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Biomedical subjects

Y Takeda

Publications and source records attributed to Y Takeda.

At least 415 records · Page 23Linked to original sources

Pilot study for preoperative administration of l-OHP to patients with advanced scirrhous type gastric cancer.

A new DACH platinum complex, l-OHP, was developed by Kidani as an anticancer agent. A clinical trial took place in Europe which demonstrated its therapeutic efficacy for colorectal cancer. An effective treatment, especially chemotherapy for patients with a advanced scirrhous type gastric cancer, has not yet been established. An in vitro study showed that l-HOP inhibited cell growth in human gastric cancer cell lines. Our pilot study determined the efficacy of preoperative administration of l-OHP, 67 mg/m2 to 100 mg/m2, every 2-3 weeks, for two to three cycles, in five patients with this disease (Stage III and IV) roentogenoscopically and histologically. The platinum concentration in the tissues was also measured. By X-ray examination of the stomach at the time of pre- and post-administration of l-OHP, extension of the lesional gastric wall was observed. Histologically three Grade 2 responses and two Grade 1a responses were obtained according to the criteria presented by Japanese Research Society for Gastric Cancer. The mean platinum concentrations in the lesional tissues were 0.98 ppm and 0.5 ppm in the patients administered l-OHP for three and two cycles respectively. There was no toxicity that prevented surgery. These preliminary results showed the possibility that 1-OHP would be effective for patients with advanced scirrhous type gastric cancer as a neoadjuvant therapy.

Adenocarcinoma, Scirrhous↗

Surgery in patients with HIV infection: indications and outcome.

We reviewed the records of 12 patients with HIV infection (one stage I, three stage II, two stage III, six stage IV) who received 15 surgical procedures under general or lumbar/epidural anesthesia. We discussed surgical indications, their poor wound healing and precautions for preventing the risk of transmission of HIV to health care workers. Six emergency and nine elective operations were performed. Postoperative complications developed after three emergency and three elective operations. Ten patients showed delay of wound healing which was not directly correlated with the CD4+ cell count. No operative deaths occurred. In any stage of HIV infection, not only palliative but also curative operations can be performed as long as HIV infection, opportunistic infections and HIV-related neoplasms can be controlled. Late stage wound healing is poor, but the wound will heal without keloid formation, although it takes two to three times longer than usual. For operating on patients with HIV infection precautions for preventing needle sticks, sharp injuries and blood exposure should be learned and used by health care workers. As a result, surgical staff members will be able to perform operations safely on HIV-infected patients to improve both quality of life and the prognosis of their disease.

Adult↗

Suppression of neointimal thickening by a newly developed HMG-CoA reductase inhibitor, BAYw6228, and its inhibitory effect on vascular smooth muscle cell growth.

1. The aim of this study was to determine whether BAYw6228 (BAYw), a newly developed 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor, could suppress an atherogenic process such as intimal thickening by a mechanism other than lowering the level of serum cholesterol. 2. First, we evaluated the in vitro effect of BAYw on the proliferation of vascular smooth muscle cells (SMC) from various species: Sprague-Dawley (SD) rats. New Zealand (NZ) white rabbits, intimal cells from Watanabe hereditary hyperlipidemic (WHHL) rabbit and SMC from the new-born human aorta. The increasing rate of total protein content of these cells was inhibited by the addition of BAYw in a dose-dependent fashion. In the presence of 2% foetal calf serum (FCS), the value of IC50 was 1.0 microM in SD rats, 2.1 microM in NZ white rabbits, and 0.3 microM in WHHL rabbits. With human SMC, the value was 0.02 microM in the presence of 10% FCS and 0.2 microM with a mixture of growth factors. 3. Based on these above in vitro findings, we next examined the in vivo effect of the agent to determine whether it could suppress rabbit intimal thickening induced by balloon catheterization. A balloon catheter was inserted from a peripheral branch of the left external carotid artery to the aorta to denude the endothelium of the left common carotid artery in Japanese white rabbits. After 12 days they were divided into control and BAYw groups. The former were subcutaneously injected with saline and the latter with BAYw 1 mg kg-1 day-1. Two days after the beginning of treatment, a second balloon injury was performed to the previously injured left common carotid artery in both groups. After another two weeks, the left common carotid artery was removed and variously stained. Although the total serum cholesterol in the BAYw group was significantly lower than in the control (P < 0.05), the difference was not enough to affect intimal thickening. In addition, the BAYw group had a smaller intima/media ratio than the control group, decreasing to 45% of control (P < 0.05). By anti-alpha smooth muscle actin antibody staining, these intimal thickening areas were entirely occupied by SMCs, and their amount was attenuated by BAYw. By anti-rabbit macrophage antibody (RAM 11) staining, the number of positive cells in the intimal thickening was markedly decreased in the BAYw group compared to control (P < 0.01). 4. These results indicate that BAYw has an inhibitory effect on intimal thickening by attenuating intimal SMC proliferation and infiltration of macrophages, suggesting that BAYw could be effective in the prevention of the progression of atherosclerotic plaque-like restenosis after angioplasty.

