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Biomedical subjects

H Miwa

Publications and source records attributed to H Miwa.

At least 19 recordsLinked to original sources
PubMed1996

A dislocated and enlarged proliferative zone in human gastric intestinal metaplasia.

There are many published reports suggesting a close relationship between intestinal metaplasia and gastric carcinogenesis, but there are few studies that examine the cellular kinetics of these tissues in humans. Thus, we sought to characterize the proliferative zone of intestinal metaplasia of the human stomach and correlate this with its known malignant potential. We examined the incorporation of bromodeoxyuridine into 228 human endoscopic biopsy specimens from duodenal mucosa (n=35) and non-intestinalized antral mucosa (n=127) as well as antral mucosa with intestinal metaplasia (n = 66). The proliferative zone in specimens with intestinal metaplasia was deeper when compared to non-intestinalized antral mucosa, but was more superficial than that of duodenal mucosa. Although the labeling index of intestinalized mucosa was similar to that of non-intestinalized antral mucosa, the size of the proliferative zone was significantly increased in intestinal metaplasia. The dislocation of the proliferative zone with an increase in its size in intestinal metaplasia is considered to be a hallmark of gastric intestinal metaplasia.

Bromodeoxyuridine↗
PubMed1996

Thin-layer chromatography and high-performance liquid chromatography for the assay of fatty acid compositions of individual phospholipids in platelets from non-insulin-dependent diabetes mellitus patients: effect of eicosapentaenoic acid ethyl ester administration.

Eight major phospholipids were separated by a TLC method with a one-dimensional developing system without any pretreatment of the plate and the fatty acids incorporated into each phospholipid class were analysed by an improved HPLC method with a simple elution system, which has advantages with respect to resolution and analysis time. The fatty acid compositions of individual phospholipids in platelets were investigated following administration of ethyl cis-5,8,11,14,17-eicosapentaenoate for more than 13 weeks to patients with non-insulin-dependent diabetes mellitus. The cis-5,8,11,14,17-eicosapentaenoic acid compositions of all phospholipid classes were significantly increased with decreasing platelet aggregation rates after the administration. These results suggested that the present method provides the complete separation of individual phospholipids in sufficient amounts to allow fatty acid analysis on the isolated phospholipid moieties.

Blood Platelets↗
PubMed1996

Accelerated cell-cycling of hematopoietic progenitors by the flt3 ligand that is modulated by transforming growth factor-beta.

Although hematopoietic growth factors have been extensively studied as to their roles in recruitment of hematopoietic progenitors from quiescence state to cell division state, little is known of their effects on cell-cycling of progenitors that have already transited from quiescence into active cell-cycling. We examined the effects of the flt3 ligand (FL) on cell-cycling of hematopoietic progenitors in serum-free culture. Results from our serial observations of colony formation and replating experiments suggest that FL enhances the rate of growth of interleukin-3 (IL-3)-dependent colonies by shortening the time for each progenitor in the colonies to divide. Cell-cycle analysis showed that shortening of cell-cycle time induced by FL is mainly because of alteration in the G1 phase that hematopoietic progenitors go through. We next investigated the role of transforming growth factor-beta (TGF-beta) in cell-cycling of progenitors, using TGF-beta protein and TGF-beta antisense oligonucleotides, because mRNA of TGF-beta was detected by reverse transcriptase polymerase reaction in blast cells that we used as a source of progenitors. TGF-beta lengthened the time required for IL-3-dependent progenitors to become two daughter cells, whereas the effects of TGF-beta antisense oligonucleotides were opposite to those of TGF-beta. The addition of TGF-beta neutralizing monoclonal antibodies to the cultures resulted in effects similar to those seen with TGF-beta antisense oligonucleotides. DNA studies indicated that both TBF-beta and TGF-beta antisense oligonucleotides change the length of G1 phase of the cell-cycle. TGF-beta abrogated the effects of FL on the growth rate of hematopoietic progenitors, whereas the combination of FL with TGF-beta antisense oligonucleotides exerted additive effects. These data show that FL has the potential to accelerate cell-cycling of hematopoietic progenitors, which is susceptible to the modulation by TGF-beta.

Animals↗
PubMed1996

Characterizations of the unusual dissociation properties of melanotropin peptides from the melanocortin receptor, hMC1R.

