Search PubMed⌕ Search

Biomedical subjects

M Honda

Publications and source records attributed to M Honda.

At least 217 records · Page 12Linked to original sources

[Potential role of angiotensin receptor antagonists in renal protection].

Recent clinical studies have established an important role of angiotensin converting enzyme inhibitors (ACE-I) as a tool for renal protection. Although angiotensin receptor antagonists (AII-A) share the common property with ACE-I with regard to blockade of angiotensin activity via angiotensin type 1 receptors (AT1), AII-A is also reported to stimulate AT2 that plausibly activates nitric oxide production within renal medulla and augments synthesis of vasodilatory P450-metabolites in renal afferent arterioles. In contrast, AII-A is reported to have no effect on bradykinin activity. Results obtained in experimental animals indicate that AII-A effectively prevents the progression of renal injury. Several clinical studies are in progress, and the preliminary results suggest that AII-A has potent renal protective action in a variety of renal disorders.

Angiotensin Receptor Antagonists↗

[Antitumor effect of 5'-DFUR and PyNPase activity in colorectal cancer].

Following preoperative administration of 5'-deoxy-5-fluorouridine (5'-DFUR) in patients with colorectal cancer, histologic antitumor effects as well as pyrimidine nucleoside phosphorylase (PyNPase) activities in cancerous tissues were examined. Fifty-five patients were randomly divided into two groups: Twenty-five patients received 5'-DFUR orally at a daily dose of 800 mg for 3 weeks before operation (Group A) and twenty-nine received no medication (Group B). PyNPase activities in cancerous tissues obtained from resected specimens in Group A and B were 49.7 +/- 21.6 and 66.6 +/- 40.0 U/mg prot, respectively, which were significantly higher than 25.5 +/- 14.1 and 22.1 +/- 11.2 U/mg prot in normal colorectal tissues. No significant difference was observed in PyNPase activities in cancerous tissues between Group A and B. PyNPase activities in cancerous tissues in Group A were no different either from 59.2 +/- 40.0 U/mg prot in biopsy specimens before administration of 5'-DFUR. Histologic anti-tumor effects were as follows: Grade 2, 1 case Grade 1b, 5; Grade 1a, 10; and Grade 0, 9. Although no correlation was observed between antitumor effects and PyNPase activities in cancerous tissues, antitumor effects of 2 cases in which PyNPase activities in cancerous tissues before administration of 5'-DFUR showed more than 100 U/mg prot were Grade 2 and 1b, respectively.

Adenocarcinoma↗

Association of angiotensin-converting enzyme gene polymorphism and renal pathology in Japanese children with IgA nephropathy.

Polymorphism of the gene that codes for angiotensin I-converting enzyme (ACE) is associated with increased severity of immunoglobulin A (IgA) nephropathy in adult patients. We evaluated the relationship between the polymorphism of ACE genotypes and the pathological and clinical findings in Japanese children with IgA nephropathy. Patients with moderate/diffuse mesangial proliferation, glomerular sclerosis and tubulointerstitial damage showed a significant increase of the D/D type compared to those who had mild/focal mesangial proliferation, without glomerular sclerosis or tubulointerstitial damage (p < 0.05). Proteinuria at the first renal biopsy was significantly higher in the former group compared with the latter group except glomerular sclerosis (p < 0.01). IgA nephropathy patients with tubulointerstitial damage also showed an increased serum creatinine level compared to patients without the damage (p < 0.03). We conclude that ACE gene polymorphism may be correlated with the prognosis of IgA nephropathy in Japanese children.

Biopsy↗

The 1997 Report of the Japanese National Registry data on pediatric peritoneal dialysis patients.

