Fibrosing cholestatic hepatitis in a liver transplant recipient with hepatitis C virus infection: a case report.
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Biomedical subjects
Publications and source records attributed to K Aso.
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The results of renal transplantation have improved due to advances in immunosuppression techniques of preservation, and pre- and postoperative treatments; however, both morbidity and mortality remain serious problems. To decrease the morbidity and mortality rates we analyzed the causes of death after renal transplantation in our hospital. Between 1972 and 1999, we performed 364 renal transplantations, 257 of which were living-related and 107, cadaveric. There were 178 patients given azathioprine and 186 given ciclosporin. The survival rate of the patients on ciclosporin therapy was much better than that of those on azathioprine therapy. Of the total 364 renal transplant patients, 59 (16.2%) died, and 28 (47.5%) of these 59 deaths occurred within 1 year after renal transplantation. The causes of death were infection in 19 (32.2%) patients, gastrointestinal diseases in 16 (27.1%), cardiovascular diseases in 11 (18.6%), cerebrovascular diseases in 6 (10.2%), suicide in 3 (5.1%), and other causes in 4 (6.8%). These findings reinforce that early diagnosis and treatment are essential to decrease the morbidity and mortality rates assoiated with renal transplantation.
BACKGROUND/AIMS: Macrophage inflammatory protein-2 (MIP-2), one of the CXC chemokines, is involved in the recruitment of neutrophils in several tissue injuries. In this study, we investigated the role of MIP-2 in concanavalin A (Con A)-induced liver injury in mice. METHODS: Liver injury was induced by intravenous injection of Con A (15 mg/kg) and plasma alanine aminotransferase (ALT), MIP-2 levels were determined and histological assessment of the liver was performed. Anti-mouse MIP-2 antibody was intravenously administered 30 min before Con A injection. RESULTS: The plasma ALT level significantly elevated and reached a maximum at 8 h after Con A injection. The plasma MIP-2 level was also elevated and reached a peak value at 2 h after Con A injection. The elevated ALT level by Con A injection was significantly inhibited by the MIP-2 antibody. The elevated plasma MIP-2 level after Con A injection was significantly reduced by the tumor necrosis factor alpha (TNF-alpha) antibody, and MIP-2 was induced in plasma after recombinant TNF-alpha injection. Hepatic necrosis and infiltration of neutrophils were observed after Con A injection, and these histological changes were attenuated by the MIP-2 antibody. CONCLUSIONS: These findings suggest that Con A induces TNF-alpha release, and this TNF-alpha stimulates MIP-2 induction, at least partially contributing to the liver injury mediated through the recruitment of neutrophils.
A series of novel pyrrolo[2,3-d]pyrimidine derivatives was designed and synthesized as thymidylate synthase (TS) inhibitors. Molecular design was performed on the human TS complex model built on the basis of the reported structure of TS-deoxyuridinemonophosphate (dUMP)-CB3717 ternary complex. From a docking study, we expected that a one-carbon bridge between pyrrolo[2,3-d]pyrimidine and an aromatic ring was suitable. Moreover, we found that the bridge carbon could be replaced with an alkyl group to fill out the unoccupied space. Based on this design, we synthesized five pyrrolo[2,3-d]pyrimidine derivatives with one-carbon bridge and evaluated their TS inhibitory activities. All synthesized compounds inhibited TS more potently than compound 2 (LY231514), and the C8-ethyl analogue (7) showed a remarkable inhibitory activity against TS (IC50=0.017 microM).
To study the effects of hydroxyl radicals on the sensitivity of the ATP-sensitive K+ (K+ ATP) channel to tolbutamide, we used patch clamp and microfluorometric techniques in pancreatic beta-cells isolated from rats. cell-attached membrane patches, exposure of the cells to 0.3 mM H2O2 increased the probability of opening of K+ATP channels in the presence of 2.8 mM glucose. Tolbutamide dose-dependently inhibited the K+ATP channel with half-maximal inhibition (IC50) at 0.8 microM before and immediately after exposure to H2O2. After prolonged exposure (>20 min) to H2O2, the IC50 was increased to 15 microM. The presence of both ATP and ADP at concentrations ranging from 0.01 to 0.1 mM in the inside-out bath solution significantly enhanced the inhibition of the channels by 10 microM tolbutamide. Addition of 0.3 mM H2O2 induced a transient minute increase in the cytoplasmic Ca2+ concentration ([Ca2+]i) within 10 min, followed by a sustained pronounced increase in [Ca2]i. After more than 20 min of exposure of cells to 0.3mM H2O2, [Ca2]i was increased to above 2 microM. Treatment of the cytoplasmic face of inside-out membrane patches with 1 microM Ca2+ attenuated the tolbutamide-sensitivity of the K+ATP channel, but not the ATP-sensitivity of the channel. These findings indicate that H2O2 reduces tolbutamide sensitivity by inducing a sustained increase in [Ca2+]i.
