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Biomedical subjects

H Miwa

Publications and source records attributed to H Miwa.

At least 91 records · Page 5Linked to original sources

Epithelial-mesenchymal interaction in gastric mucosal restoration.

In this review article we discuss the role of growth factors in gastric ulcer healing using an in vitro wound repair model with gastric epithelial and mesenchymal cells. Several growth factors accelerate gastric epithelial and mesenchymal wound healing in vitro with acceleration of cell migration and proliferation. Epidermal growth factor, transforming growth factor-alpha (TGFalpha), hepatocyte growth factor, and insulin accelerate predominantly gastric epithelial wound healing; and TGFbeta and basic fibroblast growth factor predominantly accelerate gastric mesenchymal wound healing. Platelet-derived growth factor-betabeta and insulin-like growth factor-1 (IGF-1) accelerate both significantly. Among these growth factors, IGF-1 produced from fibroblasts plays a key role in the gastric epithelial-mesenchymal interaction during the process of gastric wound healing.

Animals↗

Expression of B cell-associated transcription factors in B-cell precursor acute lymphoblastic leukemia cells: association with PU.1 expression, phenotype, and immunogenotype.

B-lymphocyte development progresses through discrete stages characterized by regular DNA rearrangements of the immunoglobulin (Ig) loci that lead to the transcription of Ig genes and expression of B-cell antigen receptors. These developmental processes can also be distinguished by the expression of specific cell-surface markers. Therefore, rearrangement of the Ig, T-cell receptor (TCR) genes, and surface markers are generally considered as useful markers of the B- and T-cell lineage in lymphoproliferative disorders. However, concomitant rearrangement of Ig and TCR genes (double genotype) has been reported in the most immature lymphoid malignancies (lineage promiscuity), mainly in B-cell precursor acute lymphoblastic leukemia (pre-B ALL), but the mechanism is not fully understood. DNA rearrangements and specific cell-surface markers are regulated by several specific transcription factors. To better characterize the lineage promiscuity, we studied the relationship among the expression of lymphoid-associated transcription factors, phenotype, and immunogenotype. Rearrangement of the Ig light chain kappa gene was found in 37% of pre-B ALL samples and in all B-cell chronic lymphocytic leukemia (B-CLL) samples. Rearrangement of TCR gamma gene was shown in 40% of pre-B ALL samples but was not detected in any of the B-CLL samples. Among the tested B cell-associated transcription factors, Pax5 and E47 genes were expressed in all pre-B ALL and B-CLL samples. RAG-1 gene was expressed in all pre-B ALL samples but not in the B-CLL samples. Oct-2 gene was expressed in 82% of pre-B ALL and all B-CLL samples. The expression of PU.1 gene was shown in 56% of pre-B ALL but not in the B-CLL samples. Interestingly, the samples of pre-B ALL, which did not express the PU.1 gene, showed a significantly high frequency of TCR gamma gene rearrangement. This phenomenon was not found with Oct-2 gene expression. These findings suggest that absence of PU.1 expression may result in lineage promiscuity, such as the simultaneous rearrangements of Ig and TCR genes in pre-B ALL cells.

Adult↗

[Anosognosia for hemiplegia in a patient with pontine infarction].

We report a patient with anosognosia for hemiplegia associated with a right pontine infarction. A 51-year-old woman with histories of hypertension and diabetes mellitus was admitted because of weakness of her left upper and lower extremities. On neurologic examination, she was alert and oriented without dementia. Visuospatial hemineglect was not present. Hemiparesis of her left upper and lower extremities was noted. Her brain MRIs showed a large infarction in the right pons. On admission, she could recognize her illness but was indifferent to her hemiplegia, so she said that there was not well-off for her life. Two weeks after the onset, her neurological symptoms gradually improved. Simultaneously, her interest in her hemiparesis increased. We proposed that, in the present patient, anosognosia for hemiplegia was caused by the pontine infarction. Since pontine anosognosia for hemiplegia has been rarely reported to date, it is expected that the findings of the present patient will be useful to the better understanding of mechanisms underlying anosognosia.

