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Biomedical subjects

K Yamaji

Publications and source records attributed to K Yamaji.

At least 37 records · Page 2Linked to original sources

Localization of the apoptosis-inducing activity of lupus anticoagulant in an annexin V-binding antibody subset.

Lupus anticoagulant (LAC) is associated with arterial and venous thrombosis, thrombocytopenia, and recurrent fetal loss. We have reported previously that plasma with LAC activity induces apoptosis in endothelial cells and binds annexin V (Nakamura, N., Y. Shidara, N. Kawaguchi, C. Azuma, N. Mitsuda, S. Onishi, K. Yamaji, and Y. Wada. 1994. Biochem. Biophys. Res. Commun. 205:1488-1493). In this study, we separated two IgG antibody fractions, one with and one without affinity for annexin V, from 10 patients with LAC. LAC and apoptotic activities were localized in the annexin V-binding fraction in all 10 patients. DNA fragmentation was dose-dependent, paralleling the amount of IgG added to the human umbilical vein endothelial cell culture medium, and was inhibited by preincubation with annexin V. Removal of the antiphospholipid antibodies from patient IgG with phospholipid liposomes did not abolish the apoptosis-inducing activities or binding to annexin V. These results imply that patients with LAC often have antibodies that do not bind phospholipids and are responsible for the induction of apoptosis in endothelial cells.

Adult↗

Expression of a hepatitis C virus NS3 protease-NS4A fusion protein in Escherichia coli.

Both the NS3 protease and the NS4A protein are required for efficient cleavage of the nonstructural protein region of the hepatitis C virus polyprotein. The NS3 protease domain was fused at its C-terminal end with full length NS4A and expressed in Escherichia coli. This protein (NS3 delta-NS4A) was purified to apparent homogeneity after refolding from extracts recovered from inclusion bodies. During the expression and purification process, NS3 delta-NS4A was not auto-processed in either a cis or trans manner at NS3/NS4A junction site. When the kcat/K(m) values and thermostability of NS3 delta-NS4A were compared with those for maltose binding protein-NS3 fusion protein (MBP-NS3), which contains only NS3 region, the single-chain NS3 delta-NS4A showed enhanced proteolytic activities and thermostability.

ATP-Binding Cassette Transporters↗

Age-related response to interferon alfa treatment in women vs men with chronic hepatitis C virus infection.

BACKGROUND: Interferon alfa is used widely for patients with chronic hepatitis C virus (HCV) infection. Little is known, however, of the relationship between patients' sex and the effectiveness of interferon alfa treatment in these patients. METHODS: We treated 311 patients (199 men and 112 women) with human lymphoblastoid interferon (6 million units subcutaneously every day for 2 weeks and 3 times a week for 22 weeks) and observed them for an additional 6 months. Serum HCV RNA levels and genotype were tested by polymerase chain reaction before treatment. A liver biopsy was also done. For the purposes of this study, a complete response was defined as the elimination of HCV RNA for at least 6 months after the termination of treatment. RESULTS: The rate of complete response was 27.1% for men and 24.1% for women. With multiple logistic regression analysis, the HCV RNA level (P < .001), genotype (P < .001), patients' sex (P < .05), and the interaction between sex and age were associated with a complete response to interferon alfa. The rate of complete response was 33.3% in men aged 39 years and younger, 25.0% in men aged 40 years and older. 75.0% in women aged 39 years and younger, and 15.6% in women aged 40 years and older. The odds ratio by group was 1.00, 0.72, 4.38, and 0.21, respectively. CONCLUSIONS: Our finding that women aged 39 years and younger are responsive to interferon alfa treatment suggests that hormonal activity, in particular the level of estrogen, may be associated with the sustained elimination of HCV.

Adult↗

Hepatitis C viral RNA status at two weeks of therapy predicts the eventual response.

