Biomedical subjects

H Hara

Publications and source records attributed to H Hara.

At least 271 records · Page 15Linked to original sources

PubMed1997

Molecular cloning and characterization of a novel human receptor protein tyrosine phosphatase gene, hPTP-J: down-regulation of gene expression by PMA and calcium ionophore in Jurkat T lymphoma cells.

A novel cDNA encoding a 1436 aa protein was cloned using a PCR system with degenerate primers. This new gene, hPTP-J, was found to encode a PTP protein consisting of an extracellular region containing an MAM (meprin, A5, mu)-like domain, an immunoglobulin-like domain, four fibronectin type-III repeats, a transmembrane region, and a cytoplasmic region containing two tandemly repeated PTP domains hPTP-J is thus considered to be a new member of the type II receptor PTP (RPTP) subfamily, like RPTP mu and RPTP kappa. hPTP-J gene expression was strongly detected in skeletal muscle and moderately detected in the prostate, pancreas, placenta, and heart, but was only weakly detected in the peripheral blood lymphocytes, thymus, and spleen even though gene expression was relatively high in the Jurkat T lymphoma cell line. Moreover, hPTP-J gene expression was down-regulated after Jurkat cells were stimulated by either PMA or calcium ionophore. Based on these findings, it is suggested that some signaling pathways mediated by PMA and/or intracellular calcium are involved in the regulation of hPTP-J gene expression in Jurkat cells.

Amino Acid Sequence↗

PubMed1997

Proliferating cell nuclear antigen expression in the gallbladder with pancreaticobiliary maljunction.

BACKGROUND AND OBJECTIVE: To clarify the histogenesis of cancer of the gallbladder of the patients with pancreaticobiliary maljunction (PBMJ), the proliferating cell activity of the epithelium of gallbladder was examined. METHODS: A total of 21 patients with pancreaticobiliary maljunction [8 with gallbladder cancer (MCA group) and 13 without cancer (M group)] were studied using immunohistochemical staining with a monoclonal antibody to the proliferating cell nuclear antigen (PCNA). The 23 gallbladder cancer patients without PBMJ (CA group) and 10 patients with normal gallbladders (N group) were also examined as controls. RESULTS: The PCNA-positive rates of non-cancerous epithelium of the gallbladder in patients with PBMJ (14.2% in MCA group and 11.6% in M group) were significantly higher than those without PBMJ (3.9% in CA group and 1.5% in N group). CONCLUSION: The high proliferating cell activity of epithelium of the gallbladder may be an explantation for the high incidence of gallbladder cancer in patients with pancreaticobiliary maljunction.

Aged↗

PubMed1997

Neuronal nitric oxide synthase mutant mice show smaller infarcts and attenuated apparent diffusion coefficient changes in the peri-infarct zone during focal cerebral ischemia.

Diffusion-weighted MRI at 2 T was used to monitor and assess tissue damage after permanent middle cerebral artery occlusion (MCAO) in wild-type (WT) and mice deficient in nitric oxide synthase gene expression (nNOS-). The ischemic lesion was evaluated 3 h after occlusion and subdivided into the lesion core and peri-infarct zone based on the magnitude of the apparent diffusion coefficient (ADC) change. Infarct volume, measured by using histochemical staining 24 h after MCA occlusion, correlated best with MRI infarct volume as assessed by an ADC threshold of 25% decrease from baseline at 3 h. For ADC thresholds of greater than 25% decrease, lesion size was not significantly different in nNOS- and WT mice. However, brain tissue showing ADC decreases of 10-25% was significantly smaller in the ipsilateral hemisphere of mutants (27 +/- 2% and 21 +/- 2% in WT and nNOS-, respectively; P < 0.05). These findings occurred independently of infarct volume and are consistent with a smaller peri-infarct zone in nNOS- mice. We postulate that the smaller peri-infarct zone is a reflection of less severe metabolic disturbance after ischemia in nNOS- mice, possibly related to diminished production of nitric oxide (NO) or a related product. We conclude that magnetic resonance techniques previously used to assess ischemic damage in larger animals can be extended to the mouse, raising the possibility that the molecular mechanisms leading to ischemic damage can be examined by using genetically engineered mice.