Variation in the degree of prolonged (residual) biological activity of the melanotropin peptides alpha-MSH (alpha-melanocyte-stimulating hormone, Ac-Ser-Tyr-Met-Glu- His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2) and the superpotent analogues [Nle4,DPhe7]alpha-MSH (MT-I) and Ac-[Nle4,Asp5,DPhe7,Lys10]alpha-MSH(4-10-NH2 (MT-II) has stimulated considerable interest regarding this biological phenomena. We have examined the differences in their relative dissociation rates from the melanocortin receptor, hMC1R, to try and correlate peptide dissociation rates with the observations of prolonged biological activity. Interestingly, these studies revealed that alpha-MSH remained 25% bound, MT-I 65% bound, and MT-II 86% bound 6 h after the ligand had been removed from the assay medium. The relative dissociation rate of MT-II was 4 times slower than that for alpha-MSH and 2 times slower than that for MT-I, which was 2 times slower than that for alpha-MSH. These data suggest that slow dissociation kinetics (hours) may contribute to the prolonged biological activities observed for both MT-I and MT-II peptides in vitro and in vivo. The prolonged binding, biological activities, and enzymatic stability of MT-I and MT-II make them putative candidates for clinical uses such as external scintigraphy for the localization of tumors (i.e., melanoma).

Amino Acid Sequence↗
PubMed1996

Effects of heart rate on flow velocity of the left atrial appendage in patients with nonvalvular atrial fibrillation.

BACKGROUND AND HYPOTHESIS: Flow velocity of the left atrial appendage (LAA) is thought to be important in thrombus formation in association with blood stasis and the development of spontaneous echo contrast. The effects of heart rate on peak flow velocity of LAA have not been studied in patients with nonvalvular atrial fibrillation. METHODS: Using transesophageal Doppler echocardiography, peak flow velocity of the LAA was measured at the junction between the left atrium and the LAA during left ventricular (LV) systole and diastole in 21 patients with nonvalvular atrial fibrillation. In six cases, the average peak flow velocity of the LAA for 10 consecutive beats with moderately long R-R intervals (LI beats) was compared with those of 3-5 consecutive beats with extremely short R-R intervals (SI beats). RESULTS: Average peak flow velocity of the LAA during LV diastole was significantly higher than that during LV systole (26.5 +/- 15.7 vs. 19.3 +/- 10.4 cm/s, p < 0.01). In SI beats, average peak flow velocity of the LAA was significantly lower than that in LI beats (17.1 +/- 12.1 vs. 21.2 +/- 12.9 cm/s, p < 0.01). CONCLUSION: An increased heart rate reduced the peak flow velocity of the LAA in patients with nonvalvular atrial fibrillation, which would promote blood stasis in the LAA.

Adult↗
PubMed1996

Relapsing polychondritis presented as inner ear involvement.

We report a rare case of relapsing polychondritis with an initial symptom of inner ear involvement. This 53-year-old Japanese man experienced a hearing difficulty, tinnitus in both ears, and dizziness of sudden onset, but lacked auricular chondritis at that time, which is the most frequent finding in relapsing polychondritis. Thus it was difficult to reach a correct diagnosis. Steroid therapy, with oral prednisolone 15 mg daily, was effective. Almost two months after we began the steroid therapy, the patient complained of losing interest in his work and reported a hallucination vision on the TV screen, so the dose of prednisolone was decreased to 10 mg. The hallucinations then disappeared, but the serum level of C-reactive protein increased highly. To reduce the dose of prednisolone, we tried low-dose oral methotrexate. However, we had to discontinue it when the patient experienced severe vomiting and diarrhoea. As adjuvant therapy, we then administered Sho-saiko-to, Chinese herbal medicines with few side effects. Symptoms and laboratory abnormalities then improved markedly.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

Platelet-derived growth factor accelerates gastric epithelial restoration in a rabbit cultured cell model.

BACKGROUND & AIMS: Growth factors play an important role in gastric wo und repair. The aim of this study was to assess the role of platelet-derived growth factor (PDGF) in gastric epithelial restoration. METHODS: PDGF-BB (1-50 ng/mL) was added to confluent cultures of rabbit gastric epithelial cells after wounding. Regrowth of the epithelial cells was monitored for 48 hours. The speed of cell migration was measured, and cell proliferation was detected by using a 5-bromodeoxyuridine (BrdU) staining technique. The labeling index was calculated for a 0.05-mm(2) area around the wound. RESULTS: After wounding, cells at the wound edge formed lamellipodia and showed ruffling movements. The addition of PDGF-BB significantly accelerated cell migration and proliferation as well as gastric restoration. Migration speed was 21 microm/h in control cultures and 32 microm/h and 40 microm/h in cultures containing 10 ng/mL and 50 ng/mL of PDGF-BB, respectively. In control cultures, BrdU-positive cells were rarely detected in the initial 24 hours after wounding, and maximum labeling occurred at 36 hours (labeling index, 3.4%). Cultures containing PDGF-BB showed maximum labeling at 24 hours (labeling index, 6.9%). CONCLUSIONS: PDGF-BB dose-dependently accelerated the migration rate and proliferation of cultured gastric epithelial cells after wounding. Therefore, PDGF-BB may play a role in gastric epithelial cell restoration during healing of gastric mucosal lesions.

