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M Haraguchi

Publications and source records attributed to M Haraguchi.

At least 37 records · Page 2Linked to original sources
PubMed1999

Up-regulated pyrimidine nucleoside phosphorylase in breast carcinoma correlates with lymph node metastasis.

BACKGROUND: The clinical significance of pyrimidine nucleoside phosphorylase (PyNPase) activity in breast carcinomas has never been determined. MATERIALS AND METHODS: In 41 cases of breast carcinoma, the enzyme activity of PyNPase was determined by the high performance liquid chromatography (HPLC) assay and its value was analyzed with clinicopathologic variables. The expression level of mRNA was examined by the semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay and compared with the enzyme activity. RESULTS: The higher activity of PyNPase was significantly correlated not only with the presence of vascular permeation (P = 0.02) but of lymph node metastasis (P = 0.02). The mRNA expression correlated well with the enzyme activity (r = 0.74, P < 0.01). A multivariate analysis disclosed the PyNPase factor to be associated with lymph node metastasis. In addition, 17 (41%) showed positive staining only in the tumor stromal cells and 18 (44%) cases showed positive staining in both the tumor stromal cells and the carcinoma cells by immunohistochemical study. CONCLUSIONS: These findings suggest that PyNPase activity is a new marker predicting the malignant potential of breast carcinomas, especially with respect to lymph node metastasis, and that the RT-PCR assay is a more useful method than direct evaluation of PyNPase activity.

Adenocarcinoma↗
PubMed1999

Morphometric analysis of bronchial cartilage in chronic obstructive pulmonary disease and bronchial asthma.

To clarify the changes in bronchial cartilage in diseased airways, we performed morphometric analysis of airways in autopsied lungs of 16 patients with chronic bronchitis (Group CB), pulmonary emphysema (Group PE), and bronchial asthma (Group BA), and in control patients without respiratory diseases (Group CN). Although degeneration of bronchial cartilage was clearly observed in airways from all groups except Group CN, the most extreme change was seen in Group CB. Increased perichondrial fibrosis was observed in both Groups CB and BA, and the more extreme change was seen in Group BA. Both the area proportions of degenerated cartilage (Deg%) and perichondrial fibrosis (Fib%) to total cartilage in bronchi (3 to 8 mm in diameter), cut vertically in the cross-section profile, were measured with a digitizing tablet coupled to a computer. No significant differences in the area proportion of cartilage to bronchial wall were observed among the four study groups. The Deg% values of Groups CB (mean: 15.4%), BA (mean: 12.9%), and PE (mean: 9.6%) were significantly higher than those of Group CN (mean: 1.0%) (p < 0.01 in each case). The Deg% values correlated significantly with the number of neutrophils in the bronchial walls (r = 0.63, p < 0. 01). Both Group CB (mean: 28.5%) and Group BA (mean: 33.6%) showed significantly higher values of Fib% than did Group CN (mean: 18.5%) (p < 0.01, each), and the value for Group PE (mean: 21.8%) was slightly increased (p < 0.05). The values of Fib% correlated significantly with the number of eosinophils in the bronchial walls (r = 0.51, p < 0.05), thickness of basement membrane (r = 0.77, p < 0.0002), bronchial gland area (r = 0.56, p < 0.02), and goblet-cell area (r = 0.55, p < 0.02). Further, the values of Deg% correlated significantly with those of Fib% (r = 0.64, p < 0.01). These findings indicate that airways in chronic obstructive pulmonary disease and bronchial asthma have both degenerative changes in the cartilage (chondrocytes) and increased perichondrial fibrosis, and that these alterations in bronchial cartilage may differ in chronic bronchitis and bronchial asthma.

Aged↗
PubMed1999

Relationship between exercise capacity and ventilatory equivalent for carbon dioxide in patients with stable old myocardial infarction.

The aim of the present study was to evaluate the relationship between exercise capacity and ventilatory response in patients with stable old myocardial infarction. We performed cardiopulmonary exercise test in 61 patients with stable old myocardial infarction and in 30 healthy men. Each subject exercised on a bicycle ergometer until exhaustion. Patients who had anginal pain or electrocardiographic ischemic changes during exercise were excluded. The patients were classified into three groups according to peakVO2 achieved during exercise, using Weber's method: group A, peakVO2 > or = 21 ml/min/kg (n = 4); group B, 14 < or = peakVO2 < 21 ml/min/kg (n = 45); and group C, peakVO2 < 14 ml/min/kg (n = 12). With progressive increases in VCO2, VE increased linearly below the anaerobic threshold (AT) level. The slope of the linear regression line between VCO2 and VE (SLOPE) was calculated in each subject. The mean SLOPE of the healthy men (group N) and groups A, B and C were 25.8 +/- 0.5, 25.1 +/- 0.5, 28.9 +/- 0.8 and 37.1 +/- 1.7 (x 10(-3), respectively. Thus, the SLOPE was steeper in patients with lower peakVO2. It is difficult to perform a maximal exercise tolerance test on patients with chronic heart failure to evaluate their exercise capacity. We can assess exercise capacity by the slope of the linear regression line between VCO2 and VE (SLOPE) at the lower exercise level.

