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Biomedical subjects

K Dohi

Publications and source records attributed to K Dohi.

At least 181 records · Page 10Linked to original sources
PubMed1998

Effects of miso and NaCl on the development of colonic aberrant crypt foci induced by azoxymethane in F344 rats.

The present study was designed to investigate the effects of dietary miso and NaCl supplementation on the development of aberrant crypt foci (ACF) induced by azoxymethane (AOM) in male F344 rats. A total of 76 rats, six weeks of age, were divided into seven groups and given weekly subcutaneous injections of AOM (15 mg/kg body wt) for three weeks to induce ACF. The animals were placed on diets one week before the first AOM dosing. Group 1 was fed a normal diet as a control. Groups 2-4 were fed diets containing 5%, 10%, and 20% miso, respectively, and Groups 5 and 6 were fed diets containing 2.2% and 4.4% NaCl, respectively, for five weeks. Group 7 was fed a normal diet without carcinogen exposure. Dietary miso inhibited the development of ACF in a dose-dependent manner (y = -3.9x + 140, r = -0.94). Thus the mean numbers of ACF per colon were significantly lower in Groups 3 and 4 than in Group 1 (p < 0.01), and there were fewer aberrant crypts per colon in Group 4 than in Group 1. NaCl supplementation was associated with fewer ACF, but this was not statistically significant. 5-Bromo-2'-deoxyuridine labeling indexes in the colonic epithelium were significantly lower in Group 3 than in Group 1 (p < 0.05). The present results indicate that dietary miso could act as a chemopreventive agent for colon carcinogenesis.

Animals↗
PubMed1998

Malignant phyllodes tumor of the breast with hypoglycemia: report of a case.

A surgically resected case of giant malignant phyllodes tumor of the breast associated with a hypoglycemic attack is reported. A 54-year-old woman was referred to our hospital with loss of consciousness and a huge chest wall tumor. She was diagnosed as having a malignant phyllodes tumor by core needle biopsy and underwent palliative simple mastectomy because lung metastasis was detected on computed tomography and by other imaging modalities on admission. The preoperative laboratory data revealed a very low fasting blood sugar level of 37 mg/dl. After removal of the tumor, the blood sugar level gradually normalized (90-100 mg/dl) and the plasma insulin-like growth factor-II (IGF-II) level promptly decreased. The IGF-II level of tumor extracts was high (2500 ng/g wet weight) and the majority of atypical cells stained positively for IGF-II immunohistochemically. These findings suggested that the patient's hypoglycemia was associated with IGF-II produced by a giant malignant phyllodes tumor that consumed glucose.

Biopsy↗
PubMed1998

Increased plasma concentration of adrenomedullin in patients with subarachnoid hemorrhage.

UNLABELLED: Adrenomedullin (AM) is a potent hypotensive peptide originally identified in pheochromocytoma tissues. Impaired cardiovascular conditions, such as hypertension, myocardial infarction, and septic shock, stimulate production of AM. This study was performed to determine whether subarachnoid hemorrhage (SAH) altered plasma AM concentration. Plasma concentrations of AM in 17 patients with SAH were measured for 2 wk after the onset of SAH by AM-specific radioimmunoassay. Plasma concentrations of AM were increased in patients with SAH throughout the study period, compared with those in control subjects. Plasma concentrations of AM in patients classified as Hunt and Kosnik grade III or IV were significantly higher than those classified as Hunt and Kosnik grade I or II on the day of and the day after the onset of SAH. However, plasma concentrations of AM were unaffected by angiographic vasospasm. These findings suggest that plasma concentrations of AM are increased in patients with SAH and may reflect the severity of SAH. IMPLICATIONS: Adrenomedullin has been reported to affect the cerebral circulation. This study was performed to determine whether subarachnoid hemorrhage, a typical cerebrovascular disorder, altered plasma adrenomedullin concentrations. We found that plasma adrenomedullin concentrations increased in patients with subarachnoid hemorrhage, although no relationship was found between plasma adrenomedullin concentration and angiographic vasospasm. Plasma adrenomedullin concentration may reflect the severity of hemorrhage.