OBJECTIVE: We have collected data on pediatric patients less than 16 years of age from the National Registry of Chronic Peritoneal Dialysis (PD). We present our experience with this population. DESIGN: The database details the patient numbers, age, outcome, cause of death, reason for terminating PD therapy, type of PD therapy, peritonitis, and catheter survival. PATIENTS: Of 807 patients, 70 patients (8.7%) were under 1 year of age, and 268 patients (33.2%) were under 6 years of age, clearly indicating that PD was the treatment of choice in young children. The duration on PD was 5 years or more in 200 patients (24.8%), which showed an increase in long-term PD patients from 11% in 1991. Patients on automated PD (APD) increased to 75% in 1997 from 9% in 1991. RESULTS: The outcomes for the total patient population of 807 as of the end of 1997 is: 253 patients (31.4%) were being successfully treated with PD, 87 patients (10.8%) died, 238 patients (29.5%) received a kidney transplant, and 121 (15.0%) were transferred to hemodialysis. The patient survival rate was 91% in 3 years and 86% in 5 years. The technique survival rate was 83% in 3 years and 71% in 5 years. The rate of peritonitis was 1 episode per 30 patient-months. The mean catheter duration was 2.25 years. CONCLUSION: The patient and technique survival rates, the peritonitis rate, and the catheter survival improved recently. However, these data were worse in younger children (less than 6 years of age), indicating that extra-careful management is needed for this young age group.

Adolescent↗

Bile acid synthesis in the Smith-Lemli-Opitz syndrome: effects of dehydrocholesterols on cholesterol 7alpha-hydroxylase and 27-hydroxylase activities in rat liver.

The Smith-Lemli-Opitz syndrome (SLOS) is a congenital birth defect syndrome caused by a deficiency of 3beta-hydroxysterol Delta(7)-reductase, the final enzyme in the cholesterol biosynthetic pathway. The patients have reduced plasma and tissue cholesterol concentrations with the accumulation of 7-dehydrocholesterol and 8-dehydrocholesterol. Bile acid synthesis is reduced and unnatural cholenoic and cholestenoic acids have been identified in some SLOS patients. To explore the mechanism of the abnormal bile acid production, the activities of key enzymes in classic and alternative bile acid biosynthetic pathways (microsomal cholesterol 7alpha-hydroxylase and mitochondrial sterol 27-hydroxylase) were measured in liver biopsy specimens from two mildly affected SLOS patients. The effects of 7- and 8-dehydrocholesterols on these two enzyme activities were studied by using liver from SLOS model rats that were treated with the Delta(7)-reductase inhibitor (BM15.766) for 4 months and were comparable with more severe SLOS phenotype in plasma and hepatic sterol compositions. In the SLOS patients, cholesterol 7alpha-hydroxylase and sterol 27-hydroxylase were not defective. In BM15.766-treated rats, both enzyme activities were lower than those in control rats and they were competitively inhibited by 7- and 8-dehydrocholesterols. Rat microsomal cholesterol 7alpha-hydroxylase did not transform 7-dehydrocholesterol or 8-dehydrocholesterol into 7alpha-hydroxylated sterols. In contrast, rat mitochondrial sterol 27-hydroxylase catalyzed 27-hydroxylation of 7- and 8-dehydrocholesterols, which were partially converted to 3beta-hydroxycholestadienoic acids. Addition of microsomes to the mitochondrial 27-hydroxylase assay mixture reduced 27-hydroxydehydrocholesterol concentrations, which suggested that 27-hydroxydehydrocholesterols were further metabolized by microsomal enzymes. These results suggest that reduced normal bile acid production is characteristic of severe SLOS phenotype and is caused not only by depletion of hepatic cholesterol but also by competitive inhibition of cholesterol 7alpha-hydroxylase and sterol 27-hydroxylase activities by accumulated 7- and 8-dehydrocholesterols. Unnatural bile acids are synthesized mainly by the alternative pathway via mitochondrial sterol 27-hydroxylase in SLOS.

Animals↗

[PGE1 and dopamine administration in a pediatric patient during hepatectomy].

