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Biomedical subjects

K Hara

Publications and source records attributed to K Hara.

At least 19 recordsLinked to original sources

Interleukin-3-associated expression of gangliosides in mouse myelogenous leukemia NFS60 cells introduced with interleukin-3 gene: expression of ganglioside GD1a and key involvement of CMP-NeuAc:lactosylceramide alpha 2-->3-sialyltransferase in GD1a expression.

Murine interleukin-3 (IL-3)-associated expression of gangliosides has been investigated using a gene transfection technique. A murine IL-3 cDNA was introduced into the parental NFS60-17 cells that was exclusively dependent on IL-3. We analyzed the glycosphingolipids from the parental cells and the transfected cells by fast atom bombardment mass spectrometry analyses and/or immunostaining techniques using specific antibodies. Two major gangliosides, IV3NeuAc-GgOse4Cer (GM1b) and IV3-NeuAc,III6NeuAc-GgOse4Cer (GD1 alpha), were expressed, in the parental cells. By contrast, in the IL-3 gene-transfected cells, a ganglioside IV3NeuAc,II3NeuAc-GgOse4Cer (GD1a) was strikingly expressed, in addition to GM1b and GD1 alpha that were already present in the parental cells. In spite of various IL-3-secreting capabilities, all transfectants investigated have exhibited the same ganglioside patterns and expressed GD1a. Furthermore, the appearance of GD1a was a consequence of the up-regulation of a single glycosyltransferase, CMP-NeuAc:lactosylceramide alpha 2-->3-sialytransferase (GM3 synthase). Activities of the other downstream glycosyltransferases that were involved in GD1a synthesis were not significantly different between the parental and the transfected cells. According to these data, the progression of tumor stage by the acquisition of autonomous cell growth ability after IL-3 gene transfection resulted in dramatic changes in cell surface gangliosides and their biosynthetic pathways. GD1a could be considered as an IL-3-associated ganglioside and was expressed in a tight connection with a single glycosyltransferase (GM3 synthase) up-regulation and with IL-3 expression in murine myelogenous leukemia cells.

Animals

Luminal loss and site of restenosis after Palmaz-Schatz coronary stent implantation.

Restenosis has frequently been observed at the articulation of the Palmaz-Schatz stent. However, the precise mechanism for this remains poorly understood. We measured the luminal diameter in 5 segments within the stent in 67 lesions of 63 patients with successful stenting. Luminal diameter at all 5 sites was significantly reduced 6 months after stent implantation (3.2 +/- 0.5 vs 2.4 +/- 0.7 mm, p < 0.05). Angiographic restenosis rate was 18%. Restenosis involving the articulation was found in 75% of the lesions, and that involving the articulation or edges in 83%. The diameter at the articulation was significantly smaller both immediately (3.0 +/- 0.5 mm vs 3.3 +/- 0.5 mm, p < 0.05) and 6 months after (2.1 +/- 0.8 mm vs 2.5 +/- 0.7 mm, p < 0.05) stenting than the diameter of other stent segments. The loss index was significantly greater at the proximal and distal edges than at the bodies of the stent (0.98 vs 0.60, p < 0.05). The edges of the Palmaz-Schatz stent tend to dilate more than the body of the stent during normal inflation. Although this anchoring system protects against dislodgment or migration of the stent, it may cause more injury. The articulation has 2 anchoring edges within only a 1 mm diameter. Thus, restenosis at the articulation may be ascribed to residual stenosis, increased intimal proliferation due to more severe injury, and delayed late vessel remodeling from lack of mechanical support. These characteristics may be attributed to stent design, and design improvement of the articulation may lead to more favorable results after stent implantation.

Aged

Comparison of intestinal absorption of vitamin K2 (menaquinone) homologues and their effects on blood coagulation in rats with hypoprothrombinaemia.

To examine the physiological activities of vitamin K2 (menaquinone, MK) homologues with different numbers of isoprene units, MK with 1-14 isoprene units and menadione (MK-0) were administered to rats with hypoprothrombinaemia, and the absorption, concentration in liver and ameliorating effect of these MK on hypoprothrombinaemia were compared. Hypoprothrombinaemia was induced by giving a vitamin K-deficient diet and warfarin (0.06 mg/kg body weight) for 8 days. Before MK treatment, the MK were undetectable in plasma and liver. At 6 hr after oral MK administration (0.1 mg/kg): MK was not detected in the plasma in rats treated with MK with 1, 2, 3 or more than 12 isoprene units; the MK level in the liver was increased but blood coagulation activity was not improved in rats treated with MK with 0, 9, 10 or 11 isoprene units; the MK level in the liver was increased and hypoprothrombinaemia was slightly improved in rats treated with MK with 7 or 8 isoprene units; and the MK level in the liver was increased and hypoprothrombinaemia was markedly improved in rats treated with MK with 4, 5 or 6 isoprene units. Almost identical results were observed 3 hr after intravenous injection of MK with 4, 5 or 6 isoprene units (10 nmol/kg). These findings suggest that the number of isoprene units of MK is an important factor in its absorption and incorporation into the liver and that the ameliorating effect of MK on hypoprothrombinaemia does not parallel their concentrations in the liver.