Adrenomedullin↗
PubMed1998

Nucleic acid-binding properties and subcellular localization of the 3a protein of brome mosaic bromovirus.

Brome mosaic bromovirus (BMV) 3a protein is required for cell-to-cell movement of the virus in host plants. The BMV 3a protein (B3a) was produced in Escherichia coli using an expression vector. Gel retardation analysis and UV cross-linking experiments demonstrated that B3a bound single-stranded RNA cooperatively without sequence specificity. Binding competition analysis showed that B3a bound to single-stranded nucleic acids more strongly than to double-stranded nucleic acids. Deletion mutagenesis located a nucleic acid-binding domain to amino acids 189-242. Western blot analysis of fractionated proteins of BMV-infected barley using monoclonal antibodies against B3a indicated that B3a may interact with membrane materials and form complexes in the cytoplasm. Immunogold labelling of thin sections of infected barley tissues revealed that B3a was associated with plasmodesmata and cytoplasmic inclusions.

Amino Acid Sequence↗
PubMed1998

Chemoprevention of N-nitroso-N-methylurea-induced rat mammary carcinogenesis by soy foods or biochanin A.

We examined the effects of soybeans, a soy product (miso) and biochanin A, an isoflavone derivative, on N-nitroso-N-methylurea (MNU)-induced rat mammary carcinogenesis. Seven-week-old female CD/Crj rats received a single i.v. dose (40 mg/kg body weight) of MNU. After administration of MNU, rats were fed diet containing 0% (control), 2% or 10% soybeans, or 10% miso as a soy-supplemented diet, or 10 or 50 mg/kg biochanin A. All rats were observed for 18 weeks after MNU administration. At 18 weeks, the multiplicity (mean tumors/rat) of palpable mammary tumors was significantly decreased in the 10% soybean (1.1) and 10% miso (1.2) diet groups compared to the control (2.2) (P<0.05, respectively). In the biochanin A-supplemented diet groups, the incidence (percentage of rats with tumors) was significantly decreased in the 50 mg/kg (32%) diet group compared to the control (80%) (P<0.01), and the multiplicity was significantly decreased in both the 10 mg/kg (0.7) and 50 mg/kg (0.5) diet groups compared to the control (2.2) (P<0.01 and P<0.001, respectively). The proliferative cell nuclear antigen labeling index of mammary tumors was significantly decreased in both biochanin A-supplemented diet groups compared to the control. The present results indicate that soybeans, miso, and biochanin A are useful for the prevention of mammary cancer.

Animals↗
PubMed1998

p53 gene mutation and loss of heterozygosity of chromosome 11 in methylcholanthrene-induced mouse sarcomas.

Mutations of the p53 tumor suppressor gene are the most prevalent genetic alteration observed in a wide variety of human cancers. In this study we examined 63 methylcholanthrene (MCA)-induced sarcomas from C57BL/6N x C3H/HeN F1 (BCF1) or C3H/HeN x C57BL/6N F1 (CBF1) mice for p53 gene mutations and loss of heterozygosity (LOH) of chromosome 11. Mutation analysis was done on exons 5 to 8 of the p53 gene by polymerase chain reaction-single strand conformation polymorphism analysis. This identified 53 potential mutations in 45 sarcomas. Mutations were further confirmed by direct sequencing of the region. Forty-nine of the 53 cases (94%) were missense mutations, while the rest included two nonsense mutations, one silent mutation and one insertional mutation. Spectra of base substitutions were: 25 cases (47%) of G:C-->T:A transversion, 13 cases (25%) of G:C-->A:T transition (CpG site 15%), 13 cases (24%) of G:C-->C:G transversion, a case (2%) of A:T-->T:A transversion and a case (2%) of insertion. In addition, analysis of 5 polymorphic markers of mouse chromosome 11 revealed LOH in ten cases (22%) among those carrying p53 mutations. In nine of these 10 cases, the loss involved all 5 markers. In addition, the loss was biased toward the C57BL allele (9 cases). The present study establishes the pattern of mutation of the p53 gene in MCA-induced mouse sarcomas.