Agnosia↗

Immunophenotypic and genotypic characterization of nasal lymphoma with polymorphic reticulosis morphology.

Nasal lymphoma with polymorphic reticulosis (PR) morphology is now categorized as T/natural killer (T/NK) cell lymphoma. In this study, immunophenotypes and genotypes of proliferating cells in 21 cases with PR were examined. The patients included 13 men and 8 women ranging in age from 20 to 74 (median 37) years. All patients presented with lesions in the upper respiratory tract, mostly in the nasal cavity. Histological specimens obtained from the primary lesions (19 cases) and metastatic cervical lymph nodes (2 cases) were used for analyses. Histologically, polymorphous proliferation was found in 20 cases, and these were thus diagnosed as PR. A monomorphous pattern was found in the remaining last case. Immunohistochemical analysis revealed that the proliferating cells were CD56 (123C3)+ and/or CD16 (2H7)+, TIA-1+ and frequently stained CD3 epsilon+. Tumor cells were frequently stained positively with monoclonal antibodies (mAbs) for T lymphocytes, but were negative for T-cell receptor (TCR) beta and delta chain expression. In situ hybridization analysis using an Epstein-Barr virus-encoded early RNA 1 (EBER-1) probe revealed positive signals in 13 of the 15 cases examined. Southern blotting analysis for clonality of the Epstein-Barr virus (EBV) genome in 12 positive cases confirmed the presence of monoclonal proliferation in 7 cases. The pattern of TCR gamma chain gene rearrangement was examined by PCR analysis of DNA from tumor tissues by the denaturing gradient gel electrophoresis method. The results demonstrated no clonal rearrangement in any of the 21 cases examined, including 7 cases with proven clonal proliferation of EBV-infected cells, indicating the absence of T-cell clones. Our findings strongly suggested that nasal T-cell lymphoma is in fact a NK cell lymphoma.

Adult↗

Risk of non-Hodgkin's lymphoma in patients with hepatitis C virus infection.

Hepatitis C virus (HCV) has been suggested to play an etiological role in the development of B-cell non-Hodgkin's lymphoma (NHL) in Italy. However, another study in Scotland questioned increased risk of development of NHL in patients with chronic HCV infection. A total of 2,162 patients admitted to 3 hospitals in Osaka, where the incidence of HCV-related hepatitis is highest in Japan, during the period from 1957 to 1997 were followed up from the date of diagnosis of chronic HCV-related hepatitis until 30 October 1997. Overall, 12,404.5 person-years of observation were accrued with a follow-up period ranging from 0.25 to 40.4 (average 5.74) years. NHL of the B-cell type developed in 4 patients. The interval between onset of chronic HCV and NHL ranged from 6 to 36 (median 13) years. Expected number of cases of NHL in the sex-, age- and calendar year-matched general population was 1.90, which gave a relative risk (RR) of 2.10 (95% confidence interval 0.57-5.38; p = 0.247). Taking the much higher RR for hepatocellular carcinoma among patients with HCV infection into account, chronic HCV infection was considered to be moderately associated with increased risk of NHL.

Adolescent↗

Low BCL-2 expression in acute leukemia with t(8;21) chromosomal abnormality.

In de novo t(8;21) AML which shows terminal neutrophilic differentiation, the BCL-2 expression was found to be significantly lower than that in types of other AML regardless of the phenotypic differentiation status. An inverse correlation between BCL-2 expression and the S/G2/M population cells was observed in AML. The S/G2/M population in t(8;21)AML was larger than in the other types of AML. In t(8;21)AML, spontaneous apoptosis after a 12-h liquid culture was prominent, and the autonomous DNA synthesis after a 72-h liquid culture was low. G-CSF and IL-5 promoted the colony formation of t(8;21)AML cells. The data suggest that, in vivo, the low BCL-2 in t(8;21)AML induced entry of cells from the G0/G1 phase to S phase, but the cells easily die by apoptosis, in vitro. The low BCL-2 expression and the supportive effects of G-CSF and IL-5 in t(8;21)AML is thought to be a key phenomenon which might be related to the formation of the in vivo blood picture, such as prominent neutrophilic differentiation and eosinophilia. Cellular extracts from t(8;21)AML cell line Kasumi-1 bound to both the AML1 and CRE binding sites in the bcl-2 promoter, but none of the cellular extracts from de novo t(8;21)AML bound to either of these sites. The DNA binding activity of transactivators in de novo t(8;21)AML is different from that in Kasumi-1 cells probably due to the phosphorylation status.