Administration, Oral

Highly sensitive and rapid determination of theophylline, theobromine and caffeine in human plasma and urine by gradient capillary high-performance liquid chromatography-frit-fast atom bombardment mass spectrometry.

A sensitive and reliable analytical procedure has been established for the detection of theophylline (TH), theobromine (TB) and caffeine (CA) in human plasma and urine by gradient capillary high-performance liquid chromatography (HPLC)-frit-fast atom bombardment mass spectrometry (FAB-MS) (LC-frit-FAB-MS). Two capillary columns and a column-switching valve were used in this LC system to allow all of the sample injected to be introduced into the MS system. 7-Ethyltheophylline was used as the internal standard (I.S.). The xanthines in the specimen were extracted with an Extrelut column. The lowest detected amount was ca. 5 ng/ml using this method.

Caffeine

"Malignant Spitz nevus" in a 2-year-old Japanese child.

Smith et al. (1989) have reported a variant of Spitz's nevus with histological atypical features. Despite local lymph node metastases, further metastases were not observed. They proposed the name "malignant Spitz nevus" for this variant. A 2-year-old Japanese girl had a large nodule (27 x 17 mm) surrounded by an indurated erythema over the Achilles tendon. Histologically, it proved to be a melanocytic lesion resembling spindle cell and epithelioid cell nevus (Spitz's nevus) with unusual features; the tumor extended deep into the subcutis, and the mitotic figures deep into the tumor, together with prominent lymphatic vessel invasion by melanocytes. Thus the tumor was aptly termed "malignant Spitz nevus". Flow cytometric analysis of the DNA content revealed a diploid pattern. The child is well 5 years after a wide resection of the tumor. The diploid pattern of the DNA content as well as the good prognosis could support the idea that "malignant Spitz nevus" fits within the spectrum of Spitz's nevus.

Child, Preschool

Presence of activated eosinophils, high IgE and sCD23 titers in gingival crevicular fluid of patients with adult periodontitis.

Our previous studies showed that the expression of CD23 on polymorphonuclear leukocytes (PMNLs) in gingival crevicular fluid (GCF) from adult periodontitis (AP) patients was higher than in autologous peripheral blood (PB). Percentages of eosinophils in GCF PMNLs ranged between 6 and 14%. The purpose of the present studies was to increase understanding of the potential role of eosinophils and their products, including CD23, in periodontal disease. We analysed the eosinophil fraction in GCF and PB by flow cytometry using monoclonal antibodies to CD23b (BB10), eosinophil cationic protein (ECP) in stored and secretory forms (EG1 and EG2), and CD67 (80H3). Simultaneously, we measured IgE and soluble CD23 titer and GCF and serum by ELISA. Flow cytometric analysis of BB10, EG2 and 80H3 binding showed that GCF eosinophils from AP were activated. A large BB10+ EG2+ cellular fraction was detected in GCF from AP whereas it was very low in autologous serum (9.30 +/- 2.460 vs 0.16 +/- 0.10, p < 0.001). GCF from gingivitis patients exhibited no flow cytometric evidence for the presence of BB10+ EG2+ cells. BB10+ EG1+ cells, or inactivated eosinophils rated lower in GCF than in PB both in gingivitis and periodontitis patients (0.45 +/- 0.63 vs 1.83 +/- 0.96 and 0.15 +/- 0.30 vs 1.30 +/- 0.20, p < 0.05, respectively). IgE titer in AP patients reached 1208.1 +/- 421.2 IU/ml in GCF while only 49.1 +/- 50.4 in sera. Soluble CD23 in GCF reached 236.1 +/- 81.3 ng/ml in GCF and 5.6 +/- 1.8 ng/ml in sera. GCF of gingivitis patients, however, contained no detectable sCD23.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Transforming growth factor-beta 1 coated beta-tricalcium phosphate pellets stimulate healing of experimental bone defects of rat calvariae.