Amino Acid Sequence↗
PubMed1998

Chemoprevention of N-nitroso-N-methylurea-induced rat mammary cancer by miso and tamoxifen, alone and in combination.

We examined the effects of a Japanese fermented soybean product, miso, and tamoxifen (TAM), alone and in combination, on N-nitroso-N-methylurea (MNU)-induced rat mammary cancer. Seven-week-old female CD/Crj rats received a single i.v. dose (50 mg/kg body weight) of MNU. After administration of MNU, the rats were divided into 4 groups: regular diet (control), 10% miso diet, regular diet + TAM, and 10% miso diet + TAM. TAM was implanted s.c. in the form of pellets containing 2.5 mg at the same time as MNU was administered. All rats were observed for 18 weeks after MNU administration. Incidence (percentage of rats with tumors) and multiplicity (mean tumors/rat) of mammary tumors were 91% and 4.5 in the control, 77% and 2.4 (P < 0.05) in the 10% miso group, 68% and 1.4 (P <0.01) in the TAM group, and 10% (P < 0.0001 or less) and 0.2 (P < 0.0001) in the 10% miso + TAM group. In the second experiment, the effect of the combination of miso and TAM on established rat mammary tumors was investigated. When the mammary tumors induced by MNU reached 10 to 25 mm, the rats were divided into 3 treatment groups: regular diet, regular diet + TAM, and 10% miso diet + TAM. At 6 weeks after the start of treatment, the mean tumor size in the control and TAM groups was 160% and 141% of the pretreatment value, but a decrease of 85% of the pretreatment value was produced by the combination of miso and TAM, and this was significantly different from both the control and TAM groups (P < 0.01) and P < 0.05, respectively). These results indicate that miso is useful in protecting against mammary cancer and it can be expected to have a potent antitumor effect, especially when used in combination with TAM.

Animals↗
PubMed1998

Leukocyte adhesion molecule expression during intense resistance exercise.

We hypothesized that expression of L-selectin and very late antigen-4 (VLA-4) integrin adhesion molecules would influence cell type-specific redistribution during exercise. Women subjects performed six sets of 10-repetition maximum squats. L-selectin and VLA-4 integrin were measured by using flow cytometry pre- and postexercise on peripheral blood neutrophils and lymphocytes (n = 29 subjects) and lymphocyte subsets (n = 70 subjects), respectively. Neutrophil concentration increased 41.8% (P < 0.001), whereas the percent expressing L-selectin was unchanged (79%). Lymphocyte concentration increased 61.8% (P < 0.001). The percent of T cells expressing L-selectin decreased from 73.5 +/- 8.9 to 68.2 +/- 11.4% (P < 0.001); the combined population of natural killer and B cells expressing L-selectin decreased from 80.4 +/- 22.5 to 62.7 +/- 25.8% (P < 0.001). VLA-4 integrin was expressed by nearly all lymphocytes both pre- and postexercise. The proportional decrease in L-selectin positive cells could have resulted from 1) shedding of L-selectin, 2) selective entry of L-selectin-negative subsets, or 3) selective removal of L-selectin-positive subsets.

Adult↗
PubMed1998

Increased excretion of urinary transforming growth factor beta 1 in patients with diabetic nephropathy.

