Search PubMed⌕ Search

Biomedical subjects

K Hata

Publications and source records attributed to K Hata.

At least 109 records · Page 6Linked to original sources

Thymidine phosphorylase activity and prodrug effects in a three-dimensional model of angiogenesis: implications for the treatment of ovarian cancer.

Platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) is associated with angiogenesis and the progression of human ovarian cancer. The enzyme converts thymidine to thymine and 2'-deoxyribose-1-phosphate and can also metabolize the prodrug 5'-deoxy-5-fluorouridine (Furtulon) to 5-fluorouracil and 5'-deoxy-D-ribose-1-phosphate. The aim of this study was to obtain information about the activities of Furtulon in an established three-dimensional model of angiogenesis. The plan was to study partial and complete effects of Furtulon (in the absence and presence of PD-ECGF/TP or ovarian cancer cyst fluids) on the formation and destruction of microvessels from cultured segments of rat aorta in serum-free media. The endpoint was the number and form of microvessels compared with controls after 4, 7, 11, and 14 (and sometimes 17) days in culture. Furtulon (10 micromol/L) gradually reduced the size and number of microvessels over 17 days of culture (100 micromol/L significantly reduced the number by day 4). PD-ECGF/TP (10 ng/ml) and ovarian cancer cyst fluids (2% in medium, v/v) stimulated the production of microvessels. The culture of explants with Furtulon and PD-ECGF/TP or ovarian cancer cyst fluids (from day 1 or day 11 of culture) enhanced the vasoclastic activity of the drug. The effect of Furtulon at the highest dose (1000 micromol/L) or at a lower dose (100 micromol/L) in the presence of ovarian cancer cyst fluid was not reversible after culture day 11.

Adult↗

High-turnover osteopenia in preterm infants: determination of urinary pyridinium cross-links of collagen.

Osteopenia is a frequent condition in preterm infants, but its pathogenesis is uncertain. In the present study, we measured longitudinal changes in the excretion of pyridinium cross-links of collagen (specific markers of bone resorption) and evaluated the relationship between collagen cross-links and other indexes of bone and renal function in preterm infants. In these infants, urinary collagen cross-links were markedly increased on day 7 and day 30 of life and at estimated full-term gestation. The values were several times higher than those of older children and almost comparable to those of healthy full-term infants. Cross-link excretion did not correlate with beta2-microglobulin (B2M) or N-acetyl-beta-D-glucosaminidase (NAG) activity (markers of renal function), indicating that cross-link excretion is not influenced directly by infantile renal function. High serum osteocalcin and low bone mineral density (BMD) in the lumbar spine were also observed at estimated full-term gestation. There was no significant correlation between collagen cross-link excretion and either serum osteocalcin or spine BMD. We conclude that a state of high bone turnover underlies the development of osteopenia in preterm infants.

Aging↗

Three-dimensional ultrasonographic assessments of fetal development.

OBJECTIVE: To visualize fetal surface anatomic structures in advancing gestation by use of three-dimensional ultrasonography with a specially developed abdominal three-dimensional transducer. METHODS: One hundred six normal fetuses from 9 to 40 weeks' gestation were studied with a specially developed abdominal three-dimensional transducer (3.5 MHz). This imaging system can provide conventional two-dimensional ultrasonography images and also can generate within seconds high-quality three-dimensional images in the surface and transparent modes with no need for an external workstation. We determined percentage of surface anatomic structures visualized at each trimester using two-dimensional and three-dimensional ultrasonography. RESULTS: The number and the clarity of surface anatomic structures increased from the first to the third trimester of pregnancy. The image quality was less distinct in the first trimester because of the small fetal size. The ability to view the fetal face, hands, and feet was better with three-dimensional ultrasonography than with two-dimensional ultrasonography in the first trimester (P < .05), whereas fetal genitals were viewed better with two-dimensional ultrasonography than with three-dimensional ultrasonography in the second and third trimesters (P < .05). CONCLUSION: Three-dimensional ultrasonography provides a new means of visualizing surface anatomic structures of the fetus in utero. Our results suggest that three-dimensional ultrasonography has the potential to be a supplement to two-dimensional ultrasonography and should be useful in evaluating fetal abnormalities in high-risk pregnancies.