Animals↗

Pioglitazone reduces smooth muscle cell density of rat carotid arterial intima induced by balloon catheterization.

The effect of pioglitazone on balloon catheterization-induced carotid arterial intimal thickening lesion of male Wistar fatty rats and its littermates (Wistar lean rats) was investigated. Pioglitazone was administered via gastric tube at 10 mg/kg/day to 12-week-old rats for 7 days. Age-matched rats without pioglitazone were used as respective controls. Each rat was catheterized using a balloon catheter inserted from the left femoral artery to the left common carotid artery, and the endothelium in the left common carotid artery was denuded. Rats were then treated with pioglitazone for 14 days post catheterization and the left common carotid artery was removed and stained with Elastica-Masson and anti-alpha-smooth muscle actin antibody. In addition, for smooth muscle cell (SMC) culture, pioglitazone was administered at 10 mg/kg/day for 28 days to a separate group of 12-week-old rats, and the aortic medial outgrowth rate of their SMCs was measured. Age-matched rats without pioglitazone were prepared as respective controls. In comparison with the area ratio of the thickened intima/media of fatty rats without treatment, those of fatty rats with treatment and lean rats without treatment were significantly decreased by approximately 60%, and also that of lean rats with treatment to 27%. With anti-alpha-smooth muscle actin antibody staining, almost all cells present in intimal thickening were positive. Treatment with pioglitazone reduced the amount of anti-alpha-smooth muscle actin antibody-staining cells. In addition, the outgrowth rate of SMCs at day 10 compared to that in fatty rats without treatment decreased to 42% in fatty rats with treatment, 29% in lean rats without treatment and 23% in lean rats with treatment, respectively. Therefore, pioglitazone has an inhibitory effect on the growth of SMCs, and consequently suppressed carotid intimal thickening. Furthermore, this inhibitory effect was enhanced in diabetes.

Actins↗

Purification and characterization of alpha,beta-ketoalkene double bond reductases from bovine eyes.

PURPOSE: To explore the alpha,beta-ketoalkene double bond reductases responsible for xenobiotic metabolism in bovine ocular tissues using trans-phenyl-l-propenyl ketone as a model substrate. METHODS: A mixture of trans-phenyl-l-propenyl ketone, NADPH or NADH, and an enzyme source in 0.1 M K,Na-phosphate buffer (pH 7.4) was incubated for 15 min at 37 degrees C. Phenyl propyl ketone formed was quantified by high performance liquid chromatography (HPLC). RESULTS: The lens, ciliary body, iris, retinal pigment epithelium (RPE)-choroid, retina, and cornea exhibited alpha,beta-ketoalkene double bond reductase activities in the presence of NADPH or NADH. An alpha,beta-ketoalkene double bond reductase was purified to homogeneity from the iris-ciliary body cytosol. The molecular weight was estimated to be 58,000 by gel filtration, and 40,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The enzyme activity was inhibited by dicumarol, quercitrin, indomethacin, disulfiram, and p-chloromercuribenzoic acid. The enzyme exhibited double bond reductase activity toward 2-alkenals as well as alpha,beta-ketoalkenes. Another alpha,beta-ketoalkene double bond reductase was also purified to homogeneity from the lens cytosol. The molecular weight was estimated to be 105,000 by gel filtration and 40,000 by SDS-PAGE. The enzyme activity was inhibited by dicumarol and quercitrin. The enzyme exhibited double bond reductase activity toward some alpha,beta-ketoalkenes. CONCLUSIONS: Two kinds of enzymes responsible for reduction of the carbon-carbon double bond of xenobiotics were purified for the first time from ocular tissues. The molecular weights, substrate specificities, and sensitivities to inhibitors of the enzymes were different from each other.

Alkenes↗

Antiviral activity of 5,6,7-trimethoxyflavone and its potentiation of the antiherpes activity of acyclovir.

A naturally occurring flavone, 5,6,7-trimethoxyflavone (TMF), isolated from the plant Callicarpa japonica, was subjected to antiviral assays. The compound exhibited relatively high inhibitory effects on herpes simplex virus type 1 (HSV-1), human cytomegalovirus and poliovirus. The anti-HSV-1 action was not due to the inhibition of virus adsorption, entry and viral protein synthesis, but might involve, at least in part, a virucidal activity, which results in a suppression of viral binding to host cells at an early replication stage. TMF and acylovir were synergic in their anti-HSV activities at levels below the 50% inhibitory concentrations for antiviral activity.

Acyclovir↗

Isolated collagen IV retains the potential to form an 18-nm sided polygonal meshwork of the lamina densa.

Polygonal meshworks were revealed in the aggregates reconstituted from isolated collagen IV as well as in the lamina densa of mouse pancreas by the quick-freezing and deep-etching technique. Collagen IV solution with acetic acid from the bovine lens capsules and that isolated from the pepsin-solubilized fraction of human placenta reconstituted polygonal meshworks, which were dimensionally similar to the meshwork seen in the lamina densa of mouse pancreas. The average lengths between branching points in the lamina densa, and the meshworks of collagen IV derived from the bovine lens capsules and from the human placenta were 20.1 +/- 7.7 nm (mode = 18 nm), 21.6 +/- 11.3 nm (mode = 14 nm), and 21.6 +/- 9.0 nm (mode = 18 nm), respectively. These observations suggest that collagen IV can, in the absence of other macromolecules including laminins, comprise a skeletal meshwork similar in dimensions to that of the lamina densa.

