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Biomedical subjects

M Hara

Publications and source records attributed to M Hara.

At least 271 records · Page 15Linked to original sources
PubMed1999

QT interval and QT dispersion before and after diet therapy in patients with simple obesity.

To evaluate whether a disordered QT interval and its dispersion in obese patients, if any, may be improved by therapeutic weight reduction, 36 obese patients admitted to our university hospital were examined over a 5-year period from April 1, 1992 to March 31, 1997. Participants included 18 males and 18 females whose mean age +/- SD was 28 +/- 9 and 33 +/- 14 years, respectively, and whose mean body mass index +/- SD was 35 +/- 5 and 38 +/- 6 kg/m2, respectively. Thirty-six control patients were matched in age and gender with the obese patients. All the obese patients were treated with behavioral therapy together with very-low-calorie conventional Japanese diet (VLCD: 370 kcal/day). A standard 12-lead electrocardiogram (ECG) revealed longer maximum (445 +/- 32 msec, mean +/- SD) and minimum (388 +/- 29 msec) heart rate corrected QT intervals (QTc intervals) in the obese group than in the control group (P < 0.0001 for each). QTc dispersion, defined as the difference between maximum and minimum QTc intervals derived from 12-lead ECG, was greater in the obese group (57 +/- 19 msec) than in the control group (32 +/- 13 msec) (P < 0.0001). Both the maximum and minimum QTc intervals in the obese patients were shortened, respectively, to 434 +/- 28 msec and 377 +/- 29 msec (P < 0.05 for each) with no significant change in either QTc dispersion, QRS voltage, or QRS duration following weight reduction. The coefficient value from the linear regression line between QT interval and RR interval in the obese group was less than in the control group. Together, the results show that obesity per se causes both a prolongation of QTc interval and an increase in QTc dispersion, and that weight reduction improves the prolonged QTc interval observed in obese patients.

Adult↗
PubMed1999

The I/D polymorphism of angiotensin-converting enzyme gene but not the angiotensinogen gene is associated with insulin response to oral glucose in Japanese.

Polymorphisms of angiotensin-converting enzyme (ACE) and angiotensinogen (AGT) genes have been reported to be associated with myocardial infarction and coronary artery disease, both of which are closely related to atherosclerosis and insulin resistance. In this study, we investigated the association between ACE and AGT genotypes and insulin sensitivity in a sample of 142 nondiabetic and 64 noninsulin-dependent diabetes mellitus (NIDDM) Japanese subjects, aged 62.7 +/- 9.5 years. The insulin response to the 75-g oral glucose tolerance test (OGTT) was significantly lower in subjects with the ACE D/D genotype compared to those with the I allele (I/D and I/I genotypes) in both nondiabetic (P < 0.05) and NIDDM subjects (P < 0.005). These homozygous D/D subjects also had lower insulin area under the curve of plasma insulin concentrations during OGTT compared to those with the I allele in nondiabetic (P < 0.05) and NIDDM subjects (P < 0.01). However, there was no significant association between AGT genotypes and either insulin response or insulin area under the curve during OGTT, in either nondiabetic or NIDDM subjects. From a viewpoint that insulin response to oral glucose is significantly correlated with insulin sensitivity, these results suggest that polymorphic variations at the ACE gene, but not the AGT gene, may be involved in the genetic regulation of insulin sensitivity in both nondiabetic and NIDDM Japanese subjects.

Aged↗
PubMed1999

Central motor conduction time in Parkinson's disease.

Central motor conduction time (CMCT) was analysed in 11 patients with Parkinson's disease and 10 age matched healthy controls. CMCT was measured during muscle relaxation, muscle contraction and in patients with Parkinson's disease before and 1 h after intravenous infusion of L-dopa (0.25%, 20 ml). Although the CMCT during muscle contraction did not differ significantly between Parkinson's disease and healthy controls, the CMCT during muscle relaxation was significantly shorter in Parkinson's disease than in healthy controls. The CMCT during muscle relaxation in Parkinson's disease was significantly longer after intravenous infusion of L-dopa than before, but the CMCT during muscle contraction did not differ significantly before and after intravenous infusion of L-dopa. The CMCT during muscle contraction was significantly shorter than the CMCT during muscle relaxation in healthy controls. However, in Parkinson's disease, the CMCT did not differ significantly between muscle relaxation and contraction. We consider that the central motor conduction pathway during muscle relaxation in Parkinson's disease is modified to be similar to that during muscle contraction in healthy subjects. Copyright 1999 Harcourt Publishers Ltd.