Embryonic and Fetal Development↗

Density of Helicobacter pylori infection in patients with peptic ulcer perforation.

BACKGROUND: A lack of change in prevalence of severe ulcer complications requiring emergency operation has been reported, despite the common use of histamine-2 (H2)-receptor antagonists and proton pump inhibitors. This may be attributable to use of ulcerogenic drugs or Helicobacter pylori (HP) infection, or both. In this study, HP infection was evaluated semiquantitatively in patients with peptic ulcer who required surgery, and the severity of histologic change was investigated. METHODS: We reviewed a total of 113 consecutive patients (98 men and 15 women) operated on for perforation, hemorrhage, or stenosis of gastroduodenal ulcer between January 1986 and December 1995. Detection of HP was carried out by immunohistochemical staining. We graded the density of HP infection according to the number of individual HP bacteria counted in a highly magnified visual field (x 1,000 of light microscopy). The grade of HP infection was defined as follows: (0) = 0; (1+) = 1-9; (2+) = 10-29; (3+) = 30-99; (4+) > or = 100. The severity of gastritis was evaluated by histologic examination using the criteria of Rauws. RESULTS: Although the number of operations for gastroduodenal ulcer declined significantly, the rate of emergency operation for gastroduodenal ulcer increased from 60% to 90%, with the result that the frequency of operations for perforation or bleeding remained virtually constant and that for stenosis significantly decreased. HP infection was more prevalent in perforated ulcer (92%) than hemorrhagic ulcer (55%) or stenotic ulcer (45%). The grades of HP infection were 3.0 +/- 0.14 (mean +/- SEM) in perforated ulcer, 2.3 +/- 0.34 in hemorrhagic ulcer, and 2.5 +/- 0.22 in stenotic ulcer. Perforated ulcer was associated with significantly more severe HP infection and gastritis changes than hemorrhagic ulcer or stenotic ulcer. CONCLUSIONS: This study indicates that patients with perforated ulcer were infected with HP more severely than those with hemorrhagic ulcer or stenotic ulcer at the time of surgery. A close relationship was observed between the perforated ulcer and the density of HP infection determined semiquantitatively using immunohistochemical stain.

Adolescent↗

Expression of thymidine phosphorylase in malignant ovarian tumors: correlation with microvessel density and an ultrasound-derived index of angiogenesis.

OBJECTIVE: The aim of this study was to determine whether the expression of thymidine phosphorylase by ovarian cancer cells correlates with the density of microvessels within the tumor, and with ultrasound-derived indices of blood flow. METHODS: Transvaginal ultrasonography with color Doppler imaging and pulsed Doppler spectral analysis was used to scan patients with an overt ovarian mass immediately before laparotomy. Sections of malignant tumors were analyzed for the cellular expression of thymidine phosphorylase and the intratumoral density of microvessels by immunohistochemistry using monoclonal antibodies to thymidine phosphorylase and factor VIII-related antigen, respectively. The main outcome measures were the histological classification of the tumor, the stage of the disease, whether or not the tumor cells were positive or negative for thymidine phosphorylase, the microvessel count and the peak systolic velocity (PSV). RESULTS: Forty-two tumors were studied (three of low malignant potential, 29 epithelial, four granulosa cell, two germ cell and four metastatic); 18 were stage I, six stage II, 11 stage III and three stage IV. Twenty-seven tumors (64%) were classified as thymidine phosphorylase-positive. The proportion of stage I tumors that was thymidine phosphorylase-positive (44%) was significantly lower (p = 0.022) than the corresponding value for stages II-IV (85%), but the values for microvessel count and PSV were similar. The microvessel count in thymidine phosphorylase-positive tumors was significantly higher than in thymidine phosphorylase-negative tumors (p = 0.005). Similarly, the PSV was significantly higher in thymidine phosphorylase-positive tumors (p = 0.009). There was a significant correlation between the microvessel count and the PSV (r = 0.354, p = 0.022). CONCLUSIONS: The expression of thymidine phosphorylase by malignant tumor cells is associated with an increase in microvessel density and PSV in patients with ovarian cancer.