OBJECTIVE: TGF-beta 1-coated beta-TCP pellets were grafted in experimental defects of rat calvariae to study the effects on new bone formation. MATERIALS AND METHODS: The grafted sites were evaluated by light microscopy using hematoxylin-eosin (H-E) staining for histology and detection of alkaline phosphatase (ALPase) and tartrate-resistant acid phosphatase (TRACPase) activities to demonstrate osteoblastic and osteoclastic cells. Confocal laser scanning microscopy (CLSM) was performed for morphometry of newly formed bone. RESULTS: H-E sections showed more new bone formation in sites grafted with TGF-beta 1-coated beta-TCP pellets (experimental sites) than those with beta-TCP pellets only (control sites). TRACPase-positive and ALPase-positive cells at experimental sites were more frequent than at control sites. The bone formation rate calculated by computerized CLSM pixel image analysis showed more new bone formation at the experimental sites than at control sites (3.4 +/- 0.8% vs 9.3 +/- 1.7% on week 2 and 11.8 +/- 2.1% vs 39.8 +/- 10.9% on week 4). CONCLUSION: TGF-beta 1-coated beta-TCP pellets promote new bone formation and may be a useful modality in synthetic bone grafting.

Acid Phosphatase

Reductions in muscle sympathetic nerve activity after long-term metoprolol for dilated cardiomyopathy: preliminary observations.

OBJECTIVE: To determine whether efferent muscle sympathetic nerve activity diminishes in subjects with dilated cardiomyopathy who improve after long term treatment with metoprolol. METHODS: Microneurographic, echocardiographic, plethysmographic, and neurohumoral data were obtained immediately before and 20 months after the addition of beta blockade in seven subjects with idiopathic dilated cardiomyopathy with clinical deterioration despite conventional treatment. RESULTS: Six subjects (three men, three women, aged 24-62 years) were restudied after a mean (SEM) of 20 (2.4) months treatment with metoprolol (45.8 (2.6) mg/d). Long term treatment was associated with decreases in left ventricular end diastolic and end systolic diameter (P < 0.005), left ventricular mass index (P < 0.05), and atrial natriuretic factor (P < 0.05), and increases in fractional shortening (P < 0.05) and mean blood pressure (P < 0.05). There was a 50% reduction in peroneal muscle sympathetic nerve activity (from 49.2 (10.1) to 24.5 (4.7) bursts/min; (P < 0.005) and a 62% decrease in calf vascular resistance (from 56.2 (4.4) to 21.2 (5.7) units; P < 0.005). This reduction in pulse synchronous nerve activity was not simply a function of bradycardia (heart rate fell from 94.2 (4.6) to 62.8 (5.7) beats/min; P < 0.005) since muscle sympathetic burst incidence also decreased (from 51 (8.7) to 37.5 (5.2) bursts/100 heart beats; P < 0.05). Similar haemodynamic improvement was observed in the seventh subject, who was switched to sotalol 200 mg/d and restudied after 20 months, but burst frequency was 50% higher and calf vascular resistance 93% higher. CONCLUSIONS: Muscle sympathetic nerve activity and calf vascular resistance decrease in patients with dilated cardiomyopathy who improve after long term treatment with metoprolol. Inhibition of central sympathetic outflow may be one mechanism by which metoprolol benefits such subjects.

Adrenergic beta-Antagonists

Increase in activated CD8+ cells in bronchoalveolar lavage fluid in patients with diffuse panbronchiolitis.

To study the role of T cells in diffuse panbronchiolitis (DPB), we investigated T-cell subsets in bronchoalveolar lavage fluid (BALF) or 33 patients with DPB, nine patients with bronchiectasis, and 20 healthy volunteers. BALF from DPB patients contained a higher percentage of neutrophils than that from patients with bronchiectasis or healthy volunteers, whereas the percentage of lymphocytes was similar in the three groups. DPB patients, however, had a higher number of lymphocytes and a reduced CD4/CD8 ratio compared with the other subjects. A two-color analysis of T-cell subsets in peripheral blood and BALF revealed a significant increase in the percentage and number of CD8+HLA-DR+ cells and in the number of CD4+HLA-DR+ cells in BALF of DPB patients. The expression of the adhesion molecules CD 11a and CD18 on lung CD3+ cells was enhanced over that on blood CD3+ cells in DPB patients. However, there was no significant difference in the expression of these antigens in peripheral blood or BALF among the groups. There was no significant relationship between BALF interleukin (IL)-8 and lymphocyte accumulation in the lungs of the DPB patients, whereas a significant correlation between the percentage of neutrophils and IL-8 levels in BALF of DPB patients was observed. After treatment with macrolide antibiotics, a significant reduction in the number of lymphocytes and activated CD8+ cells and an elevation in the CD4/CD8 ratio in BALF of DPB patients was observed. Our findings suggest an activation of CD8+ cells in the airway lumen of DPB patients, supporting the hypothesis that lymphocytes are important cellular components of bronchial inflammation in DPB.