Journal Article↗
PubMed1999

Proteins recognized by antibodies against isolated cytological heterochromatin from rat liver cells change their localization between cell species and between stages of mitosis (interphase vs metaphase).

Heterochromatin in the cell nucleus seems to concentrate various proteins, such as Drosophila heterochromatin protein 1, which maintain the repressed state of gene expression. However, it still remains obscure how protein composition related to chromatin structure is different between heterochromatin and euchromatin in interphase nuclei. We isolated cytological heterochromatin from sonicated interphase nuclei obtained from rat liver cells and prepared antisera against it. The dense heterochromatic bodies seen in the preparation of intact nuclei were duplicated in a relatively pure form during the preparation of heterochromatin. In the sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis, differences between the fractions of heterochromatin and euchromatin were noted by their protein composition. Isolated heterochromatin was then digested by DNase after partial digestion with trypsin and its dense structure changed to become highly sensitive to DNase. The prepared antibodies reacted with the heterochromatin region of rat liver cell nuclei and isolated cytological heterochromatin; however, they did not react with euchromatin. Using immunohistochemistry, the antibodies bound to each cell nucleus in all tissues observed; some cell types were distinguished by their differential stainability (e.g. staining in the cytoplasm). Staining of the mitotic cells showed that the proteins recognized by the antibodies were localized in the cytoplasm and, in part, on the chromosomes. Based on the results of molecular cloning from rat liver cDNA library using the antibodies as a probe, it seemed that the antibodies mainly recognized two proteins similar to arginase and general vesicular transport factor p115, respectively. The results obtained from these experiments reveal that some proteins located in the heterochromatin of interphase liver cell nuclei seem to play important roles in condensing a portion of the chromatin structure during interphase and suggest that proteins composing heterochromatin might be changed according to cell types or the stage of the cell cycle.

Animals↗
PubMed1999

Isolated recurrence of granulocytic sarcoma of the brain: successful treatment with surgical resection, intrathecal injection, irradiation and prophylactic systemic chemotherapy.

We describe a 40-year-old male who developed an isolated recurrence of granulocytic sarcoma (GS) of the brain 2 years following successful treatment of acute myeloblastic leukemia (AML; M2). Computed tomography (CT) scans and magnetic resonance (MR) images demonstrated a homogeneously enhanced tumor mass in the left temporal lobe and massive peritumoral edema. There was no evidence of relapse in the bone marrow. The patient underwent an emergency surgical resection of the tumor. Five courses of injection with cytarabine and prednisolone through an Ommaya reservoir and whole brain irradiation (total 40 Gy) were performed. Furthermore, prophylactic systemic chemotherapy with cytarabine and etoposide was added. He has been in complete remission for 21 months. Our results, together with other reported cases, indicate that a favorable outcome could be obtained by intensive and combined treatment for an isolated recurrence of GS of the brain if the bone marrow remained in complete remission.

Adult↗
PubMed1999

T-cell activation, proliferation, and memory after cardiac transplantation in vivo.

