Biomedical subjects

H Haga

Publications and source records attributed to H Haga.

At least 37 records · Page 2Linked to original sources

PubMed2000

Quantitative analyses of topography and elasticity of living and fixed astrocytes.

The topography and elasticity of living and fixed astrocytes cultured from the rat cerebra were studied quantitatively by atomic force microscopy (AFM). Ridge-like structures reflecting F-actin beneath the cell membrane were prominent in the contact-mode images of living astrocytes. Many of these ridges became unclear after fixation (2% glutaraldehyde). In addition, the ridge-like structures were invisible in the topography of living cells observed at zero-loading force in the force mapping mode, which is considered to show the real cell surface not pressed down by an AFM tip. The topography of fixed cells observed both in the contact mode and at zero-loading force in the force mapping mode was similar to that of living cells observed at zero-loading force in the force mapping mode, although some deformed areas were detected in the fixed cells. The elasticity map images of living astrocytes showed that the cell membrane above the nucleus was softer (2-3 kPa) than the surroundings, and that the cell membrane above F-actin was stiffer (10-20 kPa) than the surroundings. In the elasticity map images of fixed astrocytes, on the other hand, the elasticity of the cells was found to be relatively uniform (200-700 kPa) irrespective of the inner structures of cells. These results show that images observed by AFM should be carefully examined in consideration of the force introduced to specimens and the elasticity of specimens to find out the real surface topography.

Actins↗

PubMed2000

Time-lapse viscoelastic imaging of living fibroblasts using force modulation mode in AFM.

Using the force modulation mode in atomic force microscopy, we have succeeded in capturing time-lapse viscoelastic images of living mouse fibroblasts (NIH3T3) for several hours in a physiological condition without damaging the fibroblasts. Elongation of the lamellipodia and swelling of blebs were observed in time-lapse topographic images, which were taken every 10 min. The corresponding viscoelastic responses at a frequency of 600 Hz were visualized as consecutive images. The stiffer part of the cell body was fairly stable and did not show morphological changes for over 1 h. This is probably due to excess condensation of the actin network, hardening the cell cortex, and lowering the cytoskeletal activity. The nuclear portion of the cell body seems to be slightly less viscous than the peripheral region.

3T3 Cells↗

PubMed2000

Predictors for functional decline among nondisabled older Japanese living in a community during a 3-year follow-up.

OBJECTIVES: To examine predictors for functional decline in basic activities of daily living (BADL) as well as predictors for decline in instrumental activities of daily living (IADL) among nondisabled older Japanese people living in a community during a 3-year interval from 1992 to 1995. DESIGN: A prospective cohort study. SETTING: A community-based environment. PARTICIPANTS: A total of 583 men and women aged 65 to 89 at baseline who were independent in both BADL and IADL. MEASUREMENTS: Independent variables regarding various factors potentially associated with functional decline were obtained from an interview survey and medical examinations at baseline. Dependent variables were functional status in BADL and IADL obtained at the time of the 3-year follow-up. RESULTS: During the 3-year follow-up, significant predictors for functional decline in BADL and only IADL decline included (1) age of > or = 75, (2) less hand-grip strength, and (3) a history of hospitalization during the past 1 year. In addition, having poor intellectual activities and having poor social roles were identified as significant predictors for functional decline in only IADL during the 3-year follow-up. Furthermore, not having the habit of taking a walk was identified as a significant predictor of functional decline in BADL during the 3-year interval. CONCLUSION: Having a high level hand-grip strength, good intellectual activities, and good social roles are strongly associated with remaining independence in IADL for the nondisabled Japanese persons aged > or = 65.

Activities of Daily Living↗

PubMed2000

Lamivudine as an alternative therapy for interferon-resistant chronic hepatitis B and the characteristics of hepatitis B virus: a case report.