Diagnoses and symptoms are recorded by physicians in the chapter E of the Minimum Data Set (MDS), if they are relevant to disabilities of activities of daily living, cognition, behavior, medical treatments or risk of death. We improved the chapter so that it is suited to disease patterns in Japan in a format useful not only for nursing and ADL care but for medical treatment in our practice. In E1, diseases directly underlying the current disability states were recorded in the international classification of Disease, 9th Revision (ICD9). In 24, 670, 195, and 45 patients respectively, there were 0, 1, 2, and 3 separate recorded diseases. A Total of 63 ICD9 codes were observed, but only four codes; 290, 332, 431, and 434, were underlying diseases for 3% or more patients. These codes included mostly ischemic and degenerative disease of the brain.
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Purpose: To identify the amyloid protein of the corneal amyloidosis complicated by trichiasis.Methods: The two patients were 41-year-old and 38-year-old women with trichiasis. They had gelatinous drop-like corneal change in the hemilateral eye. The lesion was excised and examined by light and electron microscopy. Additionally, we performed an immunohistochemical study with immunofluorescence techniques using cryosections.Results: The amyloid deposits were confirmed with light and electron microscopy. Congo red positive staining was not reduced following pretreatment with potassium permanganate. Immunohistochemically, amyloid deposits in the cornea stained positively with serum human light chain kappa and lambda. Pretreatment of the section with 0.05% Tween-20 did not decrease the staining with fluorescence. The deposits stained negatively with serum prealbumin and keratin antibodies.Conclusions: These findings indicate the protein of the corneal amyloidosis complicating trichiasis to be an amyloid light chain (AL) protein that has never been identified in this kind of corneal amyloidosis.
We sought to elucidate the clinical features of transient seizure remission in intractable cryptogenic or symptomatic localization-related epilepsy of childhood onset. Transient seizure remission has been reported to occur in mesial temporal sclerosis or focal cortical dysplasia, but few reports have focused on this phenomenon. We retrospectively scrutinized the temporal profiles of seizure frequency of 99 patients with intractable localization-related epilepsy by reviewing their medical charts. Ten patients (10%) had transient seizure remissions that lasted for 2 years or longer. When an appropriate antiepileptic agent was administered, seizure remission occurred within 1-18 months. Without any triggering factors, the seizures recurred abruptly in seven patients and gradually in three. Epileptiform discharges on electroencephalography disappeared during the transient remission in seven patients and reappeared in five of them after recurrence. After recurrence, no antiepileptic agent was able to control the seizures. In comparison with those without transient seizure remission, these 10 patients tended to have normal intelligence and a positive family history for epilepsy. Transient seizure remission occurs in a variety of pathologic changes and may be a result of an interaction between the progressive nature of some types of epileptogenic foci and an effect of the antiepileptic drugs.
AIMS: To assess changes in alcohol consumption attributable to the Great Hanshin Earthquake to test the assumption that alcohol consumption increases after natural disasters. METHODS: Quarterly alcohol sales figures were compared for three periods: before, immediately after and subsequent to the Great Hanshin Earthquake in three areas of the Hyogo prefecture: the severely affected area, the moderately affected area and the unaffected area. Possible confounding by population movement, damage to retail outlets and normal variation in sales, was assessed. FINDINGS: The quantity of alcoholic beverages consumed in the heavily damaged areas as well as throughout the prefecture decreased from the 1994 pre-disaster level, both immediately after the Great Hanshin Earthquake (January-March 1995) and 2 years after the disaster. This finding remained once possible confounding factors were taken into consideration. CONCLUSIONS: More attention should be placed on drinking in the cultural context where a disaster occurs. It may sometimes deter, rather than encourage, drinking among the affected population.
