect well. In addition, CYFRA 21-1 was negative in all patients without distant metastasis at the end of radiation therapy. Compared with SCC-Ag, patients were less often positive for CYFRA 21-1, but there was a statistically positive correlation between the two markers (correlation matrix=0.69). CONCLUSIONS: CYFRA 21-1 can be used in monitoring the outcome of patients with squamous cell carcinoma of the uterine cervix. It may be particularly useful for patients without SCC-Ag.
Thermogenesis, especially facultative thermogenesis by brown adipose tissue (BAT), is less important in high ambient temperature and the heat-acclimated animals show a lower metabolic rate. Adaptive changes in the metabolic activity of BAT are generally found to be associated with a modification of membrane phospholipid fatty acid composition. However, the effect of heat acclimation on membrane phospholipid fatty acid composition is as yet unknown. In this study, we examined the thermogenic activity and phospholipid fatty acid composition of interscapular BAT from heat-acclimated rats (control: 25+/-1 degrees C, 50% relative humidity and heat acclimation: 32+/-0.5 degrees C, 50% relative humidity). Basal thermogenesis and the total thermogenic capacity after noradrenaline stimulation, as estimated by in vitro oxygen consumption of BAT (measured polarographically using about 1-mm(3) tissue blocks), were smaller in the heat-acclimated group than in the control group. There was no difference in the tissue content of phospholipids between the groups when expressed per microgram of DNA. The phospholipid fatty acid composition was analyzed by a capillary gas chromatograph. The state of phospholipid unsaturation, as estimated by the number of double bonds per fatty acid molecule, was similar between the groups. The saturated fatty acid level was higher in the heat-acclimated group. Among the unsaturated fatty acids, heat acclimation decreased docosahexaenoic acid and oleic acid levels, and increased the arachidonic acid level. The tissue level of docosahexaenoic acid correlated with the basal oxygen consumption of BAT (r=0.6, P<0.01) and noradrenalinestimulated maximum values of oxygen consumption (r=0.5, P<0.05). Our results show that heat acclimation modifies the BAT phospholipid fatty acids, especially the n-3 polyunsaturated fatty acid docosahexaenoic acid, which is possibly involved in the metabolic thermosuppression.
In order to develop ultimate adjuvant therapy for malignant gliomas, we analysed 77 patients with malignant gliomas (29 anaplastic astrocytomas (AAs) and 48 glioblastoma multiformes (GMs)) treated by three protocols of IMR therapy (human interferon-beta (HuIFN-beta), MCNU and radiation). In protocol 1 (n = 45: AA = 13, GM = 32), 1 x 10(6) IU of HuIFN-beta was administrated intravenously once a day for 7 days. On day 2, MCNU was administrated at a dose of 2 mg/kg b.w. intravenously and from day 3, radiation was started in five weekly fractions of 2 Gy for 6 weeks. Total dose was 60 Gy. Protocol 2 (n = 19: AA = 11, GM = 8) was comparable with protocol 1 except HuIFN-beta was administrated twice a day at a dose of 1 x 10(6) IU each. Protocol 3 (n = 13: AA = 5, GM = 8) differed from protocol 2 only in a high dose-hyperfractionated radiation which was given twice a day at a dose of 1.5 Gy each and for a total dose of 66 Gy. Antitumor effects were evaluated by survival and response rate determined by decrease of tumor size. Significant improvement was obtained in patients with AAs by protocol 2 and 3. Response rates of patients with AAs and GMs were 46.2% and 50% in protocol 1, 63.6% and 50% in protocol 2, and 80% and 50% in protocol 3, respectively. One and two year survival rates in AAs were 46.4% and 34.8% in protocol 1, both 75% in protocol 2, and both 100% in protocol 3. Survival rates in GMs were not different among them. Except of radiation necrosis, which was observed in 38.5% of the patients under protocol 3, there was no significant difference in the adverse effects among the three protocols. In the present study, the efficacy of IMR therapy for patients with malignant gliomas, especially for AAs, was cofirmed. We conclude that twice a day administrations of HuIFN-beta in combination with a high dose-hyperfractionated radiation provide increased efficacy in IMR therapy.
We report the entire open reading frames (ORFs) sequences of four TT virus (TTV) isolates, one genotype 2 (G2) and three G4 isolates. Despite a DNA virus, TTV possesses high rate of amino acid (aa) substitution: the aa sequence homology of ORF1 and 2 is lower than the nucleotide homology. The partial 'N22' region of ORF1 is suitable for genotyping of 'prototype TTV' isolates, because the phylogenetic tree from partial 'N22' sequence is consistent with that from the entire ORF1. Based on our sequence data, ORF2 from most isolates excluding G1 encode truncated 49 aa (pORF2a) because of an in-frame stop codon, although ORF2s from most G1 isolates encode 202 aa (pORF2ab). Just downstream the stop codon, another ORF encoding a protein of approximately 150 aa (pORF2b) is found, whose homology is quite low among these genotypes. Our in vitro transcription/translation study supports that all G1a and a part of G b without an in-frame stop codon dominantly encode pORF2ab, a novel 23 kDa protein, whereas the other genotypes with an in-frame stop codon encode pORF2b (17 kDa). Our data indicate TTV G1a and a part of G1b should have different characteristics from the other genotypes.