A 27-year-old man who had been diagnosed as having chronic hepatitis B suffered disease exacerbation with marked reactivation of hepatitis B virus (HBV). Treatment with interferon (IFN) did not improve his condition, and his serum HBV DNA level increased to over 10 000 pg/ml during IFN administration. Following replacement with lamivudine, there was a substantial reduction in HBV DNA to an undetectable level, and liver function parameters subsequently improved to within the normal range. Quantitative analysis of the precore mutant HBV DNA, which is a variant that cannot express hepatitis B e antigen due to a G-to-A point mutation in the precore region of the viral genome, revealed that the amount present was greater than for the precore wild-type HBV DNA in the serum taken before IFN treatment. This case suggests that lamivudine would be an appropriate alternative to IFN, particularly in patients infected with HBV containing an excess of precore mutants resistant to IFN therapy.

Adult↗

PubMed1999

Abnormal expression of tyrosine hydroxylase immunoreactivity in Purkinje cells precedes the onset of ataxia in dilute-lethal mice.

Expression of tyrosine hydroxylase (TH) immunostaining in the cerebellum was examined in dilute-lethal mice (DL) prior to and following the onset of ataxia. DL walked normally on postnatal days 7 and 8. Falling over when walking was exhibited by about 20% of DL on day 9 and by all DL by day 10. TH-positive Purkinje cells in lobules IX and X of the vermis of either ataxic or non-ataxic DL were clearly observed on day 9 when compared to control mice, and had drastically increased by day 10. These results revealed that abnormal TH expression occurred in some Purkinje cells of DL cerebella, preceding the onset of ataxia.

Animals↗

PubMed1999

Identification of an amino acid transporter associated with the cystinuria-related type II membrane glycoprotein.

We identified an amino acid transporter that is associated with the cystinuria-related type II membrane glycoprotein, rBAT (related to b(0,+) amino acid transporter). The transporter designated BAT1 (b(0, +)-type amino acid transporter 1) from rat kidney was found to be structurally related to recently identified amino acid transporters for system L, system y(+)L, and system x(-)C, which are linked, via a disulfide bond, to the other type II membrane glycoprotein, 4F2hc (4F2 heavy chain). In the nonreducing condition, a 125-kDa band, which seems to correspond to the heterodimeric complex of BAT1 and rBAT, was detected in rat kidney with anti-BAT1 antibody. The band was shifted to 41 kDa in the reducing condition, confirming that BAT1 and rBAT are linked via a disulfide bond. The BAT1 and rBAT proteins were shown to be colocalized in the apical membrane of the renal proximal tubules where massive cystine transport had been proposed. When expressed in COS-7 cells with rBAT, but not with 4F2hc, BAT1 exhibited a Na(+)-independent transport of cystine as well as basic and neutral amino acids with the properties of system b(0,+). The results from the present investigation were used to establish a family of amino acid transporters associated with type II membrane glycoproteins.

ATP-Binding Cassette Transporters↗

PubMed1999

Abnormal expression of tyrosine hydroxylase immunoreactivity in cerebellar cortex of ataxic mutant mice.

Expression of tyrosine hydroxylase (TH) was examined immunohistochemically in the cerebellum of two ataxic mutants, Rolling mouse Nagoya (RMN) and dilute-lethal mice (DL). In littermate controls of both mutants, a few TH-positive Purkinje cells were distributed sparsely and their number was smaller than in the mutants at any ages examined. In RMN, TH-positive Purkinje cells were distributed in lobule IX and X, and were arranged into parasagittal bands at 2 weeks of age. TH-positive Purkinje cells increased in number and were widely distributed throughout the vermis at 3 weeks of age. In adult RMN, TH-positive Purkinje cells were found in all lobules of the cerebellum. Their parasagittal bands also became evident in the hemisphere. In DL, TH-positive Purkinje cells were mainly distributed in vermal lobules IX and X, and the flocculus at 3 weeks of age. They were also found as bands in lobules IX and X. The results suggest that abnormal expression of TH in Purkinje cells may not be specific to the allelic group. Since TH promoter is activated by Ca2+, TH expression in the mutant Purkinje cells may predict neuronal dysfunction caused by alterations in cellular Ca2+ currents.

Animals↗

PubMed1999

Living related liver transplantation: histopathologic analysis of graft dysfunction in 304 patients.