Aged↗
PubMed1999

[An autopsy case of Goodpasture's syndrome with P-ANCA and systemic vasculitis].

A 72-year-old woman was admitted because of anorexia and dyspnea. She was given a diagnosis of pulmonary hemorrhage and renal failure. Despite treatment with high-dose steroid and hemodialysis, the patient died of disseminated intravascular coagulation on the 9th hospital day. Autopsy revealed intra-alveolar hemorrhage, crescentic glomerulonephritis, and systemic vasculitis with fibrinoid necrosis. A direct immunofluorescence study demonstrated linear deposition of IgG along the glomerular basement membrane (GBM). Both anti-GBM antibody and anti-neutrophil cytoplasmic antibody with perinuclear pattern (P-ANCA) were detected in the patient's serum by enzyme immunoassay. Goodpasture's syndrome with P-ANCA was diagnosed. There has been some controversy as to whether vasculitis occurs in patients with Goodpasture's syndrome. This was a rare example of well-documented Goodpasture's syndrome with P-ANCA and systemic vasculitis, the exact etiologic relationships among which remain to be clarified.

Aged↗
PubMed1998

Complex gangliosides are essential in spermatogenesis of mice: possible roles in the transport of testosterone.

Mice, homozygous for disrupted ganglioside GM2/GD2 synthase (EC 2.4. 1.94) gene and lacking all complex gangliosides, do not display any major neurologic abnormalities. Further examination of these mutant mice, however, revealed that the males were sterile and aspermatogenic. In the seminiferous tubules of the mutant mice, a number of multinuclear giant cells and vacuolated Sertoli cells were observed. The levels of testosterone in the serum of these mice were very low, although testosterone production equaled that produced in wild-type mice. Testosterone was found to be accumulated in interstitial Leydig cells, and intratesticularly injected testosterone was poorly drained in seminiferous fluid in the mutant mice. These results suggested that complex gangliosides are essential in the transport of testosterone to the seminiferous tubules and bloodstream from Leydig cells. Our results provide insights into roles of gangliosides in vivo.

Animals↗
PubMed1998

Increased sensitivity to vincristine of MDR cells by the leukotriene D4 receptor antagonist, ONO-1078.

The leukotriene D4 (LTD4) receptor antagonist, 4-oxo-8-[p-(4-phenylbutyloxy)benzoylamino]-2-(tetrazol-5-yl) -4H-1-benzopyran hemihydrate (ONO-1078) is used for the treatment of allergic asthma and other immediate hypersensitivity diseases. We examined the effect of ONO-1078 on the sensitivity to vincristine (VCR) of MRP overexpressing multidrug-resistant CV60 and its parental drug-sensitive KB-3-1 cell lines. The sensitivity to VCR of KB-3-1 and CV60 cells was increased 13- and 15-fold, respectively, by ONO-1078 at the maximum non-toxic concentration (100 microM). The VCR sensitivity of multidrug-resistant KB-C2 cells that overexpressed P-gp was increased 2.6-fold by ONO-1078. The accumulation of VCR in KB-3-1, CV60 and KB-C2 cells was significantly increased by ONO-1078. The efflux of VCR from KB-3-1 cells was not inhibited, but that from CV60 cells was enhanced compared with that from KB-3-1 cells and was partially inhibited by ONO-1078. ONO-1078 competitively inhibited the ATP-dependent [3H]LTC4 uptake in membrane vesicles isolated from CV60 cells. These findings suggest that ONO-1078 inhibits the transporting activity of MRP and that ONO-1078 increases the sensitivity to VCR of KB-3-1 cells by increasing the VCR uptake in the cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Reversal of MRP-mediated vincristine resistance in KB cells by buthionine sulfoximine in combination with PAK-104P.