Adolescent↗

Purification and characterization of a membrane-associated ganglioside sialidase from bovine brain.

A membrane-associated ganglioside-hydrolyzing sialidase was purified to apparent homogeneity from bovine brain. The enzyme was solubilized with Triton X-100 plus sodium cholate from the particulate fraction and purified over 100,000-fold by sequential chromatography on DEAE-cellulose, octyl-Sepharose, heparin-Sepharose, Sephacryl S-200, MonoQ, RCA-agarose, thiol-activated Sepharose, and ganglioside-affinity Sepharose. The final enzyme preparation exhibited a specific activity of 4,851.3 micromol/h/mg protein and an apparent molecular mass of 52 kDa on SDS-polyacrylamide gel electrophoresis. The enzyme preferentially hydrolyzed gangliosides other than GM1 and GM2 but demonstrated hardly any activity against glycoproteins and oligosaccharides. Gangliosides GD3, GD1a, and GT1b were much better substrates than GM3 and GD1b in the presence of Triton X-100, but the latter became more sensitive to the sialidase with addition of sodium cholate. The enzyme was activated by dithiothreitol, strongly inhibited by 4-hydroxy-mercuribenzoate, and firmly adsorbed to thiol-activated Sepharose, indicating that free sulfhydryl groups are essential for its catalytic activity. Subcellular fractionation experiments revealed that the enzyme is mainly located in the synaptosomal fraction.

Animals↗

Three-dimensional ultrasonographic assessment of the umbilical cord during the 2nd and 3rd trimesters of pregnancy.

OBJECTIVE: To evaluate the umbilical cord and its abnormalities by use of three-dimensional ultrasonography with a specially developed abdominal three-dimensional transducer. PATIENTS AND METHODS: Ninety-five pregnancies (92 normal, 2 with hydrops fetalis, and 1 with omphalocele) from 14 to 40 weeks of gestation were studied with a specially developed abdominal three-dimensional transducer (3.5 MHz). This system can provide conventional two-dimensional ultrasonography images and can also generate within seconds high-quality three-dimensional images in the surface and transparent mode with no need for an external workstation. A proportion of the umbilical cords (coiled or noncoiled free loop, abdominal insertion, and placental insertion) visualized at each gestational age interval is presented. RESULTS: The proportion of the umbilical cords visualized during pregnancy except for between 24 and 27 weeks of gestation was about 70% (range 64-83%). Optimal visualization of the umbilical cord was achieved between 24 and 27 weeks of gestation. During this period it was possible to adequately depict the umbilical cord in 93% of the cases. The proportions of the noncoiled umbilical cord depicted during pregnancy ranged from 8 to 45%. The detection rate of abdominal insertion of the umbilical cord visualized at 14-19 weeks was 44%; the detection rate decreased thereafter. Placental insertion of the umbilical cord could not be identified after 28 weeks of gestation. In 2 cases with hydrops fetalis, edematous umbilical cord was evident. In 1 fetus, omphalocele was clearly depicted. CONCLUSIONS: The new three-dimensional ultrasound technology generates within seconds high-quality three-dimensional images of the umbilical cord, although limitation of viewing direction exists. These results suggest that the new three-dimensional ultrasonography has the potential to be a supplement to two-dimensional ultrasonography and might be useful in identifying abnormal umbilical cords in utero.

Edema↗

Effects of closed-system drain in surgery: focus on methicillin-resistant Staphylococcus aureus.