A 2-year-old male underwent medial inferior hepatectomy for the treatment of metastatic tumors. Due to congenital hepatoblastoma, at 6-months of age, right lobectomy of his liver had been performed. To protect liver functions, PGE1 and dopamine were administered during the surgery. Although half of his circulating blood volume was lost, his perioperative hemodynamics was stable, with no development of postoperative liver dysfunction. PGE1 and dopamine may thus be beneficial in pediatric hepatectomy.

Alprostadil↗

Comparative study of retinal nerve fiber layer damage in Japanese patients with normal- and high-tension glaucoma.

PURPOSE: To look for possible differences in the pattern of retinal nerve fiber layer (RNFL) damage induced by normal- and high-tension glaucoma. METHODS: The study included randomly selected eyes from 27 patients with open-angle, high-tension glaucoma (mean age, 54.7 +/- 15.0 years; range 21-74 years) and from 19 age-matched patients with normal-tension glaucoma (mean age, 55.7 +/- 11.9 years; range 35-83 years). Eyes were examined using scanning laser polarimetry. RESULTS: The ratio between the superior and inferior quadrant thickness, or symmetry, was significantly lower in patients with high-tension glaucoma (1.00 +/- 0.22) than in patients with normal-tension glaucoma (1.18 +/- 0.32). Similarly, the ratio of the superior to the nasal quadrant thickness was significantly lower in patients with high-tension glaucoma (1.56 +/- 0.38) than in patients with normal-tension glaucoma (1.80 +/- 0.29). No statistically significant differences in the other parameters were detected between the two groups. CONCLUSION: These results show that the pattern of RNFL change is different in patients with high- and low-tension glaucoma. The thickness of the RNFL is reduced symmetrically in the superior and inferior quadrants in high-tension glaucoma, whereas a more localized defect on the inferior RNFL occurs in normal-tension glaucoma.

Adult↗

[Characteristics of myocardial ischemia in patients with chronic renal failure and its relation to cardiac sympathetic activity].

In order to clarify the characteristics of myocardial ischemia in patients with chronic renal failure (CRF), we performed exercise stress myocardial perfusion imaging with 99mTc-MIBI in 36 patients with CRF. In 18 patients myocardial imaging with 123I-MIBG (MIBG) and 201Tl was performed at rest to evaluate myocardial sympathetic activities: cardiac uptake of MIBG normalized by myocardial perfusion (Uptake Ratio, UR) and myocardial washout rate of MIBG (WO). Exercise-induced perfusion abnormality was observed in 25 patients, and coronary angiography was performed in 19 of them. Among 25 diseased coronary arteries, 18 developed perfusion abnormalities in the myocardial segments which were supplied by each coronary artery. However in 5 patients without coronary artery stenosis and 2 patients with left anterior descending coronary artery disease, transient perfusion abnormalities were observed in the inferior segments. In 6 of them, MIBG imaging was obtained (Group A). MIBG imaging was also performed in 5 patients with transient inferior perfusion abnormality with coronary artery stenosis which supplied the inferior wall (Group B), and 7 patients without perfusion abnormality (Group C). In the patients of Group B, inferior UR was significantly lower than in Group C (0.58 +/- 0.07 vs. 0.68 +/- 0.08, p = 0.0485) and inferior WO was more accelerated than in Group C (18.6 +/- 7.7 vs. 12.1 +/- 6.0%, NS). However anterior UR and Wo levels were identical with those in Group C. In Group A, inferior UR (0.43 +/- 0.05) was significantly lower than in Group B and C, and WO in Group A (27.2 +/- 8.3%) was accelerated significantly compared to that in Group C. Besides in Group A, anterior UR was significantly smaller and WO was greater than in Group B and C. These findings suggested that in some patients with CRF, myocardial ischemia could arise without coronary artery stenosis, and this phenomenon might be related to abnormalities of cardiac sympathetic activity.

Aged↗

Nasal immunization of nonhuman primates with simian immunodeficiency virus p55gag and cholera toxin adjuvant induces Th1/Th2 help for virus-specific immune responses in reproductive tissues.