The mechanism of multidrug resistance protein (MRP)-mediated multidrug resistance (MDR) is still unclear. MRP reportedly transports some GSH conjugates. Recently, we demonstrated that a pyridine analog, 2-[4-(diphenylmethyl)-1-piperazinyl]ethyl 5-(trans-4,6-dimethyl-1,3,2-dioxaphosphorinan-2-yl)-2,6-dimethyl-4 -(3-nitrophenyl)-3-pyridinecarboxylate P-oxide (PAK-104P), that reversed P-glycoprotein (P-gp)-mediated MDR directly interacted with MRP and completely reversed the vincristine (VCR) resistance in MRP-mediated MDR C-A120 cells. We investigated the reversing effect of PAK-104P in C-A120 cells in combination with buthionine sulfoximine (BSO), another MDR-reversing agent with a different reversing mechanism. In immunoblots, MRP was overexpressed in C-A120 cells. The level of ATP-dependent [3H]VCR uptake was high in membrane vesicles from KB-C2 cells, but low in those from C-A120 and parental KB-3-1 cells. The sensitivity to VCR of C-A120 cells, but not of KB-C2 cells, was considerably increased by 100 microM BSO. VCR accumulation in C-A120 cells, but not in KB-C2 cells, was also enhanced by BSO. BSO did not inhibit ATP-dependent [3H]LTC4 uptake in C-A120 vesicles. The combination of BSO with PAK-104P at their low concentrations resulted in complete reversal of VCR resistance in C-A120 cells. These findings suggested that BSO might not directly interact with MRP and reversed resistance in MRP-mediated MDR cells by reducing the intracellular glutathione (GSH) level that was needed for the transport of drugs by MRP and suggested a role for the combination of drug resistance-modulating agents with different reversing mechanisms in the reversal of MRP-mediated MDR.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

An active efflux system for heavy metals in cisplatin-resistant human KB carcinoma cells.

The mechanism for cisplatin resistance in cisplatin-resistant KCP-4 cells was studied. Although multidrug resistance-associated protein (MRP) was not detected in KCP-4 cells, the cells were more resistant to heavy metals than multidrug-resistant C-A120 cells that overexpressed MRP. KCP-4 cells expressed metallothionein, but it was scarcely involved in cisplatin resistance in these cells. KCP-4 cells did not express canalicular multispecific organic anion transporter (cMOAT). The glutathione (GSH) level was 4.7-fold higher in KCP-4 cells than in KB-3-1 cells. When the GSH level in KCP-4 cells was decreased by treating the cells with buthionine sulfoximine and nitrofurantoin, the accumulation of and sensitivity to cisplatin in the cells were increased. C-A120 cells were only 3.0-fold more resistant to cisplatin than KB-3-1 cells and this resistance was not affected by the increased glutathione level. The accumulation of platinum in C-A120 and KCP-4 cells was 68.5 and 20.4% of that in KB-3-1 cells, respectively, while the intracellular levels of antimony potassium tartrate in C-A120 and KCP-4 cells were 13.2 and 9.9% of that in KB-3-1 cells, respectively. The ATP-dependent efflux of antimony was enhanced in both C-A120 and KCP-4 cells. These results, taken together, suggest an efflux pump for heavy metals different from MRP and cMOAT is involved in cisplatin resistance in KCP-4 cells.

ATP-Binding Cassette Transporters↗
PubMed1998

Distribution of the tetrodotoxin-resistant sodium channel PN3 in rat sensory neurons in normal and neuropathic conditions.

The novel sodium channel PN3/alpha-SNS, which was cloned from a rat dorsal root ganglion (DRG) cDNA library, is expressed predominantly in small sensory neurons and may contribute to the tetrodotoxin-resistant (TTXR) sodium current that is believed to be associated with central sensitization in chronic neuropathic pain states. To assess further the role of PN3, we have used electrophysiological, in situ hybridization and immunohistochemical methods to monitor changes in TTXR sodium current and the distribution of PN3 in normal and peripheral nerve-injured rats. (1) Whole-cell patch-clamp recordings showed that there were no significant changes in the TTXR and TTX-sensitive sodium current densities of small DRG neurons after chronic constriction injury (CCI) of the sciatic nerve. (2) Additionally, in situ hybridization showed that there was no change in the expression of PN3 mRNA in the DRG up to 14 d after CCI. PN3 mRNA was not detected in sections of brain and spinal cord taken from either normal or nerve-injured rats. (3) In contrast, immunohistochemical studies showed that major changes in the subcellular distribution of PN3 protein were caused by either CCI or complete transection of the sciatic nerve. The intensity of PN3 immunolabeling decreased in small DRG neurons and increased in sciatic nerve axons at the site of injury. The alteration in immunolabeling was attributed to translocation of presynthesized, intracellularly located PN3 protein from neuronal somata to peripheral axons, with subsequent accumulation at the site of injury. The specific subcellular redistribution of PN3 after peripheral nerve injury may be an important factor in establishing peripheral nerve hyperexcitability and resultant neuropathic pain.