Acute Disease↗

Expressions of four major protein Ser/Thr phosphatases in human primary leukemic cells.

Activity and expression of four major protein serine/threonine (Ser/Thr) phosphatases, protein phosphatase type 1 (PP1), protein phosphatase type 2A (PP2A), protein phosphatase type 2B (PP2B) and protein phosphatase type 2C (PP2C) were evaluated in normal peripheral leukocytes, and in various leukemic cells from patients with acute myelogenous leukemia (AML), common acute lymphocytic leukemia (cALL), or chronic lymphocytic leukemia (CLL). PP1 was the most abundant phosphatase in blood cells, and relative abundance of each phosphatase was: PP1 > PP2A > PP2B approximately = PP2C. PP1 activity and its expressions were higher in blasts of AML-M4 and -M5 than in cells of AML-M1, cALL and CLL. PP2A activity and its expression were higher in blasts of AML-M3, -M4 and -M5 than in cells of AML-M1, cALL and CLL. Activity and expression of both PP1 and PP2A in normal monocytes were highest, and PP2A activity in normal neutrophils was lowest among normal leukocytes. PP2B activity and its expression were higher in blasts of AML-M2, -M3 and normal lymphocytes. PP2C activity and its expression were relatively constant in various leukemic cell types. Activities of PP1 and PP2A of AML blasts correlated positively with the expression of CD11b, whereas activities of PP1 and PP2B correlated negatively with the expression of CD7. Thus, each phosphatase was ubiquitously but differently expressed in various leukemic cell types and in normal leukocytes. These data also suggest that expressions of PP1, PP2A and PP2B are relatively low in leukemic blasts arresting at the stage of early pluripotent stem cells, and are differently modulated during the course of myelomonocytic commitment and maturation.

Acute Disease↗

Impact of rabeprazole, a new proton pump inhibitor, in triple therapy for Helicobacter pylori infection-comparison with omeprazole and lansoprazole.

BACKGROUND: A recent trend in curative therapy for Helicobacter pylori infection is the so-called triple therapy, which consists of a proton pump inhibitor (PPI) and two different antimicrobials. Various regimens employing this triple therapy have been reported. However, little is known about the effectiveness of rabeprazole, a recently developed proton pump inhibitor, when used in the triple therapy. AIM: To validate its usefulness by comparing rabeprazole with omeprazole and lansoprazole, in combination with amoxycillin and clarithromycin. PATIENTS AND METHODS: 221 H. pylori-positive patients with peptic ulcer disease were randomized to receive one of three different proton pump inhibitor/amoxycillin-clarithromycin (PPI/AC) regimens for 7 days. (i) OAC regimen (n = 75): omeprazole 20 mg b.d., amoxycillin (AMOX) 500 mg t.d.s. and clarithromycin (CAM) 200 mg b.d.; (ii) LAC regimen (n = 74): lansoprazole 30 mg b.d. , AMOX 500 mg t.d.s. and CAM 200 mg b.d.; and (iii) RAC regimen (n = 72): rabeprazole 20 mg b.d., AMOX 500 mg t.d.s. and CAM 200 mg b.d. Cure of the infection was determined by the 13C urea breath test 1 month after completion of the treatment. RESULTS: Intention-to-treat based cure rates for OAC, LAC and RAC regimens were 85% (95% CI, 75-92), 84% (95%, CI 73-91) and 88% (95% CI, 78-94), respectively, and per protocol based cure rates of these regimens were 88% (95% CI, 78-94), 91% (95%, CI 82-99) and 93% (95% CI, 84-98), respectively. Adverse effects in the entire study population, which included diarrhoea, glossitis or skin rash, were reported by 15% of the patients, and complete compliance was achieved in 95% of these patients. CONCLUSION: 1-week proton pump inhibitor/AC regimens for H. pylori infection were effective in the Japanese population. Rabeprazole can be considered as equivalent to omeprazole and lansoprazole in the PPI/AC triple therapy.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Survival of human leukaemic B-cell precursors is supported by stromal cells and cytokines: association with the expression of bcl-2 protein.