We investigated the timing of the disappearance and reappearance of serum hepatitis C viral (HCV) RNA in patients with chronic hepatitis C during interferon treatment and follow-up. Serum samples were tested for HCV RNA by polymerase chain reaction in 62 patients with chronic hepatitis C treated with interferon-alpha for 24 weeks. We found that 17 patients obtained complete response, with absence of serum HCV RNA for 6 months after the treatment. Twenty-nine patients had a partial response, with reappearance of serum HCV RNA within 6 months of follow-up, and 16 patients were nonresponders who were positive for serum HCV RNA throughout the observation period. HCV RNA disappeared within 2 weeks of treatment in 31 patients, including all 17 (100%) complete responders and 14 (48.3%) of the 29 partial responders. The patients remaining positive for HCV RNA at the second week were 15 (51.7%) of the 29 partial responders and the 16 nonresponders. In all of the 29 partial responders, viremia recurred within 1 month after the treatment. These results indicate that the status of HCV RNA at the second week of treatment is a useful predictor of effective treatment, whereas status at the first month after cessation of treatment is useful for assessing the effectiveness of interferon itself.

Adult↗

Current therapeutic apheresis technologies for inflammatory bowel disease.

A large number of physicians have indicated that patients with inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD) respond to current apheresis technology treatment. However, the mechanism of the apheresis procedure is undefined for patients with IBD. IBD appears to be caused by a complex of interactions from the genes, environment, and the immune system; therefore, the immune system plays a crucial role in the inflammatory responses. In this process, lots of interactions occur simultaneously, and they cross relate with each other. This review paper briefly discusses the etiology and pathogenesis of IBD and attempts to elucidate the mechanism that occurs after apheresis treatment.

Blood Component Removal↗

[Impact of influenza epidemics and efficacy of vaccination among geriatric inpatients].

To determine the impact of influenza epidemics among geriatric inpatients and to monitor the clinical efficacy of influenza vaccination, the influenza infection rate in non-vaccinated inpatients was determined serologically and the incidence of febrile episodes and death were compared between the vaccinees and non-vaccinees hospitalized in the referred hospital from January through September, 1995. Three influenza subtypes, influenza A/H1N1, A/H3N2, and B, were endemic simultaneously from January to March in 1995. The pattern of incidence of febrile episodes varied for each ward. A total of 123 non-vaccinated inpatients were tested for elevation of serum hemagglutination inhibition titer to the three subtypes of influenza virus. Of these, 58 (47.2%) patients were infected with at least one of the influenza viruses during the epidemic of 1995. No patient with pre-existing HI titer over 128X was infected with any of three types of influenza, indicating that HI titer over 128X is the protective level. The febrile episode frequency was significantly higher in the non-vaccinees than in the vaccinees (49.6% vs. 32.6%), but it was quite comparable in the two groups after the influenza epidemic (34.9% vs. 35.8%). The number of observed deaths from January to September of 1995 was 4 (4.9%) in the vaccinee group and 12 (9.8%) in the non-vaccinee group. These results suggest that influenza epidemics have a striking impact on geriatric inpatients and that influenza vaccination has significant efficacy for the reduction of harmful events associated with influenza infection.

Aged↗

[Antibody response to a single injection of influenza vaccine among geriatric inpatients vaccinated annually].

To determine the efficacy of a single influenza vaccine administration in the elderly receiving annual influenza vaccination, antibody response to influenza vaccine was compared between once and twice injections in a geriatric cohort. Influenza vaccination had been done for 69 inpatients in the year prior to the study, and was administered twice for 34 of them and once for the other 35 during the study period. Influenza vaccine was injected twice to 77 inpatients who had not received influenza vaccine in the year prior to the study. Hemoagglutination inhibition (HI) antibody titer for influenza A/H1N1, A/H3N2, and B was measured before vaccination, after the first vaccination, after the second vaccination, and after the epidemic period, September 1995 to April 1996. HI antibody titer prior to vaccination was significantly higher in the patients who had received influenza vaccination the previous year. The influenza vaccine induced an increase in HI titer in almost all subjects, and the geometric mean of the HI titer after vaccination in the patients who received vaccine once was comparable to that of the patients injected vaccine twice. The number of patients with HI titers of over 128x increased, and the frequency ranged from 60.0% to 97.1% for the influenza viruses of the three subtypes. The frequency of HI titers over 128x was not significantly different among the three groups. The second vaccination did not increase the number of patients with HI titers over 128x when compared with the number after the first injection in the patients who had received influenza vaccine the previous year. These results suggest that prior vaccination does not diminish the antibody response to influenza vaccine in the elderly. The efficacy of a single influenza vaccination is comparable to that achieved by twice injections in the elderly receiving annual influenza vaccination.