Severe IDDM (insulin-dependent diabetes mellitus) was produced in the musk shrew (Suncus murimus, Insectivora) by a high dose (a single intraperitoneal injection of 100 mg/kg Body Weight) of streptozotocin (STZ) injection. All shrews that were administered a high dose of STZ exhibited hyperglycemia (449 +/- 16 mg/dl vs 73 +/- 4 mg/dl in controls) and hypoinsulinemia(0.25 +/- 0.07 ng/ml vs 10.96 +/- 1.97 ng/ml in controls) with ketosuria 10 days after injection. Their livers were enlarged and exhibited ayellowish-brown color with marked triglyceride (TG) accumulation (63.25 +/- 7.10 mg/g Liver vs 2.11 +/- 0.19 mg/g Liver in controls). It is probable that the increased influx of fatty acids into the liver induced by hypoinsulinemia and the low capacity of excretion of lipoprotein secretion from liver in the musk shrew resulting from a deficiency of apolipoprotein B synthesis play important roles in fatty liver formation. Hyperlipidemia was another feature in shrews with severe IDDM. The blood TG level was especially high in these shrews (899 +/- 178 mg/dl vs 23 +/- 5 mg/dl in controls). These results indicate that the IDDM shrew, induced by high doses of STZ, is a unique model characterized by fatty liver and hyperlipidemia and may be useful for studying lipid metabolism of IDDM.
In order to examine the reactivity of active intermediate derived form iron porphyrins, competitive oxidations of alkane and alkene were carried out. It has been proposed that the first step of alkane hydroxylation is H atom abstraction and that of alkene is one-electron transfer. Therefore, it is expected that alkene-alkane competitive oxidation can be used as a probe for discrimination of differences in chemical properties among active species. Cytochrome P450 and SR complex, which is a stable thiolate-ligated iron porphyrin, mediated the oxidation of alkane much more preferentially than iron porphyrin coordinated by imidazole or chloride. These results indicate that thiolate coordination alters the reactivity of the two-electron-oxidized intermediate in a manner that is much more favorable to alkane hydroxylation than the case of chloride or imidazole coordination.
A high-performance liquid chromatographic (HPLC) method for simultaneous determination of naproxen (NAP), nabumetone (NAB) and its major metabolite, 6-methoxy-2-naphthylacetic acid (6-MNA), was developed for the application to pharmaceuticals and human urine. Isocratic reversed-phase HPLC was employed for quantitative analysis using triethylamine and 1-heptanesulfonic acid sodium salt (HSA) as ion-pair reagents. Urine samples were purified by solid-phase extraction using Bond-Elut Certify II cartridges containing reversed-phase and anion exchange functionalities. The HPLC assay was carried out using a Wakosil ODS 5C18 column (5 microm, 150 x 4.6 mm, i.d.). The mobile phase consisted of 0.5 g of HSA dissolved in 1,000 ml of a mixture of acetonitrile, water and triethylamine (500:500:1, v/v) adjusted with phosphoric acid to pH 3. The calibration curves of NAP and NAB showed good linearity in the concentration range 32-160 microg/ml with UV detection (270 nm) for pharmaceuticals. In the low concentration ranges (8-96 ng of NAP per ml, 24-288 ng of NAB per ml and 5.6-67.2 ng of 6-MNA per ml), the calibration curves were also obtained with fluorimetric detection (excitation 280 nm, emission 350 nm) for biological fluids. The correlation coefficients were better than 0.999 in all cases. The lower limits of detection (defined as a signal-to-noise ratio of about 3) were approximately 0.3 ng for NAP, 1.5 ng for NAB and 0.2 ng for 6-MNA. The procedure described here is rapid, simple, selective, and is suitable for routine analysis of pharmaceuticals and pharmacokinetic studies in human urine samples.