OBJECTIVE: To study the response of alloantigen (H2Kb)-specific T cells to a H2b+ cardiac allograft in vivo. SUMMARY BACKGROUND DATA: The response of T cells to alloantigen has been well characterized in vitro but has proved more difficult to assess in vivo. The aim of these experiments was to develop a model of T-cell-mediated rejection where the response of T cells after transplantation of a cardiac allograft could be followed in vivo. METHODS: Purified CD8+ T cells from H2Kb-specific TCR transgenic mice (BM3; H2k) were adoptively transferred into thymectomized, T-cell-depleted CBA/Ca (H2k) mice. These mice were then transplanted with a H2Kb+ cardiac allograft. Using four-color flow cytometry, the proliferative response, modulation of activation markers, and potential cytokine production of the H2Kb-specific T cells was assessed after transplantation. RESULTS: Consistent rejection of H2Kb+ cardiac allografts required the transfer of at least 6 x 10(6) CD8+ H2Kb-specific T cells. Short-term analyses revealed that the transgenic-TCR+/ CD8+ T cells proliferated and became activated after transplantation of an H2Kb+ cardiac allograft. Fifty days after transplantation, the transgenic-TCR+/CD8+ T cells remained readily detectable, bore a predominantly memory phenotype (CD44hi), and rapidly produced interleukin 2 and interferon-gamma on in vitro restimulation. CONCLUSIONS: These data show that the activation of alloantigen-specific T cells can be followed in vivo in short-term and long-term experiments, thereby providing a unique opportunity to study the mechanisms by which T cells respond to allografts in vivo.

Animals↗
PubMed1999

Osteoplastic anterolateral vertebrotomy without fusion for multilevel cervical ossification of the posterior longitudinal ligament.

OBJECTIVE: To introduce a new method for osteoplastic anterolateral vertebrotomy without fusion to resect multilevel cervical ossification of the posterior longitudinal ligament. METHODS: A multilevel vertebral column graft containing portions of the intervertebral discs is cut with a microsurgical saw from the anterolateral part of the vertebra via a thin lateral gutter placed in advance. A sufficiently wide oblique operative field is provided for resection of the ossified ligament with this method, and only a narrow bony defect remains after simple replacement of the vertebral graft. Postoperatively, patients are allowed to walk, usually within 2 to 3 days, wearing simple cervical collars. RESULTS: Twelve patients underwent resection of the ossified ligaments in two to five vertebral bodies. Clinical results were satisfactory except in one patient, who died as a result of a pulmonary embolism that occurred 10 days after surgery. In all of the other patients, the vertebral column grafts were fused within a few months, and there were no graft-related problems. Postoperative lateral radiographs revealed that cervical alignment was preserved, with intervertebral mobility at the operated segment in flexion-extension views. CONCLUSION: The osteoplastic anterolateral vertebrotomy method provided a sufficiently wide operative field for satisfactory resection of multilevel cervical ossification of the posterior longitudinal ligament, simplifying graft replacement and postoperative patient care. The cervical alignment was preserved.

Adult↗
PubMed1999

Characterization of two novel retinoic acid-resistant cell lines derived from HL-60 cells following long-term culture with all-trans-retinoic acid.

Either all-trans-retinoic acid (RA) or vitamin D3 (VD) induces differentiation of the myeloid leukemia cell line HL-60. RA is available for the treatment of acute promyeloleukemia, although the development of resistance to the agent is a serious problem for differentiation-inducing therapy. To approach the mechanisms of resistance to RA, we developed two novel cell lines, HL-60-R2 and R9, which were subcloned after exposure to increasing concentrations of RA. The growth rate of HL-60-R2 cells was significantly increased by RA treatment, whereas the growth rate of HL-60-R9 was not affected. RA induces apoptosis in the parental HL-60 cells. The number of apoptotic cells, however, was not increased and nitroblue tetrazolium (NBT) reduction was not altered by 1 microM RA in either of the cloned cell lines. Treatment with VD induced monocytic differentiation and increased the expression of CD11b in HL-60 and HL-60-R9 cells, but not in HL-60-R2 cells. Flow cytometric and G-banding analysis demonstrated that R2 cells were near-triploid. The sequencing analysis revealed a deletion of three nucleotides in the sequence of the RAR alpha gene in HL-60-R9 cells, resulting in deletion of codon 286. No mutation was found in HL-60-R2 cells. Taken together, these data indicate that the resistance to RA is caused by the mutation in RAR alpha of HL-60-R9, but by other factor(s), which also affect the VD-response pathways, in HL-60-R2. The abnormal response to VD may be associated with the abnormal ploidy of the R2 cells.

Antineoplastic Agents↗
PubMed1999

Origin of hyperplastic epithelial cells in idiopathic collapsing glomerulopathy.