Aged↗

[Bilateral homonymous hemianopsia with atrial fibrillation].

We encountered an 80-year-old man with sudden bilateral visual disturbance. When he was admitted to the hospital, his blood pressure was 138/70 mmHg, and an ECG revealed atrial fibrillation. Neurological examination showed only bilateral homonymous hemianopsia with no nystagmus or impairment of eye movement. He did not have paralysis cerebellar ataxia, or speech disturbance. Therefore, there was no evidence of obstruction of the thalamogeniculate or thalamoperforating artery. Magnetic resonance imaging of the brain showed cerebral infarctions in both occipital lobes. Perimetry showed bilateral homonymous hemianopsia; the left side of the macula was spared. The lack of neurological deficit other than bilateral homonymous hemianopsia indicates that only the right and left cortical branches of the posterior cerebral artery were occluded.

Aged↗

Effect of gonadotropin releasing hormone on thermoregulatory vasomotor activity in ovariectomized female rats.

To investigate the effect of gonadotropin releasing hormone (GnRH) on thermoregulatory skin vasomotion, we injected GnRH into various brain regions in both anesthetized and unanesthetized ovariectomized female rats. Local warming of preoptic area (PO) elicited skin vasodilation in anesthetized rats. Injection of 2 microg GnRH into the septal area lowered the threshold hypothalamic temperature for skin vasodilation at least for 2 h. Similar injections of 2 microg GnRH into the lateral ventricle (LV) and PO were ineffective. Although this vasodilative effect was also obtained after the injection of 20 ng GnRH into the septal area, injections of 2 ng GnRH were without effect. Not only injections of 20 ng Antide, a potent GnRH antagonist, but also injections of the mixed solution of 20 ng GnRH and 20 ng Antide were also without effect. In unanesthetized and unrestrained rats at an ambient temperature of 17 degrees C, injections of 20 ng GnRH into the septal area elicited tail vasodilation lasting for 30 minutes, whereas vehicle injections were ineffective. Injections of 20 ng GnRH into LV and PO were also ineffective. These results indicate that GnRH can elicit thermoregulatory skin vasomotion by acting on GnRH receptors in the septal area. This thermoregulatory vasodilative effect of GnRH might be possibly related to the etiology of climacteric hot flush.

Animals↗

Hepatitis C viral quasispecies and liver damage in patients with chronic hepatitis C virus infection.

To clarify the virological differences in patients with chronic hepatitis C virus (HCV) infection with and without liver damage, we assessed HCV markers in 306 patients from a rural area of Japan. Genotypes of HCV RNA were determined by polymerase chain reaction, and levels of RNA were determined by branched DNA signal-amplification assay. All patients had undergone annual tests for alanine aminotransferase (ALT) levels from 1986 to 1995. Patients were categorized into three groups: group A, 121 patients (39.5%) with normal ALT levels on all occasions for 10 years; group B, 127 patients (41.5%) with intermittently abnormal ALT levels; and group C, 58 patients (19.0%) with consistently abnormal ALT levels. There were no significant differences in serum RNA levels or distribution of genotypes among the three groups. We selected 10 patients from group A with normal ALT levels and 10 from group C with abnormal levels for sequence analysis of the HCV core region (nt 169-378) of five clones from each patient. More mutations were found in the 50 clones from the 10 patients from group C than in the 10 patients from group A. In group A, all mutations were synonymous so that the deduced amino acid sequences were identical among clones from each patient, whereas in group C 16 of 57 mutations were nonsynonymous so that the deduced amino acid sequences showed differences in the five clones of eight of 10 patients. In conclusion, the HCV core region was highly conserved in patients with normal liver biochemical test results but not in those with abnormal results. Our results suggest that abnormal liver biochemical test results in patients with chronic HCV infection may be associated with high degrees of virus quasispecies diversity.