Animals↗
PubMed1998

Toxic peripheral neuropathy of chicks fed Senna occidentalis seeds.

Plants of the genus Senna (formerly Cassia) are poisonous to livestock and other laboratory animals, leading to a syndrome of a widespread muscle degeneration, incoordination, recumbence, and death. The main histologic lesion is necrosis of skeletal muscle fibers. Recently, a mitochondrial myopathy with ragged-red and cytochrome oxidase (COX)-negative muscle fibers was recognized in hens chronically intoxicated with parts of seeds of S. occidentalis. The purpose of the present work was to investigate if there was peripheral nerve involvement in the acute intoxication of chicks with S. occidentalis seeds. Teasing of individual fibers revealed signs of extensive axonal damage with myelin ovoids. Ultrathin sections confirmed the axonal damage. Axons were filled with membranes, some residual disorganized filaments, and enlarged mitochondria. In some instances the axon disappeared and there was secondary degeneration of the myelin sheath. The present work is the first description of the neurotoxic effect of S. occidentalis intoxication. Future work should attempt to determine the mechanisms involved in this neuropathy.

Animal Feed↗
PubMed1998

Acinar cell carcinoma of the pancreas associated with hypoglycemia: involvement of "big" insulin-like growth factor-II.

Apart from insulinomas, pancreatic tumors are rarely complicated by hypoglycemia and some may produce insulin-like growth factor II (IGF-II). To our knowledge, IGF-II-producing pancreatic tumors associated with hypoglycemia have not been reported previously. We describe what we believe to be the first case of "big" IGF-II-producing pancreatic acinar cell carcinoma. A 68-year-old man presented with a history of recurrent hypoglycemia. Abdominal computed tomography scan and magnetic resonance imaging showed a mass, approximately 5 cm in diameter, in the tail of the pancreas and two low-density areas in the liver. Low serum glucose was associated with low insulin levels and high levels of hormones (i.e., glucagon and IGF-II) that are functionally opposite to insulin. Although serum IGF-II level was within the normal range, most IGF-II was of the high molecular weight form, as determined by Western immunoblot analysis. Based on these findings, a diagnosis of hypoglycemia induced by IGF-II-producing pancreatic tumor was made. Surgery was not possible because of the patient's poor general condition. The patient ultimately died as a result of malignant cachexia. At autopsy, a yellowish-white tumor was found in the tail of the pancreas, and a histopathologic diagnosis of acinar cell carcinoma was made. Immunohistologically, the tumor cells contained IGF-II in an irregular staining pattern, suggesting that the hypoglycemia was caused by a pancreatic tumor producing "big" IGF-II.

Aged↗
PubMed1998

Anxiolytic effect of Rubus brasilensis in rats and mice.

The aim of the present work was to investigate if infuse and ethanolic extracts (aqueous, butanolic and wax fractions) of Rubus brasiliensis Martius (Rosaceae) induce anxiolytic effect. The extracts were administered to male Wistar rats and Swiss mice per oral route, at 50, 100 and 150 mg/kg, 30 min before the behavioral evaluation in the elevated plus maze (EPM). Both infuse and wax ethanolic fraction at the dosage 150 mg/kg, vo, increased the number and the percentage of open arm entries of rats and mice. The aqueous and butanolic fractions, obtained from ethanolic extract, failed to induce anxiolytic effect. The treatment of mice with flumazenil (Ro 15-1788), 1.5, 2.0 and 2.5 mg/kg, i.p., 15-min before the administration of infuse or wax fraction, 150 mg/kg, vo, blocked the infuse or wax fraction-induced anxiolytic effect. The LD50 for the wax fraction was 1000 mg/kg. In conclusion, the infuse and wax ethanolic fraction of R. brasiliensis present anxiolytic effect in rats and mice. In addition, it is suggested that the anxiolytic effect may be attributed at least to one liposoluble principle with low acute toxicity which may be acting as an agonist on GABA(A)-benzodiazepine receptor complex.

Animals↗
PubMed1998

Muscle atrophy induced in broiler chicks by parts of Senna occidentalis seeds.