Animals↗
PubMed1996

Evaluation of ethanol on gastric epithelial restoration in vitro.

Ethanol exerts damaging effects on gastric mucosa and delays ulcer healing. To investigate the effect of ethanol on the wound repairing process, we used a wound repair model using primary cultured gastric mucosal cells. A confluent monolayer gastric mucosal cell sheet consisting mainly of mucous cells was wounded to make a cell-free area of constant size. Cell-free area was restored with time after wounding and monitored every 12 hr using a computer image analyzer to observe epithelial cell restoration quantitatively in the presence and absence of ethanol (2.0%). It was found that, although the control wound was completely repaired in 36 to 48 hr, the group treated with 2.0% ethanol showed a significant delay of repair. In the control, 5-bromodeoxyuridine-positive cells appeared around the wound in 24 to 36 hr. In contrast, the group treated with 2.0% ethanol showed no 5-bromodeoxyuridine-positive cells during the experiment. In conclusion, 2.0% ethanol retarded the repair of gastric mucosal restoration by inhibiting the initial gastric cell migration, followed by inhibition of proliferation of cells.

Animals↗
PubMed1996

Evaluation of the somatosensory evoked blink response in patients with neurological disorders.

BACKGROUND: The somatosensory evoked blink response (SBR) is a characteristic reflex blink elicited by electrical stimulation of peripheral nerves or other anatomical sites. METHODS: 139 patients with neurological disorders were examined for presence of the SBR. Although the SBR was not usually elicitable, it was present in a subset of patients with Parkinson's disease and with hemifacial spasm. It was also present in a patient with Guillain-Barré syndrome before the recovery phase. The latency of the EMG activities responsible for the SBR was significantly shorter than that of the startle blink. CONCLUSIONS: The SBR is not a variant of the startle blink, but is a release phenomenon transmitted via the brainstem reticular formation. This response may be clinically relevant in disorders associated with brainstem lesions and abnormal blinking.

Blinking↗
PubMed1996

Thalamic tremor: case reports and implications of the tremor-generating mechanism.

We report two patients with unilateral resting and postural tremor of the upper limb as a delayed manifestation of thalamic stroke. Neuroradiologic examination showed a lesion in the posterolateral thalamic region in both patients, but with no obvious involvement of the brainstem, the cerebellum, or the cerebellar outflow tract to the thalamic ventrolateral nucleus.

Adult↗
PubMed1996

[A case of advanced gastric cancer remarkably responding to preoperative UFT-E therapy].

We here reported a case of advanced gastric cancer remarkably responding to preoperative short-term UFT-E chemotherapy. UFT-E was orally administered preoperatively for about a month to the patient with type 2 advanced gastric cancer. After the chemotherapy the cancer was found to be remarkably decreased in size and denatured. The amount of residual cancer cells was limited by histopathological examination following the operation and diagnosed as Grade 3 based on the criteria of histological evaluation of chemotherapy for cancer. We continued to administer UFT-E postoperatively and the patient is still alive without symptoms.

Adenocarcinoma↗
PubMed1996

Biological characteristics of CD7(+) acute leukemia.