Animals↗

PubMed1997

Expression of CD23 in the germinal center of thymus from myasthenia gravis patients.

In order to investigate a pathogenic role of germinal centers which appear in the hyperplastic thymus of myasthenia gravis (MG) patients, we performed an immunohistochemical study using various monoclonal antibodies including CD23. In contrast with tonsilar germinal centers from non-MG individuals, CD23 was strongly and diffusely expressed in the whole area of germinal centers of MG thymi, including the outer zone. In addition, we measured the serum level of soluble CD23 (sCD23) in MG patients at various clinical stages. The high serum sCD23 levels, which were noted in the unthymectomized patients, fell to within normal range over 5 years after thymectomy, and the decline of serum sCD23 correlated well with clinical improvement. CD23 is thought to be responsible for preventing unselected germinal center B cells from entering apoptosis and, in turn, leads to the survival of auto-reactive B cell clones.

Antigens, CD19↗

PubMed1997

Follicular dendritic cell tumor of the mesentery.

Follicular dendritic cell (FDC) tumor is an exceedingly rare malignant neoplasm and occurs mainly in the cervical lymph nodes. We report a mesenteric FDC tumor occurring in a 66-year-old female, that manifested with intraabdominal multifocal recurrence 7 years after resection of the primary tumor. Histologically, both primary and recurrent tumors were composed of oval to spindle cells with paley eosinophilic cytoplasms, indistinct cell borders, round to elongated nuclei with clear or finely dispersed chromatin, and medium to large nucleoli. Characteristically, the tumor cells were growing in sheets, fascicles, and sometimes in whorls and a storiform pattern. In addition, focal necrosis, nuclear pleomorphism and abnormal mitoses were also observed. The neoplastic cells were intimately admixed with small lymphocytes. The diagnosis was confirmed by positive immunoreactivity with CD21 and CD35 antibodies and by ultrastructural demonstration of convoluted interdigitating cell processes connected by scattered desmosome-like junctions. Although our case showed a low proliferative activity evaluated by MIB-1, multifocal recurrence has occurred. The clinicopathologic features and differential diagnosis of FDC tumors are discussed with the review of the literature.

Aged↗

PubMed1997

The U3 region of the long terminal repeat of a subgroup A transformation-defective rous sarcoma virus (tdPH2010) converts a noncytopathic virus to a cytopathic virus.

The molecular basis of the cytopathic effects (CPE) of the transformation-defective avian retrovirus mutant, tdPH2010, was studied. tdPH2010 is a subgroup A virus isolated from the Schmidt-Ruppin (NY) subgroup A strain (SRA(NY)). Subgroup A avian retroviruses are generally considered noncytopathic. Integrated tdPH2010 was molecularly cloned from infected quail cells. A noncytopathic, transformation-defective control strain, BSU, was created by deleting the src gene from the molecularly cloned wild type SRA(NY) virus. Chimeras between tdPH2010 and BSU were constructed and viruses were recovered from transfected chick embryo fibroblasts. Growth curves of cells infected with chimeric viruses indicated that the long terminal repeat (LTR) of tdPH2010 converts BSU to a cytopathic virus. Nucleotide sequencing revealed two point mutations unique to tdPH2010 in the U3 region of LTR at positions -126 and -23 from the transcription start site. Both mutations were located inside or near the promoter/enhancer elements of U3. The mutation at -126 (G to T) converted one of the very well-conserved pentanucleotide repeat (PRE) motifs from GGTGG to GGTGT. The other at -23 (G to A) is located next to the TATA box. The G at this position is conserved in all other known avian retrovirus promoters.