OBJECTIVE: The emergence of methicillin-resistant Staphylococcus aureus (MRSA) has made a strong impact on the strategy of peri-operative antibiotic prophylaxis, since MRSA has become one of the most common causative organisms of nosocomial infection in recent years. In this study, we conducted a bacteriological evaluation of surgical drains before and after introducing strategies to decrease MRSA infection rates. DESIGN AND PATIENTS: Between January 1987 and December 1994, we performed a total of 2, 755 surgical operations on inpatients, including 1,635 major and 1, 120 minor operations. Almost all surgical drains were examined bacteriologically when they were removed. The number of drains examined was 460 +/- 47 (mean +/- SEM) per year. Since the increased incidence of MRSA infection, we started exclusively using a closed drainage system and first-generation cephalosporins in 1991. The strategy was evaluated by comparing the positive rates of drain cultures, changes in bacteriological features, and incidence of MRSA infection for the 4-year periods before and after 1991. RESULTS: The positive rate of bacteria in the drains decreased significantly (p < 0.01) from 25 +/- 2 to 16 +/- 1%. Bacteriologically, the positive rate of Staphylococcus spp. decreased significantly (p < 0.05) from 7 +/- 2 to 3 +/- 0.3%. Positive rates of MRSA decreased significantly (p < 0.05) from 2.1 +/- 0.3 to 1.3 +/- 0.3%. Streptococcus declined dramatically from 3.0 +/- 0.3 to 0.3 +/- 0.1%. Of gram-negative strains, Pseudomonas and Escherichia coli were most often isolated. They showed no significant difference in positive rates between the terms. CONCLUSION: A closed drainage system and thorough use of the first-generation cephalosporins for prophylaxis were effective in decreasing positive bacterial culture of drains and reducing the incidence of MRSA on drains after surgery.

Adult↗

Three-dimensional sonographic visualization of the fetal face.

OBJECTIVE: This study was done to show the potential of using three dimensional (3D) sonography to reveal fetal facial anomalies. SUBJECTS AND METHODS: Ninety-four healthy fetuses from 15 to 40 weeks' gestation were studied with a specially developed 3.5-MHz abdominal 3D transducer. This imaging system provided conventional two-dimensional (2D) sonographic images and also generated within seconds high-quality 3D images in the surface and transparent modes with no need for an external workstation. RESULTS: Using this imaging system, we obtained 2D and 3D images of fetal faces (forehead, eyes, nose, lips, and chin) at six gestational ages. At less than 24 weeks' gestation, 65% of facial structures were visualized. The image quality was slightly degraded because of the small fetal size. At or after 24 weeks' gestation, 84% of facial structures were revealed. We found no significant difference in image quality of the fetal face between 2D and 3D sonography. CONCLUSION: The new 3D sonographic technology can generate within seconds high-quality 3D images of the fetal face. The 3D technology seems to perform at least as well as conventional 2D sonography. Our results suggest that 3D sonography has the potential to supplement 2D sonography and might be useful in identifying malformations of the fetal face and chromosomal abnormalities in utero.

Face↗

[Combination chemotherapy with cis-platinum and ifosfamide for hormone unresponsive prostate cancer].

PURPOSE: There is no effective therapy against hormone refractory prostate cancer. This led us to evaluate the effectiveness and toxicity of cis-platinum (CDDP) and ifosfamide (IFM) combination chemotherapy in the patients with hormone-unresponsive carcinoma of the prostate. METHODS: Patients with hormone-unresponsive prostate cancer were scheduled to receive CDDP 70 mg/m2 intravenously on day 1 and IFM 1.2 g/m2/day intravenously on day 1 through day 5 of 28-day cycle. RESULTS: Twenty seven patients with hormone unresponsive prostate cancer were enrolled onto this trial. Of these patients, seven (26%) demonstrated a partial objective response (PR), and ten (37%) a stable disease (ST). The response duration of PR cases lasted from 6 to 49 months with a median of 16 months and the response duration of PR + ST cases lasted from 3 to 36 months with a median of 10 months. Subjective improvement was obtained in 11 patients (41%). Survival duration of all cases were 4 to 89 months with a median of 23 months and probabilities of survival at 3 years and 5 years were 36% and 24%, respectively. The toxicity of this treatment was mostly mild to moderate, anemia (96%), leukocytopenia (89%), anorexia (81%), alopecia (67%), thrombocytopenia (44%), hematuria (38%), renal dysfunction (19%) and liver dysfunction (7%) were noticed. Severe toxicity was observed in two cases, one acute renal failure and one endotoxin shock. CONCLUSION: We conclude that CDDP and IFM combination chemotherapy was active regimen for hormone unresponsive prostate cancer.