We retrospectively examined 169 patients who had cryptogenic or symptomatic localization-related epilepsies (LRE) and were followed-up for more than 5 years. The probability of seizure control was 0.13 during the first year of treatment, 0.25 during the first 5 years, and 0.09 during the second and third 5 years. No patients who continued to have intractable seizures for 15 years became free of seizures. The onset of LRE at the age of 3 years or less, seizure cluster, mesial temporal sclerosis (MTS), and temporal lobe epilepsy (TLE) were significantly associated with a poor seizure control. If an antiepileptic drug (AED) failed to control seizures, probability of seizure control by the next drug was low, in particular in patients in whom more than 4 AEDs have already been tried, and seizure control could not be expected after a trial of 6 AEDs. A tentative indication of epilepsy surgery for LRE of childhood onset may be 5 years of poor seizure control and/or failure of four AEDs.
Diagnoses recorded in the chapter E of Minimum Data Set (MDS) were analyzed in patients requiring care admitted in a geriatric hospital in Sapporo, Japan. They were classified as: A-diseases causing care-requiring conditions, B-their symptoms, and C-coexisting diseases requiring no care. Orthopedic diseases were not analyzed because they were not adequately recorded in MDS system. Class A diagnoses varied, but only five diagnoses were responsible for 3% or more of the total patients who required care. They were 1) Alzheimer's disease (AD), 2) Parkinson's disease, 3) dementia other than AD without neurological symptoms, 4) dementia other than AD with sequelae of stroke, and 5) sequelae of stroke without dementia. These diagnoses pooled represented over 90% of all patients. "Diagnoses and symptoms" in MDS were useful to 1) describe medical problems briefly in a predetermined format, 2) evaluate urgent or unstable conditions separately from stable diagnoses and symptoms, and 3) use common information by various professions, but have difficulties because 1) preselected diagnoses were few and unsuited to practices in Japan, 2) it is impossible to record a previous disease in the past that initiated the process leading to the present disabilities, and 3) it is also impossible to record the severities of the diseases and symptoms.
To elucidate the clinical characteristics of disability due to various basic disease groups, by using Japanese Minimum Data Set (MDS), Nishimura's mental scale (NM) and activity of daily living scale (N-ADL), cognitive function and basic activity of daily living (ADL) together with the grading scale of nursing care (freedom-grade of daily living: N1. frequency of bedside visits by a nurse: N2) and nutritional function (serum albumin: SA) were assessed in 926 elderly disabled inpatients in April 1998 in our long-stay chronic care hospital. Basic diseases were divided into five groups: cerebrovascular (C), senile dementia (D), bone and joint (B), Parkinson's disease (P) and other diseases (O). (1) In all patients, women were 2.9 years significantly older than men. Mean age in disease groups was significantly greater in the following decreasing order, B > D > C > P. (2) In all patients and patients with C, significant negative correlations were found between age and the scores of various scales (NM, N-ADL, N1, SA). In patients with D and B, significant negative correlations were found only between age and N-ADL and N1, but not NM or SA. In patients with P, no correlations were found between age and the various scales. (3) The cognitive function score decreased significantly as follows, B > C > P > D and the score of ADL decreased significantly as follows, B > D > C > P. (4) In patients with C and P, significant positive correlations were found between 3 scores (Cognition, ADL, SA). In patients with D, significant positive correlation was found between only two scores (ADL, SA) and in patients with B, no correlations were found between SA and other scores. (5) Because in all patients and in patients with all disease groups, significant positive correlations were found between the scores of cognition, ADL by MDS and the scores of NM, N-ADL respectively, the scales of cognition and ADL evaluated by MDS were validated for us to assess cognitive function and ADL and are probably suitable tools for evaluating elderly disabled patients. The other various functional states should also be assessed in elderly disabled patients where the quality of life of the patients must take priority over other considerations in decision making for medical interventions, including care. We should discuss care in detail and continue more medical studies to improve the quality of care.
