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Biomedical subjects

S Haga

Publications and source records attributed to S Haga.

At least 73 records · Page 4Linked to original sources
PubMed1998

Isolation of a novel human canalicular multispecific organic anion transporter, cMOAT2/MRP3, and its expression in cisplatin-resistant cancer cells with decreased ATP-dependent drug transport.

The human multidrug resistance protein (MRP) gene encodes a membrane protein involved in the ATP-dependent transport of hydrophobic compounds. We previously isolated a canalicular multispecific organic anion transporter, cMOAT1/MRP2, that belongs to the ATP binding cassette (ABC) superfamily, which is specifically expressed in liver, and cMOAT1/MRP2 is responsible for the defects in hyperbilirubinemia II/Dubin-Johnson syndrome. In this study, we isolated a new cDNA of the ABC superfamily designated cMOAT2/MRP3 that is homologous to human MRP1 and cMOAT1/MRP2: cMOAT2/MRP3 is 56% identical to MRP1 and 45% identical to cMOAT1/MRP2, respectively. Fluorescence in situ hybridization demonstrated the chromosomal locus of this gene on chromosome 17q22. The human cMOAT2 cDNA hybridized to a 6.5-kb mRNA that was mainly expressed in liver and to a lesser extent in colon, small intestine, and prostate. The cMOAT2/MRP3 gene was not overexpressed in cisplatin-resistant cell lines with increased ATP-dependent transport of cisplatin over their parental counterparts derived from human head and neck cancer and human prostatic cancer cell lines. The human cMOAT2/MRP3, a novel member of the ABC superfamily, may function as a membrane transporter in liver, colon, and prostate.

Adenosine Triphosphate↗
PubMed1998

Acinic Cell Adenocarcinoma Arising in the Breast of a Young Male: A Clinicopathological, Immunohistochemical and Ultrastructural Study.

A 23-year-old man with acinic cell adenocarcinoma of the breast is reported. He presented with a 4.8 x 4.2 cm mass in his left breast, and excisional biopsy was performed. Under the light microscope, tumor cells had abundant periodic acid-Schiff-positive secretory granules and eosinophlic cytoplasms. Electron microscopy revealed the granules to have various electron densities, a finding characteristic of acinic cell adenocarcinoma. Immunohistochemically, the tumor cells were stained with salivary-type amylase. Electron microscpic and immunohistochemical investigation greatly facilitated the diagnosis of this acinic cell adenocarcinoma, which was in an unusual location. We believe this is the first case report of acinic cell adenocarcinoma of the mammary gland studied utilizing light microscopic, ultrastructural and immunohistochemical techniques.

Journal Article↗
PubMed1998

Stroke due to a fusiform aneurysm of the cervical vertebral artery: case report.

Aneurysms of the cervical vertebral artery (VA) are uncommon; they are often caused by trauma or spontaneous dissection. A fusiform aneurysm without evidence of atherosclerosis or dissection has not been reported previously. A 46-year-old man presented with a pontine infarct. Imaging revealed a fusiform aneurysm of the left VA at the C5-6 level, with occlusion of the basilar artery. Associated minor anomalies included fusion of the vertebral bodies of C5 and C6, cervical rib and platybasia. The left VA arose directly from the aortic arch and entered the transverse foramen at the C4 level. Hyperextension and left lateral flexion of the neck caused kinking of the VA proximal to the aneurysm. Turbulent flow in the aneurysm lumen was noted on angiography.

Cerebral Angiography↗
PubMed1998

The effect of exhaustive exercise on the antioxidant enzyme system in skeletal muscle from calcium-deficient rats.