Between June 1990 and August 1997, 304 mainly pediatric patients underwent a total of 311 orthotopic living related liver transplantations (LRLTs) under tacrolimus immunosuppression at Kyoto University Hospital. Congenital biliary atresia was the most common underlying disease. The donor was a parent, and the left lateral segments were used as grafts in most cases. The average number of loci of HLA-A, -B, and -DR mismatches between the donor and the recipient were 2.1. Forty-three transplants were ABO-incompatible. Liver histology at the time of abnormal liver function after transplantation was analyzed. Preservation injury was rare and mild. Acute cellular rejection (ACR) occurred in 36% of transplants during the first 6 months. Average rejection activity index (the Banff schema) was 4.2 and severe rejection was rarely seen. The number of mismatching HLA loci and immunosuppression regimens affected the incidence of ACR. Chronic rejection (CR) occurred in 2% of transplants. Concerning humoral rejection, no hyperacute rejection was seen. However, hepatic artery thrombosis (delayed hyperacute rejection) was seen in an ABO-incompatible transplant. Acute hepatitis, including those related to cytomegalovirus and Epstein-Barr virus, occurred in 17% of transplants. Chronic hepatitis, including hepatitis B and C, developed in 3%. Acute or chronic cholangitis occurred in 16%, and a significantly higher incidence of cholangitis was found in ABO-incompatible transplants. Posttransplantation lymphoproliferative disease developed in 2%. In LRLT, milder preservation injury and less frequent ACR and CR were suggested, probably because of the short cold-ischemia time and the advantages of HLA histocompatibility, respectively.

Adolescent↗

PubMed1999

Increased frequency of cells secreting interleukin-6 and interleukin-10 in peripheral blood of patients with primary Sjögren's syndrome.

Sjögren's syndrome (SS) is a chronic autoimmune disease of exocrine glands. There is increasing evidence that interferon-gamma (IFN-gamma) plays a role in the pathogenesis of SS. It has also been suggested that other type 1 cytokines, as well as interleukin-6 (IL-6), IL-10 and transforming growth factor-beta, are important in the induction and/or maintenance of SS. The aim of this study was to investigate the type 1/type 2 cytokine pattern in peripheral blood of primary SS patients. The enzyme-linked immunospot (ELISPOT) assay was performed to quantify the number of mononuclear cells (MNC) secreting IFN-gamma, IL-6 and IL-10 in peripheral blood samples from 33 patients with primary SS and 12 healthy controls. The mean number of cells secreting IFN-gamma was 9/105 MNC in the SS patient group, and 4/105 MNC in the control group (P = 0.73). Fifteen of the SS patients had anti-Ro 52 kDa antibodies in serum. In this patient group the mean number of cells secreting IFN-gamma was 4/105 MNC, while in the patient group without such antibodies the mean number of cells secreting IFN-gamma was 14/105 MNC (P = 0.04). The mean number of cells secreting IL-6 was 12 000/105 MNC in the SS patient group, and 5000/105 MNC in the control group (P = 0.01). The mean number of cells secreting IL-10 was 270/105 MNC in the SS patient group, and 180/105 MNC in the control group (P = 0.04). The SS patients had a significantly higher number of cells secreting IL-6 and IL-10 in peripheral blood than the healthy controls, which may facilitate B-cell activation and production of autoantibodies.

Adult↗

PubMed1999

Analysis of liver single photon emission computed tomography in a case of fulminant hepatic failure.

Fulminant hepatic failure is associated with a high mortality rate. Thus, accurate assessment of hepatic functional reserve and hepatic regeneration is important. We describe a 67-year-old woman who survived subacute hepatic failure. We had an opportunity to monitor the clinical course of the patient using single photon emission computed tomography (SPECT) with 99mTc-galactosyl-human serum albumin (99mTc-GSA) and frequent hematological examinations. On admission, prothrombin time was remarkably prolonged (23.1% of control). The liver uptake of 99mTc-GSA was also considerably low. She responded well to treatment. Four weeks after admission, SPECT analysis showed a dramatic increase in liver uptake of 99mTc-GSA, suggesting promotion of hepatic regeneration. Moreover, functional liver volume calculated from the SPECT data showed a marked increase at 4 weeks after admission, whereas CT scan showed no change at that point. This indicated that SPECT with 99mTc-GSA reflected functional hepatocytes more accurately than liver volume determined by CT scan, which cannot exclude nonfunctional hepatocytes. The patient's condition improved in parallel with the improvements in the indices measured by SPECT and hematological examinations. SPECT analysis is practically useful for the prompt assessment of improvement in patients with fulminant hepatic failure.