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BACKGROUND: Hypergammaglobulinaemia and various auto-antibodies which are commonly seen in autoimmune hepatitis are also found in patients with chronic hepatitis C. We recently reported that ursodeoxycholic acid (UDCA) improved liver function tests and immunoserological markers in patients with type I autoimmune hepatitis. The aim of this study was to prospectively evaluate the efficacy of UDCA on autoimmune-associated chronic hepatitis C. METHODS: Immunoglobulin G (IgG), anti-nuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA) were determined in 95 patients with chronic hepatitis C. All patients were positive for hepatitis C virus RNA. Autoimmune-associated chronic hepatitis C (C-AIH) was defined by elevated serum IgG level (> or = 2.0 g/dL) and high titres of ANA and/or ASMA (> or = 1 : 160). Nine (9%) of 95 patients were diagnosed as C-AIH. All the C-AIH patients and 30 of the remaining 86 chronic hepatitis C patients without autoimmune features (CHC) were treated with UDCA (600 mg/day) for 1 year. RESULTS: Autoimmune-associated chronic hepatitis C patients included one man and eight women and their AIH scores, as defined by the International Autoimmune Hepatitis Group, were significantly higher than the CHC patients. Before UDCA therapy, there were no significant differences in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and y-glutamyl transpeptidase (gamma-GTP) levels between C-AIH and CHC patients. However, after 1 year UDCA therapy, AST, ALT and gamma-GTP were significantly lower in C-AIH patients (P< 0.05) than in CHC patients. In C-AIH, ANA titres in seven of nine patients and ASMA titres in five of seven patients were reduced after 1 year UDCA treatment. CONCLUSIONS: These results suggest that UDCA is a useful therapeutic agent for autoimmune-associated chronic hepatitis C.
The homeodomain-leucine zipper (HD-Zip) genes encode transcription factors that are characterized by the presence of both a homeodomain and a leucine zipper motif. They belong to the homeobox gene superfamily and have been reported only from flowering plants. This article is the first report on the ferm HD-Zip genes (named Crhb1-Crhb11) isolated from the homosporous ferm Ceratopteris richardii. Phylogenetic analyses of the II Crhb genes with previously reported angiosperm HD-Zip genes show that the Crhb genes belong to three of the four different angiosperm HD-Zip subfamilies (HD-Zip I, II, and IV), indicating that these subfamilies of HD-Zip genes originated before the diversification of the ferm and seed plant lineages. The Crhb4-Crhb8 and Crhb11 genes belong to the HD-Zip I subfamily but differ from angiosperm HD-Zip I genes by the presence of a seven-amino-acid indel in the leucine zipper motif. By the northern analyses, Crhb1 and Crhb3 were expressed only in gametophyte tissue. Expression of Crhb2 and Crhb11 genes could not be detected in any tissue examined, while all other Crhb genes were expressed in most sporophytic and gametophytic tissues. Although the functions of the Crhb genes in Ceratopteris are unknown, their patterns of expression suggest that they regulate developmental or physiological processes common to both the gametophyte and the sporophyte generations of the fern. Differences in the expression of Crhb1 between male gametophytes and male-hermaphrodite mixed populations of gametophytes suggests that the Crhb1 gene is involved in gametophytic sex determination.
PURPOSE: A large number of children had fits while watching the animated cartoon television (TV) program "Pocket Monster." To elucidate the seizures associated with the TV program, we administered a questionnaire survey in Aichi Prefecture, Japan. METHODS: The questionnaires were sent to 75 hospitals located in and around Aichi prefecture. The presence of epileptic seizures and the types of seizures were determined by three pediatric neurologists. RESULTS: Sixty-one hospitals responded to the questionnaire survey. Among 95 patients living in Aichi prefecture for whom enough information on seizure manifestations and EEG was available, < or =93 patients were considered to have epileptic seizures while watching the TV program. Most seizures occurred at a scene in which red and blue frames alternated at 12 Hz. Sixty-nine (74%) patients had no history of epilepsy. Thirty-nine patients had generalized seizures, and 49 patients had partial seizures. Partial seizures occurred more frequently in the younger age group than did generalized seizures. The EEG revealed a photoparoxysmal response (PPR) in 43% of patients. PPR was present not only in patients with a history of epilepsy (54%) but also in those with no history of epilepsy (38%). CONCLUSIONS: Almost all seizures induced by the TV program "Pocket Monster" were epileptic, and partial seizures were induced more frequently than generalized seizures. The incidence of this "Pocket Monster"-induced seizures was roughly estimated as > or =1 in 4,923 individuals aged 6-18 years.