The aim of the current study was to elucidate the synergism of dietary calcium restriction and exhaustive exercise in the antioxidant enzyme system of rat soleus muscle, and to investigate the involvement of neutrophils in exercise-induced muscle damage. Forty-eight male Wistar rats were assigned to the following groups: control (C) or calcium-restricted [1 month (1 M) or 3 months (3 M)]. Each group was subdivided into acutely exercised or non-exercised groups. Soleus muscle from each rat was analysed to determine the levels of antioxidant enzymes [Mn-superoxide dismutase (SOD), Cu, Zn-SOD, glutathione peroxidase (GPX), and catalase (CAT)]. Dietary calcium restriction resulted in calcium deficiency and upregulated the antioxidant enzymes examined except GPX. Conversely, exhaustive exercise significantly decreased GPX and CAT, but not SODs activities in the calcium-restricted (1 M and/or 3 M) rats. Contents of immunoreactive Mn-SOD and Cu,Zn-SOD were only increased in the 3 M rats. During calcium restriction, the mRNA expression of both forms of SOD showed initial upregulation, followed by downregulation. Exhaustive exercise significantly increased the mRNA expressions only in the 3 M rats. Moreover, exhaustive exercise markedly increased myeloperoxidase activity in soleus muscles from the 1 M and 3 M rats compared with the C rats, and significantly enhanced the ability of neutrophils to generate superoxide in the 3 M rats. The results demonstrate that dietary calcium restriction upregulates certain antioxidant enzyme activities in rat soleus muscle, indicating an enhanced resistance to potential increases in intracellular reactive oxygen species. The results also suggest that exhaustive exercise may cause oxidative damage in soleus muscle of calcium-deficient rats through the activation of neutrophils.

Animals↗
PubMed1998

Histologic findings in polyacrylamide-coated polytetrafluoroethylene (PTFE) arterial grafts in the rat abdominal aorta.

To improve cell attachment without inducing thrombogenesis, the authors coated the inner surface of polytetrafluoroethylene (PTFE) prostheses (I.D.: 1 mm; length: 10 mm; wall thickness: 0.5 mm; fibril length: 30 microm) with polyacrylamide (PAA), known to have a strong antithrombotic effect (PAA-PTFE). They implanted the prostheses into the abdominal aorta of rats, and retrieved them at intervals of up to 9 months. Graft healing was observed under light and scanning electron microscopy. All the inner surfaces of the grafts examined were barely covered with fibrin or platelets. The PAA-coated fibers had many projections, in contrast to the original PTFE prostheses. Neo-endothelium was observed to be directly attached to these structural fibers of the PAA-PTFE grafts. Restoration of the neointima was also observed in these vascular prostheses.

Acrylic Resins↗
PubMed1998

Fermentation products of sugar-beet fiber by cecal bacteria lower plasma cholesterol concentration in rats.

Plasma cholesterol concentration is reduced by feeding some dietary fibers but the mechanism is not fully understood. We examined whether cecal fermentation products are involved in lowering plasma cholesterol by feeding rats a highly fermentable sugar-beet fiber (SBF) in four separate experiments. These were designed to investigate the effects on plasma cholesterol of oral ingestion of fermentation products on plasma cholesterol, the effects of the products in comparison with that of a short-chain fatty acid (SCFA) mixture, effects of individual SCFA and effects of alteration of energy and nitrogen ratio in the diet by the addition of the SCFA mixture. Cecal contents of rats were cultured with SBF by using a jar fermenter under anaerobic conditions, and the supernatant from the culture medium, containing fermentation products of SBF, was collected and freeze-dried before feeding to rats. Yield of fermentation products as dry weight from the fiber was 80-90%. In rats fed a diet containing fermentation products (80 g/kg diet), plasma cholesterol concentrations were lower than in rats of the fiber-free group 3, 7 and 14 d after feeding the test diet. Major SCFA in the fermentation products were sodium salts of acetic, propionic and butyric acids. Plasma cholesterol concentration in rats fed the diet containing a mixture of equal amounts of the three SCFA salts (66 g/kg diet) as the fermentation products diet was also lower than that in the fiber-free group and was not different from those in rats fed SBF (100 g/kg diet) and the fermentation products. In rats fed an acetate-containing diet but not in rats fed diets without acetate, plasma cholesterol was significantly lower than in the fiber-free group. In conclusion, absorption of SCFA from cecal fermentation products lowers plasma cholesterol. Acetate, and not propionate, may be responsible for lowering plasma cholesterol concentration.

Animals↗
PubMed1998

Summary report on the ISOBM TD-4 Workshop: analysis of 56 monoclonal antibodies against the MUC1 mucin. San Diego, Calif., November 17-23, 1996.