We searched for cytokines with the potential to support the survival of human B-cell precursor acute lymphoblastic leukaemia (pre-B ALL) cells. 47 patients with pre-B ALL were classified into four stages: stage I, CD19+CD10-CD20-; stage II, CD19+CD10+CD20-; stage III, CD19+CD10+CD20+cytoplasmic mu-heavy chain (cmu)-; stage IV, CD19+CD10+CD20+cmu. Interleukin (IL)-3 receptor alpha chain (IL-3Ralpha) was expressed in all stages, whereas the expressions of IL-7Ralpha and IL-2Ralpha were pronounced in stages IV and II, respectively. Neither IL-3, IL-7 nor IL-2 supported the survival of pre-B ALL cells. When pre-B ALL cells were layered on stromal, MS-10, cells, viability of the pre-B ALL cells increased. Addition of IL-3 to culture containing MS-10 cells enhanced the survival of pre-B ALL cells in all cases, whereas addition of IL-7 augmented the survival of pre-B ALL cells of some cases of stage III and all cases of stage IV. The survival of pre-B ALL cells was also supported by the conditioned media of MS-10 cells. Stromal-cell-derived factor 1 (SDF-1) supported the survival of pre-B ALL cells. Effects of the conditioned media of MS-10 cells were abrogated by an anti-SDF-1 neutralizing antibody. The extent of survival of pre-B ALL cells supported by stromal cells and IL-3 and IL-7, correlated with the expression level of bcl-2 protein. The effects of stromal cells may be in part related to SDF-1.

Adult↗

Myeloid differentiation antigen and cytokine receptor expression on acute myelocytic leukaemia cells with t(16;21)(p11;q22): frequent expression of CD56 and interleukin-2 receptor alpha chain.

We report the cellular characteristics of cells from three patients with de novo acute myelocytic leukaemia (AML) with t(16;21)(p11;q22), two M4 and one M5a according to the FAB classification, and two permanent cell lines with t(16;21)(p11;q22), TSU1621MT and YNH-1. The FUS/ERG fusion mRNA was demonstrated in all cases by reverse transcriptase-polymerase chain reaction (RT-PCR). The immunophenotypes of the AML cells, and YNH-1 and TSU1621MT cell lines with t(16;21) were characterized as CD34+CD33+CD13+CD11b+CD18+CD56+ HLA-DR-/+. Cells from all samples strongly expressed c-kit, granulocyte colony-stimulating factor receptor (G-CSFR), c-fms (macrophage colony-stimulating factor receptor), interleukin-3 receptor alpha chain (IL-3Ralpha), and granulocyte macrophage colony-stimulating factor receptor alpha chain (GM-CSFRalpha), and these data corresponded well to the growth responsiveness to the cytokines. IL-2Ralpha expression was also found in all t(16;21) samples, but IL-2 did not act on the proliferation of the leukaemic cells in in vitro cultures. G-CSF distinctly promoted the proliferation of leukaemic cells of t(16;21) AML, but did not enhance the expression of MPO and neutrophil differentiation of these cells. Our findings indicate that AML cells with t(16;21) preserve stem cell properties such as CD34 and c-kit expression, and suggest that they have the potential to differentiate into a monocytic lineage. The relationship between the unique cellular characteristics (especially CD56 and IL-2Ralpha expression) and FUS/ERG protein remains undetermined.

Adolescent↗

Efficacy of 1 week omeprazole or lansoprazole-amoxycillin-clarithromycin therapy for Helicobacter pylori infection in the Japanese population.