The accumulation of extracellular matrix in the glomeruli of human and experimental models of diabetic nephropathy is associated with disease progression. Transforming growth factor beta 1 (TGF-beta1), which is a multifunctional peptide growth factor, plays a key role in the synthesis of extracellular matrix protein in vitro, and the expression of TGF-beta1 is elevated in human and rat diabetic nephropathy. In this study, we measured the urinary TGF-beta1 excretion in 57 patients with non-insulin-dependent diabetes mellitus and in 20 healthy volunteers to examine whether the determination of urinary TGF-beta1 excretion would facilitate the evaluation of the degree of mesangial expansion in patients with diabetic nephropathy. Both active and total TGF-beta1 levels in 24-hour urine samples collected from patients with diabetes mellitus and normal controls were measured using an enzyme-linked immunosorbent assay. We observed a higher excretion of urinary TGF-beta1 in patients with diabetes mellitus than in normal controls. In addition, the urinary TGF-beta1 excretion was elevated in patients with severe mesangial expansion. These results suggest that urinary TGF-beta1 may represent one parameter that can be used to evaluate the progression of diabetic nephropathy.

Biomarkers↗
PubMed1998

Cell proliferation and apoptosis of the glomerular epithelial cells in rats with puromycin aminonucleoside nephrosis.

Injury and repair of the glomerular epithelial cells (GECs) play an important role in the pathogenesis of focal segmental glomerulosclerosis (FSGS). To obtain a better understanding of proliferation and apoptosis of GECs, we examined immunohistochemical and in situ hybridization findings in puromycin aminonucleoside nephrosis (PAN) of rats. The minimal-change nephrotic syndrome model (PAN-MCNS) was induced by administering 5 subcutaneous injections of puromycin aminonucleoside (PA; each 1.5 mg/100 g B/W to one group of rats), whereas the FSGS model (PAN-FSGS) was induced by administering an additional 5 injections of PA to another group of rats. The cell kinetics of the GECs were assessed with labeling 5-bromo 2'-deoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA). To investigate regulation of apoptosis in rats with PAN, we evaluated the expression of p53, Fas antigen, Fas ligand and Bc1-2. Rats with PAN-MCNS exhibited a significantly greater number of BrdU- and PCNA-labeled GECs as compared with control rats. In rats with PAN-FSGS, the number of PCNA-labeled GECs was greater than in rats with PAN-MCNS, but the number of BrdU-labeled GECs was lower. Apoptotic cells were occasionally observed in the sclerotic lesions, with the number being significantly higher in rats with PAN-FSGS than in rats with PAN-MCNS and control. Apoptotic cells were observed in the GECs of PAN-FSGS rats. However, they were negative for p53, Fas antigen, and Fas ligand. Immunohistochemical and in situ hybridization studies revealed a greater intraglomerular overexpression of Bc1-2 protein and bc1-2 mRNA in the PAN-FSGS rats as compared with control rats. These results suggest that insufficient proliferation and apoptosis in GECs may be involved in the progression of FSGS.

Animals↗
PubMed1998

Measurement of plasma and urinary adrenomedullin in patients with IgA nephropathy.

In this study, we measured plasma and urinary adrenomedullin (AM) concentrations in 47 patients with IgA nephropathy. Controls were 39 healthy volunteers. Plasma and urinary AM values were measured by specific radioimmunoassay. The plasma AM concentrations were higher, and the urinary AM levels were lower in patients with IgA nephropathy than in healthy volunteers. Plasma AM concentrations showed a positive correlation with serum creatinine and blood urea nitrogen, whereas urinary AM levels correlated negatively with serum creatinine and blood urea nitrogen. The plasma AM concentrations showed a positive correlation with fractional excretions of sodium and potassium. Renal biopsy specimens of patients without renal failure were scored for activity (percentage of glomeruli demonstrating cellular crescent formation, degree of mesangial proliferation and interstitial infiltration; total score = 9). Urinary AM levels were shown to be lower in the group with a high activity (score 3-9) as compared with the group with a low activity (score 0-2) based on renal biopsy. Thus, urinary levels of AM are affected by the degree of the activity in IgA nephropathy, and AM may participate in the pathophysiology of IgA nephropathy.

Adrenomedullin↗
PubMed1998

Discordance between retinopathy and nephropathy in type 2 diabetes.