AIMS: Glomerular epithelial cell hypertrophy and hyperplasia are listed as the primary criteria for the diagnosis of collapsing glomerulopathy (CG), a distinct variant of focal segmental glomerulosclerosis. However, the extent of podocyte phenotypic alterations that occur in CG, and the origin of the hyperplastic epithelial cells remain to be established. METHODS AND RESULTS: Renal biopsy materials from seven out of three patients with CG were studied by serial section analysis for immunohistochemistry and electron microscopy. Markers for podocytes (PHM5 and synaptopodin), parietal epithelial cells (PECs: cytokeratin) and macrophages (CD68) were used for the immunohistochemistry. Multiple ultrathin sections from a total of 15 glomeruli, including some from patients with CG, were examined by electron microscopy. Glomerular adhesions occurred in 71% of the serially sectioned glomeruli taken from patients with CG. Hyperplastic epithelial cells were immunonegative for podocyte markers and CD68, but invariably immunopositive for cytokeratin. Electron microscopy revealed that detachment of the podocytes from involved glomerular capillary walls was extensive. Many of the detached podocytes appeared to be necrotic and apoptotic. In contrast, junctional complexes of desmosomes and zonula adherens connected hyperplastic epithelial cells to each other. Cilia were also often observed. CONCLUSIONS: The results of our ultrastructural and immunohistochemical study suggest that the hyperplastic epithelial cells observed in cases of CG are derived from PECs. Our results raise the possibility that PECs play a general role in covering glomerular tufts from which the podocytes have disappeared.

Adult↗
PubMed1999

Evaluation of autonomic influences on QT dispersion using the head-up tilt test in healthy subjects.

Our objective was to examine the autonomic influence on QT interval dispersion using the head-up tilt test in healthy subjects. RR and QT intervals, heart rate variability, and plasma norepinephrine concentration were measured in the supine position and tilting to 70 degrees for 20 minutes using a footboard support in 15 healthy male volunteers (mean age +/- SD: 28.0 +/- 4.5 years). The rate-corrected QT interval (QTc) was calculated using Bazett's formula, and QT and QTc dispersions were defined as the maximum minus minimum values for the QT and QTc, respectively, from the 12-lead ECG. Spectral analysis of the heart rate variability generated values for the low- and high-frequency powers (LF and HF) and their ratio (LF/HF). Compared with values obtained in the supine position, tilting significantly increased QT (P < 0.05) and QTc dispersion (P < 0.01), the LF/HF ratio (P < 0.0001), and plasma norepinephrine concentration (P < 0.0001), and significantly decreased HF (P < 0.0001). QTc dispersion was positively correlated with the LF/HF ratio and plasma norepinephrine concentration, and negatively correlated with HF. These results suggest that head-up tilt testing increases QT dispersion by increasing sympathetic tone and/or decreasing vagal tone in healthy subjects.

Adult↗
PubMed1999

[Study on the verotoxin-producing Escherichia coli--isolation of the bacteria from deer dung].

To identify the source and route of verotoxin-producing Escherichia coli (VTEC) infection in humans, we tried to isolate VTEC from fresh deer dung collected from free-range animals in two parks during the period from August 1997 to January 1998. The results are presented below. 1) VTEC were isolated from 21 of 200 deer dung samples (10.5%), consisting of 15 of 100 samples (15.0%) collected in park A and 6 of 100 samples (6.0%) collected in park B, suggesting that the incidence of VTEC isolation differs depending on location. 2) With respect to typing of verotoxin, the 21 isolated VTEC strains consisted of 10 strains (47.6%) as VT1 producer, 5 strains (23.8%) as VT2 producer, and 6 strains (28.6%) as double producer of both types. 3) With respect to serogroup of the isolated VTEC strains, 2 strains belonged to O128:H2.1 strain each belonged to the O8:H10, O128:H12, and O169:HUT groups. The remaining 16 strains failed to be identified as particular serotypes. Regarding local distribution of the serotype, in park A, 1 strain each belonged to the O128:H2, O8:H10, and O169:HUT groups. The remaining 12 strains did not clearly show particular serotypes. In park B, 2 strains belonged to O128:H2, and 4 strains failed to show particular serotypes. The remaining 1 strains showed autoagglutination. In conclusion, we isolated VTEC strains from deer that showed types of toxin and serogroups identical to those of human VTEC. Therefore, VTEC found in deer dung could well be a source of VTEC-infectious diseases in humans.