Animals↗

PubMed1997

Second allogeneic bone marrow transplantation for post-transplant leukemia relapse: results of a survey of 66 cases in 24 Japanese institutes.

To assess the consequence of second BMT (BMT2) for leukemia relapse after allogeneic BMT, we analyzed the clinical course of 66 recipients who were treated by BMT2 in Japan. Diagnoses included 29 ANLL, 27 ALL, six CML and four MDS. Durations between the first BMT (BMT1) to relapse and BMT1 to BMT2 were 13.5 +/- 13.7 months and 17.4 +/- 13.9 months, respectively. Donors for BMT2 were replaced in 11 cases. Thirty-one patients were in CR (or CP) at BMT2. Earlier deaths were observed in those who received BMT2 within 12 months after BMT1, mostly caused by regimen-related toxicity and infections. Overall leukemia-free survival rate was 28% at 2 years and 16% at 4 years. Factors influencing the poor prognosis after BMT2 were early (<6 months) relapse, early (<12 months) BMT2, not in remission at BMT2, and ALL. Intensified conditioning did not affect either remission duration or LFS. Among the 39 cases observed for more than 100 days, 18 developed chronic GVHD (cGVHD) and showed longer remission duration than those without cGVHD. Our analysis indicates that BMT2 as treatment for leukemia relapse is effective in selected cases, and exploration of pre-BMT treatment and post-BMT immunotherapy is warranted.

Adolescent↗

PubMed1997

Association of intraabdominal fat and carotid atherosclerosis in non-obese middle-aged men with normal glucose tolerance.

OBJECTIVE: To investigate the association of visceral fat accumulation and carotid atherosclerosis in non-obese men with normal glucose tolerance. SUBJECTS: Ninety eight middle-aged men with normal glucose tolerance who had a body mass index (BMI) < 25 kg/m2 (mean age: 52.6 y, mean BMI: 22.5 kg/m2). METHOD: Using ultrasonography, we simultaneously measured the abdominal fat distribution and intima-media thickness (IMT) of the carotid artery wall. RESULTS: Pmax, an index of the absolute amount of visceral fat, was found to be significantly correlated with IMT and fasting Insulin concentration (r = 0.37, P < 0.005 and r = 0.54, P < 0.0001). Abdominal wall fat index (AFI), the ratio of maximum thickness of the preperitioneal fat and the minimum thickness of the subcutaneous fat, was not correlated with IMT. CONCLUSION: Visceral fat accumulation may play a role in the progression of atherosclerosis even in non-obese middle-aged men.

Abdomen↗

PubMed1997

Sexual function and clinical features of patients with Klinefelter's syndrome with the chief complaint of male infertility.

In this report, we present the overall sexual function and clinical features of patients with Klinefelter's syndrome with the chief complaint of male infertility. The study consisted of 40 patients with a control group of 55 infertile non-azoospermic males with a normal 46,XY karyotype who visited the Reproduction Center of Toho University Hospital during the 5.5-year period between January 1991 and June 1996 with the chief complaint of male infertility. Among the 40 patients with Klinefelter's syndrome, 38 cases were pure 47,XXY, one case was 47,XXY with a pericentric inversion of chromosome 9 and one case was a mosaic of 46,XY/47,XXY(2:28). Thirty-nine of these 40 patients were azoospermic and one (47,XXY) had severe oligoasthenozoospermia. The sexual function of the patients was evaluated according to their responses to a preliminary questionnaire devised by our department. There was no significant difference in the frequency of sexual function disturbances between the patients with Klinefelter's syndrome and the control group (67.5% vs. 60.0%; chi 2 analysis; p = 0.454). The mean frequency of sexual intercourse per month in the patients with Klinefelter's syndrome was significantly higher than in the control group (4.4 +/- 2.8 vs 3.3 +/- 1.6: Welch's t-test, p < 0.05). A possible explanation for this variation may lie in the fact that many of these patients were diagnosed with azoospermia poor to the administration of the questionnaire and may have wished to continue to have relations as a couple.