Anti-Bacterial Agents

Short-term outcome and long-term follow-up of percutaneous coronary intervention in patients aged 40 years or younger.

Forty five patients aged 40 years or younger were treated with coronary intervention in our institution between 1983 and 1994. This young Japanese population had a strong predisposition to risk factors but did not have extensive disease. These patients underwent 50 elective interventional procedures for angina pectoris or old myocardial infarction and 6 direct balloon angioplasty procedures for acute myocardial infarction. The initial successful result was obtained in 41 of the 45 patients (91%). The mean follow-up was 43 +/- 35 months. Angiographic follow-up was available in 31 of the 41 eligible patients (76%). Angiographic restenosis was seen in 9 of these 31 patients (29%), and in 12 of the 38 lesions (32%) with initial successful intervention. There were no deaths among the successfully treated patients. Event-free survival rate without death, myocardial infarction, or coronary artery bypass surgery was 94%; however, event-free survival rate without death, myocardial infarction, coronary artery bypass surgery, or repeat intervention was 66% at 43 months. Ninety three percent of the eligible patients were free from angina at follow-up. These short- and long-term results suggest that young Japanese patients can be treated safely and effectively with coronary interventions.

Adult

Leukotriene B4 in bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis.

Leukotriene B4 (LTB4) is a potent proinflammatory mediator that may be of particular relevance to the pathology of several respiratory diseases. We have previously reported that neutrophil chemotactic mediators in the lavage fluid of patients with diffuse panbronchiolitis (DPB) consist of many components. In this study, we evaluated the effect of erythromycin (EM) on the pathogenesis of DPB, by examining the level of LTB4 in the bronchoalveolar lavage (BAL) fluid, and determining the relationship between the level and neutrophil accumulation into the respiratory tract. Pre-EM treatment neutrophil chemotactic activity (NCA) in the patients with DPB was significantly increased compared with that in five healthy nonsmoking volunteers (HVs) (p < 0.001), and the level was markedly reduced after EM treatment (p < 0.001). The amounts of LTB4, detected in the BAL fluid from the patients, was also significantly higher than those in control subjects (3.5 +/- 1.1 ng/mL vs 0.1 +/- 0.0 ng/mL, p < 0.001), and the level was significantly reduced after EM treatment (0.6 +/- 0.3 ng/mL, p < 0.01). In addition, the percent reduction of the level of LTB4 was significantly correlated with NCA (r = 0.832, p < 0.01); the reduction was also significantly correlated with neutrophil percentage before and after EM treatment (r = 0.778, p < 0.05). These findings provide evidence for the potent role of LTB4 in the respiratory tracts of patients with DPB and suggest that this lipoxygenase metabolite is involved in the recruitment of neutrophils into the airways of the patients. Our findings suggest that LTB4 is one of the most important chemotactic mediators that has a pathogenetic role in the airway damage of DPB. Erythromycin might inhibit the production of this mediator, restrict the neutrophil accumulation, modulate the excessive inflammation in the respiratory tract, and ultimately improve the pathogenesis of DPB.

Adult

Increase of activated T-cells in BAL fluid of Japanese patients with bronchiolitis obliterans organizing pneumonia and chronic eosinophilic pneumonia.

To study the role of T cells in bronchiolitis obliterans organizing pneumonia (BOOP) and chronic eosinophilic pneumonia (CEP) and to examine the influence of differing racial background, T-cell subsets in bronchoalveolar lavage (BAL) fluid (BALF) and in peripheral blood of 8 Japanese patients with idiopathic BOOP and 5 with CEP were compared with those of 15 normal subjects. The BALF pattern in BOOP was characterized by a significantly high number and percentage of lymphocyte and by a low CD4 to CD8 ratio compared with patients with CEP and healthy volunteers. Patients with CEP showed a significantly higher percentage of BALF eosinophils compared with other groups. There was no significant difference in BALF CD4 to CD8 ratio between patients with CEP and volunteers. Two-color analysis of T-cell subsets revealed that CD3+HLA-DR+ cells (activated T cell) in BALF of patients with BOOP and CEP increased significantly compared with volunteers, while BALF CD3+CD25+ cells (interleukin 2 receptor+ T-cell) did not. In addition, BALF CD8+HLA-DR+ cells (activated suppressor/cytotoxic T cell) in patients with BOOP and CD4+HLA-DR+ cells (activated helper T cell) in patients with CEP were significantly higher than levels detected in healthy subjects. The percentage of CD8+CD57+ cells and the number of CD8+CD11b- cells (cytotoxic T cell) in BALF were significantly higher in patients with BOOP compared with patients with CEP and healthy volunteers. There were no significant differences in the expression of peripheral blood T-lymphocyte surface antigens among the groups. These findings indicate that cytotoxic T cells in Japanese patients with idiopathic BOOP and helper T cells in CEP appear in the lungs is consistent with a previous report in Caucasians, supporting the hypothesis that T cells may play an important role in the pathogenesis of these diseases.