The aim of this study was to investigate the relationship between the grade of retinopathy and the severity of glomerular lesions in patients with type 2 diabetes and to describe 5 patients without diabetic retinopathy for whom renal biopsy specimens demonstrated advanced diabetic nephropathy. A total of 221 patients with type 2 diabetes (139 males and 82 females) who consectively underwent renal biopsy between 1982 and 1996 were investigated. The severity of diffuse glomerular lesions was graded using the criteria of Gellman and coworkers, and diabetic retinopathy was classified as absent, nonproliferative, or proliferative. The incidence of advanced nephropathy without retinopathy for all 221 cases was 2.3%. Advanced nephropathy was present in 5 of the 122 (4.1%) patients without retinopathy. These 5 patients were all males and aged 50-70 (mean 61) years. Their clinical characteristics were not uniform, and no special clinical features distinguished the patients who were regarded as having possible advanced nephropathy without retinopathy. In our study, although concordance of retinopathy and nephropathy is relatively common, a little discordance was pronounced in Japanese type 2 diabetic patients. Our findings are consistent with the hypothesis that there are important differences in some aspects of the pathogenesis of retinopathy and nephropathy.

Aged↗
PubMed1998

Plasma and urinary levels of adrenomedullin in chronic glomerulonephritis patients with proteinuria.

In this study, we measured levels of plasma and urinary adrenomedullin (AM) in 37 patients with chronic glomerulonephritis including minimal change nephrotic syndrome, focal segmental glomerulosclerosis or membranous nephropathy that can induce severe proteinuria. Thirty-nine healthy volunteers were enrolled as controls. Plasma and urinary AM levels were measured by an AM-specific radioimmunoassay. Plasma AM concentrations were higher and urinary AM levels were lower in patients with chronic glomerulonephritis than in healthy volunteers. Patients were divided into two groups according to urinary excretion of protein for 24 h (UPro, g/day) which reflects the disease activity or glomerular damage of the glomerulonephritis (group I: Upro < 1, group II: Upro >= 1). Plasma AM levels positively and urinary AM-levels negatively correlated with the degree of proteinuria. These results suggest that plasma and urinary AM levels in patients with chronic glomerulonephritis reflect the disease activity or glomerular damage represented by the degree of proteinuria.

Adrenomedullin↗
PubMed1998

Relationship between lupus nephritis activity and the serum level of soluble VCAM-1.

We measured the serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin) and soluble intercellular adhesion molecule-1 (sICAM-1) in 72 patients with systemic lupus erythematosus (SLE) (including patients with active nephritis) and 33 normal control subjects, to investigate the correlation between levels of adhesion molecules and disease and histological activity. Serum samples were obtained at the time of renal biopsy in 27 patients with lupus nephritis. The 27 patients were divided into groups according to the World Health Organization (WHO) class as follows: class I + II, n = 11; class III + IV, n = 13 and class V, n = 3. We also determined the activity index (AI) in these 27 renal biopsy specimens. We obtained serial measurements of the serum levels of soluble adhesion molecules in 11 patients to examine the difference between active and remission stages. The serum level of sVCAM-1, but not sE-selectin or sICAM-1, was correlated with parameters of SLE disease activity, including the SLE disease activity index score, the anti-double stranded DNA antibody titer, the C3 level, the C4 level and the CH50 level. The serum levels of sVCAM-1, sE-selectin and sICAM-1 were significantly higher in patients with SLE than in controls (P = 0.006, P = 0.0005 and P = 0.04, respectively). The serum level of sVCAM-1 was significantly higher in patients with active lupus nephritis (WHO classes III and IV) than in patients in inactive lupus nephritis (WHO classes I and II) (P = 0.0016). The sVCAM-1 level was significantly elevated in patients with an AI > or = 4 compared with patients with an AI < 4 (P = 0.0025). The sVCAM-1 level decreased significantly during remission (P = 0.0033). The serum level of sVCAM-1 was elevated in patients with active lupus nephritis (WHO classes III and IV) and in patients with high AI scores. The serum level of sVCAM-1 was correlated with the SLE disease activity and decreased during remission. Therefore, the sVCAM-1 level may be a useful marker of lupus nephritis activity.