Eighty six of 430 acute myeloblastic leukemia (AML) patients (20.0%) and forty of 173 acute lymphoblastic leukemia (ALL) patients (23.1%) had CD7 on their leukemia cells. CD7(+) AML occurred at a younger age than CD7(-) AML, and is more frequent in males. Hepatomegaly and central nervous system involvement were also more frequent in CD7(+) AML than in CD7(-) AML. The age of onset of CD7(+) ALL is also younger than that of CD7(-) ALL. Phenotypically, CD(+) AML expressed CD34, HLA-DR, and TdT more frequently than CD7(-) AML while CD7(+) ALL expressed CD13/33 more often than CD7(-) ALL cells responded most significantly to interleukin 3 (IL-3), whereas most CD7(-) AML cells responded more significantly to granulocyte macrophage-colony stimulating factor (GM-CSF) and/or granulocyte (G)-CSF than to IL-3. CD7(+)sCD3(-)CD4(-)CD8(-) ALL expressed G-CSF receptor and c-kit mRNA more frequently, which is not usual in other types of ALL. P-glycoprotein (P-gp)/multi-drug resistance gene (MDR1), thought to be expressed in hematopoietic stem cells, is expressed in CD7(+) AML and CD7(+)sCD3(-) CD4(-)CD8(-) ALL significantly more often than in CD7(-) acute leukemias and the CR rate and overall survival of CD7(+)AML was worse than CD7(-) AML. These data, collectively, suggest the close association of CD7(+) AML and CD7(+)sCD3(-)CD4(-)CD8(-) ALL, not only the common expression of CD7 itself but also because their phenotypical immaturity, cytokine receptor expression, P-gp/MDR1 expression and clinical manifestations including the frequent occurrence in males and the poor prognosis. We propose that CD7(+) acute leukemia is an hematopoietic stem cell leukemia which may be separate entity.

Adult↗
PubMed1996

[Double chambered right ventricle in a 59-year-old man].

Surgical experience of double chambered right ventricle in a 59-year-old man was reported. The patient who had been pointed out for his systolic manner without any symptoms was admitted to our hospital because of heart failure. Cardiac catheterization revealed an about 80-mmHg peak-to-peak gradient in the right ventricle cavity with normal pulmonary pressure. Cineangiogram demonstrated double chambered right ventricle with perimembranous ventricular septal defect. Surgical repair with right ventriculotomy was performed in order to release pressure gradient and his symptoms. Right ventricular function after operation was not distorted. It is important to choose the surgical approach (right ventriculotomy or transatrial approach) for release the pressure gradient completely.

Age of Onset↗
PubMed1995

Frequent expression of P-glycoprotein/MDR1 by nasal T-cell lymphoma cells.

BACKGROUND: Lethal midline granuloma is now considered to be a malignant lymphoma derived from peripheral T cells or from natural killer cells. The therapeutic outcome of nasal T-cell lymphoma (NL) treated by conventional chemotherapy for non-Hodgkin's lymphoma is poor, although some patients have a good response to radiotherapy. To clarify the mechanisms of drug resistance, the expression of P-glycoprotein (P-gp)/MDR1, which is the product of the multidrug resistance (MDR) 1 gene, and MDR3 mRNA in NL cells, were examined. METHODS: Ten Japanese patients with NL were studied. Nine of these patients were examined before therapy. P-glycoprotein expression and phenotypes of lymphoma cells were examined by immunohistochemical staining using UIC2 as an anti-P-gp monoclonal antibody. In one case, the Rhodamine-123 efflux test was performed. MDR1 and MDR3 mRNA were detected by reverse transcription polymerase chain reaction. RESULTS: Nine of the 10 patients were P-gp positive. In one of nine, functional P-gp expression was observed. MDR1 mRNA was detected in all seven examined patients with P-gp positive NLs, whereas MDR3 mRNA was negative. Retrospectively, patients who received chemotherapy alone had poorer outcome than those treated by combination chemotherapy after irradiation. CONCLUSION: The poor prognosis for patients with NL treated with chemotherapy may be explained by P-gp expression of the NL cells.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1995

Topographical modification of melanotropin peptide analogues with beta-methyltryptophan isomers at position 9 leads to differential potencies and prolonged biological activities.