Adult↗

PubMed1997

Analysis of T-cell receptor beta of the T-cell clones reactive to the human PDC-E2 163-176 peptide in the context of HLA-DR53 in patients with primary biliary cirrhosis.

T-cell-mediated autoimmune mechanisms are considered to be involved in the pathogenesis of primary biliary cirrhosis (PBC). In the previous study, we identified the immunodominant T-cell epitope on the E2 component of pyruvate dehydrogenase complex (PDC-E2) in patients with PBC who have HLA-DRB4*0101. In this report, we revealed that the frequency of the T cells reactive to the human PDC-E2 163-176 peptide is significantly increased in the peripheral blood of patients with PBC as compared with healthy subjects. We also confirmed that these T cells were all restricted with HLA-DRB4*01 (DR53) by using HLA-DR-transfected L cells. These results together with the evidence that the immunodominant B-cell epitope overlaps with the human T-cell epitope of the PDC-E2 antigen indicate that the T cells reactive to this epitope are closely associated with the pathogenesis of PBC at least in patients who have HLA-DR53. Therefore, we analyzed the T-cell receptor (TCR) Vbeta sequence of the five different T-cell clones and the three T-cell clones derived from three patients with PBC and healthy subjects, respectively, which are reactive to the human PDC-E2 163-176 peptide in the context of HLA-DR53. The Vbeta- and the Jbeta-gene usages were diverse among the T-cell clones (Vbeta11-Jbeta1.4, Vbeta8-Jbeta1.2, Vbeta12-Jbeta2.1, Vbeta10-Jbeta1.5, and Vbeta20-Jbeta2.1) in patients with PBC. By contrast, in the third complementarity determining region (CDR3), G was frequently found and GXG or GXS motif was identified in all T-cell clones. Moreover, RGXG motif was found in three clones generated from two patients. In healthy subjects, the Vbeta- and the Jbeta-gene usages were also diverse, and GXG and RGXG motif were found. These results indicate that the T cells may recognize the ligand (the human PDC-E2 163-176 peptide/HLA-DR53 complex) using the limited motif in the CDR3 region and that the design of CDR3-specific immunotherapy would be possible using these motifs.

Amino Acid Sequence↗

PubMed1997

Attenuation of transient focal cerebral ischemic injury in transgenic mice expressing a mutant ICE inhibitory protein.

We used transgenic mice expressing a dominant negative mutation of interleukin-1 beta converting enzyme (ICE) (C285G) in a model of transient focal ischemia in order to investigate the role of ICE in ischemic brain damage. Transgenic mutant ICE mice (n = 11) and wild-type littermates (n = 9) were subjected to 3 h of middle cerebral artery occlusion followed by 24 h of reperfusion. Cerebral infarcts and brain swelling were reduced by 44% and 46%, respectively. Neurological deficits were also significantly reduced. Regional CBF, blood pressure, core temperature, and heart rate did not differ between groups when measured for up to 1 h after reperfusion. Increases in immunoreactive IL-1 beta levels, observed in ischemic wild-type brain at 30 min after reperfusion, were 77% lower in the mutant strain, indicating that proIL-1 beta cleavage is inhibited in the mutants. DNA fragmentation was reduced in the mutants 6 and 24 h after reperfusion. Hence, endogenous expression of an ICE inhibitor confers resistance to cerebral ischemia and brain swelling. Our results indicate that downregulation of ICE expression might provide a useful therapeutic target in cerebral ischemia.

Animals↗

PubMed1997

[3H]L-NG-nitroarginine binding after transient focal ischemia and NMDA-induced excitotoxicity in type I and type III nitric oxide synthase null mice.