BACKGROUND: The effectiveness of curative therapy for Helicobacter pylori may vary according to the geographic region and patient population, thus the efficacy of each treatment regimen should be determined according to the specific patient population. However, there is no literature available concerning the efficacy of 1 week omeprazole-amoxycillin-clarithromycin (OAC) regimens for the cure of H. pylori infection in Japan. METHODS: Helicobacter pylori-positive patients (224) with peptic ulcer disease or non-ulcer dyspepsia were randomized to receive one of three different omeprazole or lansoprazole-amoxycillin-clarithromycin (PPI/AC) regimens for 7 days: (1) OAC 20 regimen (n = 76), omeprazole (OPZ) 20 mg daily, amoxycillin (AMOX) 500 mg t.d.s. and clarithromycin (CAM) 200 mg b.d.; (2) LAC 30 regimen (n = 73), Lansoprazole (LPZ) 30 mg daily, AMOX 500 mg t.d.s. and CAM 200 mg b.d.; and (3) OPZ 40 regimen (n = 75), OPZ 20 b.d., AMOX 500 mg t.d.s. and CAM 200 mg b.d. Cure of the infection was determined by the [13C]-urea breath test, 1 month after completion of the treatment. RESULTS: Intention-to-treat based cure rates for OAC 20, LAC 30 and OAC 40 regimens were 75.0% (95% CI, 64-84%), 82.2% (95%, CI 72-90), and 80.0% (95% CI, 69-88), respectively and per-protocol based cure rates of these regimens were 79.2% (95% CI, 68-88%), 83.3% (95%, CI 73-91), and 83.1% (95% CI, 72-91%), respectively. Adverse effects, which included diarrhoea, glossitis or skin rash, were reported by 26.1% of the patients. However, these were mild and did not affect compliance. CONCLUSION: One week PPI/AC regimens for H. pylori infection with smaller proton pump inhibitors and antimicrobial dosages compared to regimens used in Western countries were revealed to provide sufficient cure rate (more than 80% by ITT analysis) with mild adverse effects in the Japanese population.

2-Pyridinylmethylsulfinylbenzimidazoles↗

How useful is the detection kit for antibody to Helicobacter pylori in urine (URINELISA) in clinical practice?

OBJECTIVE: Increased knowledge of the significance of Helicobacter pylori (H. pylori) infection in gastric disorders has accelerated the trend of screening patients with dyspepsia for its infection. Serological examination of antibody for H. pylori has been widely performed. Recently, a urine-based enzyme-linked immunosorbent assay (URINELISA) kit for detection of antibody for H. pylori has been developed. Accordingly, we evaluated its diagnostic accuracy in clinical practice. METHODS: Subjects of this study were 132 patients who presented at our university hospital because of dyspeptic symptoms (81 men, 51 women; age, 41.5+/-1.4 yr). 13C urea breath test, blood drawing for serological antibody for H. pylori infection by four different kits, and urine collection for the URINELISA test for detection of the antibody were performed. Diagnostic accuracy of the commercially available antibodies in serum and in urine were investigated using the results of the 13C urea breath test as the gold standard. RESULTS: Sensitivity, specificity, and accuracy of URINELISA were 86.3% (95% confidence intervals [CI], 76-93%), 91.5% (95% CI, 81-97%), and 88.6% (95% CI, 82-93%), respectively, which were comparable to those of imported serological kits. CONCLUSIONS: The URINELISA kit for detecting anti-H. pylori antibody in urine provides diagnostic accuracy comparable to that of imported kits for detecting antibodies in serum and is considered to be clinically useful for the diagnosis of H. pylori infection.

Adult↗

gamma delta T-cell lymphoma: a clinicopathologic study of 6 cases including extrahepatosplenic type.

We report 6 cases of gamma delta T-cell lymphoma (GDTL) among 115 peripheral T-cell lymphomas over a 12-year period. All patients exhibited extranodal lymphomas, comprising 3 hepatosplenic, 1 cutaneous, 1 intestinal, and 1 thyroidal lymphoma. Despite therapies, all but 1 patient died of disease within 16 months of diagnosis. The cytologic features of lymphoma cells in 4 of 5 cases examined were very similar: coarsely reticulated nuclear chromatin, multiple small nucleoli, abundant faintly eosinophilic granular cytoplasm, and focal angiocentric proliferation. All 6 lymphomas showed Cd3+CD4-CD8-/+ phenotype. CD56 was positive in 3 cases, 1 of which was also CD16 positive. Perforin and T-cell intracellular antigen-1 were positive in all 5 cases examined. Southern blot analysis revealed clonal gene rearrangements of the T-cell receptor delta-chain gene in all 5 cases examined. Based on these findings, together with a review of the literature, GDTLs seem to have several common lineage-specific features, although clinical presentation and course of GDTL are heterogeneous.