Animals↗
PubMed1999

[Efficacy of immunized milk for preventing viral infection].

This paper investigated the efficacy of passive protection provided by milk (immunized milk) against enterovirus infection in mice experimentally infected with enterovirus. Milk with a high antibody titer against six enterovirus serotypes was prepared from hyperimmunized goat. In vivo and in vitro experiments were performed and the results showed that immunized milk has an antiviral activity against enterovirus infection. Further observation was performed using Coxsackie B 3 virus (CVB 3). When immunized milk was orally applied to mice prior to oral inoculation with CVB 3, preventive effects against viral infection such as reduction of histopathological changes in the heart and reduced detection of the virus genome in the organs were seen. The antiviral effect was also indicated by the increase of CD4+T cells proportion in the i-IEL. The proportion of virus specific CD4+T cells was increased in mice treated with immunized milk, whereas no such increase was detected in control mice. These results suggest that oral application of immunized milk is not only capable of preventing viral infection but also induces specific immunological responses. These phenomena may play an important role in host defense mechanisms.

Animals↗
PubMed1999

[Prevalence and serotypes of verocytotoxin-producing Escherichia coli (VTEC) isolates from dairy cattle].

To clarify the source of infection and route of transmission of Verocytotoxin-producing Escherichia coli (VTEC) in humans, we collected fresh feces from healthy dairy cattle reared in Hokkaido, Fukushima, Kanagawa and Okinawa prefectures between June 1996 and March 1997, and attempted to isolate VTEC. The results are described below. 1) VTEC was isolated from 68 (27.1%) of 251 fecal samples tested. VTEC was isolated from 14 (28.0%) of 50 in Hokkaido, 13 (26.0%) of 50 in Fukushima, 20 (39.2%) of 51 in Kanagawa and 21 (21.0%) of 100 in Okinawa. There were no difference in the prevalence among the prefectures. 2) Toxin type and serotype of 85 isolates were determined. Thirty-three isolaties (38.8%) were classified into VT1 toxin and VT2 toxin, respectively, and 19 isolates (22.4%) were classified as the strain that produces both VT1 and VT2 toxins. The toxin types of these isolates were divided by serotypes. The VT1-producing isolates were the most frequent among O111:H-. The VT2-producing isolates included O2:H12, O2:H29, O2:H-, O82:H8, O82:HUT, O153:H19, O153:H42 and O153:H-. Among the isolates producing both VT1 and VT2 toxins, O153:H19 was relatively frequent. Based on findings that many bacterial strains coinciding with toxin types and serotypes of human-derived VTEC isolated from dairy cattle, it was suggested that dairy cattle are closely related to VTEC infection in human as a source of infection.

Animals↗
PubMed1999

[A case of systemic lupus erythematosus complicated by Nocardia farcinica].

We report a patient with systemic lupus erythematosus (SLE) complicated with nocardiosis. This case is very important that the complication of nocardiosis in SLE is very rare and the treatment to both SLE and nocardiosis is very difficult. A twenty-one-year old female was admitted to our hospital because of thoracic empyema and active lupus nephritis. Her medical history revealed that the diagnose of SLE was made when she was 18 with lymphocytopenia, proteinuria, positive antinuclear antibodies, and high titer of antibodies to native DNA. She was treated with prednisolne 60 mg daily and became better. Proteinuria appeared again in September 1995 and she was admitted to the former hospital. Renal biopsy proved diffuse proliferative glomeluronephritis (WHO IVb). She was treated with 1 g per day of methylprednisolone for 3 days and succeeded with 60 mg day of prednisolone. In early November she developed left chest pain and fever and chest X-ray demonstrated left pleural effusion. Antibiotics, antituberculosis, and antifungal therapy failed to subside her pleuritis and it turned to empyema. Then she was transferred to our hospital for further treatment. Nocardia farcinica was detected from the aspirated pleural fluid obtained at the former hospital. Drainage and intrathoracic impenem injection were effective. While long usage of minocycline was continued for the nocardiosis, 500 mg of cyclophosphamide pulse therapy to lupus nephritis was administrated. Two weeks later a new pulmonary lesion with left chest pain and liver abscess developed. Administration of trimethoprim-sulfamethoxazole subsided the nocardiosis. She was discharged with 1 g per day of proteinuria the prescribed 13 mg per day of prednisolone and continuous TMP-SMZ intake for nocardial infection. When immunosuppressive therapy must be given to the immunocompromised host, a more potent therapy must be added to avoid infection.