Female rhesus macaques were nasally immunized with p55gag (p55) of SIV and cholera toxin as a mucosal adjuvant. Nasal immunization induced Ag-specific IgA and IgG Abs in mucosal secretions (e.g., cervicovaginal secretions, rectal washes, and saliva) and serum. Furthermore, high numbers of p55-specific IgA and IgG Ab-forming cells were induced in mucosal effector sites, i.e., uterine cervix, intestinal lamina propria, and nasal passage. p55-specific CD4+ T cells in both systemic and mucosal compartments expressed IFN-gamma and IL-2 (Th1-type)- as well as IL-5, IL-6, and IL-10 (Th2-type)-specific mRNA. Moreover, p55-specific CTL activity was demonstrated in lymphocytes from blood, tonsils, and other lymphoid tissues. These results show that nasal immunization with SIV p55 with cholera toxin elicits both Th1- and selective Th2-type cytokine responses associated with the induction of SIV-specific mucosal and serum Abs, and CTL activity. These results offer a promise for the development of protective mucosal immunity to SIV.

Adjuvants, Immunologic↗

Transglutaminase activity in serum and cerebrospinal fluid in sporadic amyotrophic lateral sclerosis: a possible use as an indicator of extent of the motor neuron loss.

The activity of transglutaminase (TGase), a marker enzyme for tissue degeneration, was examined in serum and cerebrospinal fluid (CSF) obtained from patients with sporadic amyotrophic lateral sclerosis (SALS), and compared to those from patients without SALS. When the serum TGase activity values from SALS patients were compared against the 'ALS-scale', which is used for clinical evaluation of the progression of ALS, the TGase activity values were higher at the initial stage of the disease than in non-ALS subjects, whereas they became extremely low at the late stage of ALS. The TGase activity in the CSF taken at later than middle stage from ALS patients with definite clinical motor dysfunctions was significantly lower than in that from non-ALS subjects. We have previously demonstrated marked reduction of tissue TGase activity in all regions of spinal cord tissue transections from ALS patients, not only in ventral but also lateral and dorsal regions, relative to that in non-ALS patients. These results suggest that some TGase may be leaked out of the spinal cord tissue into the CSF and then into the blood-stream during the progression of ALS, and the enzymic activity finally becomes depleted at the terminal stages of the disease when most of the spinal motor neuronal perikarya have been destroyed.

Aged↗

Immunohistochemical evidence for a macrophage scavenger receptor in Mato cells and reactive microglia of ischemia and Alzheimer's disease.

Macrophage scavenger receptors (MSR) are implicated in the development of atherosclerosis and amyloid b-protein deposition in Alzheimer's disease. However, histopathological studies of MSR expression in human tissues have been hampered by a lack of specific antibodies. Using MSR-deficient mice, we successfully raised a novel monoclonal antibody against human MSR together with high-titer antisera. These antibodies specifically recognized human tissue macrophages and human MSR protein purified from differentiated THP1 cells. In normal brain, MSR staining was mainly distributed to the perivascular cells, which correspond to Mato's fluorescent granular perithelial cells (Mato cells). In the lesions of ischemia and Alzheimer's disease, a subset of microglia stained positive for MSR. These novel antibodies are useful tools for analysis of MSR expression in human tissues.

Alzheimer Disease↗

Identification and molecular characterization of human T lymphotropic virus type II infections in intravenous drug abusers in the former South Vietnam.

Previous serological studies have demonstrated that some 60% of intravenous drug abusers (IVDAs) in urban areas of the former South Vietnam are infected with HTLV-II. In the present report we have attempted to characterize the viruses using restriction fragment length polymorphism (RFLP) and nucleotide sequence analysis of the provirus long terminal repeat (LTR) region. RFLP analysis of nine samples demonstrated that all were infected with the HTLV-IIb subtype. The HTLV-IIa subtype was not detected. Phylogenetic analysis of the nucleotide sequences demonstrated that the viruses clustered closely with HTLV-IIb isolates present in IVDAs from the New York City area. The present molecular analysis together with the previously reported absence of HTLV-II infection in North Vietnam supports the view that HTLV-II may have been introduced from the United States to this part of Asia by military personnel during the Vietnam conflict.