Sixteen research groups participated in the ISOBM TD-4 Workshop in which the reactivity and specificity of 56 monoclonal antibodies against the MUC1 mucin was investigated using a diverse panel of target antigens and MUC1 mucin-related synthetic peptides and glycopeptides. The majority of antibodies (34/56) defined epitopes located within the 20-amino acid tandem repeat sequence of the MUC1 mucin protein core. Of the remaining 22 antibodies, there was evidence for the involvement of carbohydrate residues in the epitopes for 16 antibodies. There was no obvious relationship between the type of immunogen and the specificity of each antibody. Synthetic peptides and glycopeptides were analyzed for their reactivity with each antibody either by assay of direct binding (e.g. by ELISA or BiaCore) or by determining the capacity of synthetic ligands to inhibit antibody binding interactions. There was good concordance between the research groups in identifying antibodies reactive with peptide epitopes within the MUC1 protein core. Epitope mapping tests were performed using the Pepscan analysis for antibody reactivity against overlapping synthetic peptides, and results were largely consistent between research groups. The dominant feature of epitopes within the MUC1 protein core was the presence, in full or part, of the hydrophilic sequence of PDTRAPAP. Carbohydrate epitopes were less easily characterized and the most useful reagents in this respect were defined oligosaccharides, rather than purified mucin preparations enriched in particular carbohydrate moieties. It was evident that carbohydrate residues were involved in many epitopes, by regulating epitope accessibility or masking determinants, or by stabilizing preferred conformations of peptide epitopes within the MUC1 protein core. Overall, the studies, highlight concordance between groups rather than exposing inconsistencies which gives added confidence to the results of analyses of the specificity of antimucin monoclonal antibodies.

Amino Acid Sequence↗
PubMed1998

Epitope characterization of MUC1 antibodies.

The 56 MAbs submitted to the ISOBM TD-4 Workshop were analysed by ELISA assay for reactivity against synthetic MUC1 mucin protein core-related peptides. With peptides comprising 5, 7 and 20 amino acids, 4/56 (7.1%), 33/56 (58.9%) and 51/56 (91.1%) of antibodies showed positive reactivity, respectively. Peptides with 60, 80, 100 and 120 amino acids showed 50/56 (98.2%), 54/56 (96.4%), 53/56 (94.6%) and 47/56 (83.9%) antibodies with positive reactivity, respectively. The reactivity of each MAb with synthetic peptides was classified into 3 groups. In group A (15 MAbs), the reactivity increased depending on the peptides in length and was maximal with 20-, 60-, 80-, 100- and 120-mer peptides. In group B (24 MAbs), most antibodies showed very weak binding affinity to peptides with a small increase in reactivity with the 100- and 120-mer peptides. In group C (17 MAbs), the reactivity showed strong binding affinity with the 20-mer peptide followed by a reduced uneven pattern of reactivity with the 60-, 80-, 100- and 120-mer peptides. These results show that the binding affinity of MAbs against synthetic peptides does not depend on the recognition of antibodies to the epitopes of core protein.

Amino Acid Sequence↗
PubMed1998

[Phase I study of TAT-59 (a new antiestrogen) in breast cancer. TAT-59 Study Group].

Phase I study of TAT-59 (Miproxifen), an antiestrogen developed in Japan for breast cancer, was conducted with the collaboration of 12 hospitals. A single dose of 1.25, 5, 10, 20, 40 and 80 mg, or 5 consecutive daily doses of 1.25, 5, 10, 20 and 40 mg/day, were given orally. After single dosing, no clinical adverse effects were found. Decrease of serum Na, Cl, Ca level and increase of serum LDH level were observed in one patient after a single dose of 5 mg of TAT. An increase in the serum LDH level was also observed in one patient after a single dose in the of 10 mg of TAT. An increase in the serum LDH level and total bilirubin, increase of eosinophil, K and milky serum were also observed in one patient after a single dose of 40 mg of TAT, respectively. All of these abnormal values returned to the normal level within 26 days after final administration of TAT. No adverse clinical findings nor abnormal laboratory findings were observed after consecutive administration of TAT. After postprandial single dosing, the time to reach the maximum serum concentration (Tmax) of DP-TAT, dephosphorylated metabolite of TAT, and its demethylated metabolite, DMDP, ranged from 5.0 to 7.3 hr and from 17.0 to 42.8 hr, respectively. The maximum serum concentration (Cmax) and AUC of DP and DMDP elevated in a dose-dependent manner. T1/2 of DP and DMDP ranged from 24.2 to 41.5, and from 91.9 to 214.7 hr, respectively. There were no significant differences between pharmacokinetics of TAT before and after food intake. Based on the above results, we concluded that a Phase II study should be conducted to evaluate the efficacy, safety and optimal dose of TAT.