Adolescent↗

[Striatonigral degeneration and sporadic olivopontocerebellar atrophy: a consideration of the clinical entity of multiple system atrophy].

Striatonigral degeneration (SND) and sporadic olivopontocerebellar atrophy (sOPCA) are categorized under multiple system atrophy (MSA), since these disorders have common clinical and pathological features. However, it is still uncertain whether these disorders are manifestation of the same disease. In this study, we performed both clinical and neuroradiological studies on patients with SND or sOPCA in whom clinical diagnosis was based on a criteria during eight years in our hospital. A total of forty patients had SND and thirty-one patients had sOPCA. The onset ages of patients with SND (60.7 +/- 8.7, mean +/- SD) were significantly higher than those with sOPCA (55.4 +/- 7.9). In both SND and sOPCA patients, about 20% had clinical symptoms suggesting the involvement of multiple systems: pyramidal, cerebellar, extrapyramidal and autonomic symptoms. In 55% of the SND patients, cerebellar symptoms could be observed, and the same percentage of sOPCA patients had parkinsonism. Although, as defined, cerebellar symptoms were predominant in sOPCA patients and parkinsonism was predominant in SND patients, the SND patient group was particularly homogeneous with respect to clinical characteristics. The initial symptoms of SND were parkinsonian gait or tremors. Almost all patients exhibited asymmetrical appearance of the parkinsonian symptoms, such as rigidity, tremors, and bradykinesia. Tremors at rest were observed in two-thirds of the patients with SND during the course of their illness, but dementia was infrequently observed. There was no detectable limitation in horizontal eye movements in patients with SND. The progression of the disability of patients with SND was rapid; according to the clinical rating scale of parkinsonism, the average level of disability deteriorated to Hoehn-Yahr's stage III after three years from disease onset, and then deteriorated to stage IV after four years. Neuroradiologically, only a small proportion of patients with SND (27%) showed magnetic resonance image (MRI) findings suggesting OPCA pathology, such as volume loss in the brainstem or cerebellum with/without T2-high signaling of transverse fibers of pons or T2-high signaling of the middle cerebellar peduncle. Simultaneously, a small proportion of the patients with sOPCA (20%) showed MRI findings suggesting putaminal pathology, such as T2-low intensity signals of the putamen with linear T2-high intensity signals around the lateral putamen. Our results suggest that SND and sOPCA can be clearly differentiated, at least from clinical or neuroradiological aspects. Since there is still no evidence indicating that each disorder is a clinical variant of a single disease caused by the same etiology, a differentiation might be important for future pathogenetical studies.

Adult↗

[Clinical and neuroradiological features of spontaneous intracranial hypotension: report of two cases].

We report two patients with spontaneous intracranial hypotension (SIH) showing bilateral subdural hematoma. One of the two patients was a 32-year-old woman, and the other was a 27-year-old healthy woman. Both patients presented chronic, intractable, orthostatic headache with dizziness and nausea. In both patients, both general and neurological examinations were normal, and routine laboratory tests were all normal, except for dry taps of the lumbar puncture. Brain CT scans and MRI revealed thin, bilateral subdural hematomas. RI-cisternography and CT-myelography disclosed multiple extraspinal CSF leakages along the nerve root sheathes of the cervical segments and early bladder filling of the radionucleotides in both patients. These findings support an emerging hypothesis that the extraspinal CSF leakage may play a role for inducing SIH. Anatomical fragility around the nerve sheath, especially that of the lower cervical segments, may contribute to the pathophysiological mechanism underlying SIH. For making a prompt diagnosis of SIH and for the better understanding of the pathophysiological mechanism of SIH, RI-cisternography of the whole spinal segments is important.

Adult↗