Adolescent↗
PubMed1998

Association of an insertion polymorphism of angiotensin-converting enzyme gene with the activity of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) shows various clinical manifestations, which are characterized by inflammation in many different organ systems. The cause of SLE is still unclear; however, the immunological abnormalities are considered to be responsible for the pathogenesis of SLE. As angiotensin I-converting enzyme (ACE) has been reported to be associated with various immunological phenomena, we investigated the correlation between insertion (I)/deletion (D) polymorphism of the ACE gene and the disease activity of SLE. Ninety-three patients with newly diagnosed SLE were enrolled in this study. ACE genotype was determined by the polymerase chain reaction (PCR). We measured serum levels of anti-double-stranded (ds) DNA antibody (Ab) and serum levels of total complements (CH50) as the parameter for lupus activity. Moreover, we evaluated the clinical disease activity by calculating SLE disease activity index (SLEDAI). Individuals with II genotype showed a significant increase in SLE activity. Patients with the ACE II genotype showed a higher serum level of anti-dsDNA Ab (14.3 IU/ml (5.475, 74.6, median (25th centile, 75th centile)) than those with the DD genotype (4.65IU/ml (4.05, 6.8)) (P<0.01). Moreover, patients with the 11 genotype also showed lower levels of serum CH50 than those with the DD genotype (P < 0.01). Patients with the II1 or DI genotype had significantly higher SLEDAI score than those with the DD genotype (P < 0.01). These results suggest that the ACE genotype could be associated with the disease activity of SLE. ACE insertion polymorphism might be used as one of predictive factors for the activity of lupus.

Adult↗
PubMed1998

Motility of the canine pyloric ring following a pylorus-preserving pancreatoduodenectomy.

Recently, function-preserving operations have become popular, and pylorus-preserving pancreatoduodenectomy (PPPD) is frequently performed for diseases of the head of the pancreas. However, there are only a few basic studies on the pyloric function after PPPD. Using strain gauge force transducers (SGTs), we studied the pyloric motility of normal and PPPD dogs. We prepared three normal and three PPPD dogs in which the SGTs were implanted onto the antrum and pyloric ring, etc. In conscious dogs, the spontaneous gastrointestinal motility was recorded, and the plasma motilin concentration was measured during the interdigestive state. Following the administration of exogenous Leu13-motilin, the motility was again recorded. The relaxation and opening of the pyloric ring was observed synchronously with intense contractions of the antrum during the phase III of normal dogs. Phase III-like motility was recorded in the PPPD dogs, which was not a typical periodic motility. The plasma motilin concentration of one PPPD dog could be measured, and the motilin levels during the phase III-like motility were higher than during phase I. The phase III-like motility was induced by Leu13-motilin in both normal and PPPD dogs. The phase III-like motility recorded in the PPPD dogs was not a typical periodic one, and this aberrant motility was considered to be one of the causes of delayed gastric emptying. Phase III-like motility was induced by the administration of Leu13-motilin; therefore, it is possible that Leu13-motilin improved the motility of the pyloric ring after PPPD.

Animals↗
PubMed1998

Apical hypertrophy with massive myocardial fibrosis: comparison with electrocardiographic changes.

We report the case of a 48-year-old woman with apical hypertrophy with massive myocardial fibrosis. She was admitted to our hospital because of general malaise. Echocardiographic examination showed asymmetrical apical hypertrophy, and an electrocardiogram showed a giant negative T wave on V3-V6. Right ventricular endomyocardial biopsy revealed massive myocardial fibrosis. Apical hypertrophy can lead to disorders that vary in severity, including rare massive myocardial fibrosis.

Biopsy↗