Aged↗

Effect of regular aerobic exercise on cerebrovascular tone in young women.

Our objective was to evaluate the effect of regular aerobic exercise on cerebrovascular tone in young women. Color and pulsed Doppler ultrasonography were used to determine the pulsatility index in the ophthalmic artery in 20 normotensive, nonpregnant young women (aged 19 to 26 years) with a regular menstrual cycle on cycle day 5. Blood pressure and heart rate were recorded at each examination. Blood samples were collected from all the subjects to measure serum estradiol levels and serum lipid profiles. Ten of the 20 women (exercise group) have maintained aerobic exercise for 50 min, 3 to 5 days a week, for at least a year. The other 10 women (nonexercise group) never did regular exercise. There were no significant differences between the two groups regarding age, body mass index, mean blood pressure, and heart rate and serum estradiol, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride levels. The pulsatility index value (mean, 1.89; standard deviation, 0.33) of the ophthalmic artery in the exercise group was significantly lower than that (mean, 2.53; standard deviation, 0.26) in the nonexercise group. Regular aerobic exercise in young women significantly decreases the peripheral cerebrovascular tone, and this might be a favorable adaptation for early prevention of cerebrovascular disease, which is common in older women.

Adaptation, Physiological↗

[Efficacy of granisetron as anti-emetic agent for emesis induced by intra-arterial injection therapy for hepatocellular carcinoma].

The effect of granisetron in preventing nausea and emesis induced by intraarterial chemotherapy was comparatively studied with a historical control group (46 cases) in 50 patients with hepatocellular carcinoma receiving intraarterial anti-tumor drugs such as cisplatin and doxorubicin. Emesis was perfectly controlled in 39 out of 50 patients in the treatment group (78%), in comparison to 33 out of 46 patients (71.7%) in the historical control group. This represented no statistical significance between the two groups. In terms of the severity of nausea, however, the granisetron group demonstrated significant superiority to the control group with 27 out of 50 patients (54%) being free of symptoms compared with 16 out of 46 patients (34.8%) in the control group. A stratified analysis of the data also demonstrated significant superiority of the granisetron group over the historical group in the number of emetic episodes and the severity of nausea in female patients, who are more predisposed to emesis. The above results confirm the usefulness of granisetron as an antiemetic agent used for the prevention of acute nausea and emesis induced by intraarterial chemotherapy.

Adult↗

Hyperosmolarity-induced gene stimulation is mediated by the negative calcium responsive element.

The negative calcium responsive elements of the parathyroid hormone gene bind to a specific set of nuclear proteins in an extracellular calcium (Ca2+e)-dependent manner. We have found that one of the negative calcium responsive elements, named oligo B, is found in the 5'-flanking region of such vasoactive genes as the vasopressin and atrial natriuretic polypeptide genes. Furthermore, the oligo B-like sequence in the former gene is conserved throughout evolution. Because expression of some of these vasoactive genes is altered by external stimuli which change cell volume, we examined whether oligo B is involved in gene regulation by hyperosmolarity. Here, we demonstrate that the binding between oligo B and its binding nuclear proteins including a redox factor 1 was reduced by hyperosmolarity generated by sodium chloride but not by urea. Such attenuated binding was reversed by dephosphorylating nuclear proteins by a potato acid phosphatase, suggesting that NaCl treatment elicited phosphorylation of these nuclear proteins to weaken their binding activity to oligo B. Furthermore, these nuclear events led to hyperosmolarity-mediated transcriptional stimulation of the genes bearing this DNA element in the cultured cells.

Calcium↗