We investigated the density and distribution of nitric oxide synthase (NOS) binding by quantitative autoradiography using [3H]L-NG-nitroarginine ([3H]L-NNA) after transient focal ischemia or intrastriatal injection of N-methyl-D-aspartate (NMDA) in wild-type (SV-129 and C57black/6) and type I (neuronal) and type III (endothelial) NOS-deficient mice. The middle cerebral artery (MCA) was occluded by an intraluminal filament for 3 h followed by 10 min to 7 days of reperfusion. Specific [3H]L-NNA binding, observed in the wild-type and type III mutant mouse at baseline, increased by 50-250% in the MCA territory during ischemia and the first 3 h of reperfusion. The density of binding sites (Bmax), but not the dissociation constant (Kd), increased significantly during the ischemic period as did type I NOS mRNA as detected by quantitative reverse transcription polymerase chain reaction. [3H]L-NNA binding after intrastriatal NMDA injection also increased by 20-230%. In the type I NOS-deficient mouse, [3H]L-NNA binding was low and only a very small increase was observed after ischemia or excitotoxicity. Under conditions of this study, [3H]L-NNA did not bind to type II NOS as there was no difference in the distribution or density of [3H]L-NNA binding in the rat spleen obtained after lipopolysaccharide treatment despite induction of NOS type II catalytic activity. Our data suggest that an ischemic/excitotoxic insult up-regulates type I NOS gene expression and [3H]L-NNA binding and that this up-regulation may play a pivotal role in the pathogenesis of ischemic/excitotoxic diseases.

Animals↗

PubMed1997

Stimulation of exocrine pancreatic secretion by soybean trypsin inhibitor does not depend on the masking of luminal trypsin activity in rats that have bile-pancreatic juice diverted into the ileum.

We reported previously that dietary proteins stimulate pancreatic secretion by a mechanism not involved in masking trypsin activity in rats that have bile-pancreatic juice (BPJ) diverted from the proximal small intestine for 7 days. However, BPJ in the distal small intestine is possibly responsible for the stimulation of pancreatic secretion in chronic BPJ-diverted rats. To examine whether the BPJ-dependent mechanism operates in the distal small intestine of chronic BPJ-diverted rats, we investigated pancreatic responses after inhibition or removal of pancreatic trypsin activity in the distal small intestine of conscious rats. Duodenal instillation of soybean trypsin inhibitor (SBTI), which is a proteinaceous trypsin inhibitor, stimulated pancreatic secretion in the chronic BPJ-diverted rats, whereas a nonpeptidic trypsin inhibitor, FOY 305, did not. Ileal administration of both trypsin inhibitors did not enhance pancreatic secretion in the diverted rats. Exclusion of luminal BPJ from the distal small intestine was also ineffective in causing pancreatic exocrine secretion in the chronic BPJ-diverted rats. These observations reveal that ileal BPJ does not contribute to the stimulation of pancreatic secretion in rats that have BPJ chronically diverted into the ileum, as in intact rats, and that a duodenal instillation of SBTI stimulates pancreatic secretion as a protein, and not as a trypsin inhibitor.

Animals↗

PubMed1997

A case of X-linked alpha-thalassemia/mental retardation syndrome: analysis of hemoglobin by an automated glycated hemoglobin analyzer.

A 5-year-old male patient with X-linked alpha-thalassemia/mental retardation syndrome is reported. He showed multiple minor anomalies including characteristic facial abnormalities, alpha-thalassemia, severe mental retardation, and hypogonadism. Analysis of his hemoglobin by high performance liquid chromatography using an automated glycated hemoglobin analyzer revealed an abnormal peak. Identification of an abnormal peak by an automated glycated hemoglobin analyzer will aid in the diagnosis of patients with X-linked alpha-thalassemia/mental retardation syndrome.

Abnormalities, Multiple↗

PubMed1997

[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↗

PubMed1997

[A case of an elderly patient with dementia and gait disturbance associated with influenza].