Administration, Oral↗
PubMed1998

[Detection of telomerase activity in intestinal lavage solution from colorectal carcinoma patients].

In terms of colorectal carcinoma, the fecal occult blood test is widely used for mass survey, but has many complicated problems to be overcome. Telomerase activity has been reported in a wide range of malignancies. We have examined telomerase activity of intestinal lavage solution collected from 16 colorectal carcinoma patients and from 10 volunteers (control) by the method of telomeric repeat amplification protocol (TRAP) assay. Patients drunk polyethylene glycol-electrolyte lavage solution (PEG-ELS) before examination. Sample solutions were collected by colonoscope at the beginning of colonoscopy. The telomerase activity from colorectal carcinoma patients were positive 9/16 (56.3%) including 2 cases of early stage. In volunteers, were positive 1/10 (10.0%). This method has, therefore, possibility for a new useful method of diagnosis for colorectal carcinoma.

Aged↗
PubMed1998

[Adjuvant chemotherapy with UFT or UFT with OK-432 to patients with gastric and colorectal cancer. Kanto Adjuvant Study Group].

In Japan, long-term oral therapy with tegafur in combination with immunopotentiators is commonly used as adjuvant therapy after curative resection of gastric or colorectal can for gastric and colorectal cancer. When the outcome was analyzed in terms of the relative performance (R.P.) and the individual dose intensity (I.D.I.) of OK-432, gastric cancer patients with a R.P. of 0.5 or higher tended to have a better survival curve. There were no marked differences in lymphocytes subsets, except that the Leu 7 level at 3 months after gastric cancer resection was significantly higher (p < 0.05) in group B than in group A. Thus, no inhibition of the anticancer effect of UFT was noted during long term combination therapy with UFT and an immunopotentiator as postoperative adjuvant therapy for patients who underwent curative resection of gastric or colorectal cancer. The results suggest that UFT combined with long-term OK-432 maintenance therapy may contribute to improve survival rates in gastric cancer patients.

Adjuvants, Immunologic↗
PubMed1998

MPB64 mycobacterial antigen: a new skin-test reagent through patch method for rapid diagnosis of active tuberculosis.

SETTING: A collaborative study between the Japan BCG Laboratory, Tokyo, Japan, and the Infectious Disease Section, Philippine General Hospital, Manila, the Philippines. Tuberculosis patients from four clinics in the vicinity of Manila, Our Lady of Grace Parish, Sto. Niño de Tondo Parish, the Canossa Health and Social Center, and the Health Care Development Center, were examined. OBJECTIVE: To develop a new, simple and rapid diagnostic method for active tuberculosis. Subjects were tested for skin reaction to a special antigen, MPB64, by the patch test method instead of intradermal injection of purified protein derivative (PPD). DESIGN: Fifty-three active tuberculosis patients and 43 healthy PPD-positive controls were tested to determine whether or not the reaction to MPB64 was positive only in active tuberculosis patients. RESULTS: Fifty-two of the 53 active tuberculosis patients showed a positive reaction to MPB64, while none of the 43 PPD-positive controls did. The specificity of MPB64 to active tuberculosis was 100%, and the sensitivity was 98.1%. The efficacy of the test was 98.9%. CONCLUSION: The patch test with MPB64 is a promising method for the diagnosis of active tuberculosis, distinguishing tuberculous patients from those who are infected but have not developed the disease, and also from BCG-vaccinated individuals. This new skin test is a subject for further evaluation and it is important to compare the results with PPD Mantoux.

Animals↗
PubMed1997

Detection of Borna disease virus genome in normal human brain tissue.

Borna disease virus (BDV), a neurotropic virus naturally infecting horses and sheep, has been suggested to be associated with human psychiatric disorders. Thus far no extensive studies have been done, providing the evidence of BDV genome in normal human brain tissue. We therefore examined four brain regions of 30 normal autopsy brains for BDV p24 genome. By highly sensitive nested reverse transcriptase (RT)-mediated PCR analysis, we found positive PCR products in two brains: one in frontal and temporal cortices and hippocampus and another in frontal cortex and olfactory bulb. Our results suggest that BDV can infect human brain tissue latently, without causing an apparent neuropsychiatric disorder.