Aged↗

No significant changes in levels of hepatitis C virus (HCV) RNA by competitive polymerase chain reaction in blood samples from patients with chronic HCV infection.

To determine if levels of hepatitis C virus (HCV) RNA change over a several-year period, we quantified the amount of HCV RNA by competitive polymerase chain reaction. The population studied included 44 residents of a rural area with chronic HCV infection, 39 had chronic hepatitis C and 37 were patients on hemodialysis. All these Japanese patients had HCV RNA of genotype II. Blood samples were collected once a year from 1992 to 1995. From 1993 to 1995 between the groups, there was no significant difference in change of HCV RNA levels of 44 residents with chronic HCV infection, with and without liver dysfunction, nor was there any change in the 31 hemodialysis patients from 1992 to 1995. The HCV RNA levels in the 25 with chronic hepatitis who did not respond to interferon-alpha during 1992-1993 returned to pretreatment levels after the cessation of interferon treatment. In two of six hemodialysis patients who were infected with HCV during this observation period, HCV RNA was eliminated within one year, and the remaining four became HCV carriers. HCV RNA levels in the latter rose rapidly after infection and were sustained at a high level throughout the study period. Thus, HCV RNA level did not change remarkably during a three-year period, a finding which supports that it does not correlate with deterioration of liver damage and aging of HCV carriers.

Carrier State↗

Effects of ultrathin silicone coating of porous membrane on gas transfer and hemolytic performance.

To assess the effect of an ultrathin (0.2 microm) silicone-coated microporous membrane oxygenator on gas transfer and hemolytic performance, a silicone-coated capillary membrane oxygenator (Mera HP Excelung-prime, HPO-20H-C, Senko Medical Instrument Mfg. Co., Ltd., Tokyo, Japan) was compared with a noncoated polypropylene microporous membrane oxygenator of the same model and manufacturer using an in vitro test circuit. The 2 oxygenators showed little difference in the oxygen (O2) transfer rate over a wide range of blood flow rates (1 L/min to 8 L/min). The carbon dioxide (CO2) transfer rate was almost the same in both devices at low blood flow rates, but the silicone-coated oxygenator showed a decrease of more than 20% in the CO2 transfer rate at higher blood flow rates. This loss in performance could be partly attenuated by increasing the gas/blood flow ratio from 0.5 or 1.0 to 2.0. In the hemolysis study, the silicone-coated membrane oxygenator showed a smaller increase in plasma free hemoglobin than the noncoated oxygenator. The pressure drop across both oxygenators was the same. These results suggest that the ultrathin silicone-coated porous membrane oxygenator may be a useful tool for long-term extracorporeal lung support while maintaining a sufficient gas transfer rate and causing less blood component damage.

Adult↗

Membrane apheresis technology: historical perspective and new trends toward bioincompatible systems.

During the past 25 years, membrane apheresis technology has been well developed through the use of biocompatible devices and immunomodulation. Now, however, we must move into a new era reconsidering the concepts of apheresis technology and considering the urgent need to develop a bioincompatible apheresis system. In the past, our aim in this field was to develop the best blood compatible system possible. With these systems, best efforts were made to reduce procedurally induced immunomodulation effects. However, it is these authors' opinion that procedurally induced immunomodulation effects should be augmented rather than reduced by incorporating such a bioincompatible apheresis system. Augmented immunoactivation and immunosuppression introduced by such systems should add therapeutic effects to the apheresis procedures. Therefore, we anticipate that the current marginally effective diseases may benefit from this strategic change in apheresis procedures.