Aged↗

PubMed1999

Dynamics of astrocyte adhesion as analyzed by a combination of atomic force microscopy and immuno-cytochemistry: the involvement of actin filaments and connexin 43 in the early stage of adhesion.

We observed the time-dependent morphological alteration of astrocytes during their adhesion by atomic force microscopy (AFM) and investigated the relationships between this morphological alteration and the localization of actin filaments and connexin 43 by immunocytochemistry. The fine processes observed as fine ridge-like structures by AFM were closely concerned with actin filaments by immunocytochemistry. During the adhesion of astrocytes, actin filaments appeared to be aligned regularly beyond the borders among different cells. Detectable connexin immunoreactivity was changed in the following regions: 1) the tips of fine cell processes and the cell margin when astrocytes started to adhere; 2) the border of cells when astrocytes tightly adhered; and 3) non-specific sites when astrocytes became a cluster. In the former two cases, the immunopositive spots for connexin were observed to colocalize with the tips of cell processes with actin filaments. These results strongly suggest that connexin associated with actin filaments at the tip of cell processes plays an important role in the early stage of the adhesion of astrocytes. These observations afford valuable clues for understanding the glial communication.

Actin Cytoskeleton↗

PubMed1999

[Compliance concerning external protectors for hip fractures among the institutionalized elderly in Japan].

An external protector (EHP) which was developed in Europe to protect the femoral neck from direct impact on falling is available but has not been examined sufficiently in Japan. In order to explore the compliance of use of the EHP among the institutionalized elderly with in case of hip fracture who are at high risk of falling, we conducted the four-week intervention study using two types of a EHP. The subjects of a study consisted of 10 elderly people (2 men, 8 women) with a mean age 85.7 living in nursing home in a village. Informed consent was obtained from all participants. At the end of the study, rate of subjects who wore EHP was relatively high for the Finnish EHP (Safety Pants) group compared to the Danish EHP (Hip Protector) group. There were no significant differences between variables in age, sex, fall experience during the previous year, history of diseases etc. The reasons for dropout were first: difficult in wearing EHP and accompanying delay in toilet, secondly: taking much time to wear, thirdly: a sense of incongruity, too small or too tight'. If the EHP is redesigned to suit Japanese elderly, the compliance might increase. Thorough explanation to institutionalized elderly who may have cognitive impairment, physical problems, or both, is required.

Aged↗

PubMed1999

[Compliance in use of external protectors for hip fractures among the community elderly in Japan].

To protect femoral neck fractures which are the most serious complication of osteoporosis and are increasing in frequency in Japan, an external hip protector (EHP) fixed in special underwear has been proven to absorb a direct impact to the greater trochanter during a fall from standing height. In this study, we investigated compliance concerning the use of EHPs, for six months using two types of EHP, i.e., hard pad type (Hip Protector, Sahvatex) from Denmark (Fig. 1) and soft pad type (Safety Pants, Rounomo Oy) from Finland. The subjects were 20 elderly women aged 70 years or more who had at least one experience of falling within the year preceding the baseline survey in September of 1997. The compliance rate is shown in Fig. 2. Though the soft type EHP had relatively better compliance than the hard type EHP, there was no significant difference between them. The main reason for early dropout (one or two weeks after base-line) was "difficulty to remove especially with regard to using the toilet". The main reason for later dropout was "too tight to wear in winter". There were no significant differences with regard to anthropometric measurements, physical activity, ADL, and rate of falls between compliers and dropouts except age (73.6 vs 78.5 yrs). Sufficient explanation at baseline and generatively good motivation for wearing the EHP will maintain a high compliance which may result in the effective prevention of hip fractures among the community elderly.