Senna occidentalis (formerly Cassia occidentalis) is a common contaminant of agricultural commodities. It is toxic to cattle and poultry, reportedly being responsible for skeletal myodegeneration in these animals. All parts of the plant present toxicity, but the seeds are the most toxic. The toxin(s) responsible for the myodegeneration have not been definitively identified, nor is it known which part of the seeds is most toxic. Intoxication by this plant leads to weight loss with considerable economic repercussions. The effects of the whole seed and of parts of S. occidentalis seeds (1% in commercial feed) were compared on the pectoralis major muscle of broiler chicks intoxicated from birth until 22 days of life. There were severe clinical signals and reduced body weight in birds that received the external tegment of the seed, whereas no adverse effects were observed in birds that received the whole seed or other parts of the seed. Histological and morphometric studies showed an intense muscle fibre atrophy (both type 1 and type 2 fibres were affected) in the group that received 1% external tegment. This study may be the first step to identifying the substance(s) involved in this pathological process.

Animal Feed↗
PubMed1998

Association between restriction fragment length polymorphism of the L-myc gene and susceptibility to gastric cancer.

BACKGROUND: L-myc polymorphism has been documented to be a representative genetic trait which is related an individual's susceptibility to several cancers. However, there have been no reports concerning any significant association between susceptibility to gastric cancer and L-myc polymorphism. METHODS: The distribution of L-myc polymorphism in 61 patients with gastric cancer was determined by polymerase chain reaction-based restriction fragment length polymorphism and compared with that of 107 healthy control subjects. RESULTS: There was a significant difference in the distribution of both genotypes (P = 0.024) and allele frequencies (P = 0.026) between the two groups. The relative risk of gastric cancer for genotypes with the shorter (S) allele was 3.09 compared with the longer (L) allele homozygote. No significant correlation with clinicopathological features of the cancers except for prognosis was found. The patients with SS genotypes had a worse prognosis than those with LL or LS genotypes (P = 0.029). CONCLUSION: L-myc polymorphism may be significant in an individual's susceptibility to gastric cancer in Japan, and may be a useful marker for identifying patients at high risk of developing gastric cancer.

Disease Susceptibility↗
PubMed1998

Pulmonary function and regional distribution of emphysema as determined by high-resolution computed tomography.

In patients with pulmonary emphysema, emphysematous changes are not uniform and vary from minimum alveolar destruction to advanced bullous formation, depending on the lobe or site in the lungs. However, we have little knowledge on whether or how this nonuniformity or localization affects pulmonary function in PE patients. Therefore, we measured the computed tomography (CT) density of divided sites in lungs with high-resolution CT images from 25 PE patients (FEV1.0%, mean +/- SD 36 +/- 9%, %DLCO 48 +/- 16%, all men, 68 +/- 4 years) and compared them to various parameters of pulmonary function. The mean CT density of whole lungs correlated with 12 pulmonary function parameters including FEV1.0 and diffusion capacity. When both lung fields were divided into peripheral, intermediate and central portions, the CT density of the central portion correlated with all pulmonary function parameters with which CT density of whole lungs correlated. In contrast, the CT density of the peripheral portion significantly correlated with only 7 parameters with smaller correlation coefficient values than those of the central portion. When divided into upper, middle and lower portions, the CT densities of upper, middle and lower portions correlated with 6, 8 and 10 of the 12 pulmonary function parameters which correlated with the density of whole lungs, respectively. The delta value of CT densities between the upper and lower portions or between the lateral and medial portions correlated with obstructive impairment (FEV1.0 and FEV1.0%). These findings suggest that (1) central rather than peripheral emphysematous changes affect pulmonary function, and (2) uniformity of emphysematous change correlates with the severity of airway obstruction in PE patients.

Adult↗
PubMed1998

Clinical features of polymyositis/dermatomyositis with steroid-resistant interstitial lung disease.

Polymyositis and dermatomyositis (PM/DM) without creatine kinase (CK) elevation shows a poor prognosis. PM/DM is complicated with interstitial lung disease (ILD), some of which progress rapidly. To clarify the clinical features of PM/DM from the viewpoint of ILD progression, the clinical data of 25 PM/DM patients with ILD were reviewed. They were classified as responders or non-responders. The patients whose ILD responded to steroid therapy and elicited good clinical courses were termed as responders. On the other hand, the patients who had rapidly progressive ILD resistant to steroid therapy were considered as non-responders. The patients diagnosed to have DM were likely to be steroid-resistant. The non-responder group revealed significantly high aspartate aminotransferase (AST), low CK, low white blood cell (WBC), and low absolute lymphocyte counts in their peripheral blood. High CK/AST may be a favorable predictor of the disease. The percentages of lymphocytes in bronchoalveolar lavage fluid were increased in both groups. However, the percentages of two responders with low CK/AST were lower than those of three non-responders. A steroid-resistant ILD group with PM/DM may be clinically different from a steroid-responsive ILD group.

Aged↗