HTLV-II Infections↗

Effect of the Kobe earthquake on stress and glycemic control in patients with diabetes mellitus.

OBJECTIVE: To examine the effects of the Kobe, Japan, earthquake, a life-threatening event, on stress and glycemic control in diabetic patients. PATIENTS AND METHODS: Hemoglobin A1c levels before and after the earthquake were evaluated in diabetic patients in Kobe (N = 157; magnitude, 7.2) and in Osaka, Japan, as a control (N = 277; magnitude, 4.2), where little damage to houses and traffic facilities occurred. Glycosylated hemoglobin levels were also compared with those of 2 years before and 1 year after the earthquake. The General Health Questionnaire (GHQ) and a self-administered questionnaire regarding damage to houses and relatives killed or injured were used to assess psychological and mental stresses on earthquake survivors. RESULTS: Glycemic control was aggravated in diabetic patients after the earthquake in Kobe but not in Osaka. THe GHQ scores were significantly higher in the patients in Kobe than those in Osaka. Increased hemoglobin A1c concentrations and high scores on the GHQ were especially evident in diabetic patients with severe damage to houses and/or with relatives killed or injured. CONCLUSION: These results suggest an association between chronic, life-threatening stress and the worsening of metabolic control in patients with diabetes mellitus.

Adult↗

In SCID-hu mice, passive transfer of a humanized antibody prevents infection and atrophic change of medulla in human thymic implant due to intravenous inoculation of primary HIV-1 isolate.

Using SCID-hu mice, it was tested whether humanized mAb Rmu5.5 could prevent infection by HIV-1 i.v. inoculation. The Ab that recognizes the IHIGPGRAFYT motif in the principal neutralizing determinant (PND) of HIV(MN), as well as the original mouse mAb mu5.5, neutralized HIV(MN) with high activity. Seven primary field isolates from Japanese hemophiliacs seropositive for HIV-1 clade B were compared for their reactivities to Rmu5.5. Rmu5.5 was effective, particularly against the viruses that matched amino acid sequences of the PND region of HIV-1, and it completely neutralized primary isolates. Moreover, the passive transfer of the Ab elicited protection against challenge by the primary isolates in SCID-hu or hu-PBL-SCID mice after i.v. inoculation with the virus by both quantitative PCR and PBMC-based virus isolation in vitro. Further, inoculation with the Ab also prevented the atrophic change in the medulla of the thymic transplant that was induced by i.v. inoculation of the virus. Thus, the humanized neutralizing Ab Rmu5.5 appears to protect SCID-hu mice from infection by primary field isolates.

Adult↗

Cerebral processes related to visuomotor imagery and generation of simple finger movements studied with positron emission tomography.

Positron emission tomography was used to compare the functional anatomy of visual imagination and generation of movement. Subjects were asked to generate visual images of their finger movement in response to a preparatory signal. Four conditions were tested: in two, no actual movement was required; in the other two, a second signal prompted the subjects to execute the imagined movement. Which movement to imagine was either specified by the preparatory stimulus or freely selected by the subjects. Compared with a rest condition, tasks involving only imagination activated several cortical regions (inferoparietal cortex, presupplementary motor area, anterior cingulate cortex, premotor cortex, dorsolateral prefrontal cortex) contralateral to the imagined movement. Tasks involving both imagination and movement additionally increased activity in the ipsilateral cerebellum, thalamus, contralateral anteroparietal, and motor cortex and decreased activity in the inferior frontal cortex. These results support the hypothesis that distinct functional systems are involved in visuomotor imagination and generation of simple finger movements: associative parietofrontal areas are primarily related to visuomotor imagination, with inferior frontal cortex likely engaged in active motor suppression, and primary motor structures contribute mainly to movement execution.

Adult↗