Antibody Formation↗

Strategy of leukocyte filtration for immunomodulation: development of stainless steel leukocyte filter.

Commercially available leukocyte filters are frequently used to prepare leukocyte depleted blood products for prevention of transfusion reactions. Recently, immunomodulation by using leukocyte filtration was evaluated. At this time, a new leukocyte filter was fabricated with a 4 microm diameter stainless steel fiber. The goal of this study was to assess the efficiency of the stainless steel filter for leukocyte and platelet removal by comparison with the polyester filter that is commercially available. The production of humoral factors, including interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-1 receptor antagonist (IL-1 Ra), was also evaluated. The results show that the stainless steel filter has more than 2 times greater efficiency in leukocyte removal than the polyester filter. Furthermore, the cytokine studies indicate good biocompatibility of the filter, and the stainless steel filter has a possibility of inhibiting inflammatory cytokines by inducing interleukin-1 receptor.

Antibody Formation↗

[Effect of the prior influenza vaccination on serum antibody titer induction by subsequent inactivated influenza vaccine in the elderly].

In order to investigate the effects of prior influenza vaccination on subaequent annual influenza vaccination in the geriatric population, we analyzed serum hemagglutinine inhibition antibody tirers (HI titer) before and after vaccination with inactivated influenza vaccine in elderly inpatients. A total of 163 inpatients of 60 years or older were enrolled with informed consent. They were classified by vaccination status in the previous year, 53 patients had inactivated vaccine (inactivated). 52 patients had genetically assorted cold-adapted influenza live attenuated vaccine (cold-adapted), and 53 had no influenza vaccine history during the past year. The HI titer was higher in the inactivated group than in the cold-adapted and non-vaccinated groups, suggesting residual immunological effects of inactivated influenza vaccine from the previous year vaccination. The HI titer after the inactivated vaccine in 1993 was higher in both the inactivated and cold-adapted groups than in the non-vaccinated group. The number of patients with HI titers of 2(7) or higher, which is the putative protective HI titer level for influenza infection, was significantly higher in both the inactivated and cold-adapted groups than the non-vaccinated group. These results suggest that continuous annual influenza vaccination does not impair the effects of vaccination, and may actively promote elevated HI titers.

Aged↗

[Clinical significance of peak body temperature, white blood cell count, and C-reactive protein level in febrile episodes among geriatric inpatients].

To investigate the clinical implication of peak body temperature, peripheral blood white blood cell (WBC) count, and serum C-reactive protein (CRP) level in febrile symptoms among geriatric hospitalized patients, they were analyzed in 968 febrile episodes obtained from 433 hospitalized patients in the referred hospital. Episodes of one day duration were most frequent (41.6%). WBC count was elevated over 8000/microliters in 475 episodes (49.1%) and CRP exceeded 1.0 mg/dl in 770 episodes (79.5%). Frequency of WBC elevation decreased and frequency of CRP elevation increased according to the time course. The mean value of CRP increased significantly according to the time course. The frequency of WBC count increase and CRP elevation and their averages correlated to the peak body temperature. The peak body temperature displayed the most striking correlation to the length of febrile episodes among three clinical indicators, peak body temperature, WBC count, and CRP level. These results indicate that the elevation of WBC count and/or CRP level is frequent in geriatric patients with febrile symptoms. Peak body temperature may serve as a clinical indicator of the severy of the febrile disease occurring in geriatric patients.

Aged↗

[A case of reactive arthritis fallen after shigellosis infection].

A 25-year-old woman was admitted for general arthralgia in July, 1989. Reactive arthritis with arthralgia after Shigellosis was diagnosed by sex, localization of arthralgia and positive for HLA-B 27. Within 3 weeks after starting diclifenac sodium 75 mg/day, the arthralgia remitted. It has been reported that patients who are positive for HLA-B 27 have a more severe acute or chronic sacroiliitis, and our case may support this report.

Adult↗