Aged

Clinical evaluation of catheter-related fungemia and bacteremia.

Forty-four patients with catheter-related infection admitted to Hokusho Central Hospital between 1985 and 1991 were studied retrospectively. The rate of catheter-related fungemia or bacteremia to all corresponding cases of fungemia and bacteremia increased from 7.7% in 1985 to 28.8% in 1991. The isolated pathogens were Candida parapsilosis (8 strains), Candida tropicalis (6 strains), methicillin-resistant Staphylococcus aureus (MRSA) (6 strains), methicillin-sensitive S. aureus (MSSA) (5 strains) and Streptococcus epidermidis (3 strains). Bacteremia occurred after catheterization of the femoral vein for a mean duration of 37 days. The period was significantly shorter than that after catheterization of the subclavian vein (56 days). The major isolates from the subclavian vein were Candida spp. (14/17, 82.4%), followed by MRSA (1/17, 5.9%) and MSSA (1/17, 5.9%), while isolates from the femoral vein were Candida spp. (6/16, 37.5%), MRSA (5/16, 31.3%) and MSSA (3/16, 20.8%). Catheter removal alone did not improve the clinical condition, particularly in MRSA bacteremia; the combination of antimicrobial therapy and removal of the catheter was necessary for a better prognosis.

Aged

Infections in patients with liver cirrhosis and hepatocellular carcinoma.

Infections in immunocompromised hosts have been an important clinical problem. Patients with liver cirrhosis and/or hepatocellular carcinoma are at a high risk of infection due to multiple factors. Five hundred and two patients admitted with liver cirrhosis and/or hepatocellular carcinoma were evaluated for infection. The infection rate was not influenced by the etiology of hepatic diseases or the presence of hepatocellular carcinoma, however, it increased with the advance of clinical stages of liver cirrhosis and hepatoma. The respiratory tract and urinary tract were the most common sites of infection, being involved in 50% and 28% of cases, respectively. The major pathogens of respiratory tract infection were S. aureus, H. influenzae, and P. aeruginosa. Gram-negative bacteria was the common isolate from sputum and urine, and S. aureus was also common in gram-positive bacteria. The infection rate was high in patients who died although infections could rarely be implicated as the direct cause of death. These findings should be a guide for the clinicians in treating patients with liver cirrhosis and/or hepatocellular carcinoma who exhibit signs of infection.

Carcinoma, Hepatocellular

Relaxation effect of an audiovisual system on dental patients. Part 2. Palus-amplitude.

Dental care services include relaxation of patients to reduce their displeasure at and tension during treatment. For this purpose, it is common to use audio or audiovisual programs, that is, to let them listen to music or watch TV. However, the former utilizes only the auditory sense, and the latter is disadvantageous in that a TV set is a rather large-scale unit. In the present study, we determined the relaxation effect of an audiovisual instrument on dental patients. The instrument, which gives virtual vision, was composed of a lightweight eyeset of the snow goggle type that has a built-in TV screen, with earphone and accessories. The relaxation effect was determined using a polygraph.

Adult

Signet ring cell carcinoma in hyperplastic polyp.

BACKGROUND: A polypectomy was performed on a 68-year-old woman who had three gastric hyperplastic polyps. A focal signet ring cell carcinoma was discovered in one of the polyps, which was 2.2 cm in diameter and was located in the antrum. METHODS: To study the carcinoma's phenotype expression, special mucin histochemical stainings were performed. RESULTS: The carcinoma infiltrated only into the mucosa. Intestinal metaplasia was scant. In the neoplasm neutral and foveolar mucin was predominant over acid mucin. The surrounding hyperplastic foveolar epithelium showed positivity for neutral mucin, and the intestinal metaplasia foci for acid mucin. CONCLUSIONS: This neoplasm has a mixed composition of mucins and shares histochemical characteristics with the surrounding hyperplastic foveolar epithelium.

Aged