We report a case of progressive dementia and prolonged gait disturbance correlated with influenza A/H3N2 infection in 91-year-old female patient, admitted because of in ability to take care of herself due to aging and cerebral infarction. At admission, conversation and comprehension were not significantly impaired, and she was able to walk by herself. Flu symptoms such as high grade fever, chills, arthralgia, and cough appeared after a short stay at home. Influenza A/ H3N2 was confirmed serologically. Delirium occurred on the sixth day after influenza onset, persisted for three weeks, followed by recovery. Dementia symptoms such as memory defects and disorientation continued and did not improve. Due to this febrile episode, she was unable to walk unassisted. The results of computed tomography performed before and after the influenza episode were unremarkable for additional cellebro-vascular events during the observed period. Influenza infection may be an important risk factor for reducing the quality of life in the elderly. In geriatric cases, influenza should not be treated as a mere transient illness, but rather one which has important consequences for the elderly population, including the possibility of life threatening complications.

Aged↗

PubMed1997

A promoter for the first nine genes of the Escherichia coli mra cluster of cell division and cell envelope biosynthesis genes, including ftsI and ftsW.

We constructed a null allele of the ftsI gene encoding penicillin-binding protein 3 of Escherichia coli. It caused blockage of septation and loss of viability when expression of an extrachromosomal copy of ftsI was repressed, providing a final proof that ftsI is an essential cell division gene. In order to complement this null allele, the ftsI gene cloned on a single-copy mini-F plasmid required a region 1.9 kb upstream, which was found to contain a promoter sequence that could direct expression of a promoterless lacZ gene on a mini-F plasmid. This promoter sequence lies at the beginning of the mra cluster in the 2 min region of the E. coli chromosome, a cluster of 16 genes which, except for the first 2, are known to be involved in cell division and cell envelope biosynthesis. Disruption of this promoter, named the mra promoter, on the chromosome by inserting the lac promoter led to cell lysis in the absence of a lac inducer. The defect was complemented by a plasmid carrying a chromosomal fragment ranging from the mra promoter to ftsW, the fifth gene downstream of ftsI, but not by a plasmid lacking ftsW. Although several potential promoter sequences in this region of the mra cluster have been reported, we conclude that the promoter identified in this study is required for the first nine genes of the cluster to be fully expressed.

Bacterial Proteins↗

PubMed1997

Serial computed tomographic evaluation in desquamative interstitial pneumonia.

BACKGROUND: Desquamative interstitial pneumonia (DIP) may represent the early stage and usual interstitial pneumonia (UIP) the late stage of the same disease. The purpose of this study was to evaluate the computed tomographic (CT) features of DIP, to evaluate the changes in pattern and extent of disease over time, and to determine whether the appearances of DIP on the CT scan change to those of UIP during follow up. METHODS: Sequential CT evaluation was conducted on eight patients with DIP over a mean (SD) follow up period of 3.2 (1.3) years (range 1.6-6.5). The relative extents of ground glass and honeycombing were determined from serial CT scans. Changes in the extent and appearance of the disease were examined in paired anatomically comparable CT sections. RESULTS: Common features on the CT scans of patients with DIP were a homogeneous increase in lung attenuation (n = 5), linear areas of attenuation (n = 5), relatively well preserved lung architecture (n = 5), and the presence of small cysts (n = 6). Uncommon features were architectural distortion (n = 3), and traction bronchiectasis (n = 1). In six patients with DIP with cystic spaces these did not change with time in three cases, in two they regreased, and in one patient they increased. Open lung biopsy samples from patients with DIP with many cystic lesions showed dilated alveolar ducts and bronchioles and/or pulmonary cysts, as well as numerous macrophage-filled air spaces and mild fibrosis, but no typical honeycomb cysts were seen. CONCLUSIONS: Some of the microcysts in DIP are different from the honeycomb cysts seen in UIP, and some of the cysts seen in patients with DIP resolve with time. DIP does not progress to UIP in the short term.

Biopsy↗