Adult↗
PubMed1997

Detection of a prothrombotic state after acute aerobic exercise.

Angina, myocardial infarction, and sudden cardiac death are associated with thrombus formation in coronary arteries. It is generally believed that these conditions benefit from long-term exercise. However, the evidence for such amelioration or prevention is inconclusive and so is the mechanism through which long-term exercise exerts its beneficial effect on various ischaemic conditions. Because of the thrombotic events, the effects of exercise on platelet reactivity, blood coagulation and fibrinolysis have been extensively studied, but the findings are not consistent (1-9). This is mainly due to methodological problems. Analysis of platelet response to a variety of agonists and the dozen of coagulation and fibrinolysis variables makes the assessment of the overall platelet function, coagulation and fibrinolysis status extremely difficult.

Adult↗
PubMed1997

Motor neurons in human and rat spinal cord synthesize fibroblast growth factor-9.

Fibroblast growth factor (FGF)-9, initially referred to as a glia-activating factor, is a recently identified member of the FGF family. In the present study we demonstrated that spinal cord motor neurons and dorsal root ganglion neurons were strongly immunostained with specific antibodies to FGF-9 in human and rat tissues. By in situ hybridization using digoxigenin-labeled antisense probe to FGF-9 mRNA, we found specific signals in these neurons in rat. By immunoblotting analysis, we detected a 30/29 kDa doublet band in human spinal cord proteins, which corresponded to the doublet band of originally isolated FGF-9 from culture media. Our results indicate that these neurons synthesize FGF-9.

Animals↗
PubMed1997

Analysis of the tumor staining obtained by preoperative IV-DSA for breast cancer patients: density and metastasis correlation.

We examined the density of tumor enhancement on intravenous digital subtraction angiography (IV-DSA) in patients with breast cancer in relation to disease-free survival. The subjects of the present study consisted of 103 patients with invasive ductal carcinoma measuring 5 cm or less treated from July 1988 to September 1993. In the 103 patients, 15 had distant metastasis. The region of interest was set in the areas enhanced by IV-DSA of the breast. The maximum density (MAX) was calculated by the time-density curve. When the patients were divided according to three classes of MAX, i.e., 0-5.0 pixels (group A, n = 23), 5.1-9.0 pixels (group B, n = 50), 9.1 pixels or more (group C, n = 30), disease-free survival was highest in group A followed by group B and C, respectively. The disease-free survival rate in group C was significantly lower than that of group A or B (p < 0.05). Thus, high values of MAX were associated with low rates of disease-free survival. Since the value of MAX was found to be independent from other prognostic factors by multivariate analysis, these results indicate that MAX has a close correlation with metastasis or recurrence of breast cancer, making IV-DSA a promising prognostic factor.

Adult↗
PubMed1997

MIB1-determined proliferative activity in intraductal components and prognosis of invasive ductal breast carcinoma.

Intraductal components of breast carcinoma may have prognostic significance. In this study, we divided 181 invasive ductal breast carcinomas into comedo and non-comedo groups based on intraductal component morphology, and differences between the two groups in clinicopathological variables, including proliferative activity and survival, were assessed. Proliferative activity was evaluated by using MIB1 antibody, which reacts with the cell-proliferation-associated Ki-67 antigen, and was expressed as the number of MIB1-positive nuclei per 1000 cancer cells in intraductal components (MIB1 labeling index). We also investigated which variables had an impact on survival. The comedo group showed a significantly higher MIB1 labeling index than the non-comedo group (P < 0.0001). The differences in disease-free and overall survival between the two groups were not significant (P = 0.2477, P = 0.2069). Multivariate analysis of the entire series showed the MIB1 labeling index to be an independent prognostic factor predicting both disease-free survival and overall survival (P = 0.0160, P = 0.0035). When multivariate analysis was repeated separately for the non-comedo and comedo groups, the MIB1 labeling index remained the most important variable predicting disease-free and overall survival in the non-comedo group (P = 0.0122, P = 0.0040). Moreover, non-comedo patients with a high MIB1 labeling index had significantly shorter disease-free and overall survival than those with a low MIB1 labeling index (P = 0.0040, P = 0.0402). These findings imply that MIB1-determined proliferative activity of intraductal components is an independent predictor of survival, and is the most important predictor in non-comedo cases.

Adult↗