Aged↗

PubMed1999

[An intervention trial to postpone aging in competent elderly. Trial of nutritional improvement in the retirement home].

The purpose of this study was to evaluate the effectiveness of a comprehensive intervention program in changing dietary habits and nutritional status, for postponing aging in competent elderly. The intervention group (n = 44, 11 men, 33 women, mean age: 74.3 +/- 5.4 years) comprised residents of a retirement home in a suburb of Tokyo. The intervention program, which consisted of 82 lectures and practice sessions focusing mainly on improvement of life styles, was performed between May 1993 and May 1995. In addition, individualized dietary consultations were provided every week during the intervention period. The age and sex matched control group (n = 133, 33 men, 100 women) was randomly selected from participants of the community-based health examination in Tokyo. Changes in dietary habits were measured by a 15-food frequency questionnaire method. As parameters of nutritional status, serum albumin (ALB), total cholesterol (TC), HDL cholesterol (HDL-C) and body mass index (BMI) were simultaneously examined at pre- and post-intervention. The results obtained were as follows: 1) The mean score of Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG Index of Competence) was 11.3 +/- 1.6 in the intervention group, 12.0 +/- 1.6 in the control group, the competent level of functional capacity was equally high in both groups. 2) Food frequencies of meat, fruit, and fat and oil significantly increased in the intervention group. A significant increase in the food frequency of meat was seen in the control group. 3) Significant increases in ALB, HDL-C and BMI were consequently observed in the intervention group, whereas levels of ALB and BMI significantly decreased in the control group. 4) The number of times of participation in the comprehensive intervention program was significantly positively related to the change in ALB between pre- and post-intervention, after adjusted for age, sex, education, TMIG Index of Competence score and ALB level at baseline. These results indicate that the comprehensive intervention program is effective for postponing aging in the competent elderly.

Aged↗

PubMed1999

[Mental and physical symptoms in alcoholics after alcohol withdrawal--comparing with involutional melancholia patients].

As a factor of recurrence of drinking in patients with alcoholic dependence, emotional disorders accompanied by alcohol dependence has been noted in many reports. Particularly, it is noted to be very likely that depression after abstinence is an incentive to re-start drinking. In this study, we investigated depressive feeling in aspects of psychiatric and physical subjective symptoms after abstinence in patients with alcohol dependence, and compared the symptoms with those in patients with involutional depression. On analysis of the major component of psychiatric subjective symptoms, a sense of alienation, emotional instability, anxiety, and aggressiveness were observed. In involutional depression, depressive feeling, somnipathy, anxiety, self accusation/sense of guilt, delusion of culpability were observed. On analysis of the major component of physical subjective symptoms, autonomic nervous symptoms accompanied by feebleness, hysterical neurosis-like autonomic nervous symptoms, reduced sexual libido, anorexia, hydrodipsia/sweating were observed. Similarly, in patients with involutional depression, hysterical neurosis-like autonomic nervous symptoms, anorexia, elevation of tonus, general malaise, and hydrodipsia were noted. Differences in status were emphasized in comparison between the two groups in both analyses. Unlike involutional depression that exhibits the current features of depression, patients with alcohol dependence showed a sense of alienation, emotional instability, anxiety, and aggressiveness, reflecting self-uncertainty and loss of self-respect. Drinking may be re-started to relieve or reduce tension and frustration in such conditions.

Alcoholism↗

PubMed1999

Effect of food intake pattern on all-cause mortality in the community elderly: a 7-year longitudinal study.

The purpose of the present study was to examine the relationship of a food frequency pattern and survivorship in a cohort of community elderly residents (259 men, 445 women), aged 65 years old and over, based on a 7-year follow up study. Baseline survey was undertaken in July 1988 by door-to-door method. The cohort was followed up until August 1995, during which time survivorship of subjects was investigated periodically each year. Eighty-one men (31.3%) and 71 women (19.1%) died during the follow-up period. The food frequency pattern was examined by factor analysis based on a food frequency questionnaire for 15 food-groups at the baseline survey. Results obtained were as follows: 1)The first factor was expressive of frequent intake pattern of plant foods, the second factor was frequent intake pattern of meat, fat, and oil, the third factor was frequent intake pattern of bread and rice(negative), and the fourth factor was frequent intake pattern of salty pickled vegetables, fish, and shellfish. 2)The first factor as represented by frequent intake pattern of plant foods had significant negative effect on all-cause mortality for both the whole 7 years and the last 4 years surveys, adjusted for age, sex, education level, drinking habit, smoking habit, exercise habit, history of hypertension, and instrumental activities of daily living.