Adult↗
PubMed1999

Nummular eczema: An addition of senile xerosis and unique cutaneous reactivities to environmental aeroallergens.

BACKGROUND: The pathogenesis of nummular eczema (NE) is still unknown. It often develops on the lower legs of elderly individuals with xerotic changes during the winter months. Such winter exacerbation is also observed in atopic dermatitis, in which there is a high incidence of cutaneous immune reactivities against environmental aeroallergens. OBJECTIVE: Because of the total lack of information about skin reactivities in NE patients, we performed immunological as well as functional studies in their uninvolved skin. METHOD: Prick tests and chamber scarification patch tests for representative aeroallergens were conducted on the flexor surface of the forearm in 26 NE patients, in 21 age-matched elderly persons without NE and in 43 healthy young controls. RESULTS: We found that the elderly subjects, regardless of their background, showed a significantly higher immediate skin reactivity to Candida albicans than the young controls. In contrast, patch testing revealed that, unlike the age-matched elderly subjects who showed a decrease in incidence of positive patch test reactions, the NE patients retained delayed contact sensitivity at a level comparable to that of the young healthy controls. They showed a significantly higher percentage of positive patch test reactions to Dermatophagoides farinae allergen (46%) and house dust allergen (35%) than the age-matched controls. Moreover, they also showed a significantly higher percentage of delayed hypersensitive reactions to C. albicans allergen (85%) than the age-matched controls (48%). Noninvasive functional assessment of the stratum corneum (SC) in unaffected skin areas of the lower legs in 8 NE patients demonstrated that, though the water barrier function of the SC was comparable to that of the age-matched controls, they showed a significantly lower hydration state of the SC than the age-matched controls. CONCLUSION: The xerotic skin of elderly individuals facilitates the development of cracking and fissuring of the skin surface in dry and cold winter. Such damage in the SC is sometimes aggravated by inadvertent scratching due to pruritus, allowing skin permeation of various environmental allergens. They may induce eczematous changes in those with preserved adequate delayed hypersensitivity despite their advanced age.

Aged↗
PubMed1999

Endogenous IL-1alpha from systemic sclerosis fibroblasts induces IL-6 and PDGF-A.

It is reported that fibroblasts derived from clinically affected skin areas of patients with systemic sclerosis (SSc) have the ability to overproduce several cytokines and growth factors (i.e., IL-6, PDGF), an ability that might be involved in the pathogenesis of SSc. We have previously shown that the expression of IL-1alpha was constitutively observed in SSc fibroblasts, whereas this was not detected in normal fibroblasts. Although it was suggested that the aberrant IL-1alpha production could be associated with the fibrogenic phenotype of SSc fibroblasts, little is known about the roles of IL-1alpha in SSc fibroblasts. IL-1alpha induced IL-6 and PDGF-A, which are potent stimulators of collagen production and proliferation in normal fibroblasts. This article examines the proposal that IL-6 and PDGF-A are elevated through the action of endogenous IL-1alpha in SSc fibroblasts. An antisense oligodeoxynucleotide complementary to IL-1alpha mRNA was used to suppress endogenous IL-1alpha. Inhibition of endogenous IL-1alpha led to decreased levels of IL-6 and PDGF-A expression in SSc fibroblasts. Moreover, the blocking of the IL-6 response using anti-IL-6 antibody resulted in a significant reduction of procollagen type I in cultured SSc fibroblasts. These results suggest that endogenous IL-1alpha expressed by SSc fibroblasts may play a key role in the abnormal function of SSc fibroblasts through the expression of IL-6 and PDGF-A.

Base Sequence↗