We have introduced topographical constraints at the 9 position of a superpotent cyclic alpha-melanotropin analogue, Ac-Nle4-Asp5-His6-DPhe7-Arg8-Trp9-Lys10-NH2, by incorporating a methyl group at the beta-carbon of Trp9. These studies were performed on the Trp side chain pharmacophore to identify the bioactive topography of the indole moiety with melanocortin MC1 receptors. The four beta-MeTrp9 isomers, in addition to the stereochemical controls L- and DTrp9, were used to probe differential receptor molecular recognition of the tryptophan moiety in two bioassay systems. Approximately a 460-fold difference in potency was observed between the diastereoisomeric peptides in the frog skin bioassay, with only 33- and 10-fold efficacy differences observed in binding and intracellular cAMP accumulation, respectively, on the human melanocortin receptor, hMC1R. The relative orders of potencies in the frog skin bioassay were 2R,3S > 2S,3S = 2R,3R >> 2S,3R and for the hMC1R were 2S,3S > 2R,3R > 2R,3S >> 2S,3R. Of particular interest is the ability of these topographically constrained ligands to differentially affect prolonged biological activity. The 2R,3R diastereoisomeric peptide possessed superprolonged activity, whereas the 2S,3S peptide lacked any residual activity in the frog skin bioassay. However, on the melanocortin receptor, the 2S,3S diastereoisomeric peptide maintained slow dissociation rates (t1/2 = 7 h), while the other diastereoisomeric peptides possessed dissociation t1/2 rates of ca. 2 h. These data strongly implicate ligand-receptor interactions and kinetics as contributing to the observed prolonged biological activities and clearly illustrate topographical recognition differences between these two peripheral MC1 receptors involved in skin pigmentation. This study also demonstrates that topographical modifications of pharmacophore side chain residues, in addition to identifying preferential side chain orientation, can be a useful strategy for the design of peptides to increase the duration of biological activity, relative to the native ligand.

Amino Acid Sequence↗
PubMed1995

A hybrid vascular model biomimicking the hierarchic structure of arterial wall: neointimal stability and neoarterial regeneration process under arterial circulation.

A layered-structure hybrid vascular graft, mimicking the hierarchic structure of the intima and media of a natural artery, is expected to exhibit antithrombogenicity and to accelerate neoarterial tissue formation. Two models of hybrid vascular grafts were prepared on knitted Dacron fabric grafts (inner diameter 4 mm, length 6 cm). Model I grafts consisted of an endothelial cell monolayer formed on collagenous matrix, and model II grafts consisted of an endothelial cell monolayer that formed on hybrid collagenous medial tissue in which smooth muscle cells were incorporated. Both models (n = 17 for each model) were implanted bilaterally in carotid arteries and left in place for up to 26 weeks. Although all of the implanted grafts were patent, the two models significantly differed in the degree of maturity of the regenerated neoarterial wall especially at earlier implantation periods. At 2 weeks, model II grafts showed a much higher degree of neointimal integrity than model I grafts: a smooth and organized neointimal layer was formed, which was free from leukocyte adhesion. On further increase of implantation time, the formation of neomedia (subendothelial smooth muscle cell layers) and circumferential orientation of both smooth muscle cells and collagenous extracellular matrix were much more advanced in model II grafts than in model I grafts. At 26 weeks after implantation, layered elastic laminae regenerated along circumferentially oriented smooth muscle cells in neomedia were observed only in model II grafts. Irrespective of model, little excessive smooth muscle cell proliferation occurred. A hierarchically structured hybrid graft eventually provided a more integrated neointimal layer and accelerated neoarterial tissue formation much more than model I grafts. The significance of the incorporation of smooth muscle cells into hybrid grafts is discussed.

Animals↗
PubMed1995

Alternations in atrial natriuretic peptide release after DC cardioversion of non-valvular chronic atrial fibrillation.

The response of atrial natriuretic peptide (ANP) release to haemodynamic influences after cardioversion of atrial fibrillation has not been fully examined. We measured plasma concentrations of ANP and assessed haemodynamic changes 60-120 min after DC cardioversion in 22 patients with non-valvular chronic atrial fibrillation. Passive leg elevation to enhance volume expansion was performed 60 min after DC cardioversion. Sinus rhythm was restored in 18 of the 22 patients (successful DC cardioversion group). The control group consisted of seven patients with non-valvular chronic atrial fibrillation who did not undergo DC cardioversion (atrial fibrillation control group). In the successful DC cardioversion group, the mean pulmonary artery wedge pressure decreased significantly 15 min after cardioversion (P < 0.05) and then remained unchanged. Plasma concentrations of ANP also decreased significantly 15 min after cardioversion (P < 0.05). Furthermore, there was an additional significant decrease in ANP levels for up to 60 min after cardioversion (P < 0.05 from 15 min). Passive leg elevation for 15 min led to an increase in the mean pulmonary artery wedge pressure (P < 0.01) and right atrial pressure (P < 0.05), but did not result in increased plasma concentrations of ANP (47.1 +/- 27.6 vs 43.9 +/- 34.4 pg.ml-1, mean +/- SD, P = ns). In the atrial fibrillation control group, passive leg elevation increased the mean pulmonary artery wedge pressure (P < 0.01), the mean right atrial pressure (P < 0.05) and plasma concentrations of ANP (139.9 +/- 85.8 vs 168.1 +/- 108.2, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