Activities of Daily Living↗

PubMed1998

Effects of dietary Pi on the renal Na+-dependent Pi transporter NaPi-2 in thyroparathyroidectomized rats.

Dietary Pi and parathyroid hormone (PTH) are two most important physiological and pathophysiological regulators of Pi re-absorption in the renal proximal tubule. Effects of dietary Pi on Na+/Pi co-transporter NaPi-2 were investigated in thyroparathyroidectomized (TPTX) rats. NaPi-2 protein and mRNA in the kidney cortex of TPTX rats were increased approximately 3.8- and 2.4-fold in amount respectively compared with those in the sham-operated animals. Administration of PTH to the TPTX rats resulted in a decrease in the amount of NaPi-2 protein, but not in the abundance of NaPi-2 mRNA. Deprivation of dietary Pi in the TPTX rats did not affect the amount of NaPi-2 mRNA and protein. In the Pi-deprived TPTX rats, feeding of a high-Pi diet resulted in marked decreases in Pi transport activity and the amount of NaPi-2 protein in the superficial nephrons. Immunohistochemical analysis demonstrated that administration of PTH to TPTX rats resulted in a decrease in NaPi-2 immunoreactivity from both superficial and juxtamedullary nephrons within 4 h. Switching TPTX animals from a low-Pi diet to the high-Pi diet decreased NaPi-2 immunoreactivity from superficial nephrons, but not from juxtamedullary nephrons, within 4 h. These results suggest that dietary Pi could regulate the amount of NaPi-2 protein in the superficial nephrons in a PTH-independent manner.

Animals↗

PubMed1998

Prognostic factors in uterine carcinosarcoma: a clinicopathologic study of 25 patients.

BACKGROUND: Carcinosarcoma (malignant mixed mullerian tumor) of the female genital tract is a highly malignant neoplasm. The tumor stage and histologic grade of the carcinomatous component are among the important prognostic indicators cited in the literature for this tumor. METHODS: Twenty-five patients with uterine carcinosarcoma at 4 hospitals in the Kyoto and Nara areas of Japan were studied retrospectively. The clinicopathologic and immunohistochemical data including p53, bcl-2, Ki-67, and proliferating cell nuclear antigen (PCNA) staining were analyzed using univariate and multivariate analysis with the Cox proportional hazards model to investigate potential prognostic indicators for this neoplasm. RESULTS: The 5-year survival rate was 36.4% for all stages, 62.3% for Stage I, and 0% for Stages II-IV. From the univariate analysis, stage (P = 0.0001), endometrioid adenocarcinoma as a carcinomatous component (P = 0.0006), age (P = 0.0355), and a heterologous sarcomatous component (P = 0.0421) were found to be prognostically significant for patient survival. Stage was the only independent significant factor in the multivariate analysis (t = 2.212). None of the other factors (history of pregnancy and gestation, gross appearance of the tumors, grade of the carcinomatous component, mitotic count of the sarcomatous component, Ki-67 and PCNA reactivity, or p53 or bcl-2 positive staining) was found to be a significant prognostic indicator. CONCLUSIONS: Stage appears to be the only definite independent prognostic indicator of survival in patients with uterine carcinosarcoma. It is uncertain whether age, endometrioid adenocarcinoma as a carcinomatous component, or absence of a heterologous component in the sarcomatous area are prognostic factors. Immunohistochemical expression of p53, bcl-2, Ki-67, or PCNA is not a prognostic indicator. The immunohistochemical results of the current study may support the hypothesis of a common stem cell origin of this tumor.

Adult↗