To understand the development of well-differentiated adenocarcinoma in the stomach, we examined genetic instability in 31 patients with stage Ia gastric cancer. Triplets of tissue specimens (normal/metaplasia/tumour) from 33 lesions were examined for microsatellite instability (MSI) and loss of heterozygosity (LOH), using nine microsatellite loci. Frameshift mutations in the transforming growth factor beta receptor type II (TGF-betaRII) (A)(10), Bcl-2-associated X protein (BAX) (G)(8), hMSH3 (A)(8) and hMSH6 (C)(8) genes were also studied. In this study, a high incidence of MSI (MSI-H) was defined as samples containing 30% or more MSI positive loci, and a low incidence of MSI (MSI-L) as samples which had less than 30% MSI. MSI-L was observed in 19 cancerous lesions (58%), and MSI-H in three (9%). Eleven intestinal metaplasia lesions (33%) showed MSI-L, but no metaplasia lesions exhibited MSI-H. Frameshift mutation was observed in only one cancerous lesion (3%) at the (A)(10) tract of TGF-betaRII. In contrast, LOH was observed in 24 cancerous lesions (73%), and in 15 (45%) of intestinal metaplasia lesions. Intriguingly, these alterations tend to be coincident between metaplasia and cancerous lesions in the same sets of specimens, and there was no case that showed alterations in metaplasia, but not in cancerous lesions. These findings suggest that metaplasia and well-differentiated adenocarcinoma in the stomach may have the same molecular backgrounds, and that these two lesions may be chronologically connected.
The SMXA recombinant inbred mouse strain set was produced by systematic inbreeding from the F2 generation of a cross between two progenitor inbred strains, A/J and SM/J, which differed markedly with respect to the patterns of infection with Angiostrongylus costaricensis. We have applied this set to genetic analysis of mouse susceptibility to this nematode infection. The mortality was variable among substrains of the SMXA RI strains, indicating the involvement of multiple genes. Linkage analysis showed several chromosomal regions closely linked to mortality; chromosome 6 (D6Rik86, 87; P<==0.001), 10 (D10Rik66-D10Mit12; P=0.0058), 13 (D13Rik79, 80; P=0.0096) and 17 (D17Mit28-D17Rik76; P=0.0088).
In a Korean rural area with a high incidence of liver cancer, a molecular epidemiological study was conducted to estimate the prevalence of hepatitis C virus (HCV) infection and to determine the distribution of HCV genotype and transmission routes of HCV infection. The study population is those who volunteered to participate in a health survey in 1993 and were over 10 years of age. Those who were anti-HCV-positive and 20 of their spouses were re-examined in 1995 and tested for HCV genotype. A phylogenetic tree was constructed after sequencing analysis of core and envelope regions from the subjects with genotype 2a without a blood transfusion history. The age- and sex-standardized prevalence of anti-HCV was 5.52%. In a multivariate analysis, transfusion history was not associated with anti-HCV-positivity, but a history of acupuncture (adjusted odds ratio=2.2, 95% confidence interval=1.0, 4.7) and a history of surgical operation (adjusted odds ratio=2.0, 95% confidence interval=1.0, 4.1) were associated. The prevalence of HCV genotype 2a was the highest, and genotype 1b was less frequent. The phylogenetic tree showed strong homology among our samples with Japanese HCV strains. The present study suggests that there is a highly endemic area of HCV infection in Korea and that this endemicity is probably associated with a parenteral source of HCV infection other than blood transfusion. The study also suggests that some of the HCV infection was spread through non-sterilized or non-disposable acupuncture needles in this HCV endemic area.
Combined treatment with interferon-beta, MCNU (Ranimustine), and radiotherapy was assessed in patients with malignant glioma who had not received previous cytotoxic drug therapy. Forty-three patients up to 75 years old with histopathologically confirmed malignant glioma were studied. All patients had tumors measurable by neuroimaging, a Karnofsky performance score exceeding 40, and an expected survival exceeding 2 months. A response rate of 49% (21/45) was observed, including 6 complete remissions (14%) and 15 partial remissions (35%). Of the 43 patients who completed initial therapy, 19 were given sequential maintenance therapy. Survival time was much longer with than without maintenance therapy. Toxic side effects were moderate and did not substantially affect patients' general condition. We concluded that this combination therapy had a pronounced effect on untreated malignant glioma, particularly in patients whose initial therapy was followed up with maintenance therapy.
Etoposide is a potent anticancer agent that is used to treat various tumors. We have investigated the dose-dependent effect of etoposide on apoptosis using chronic myeloid leukemia K562 cells treated with low (5 microM) or high (100 microM) concentrations of the drug. At a low concentration, etoposide induced little apoptosis at 24 h, while about 20% of the cells showed apoptosis morphologically at a high concentration. Processing of caspase-3 was slightly detected from 12 h and became obvious at 24 h with 100 microM etoposide. Caspase-3-like protease activity was detected at 24 h with a high concentration. Moreover, these changes were accompanied by cleavage of poly ADP ribose polymerase (PARP). Changes of the mRNA levels of most apoptosis-regulating genes were not prominent at both concentrations, except for the rapid induction of c-IAP-2/HIAP-1 and the down-regulation of Bcl-X(L) by 100 microM etoposide. The downregulation of Bcl-X(L) protein occurred from 6 h, while Bax protein conversely showed a slight increase from 6 h. Taken together, the present findings show that the dose-dependent apoptotic effect of etoposide is based on a change in the balance between Bcl-X(L) and Bax, which precedes the activation of caspase-3.