Animals↗

Reduced radioactivity in the periphery of the liver in a patient with idiopathic portal hypertension.

The authors report a case of idiopathic portal hypertension in which radioaccumulation in the peripheral region of the liver decreased markedly. On dynamic CT, peripheral regional enhancement of the liver was seen in the arterial phase. The region was hypointense on T1-weighted MR images and hyperintense on T2-weighted images. On portograms via the superior mesenteric artery, markedly decreased portal venous perfusion was seen in the peripheral region of the liver. Tc-99m galactosyl human serum albumin (GSA) liver scintigrams showed decreased accumulation in the peripheral region and unchanged accumulation in the central region of the liver. Tc-99m GSA liver scintigraphy clearly showed localized liver dysfunction in the peripheral region.

Female↗

Cryptic appearance of a new clone of Vibrio cholerae serogroup 01 biotype El Tor in Calcutta, India.

In this study, pulsed-field gel electrophoresis (PFGE) was applied to determine if the Vibrio cholerae 01 strains which reappeared after being temporarily displaced in Calcutta by the 0139 serogroup were different from those isolated before the advent of the 0139 serogroup. NotI digestion generated a total of 11 different patterns among the 24 strains of V. cholerae randomly selected to represent different time frames. Among the V. cholerae 01 strains isolated after July 1993, 4 PFGE banding designated as H through K were observed with pattern H dominating. Pattern H was distinctly different from all other patterns encountered in this study including patterns A, B and C of V. cholerae 01 E1 Tor, which dominated before November 1992, and pattern F, which was the dominant V. cholerae 0139 pattern. Further, pattern H was also different from the NotI banding patterns of the representative strains of the 4 toxigenic clonal groups of V. cholerae 01 E1 Tor currently prevailing in different parts of the world. NotI fragments of the new clone of V. cholerae 01 did not hybridize with an 0139 specific DNA probe, indicating that there was no 0139 genetic material in the new clone of V. cholerae 01. Hybridization data with an 01-specific DNA probe again differentiated between the clones of V. cholerae 01 existing before the genesis of the 0139 serogroup and the 01 strains currently prevalent.

DNA, Bacterial↗

Melanocytes in the human parotid gland.

A review of the literature yields about 20 reported cases of purportedly primary malignant melanoma of the parotid gland, but no convincing examples of pre-existent melanocytes in the salivary glands. The present paper reports the existence of melanocytes in the interlobular duct of the parotid gland observed during an autopsy case of a Japanese male. Melanocytes with long cytoplasmic processes were distributed in the basal and suprabasal layers of hyperplastic duct epithelium, and melanin granules were sparsely scattered in the duct epithelial cells. This is the first report of melanocytes in the human salivary gland.

Epithelium↗

Escherichia coli virulence factors and serotypes in acute bacterial prostatitis.

BACKGROUND: Escherichia coli is the most frequent pathogen in both acute bacterial prostatitis and acute uncomplicated urinary infections. To assess the virulence profiles of E. coli in acute prostatitis, the serotypes and virulence factor (VF) genotypes were determined. METHODS: We studied 107 E. coli isolates from cases of acute bacterial prostatitis, 76 isolates from acute pyelonephritis, 194 isolates from acute Cystitis and 80 fecal isolates from healthy people. All pyelonephritis and cystitis isolates were from women. Seven urovirulence determinants were analyzed by DNA colony hybridization, including the genes for type 1 fimbria (pil), P fimbria (pap), S fimbria (sfa), afimbrial adhesin AFA-I (afaI), alpha-hemolysin (hly), cytotoxic necrotizing factor 1 (cnf1) and aerobactin (aer). O:H:K serotypes were also determined. RESULTS: With the exception of pil and afaI, all VFs were significantly more often associated with prostatitis, pyelonephritis and cystitis isolates than with the fecal isolates. The prevalence of sfa, hly and cnf1 was higher in prostatitis isolates than in pyelonephritis and cystitis isolates, and the pap+sfa+hly+cnf1+ genotype was dominant among prostatitis isolates (48.8%). Nine O serotype (O1, O2, O4, O6, O16, O18, O22, O25 and O75) accounted for 79.4%, 73.7% and 78.4% of the prostatitis, pyelonephritis and cystitis strains, respectively. There was an apparent correlation between serotype and genotype in uropathogenic E. coli. CONCLUSION: The predominance of O serotypes in female urinary tract infections and a high percentage of multiple VFs among the prostatitis isolates suggested that VFs play important roles in the pathogenesis of acute bacterial prostatitis.

Acute Disease↗

Statistical analysis of perinatal outcomes in pregnancy complicated with diabetes mellitus.

OBJECTIVE: To evaluate the outcomes of pregnancies complicated with diabetes mellitus (DM) in the maternal and perinatal center of Tokyo Women's Medical College (TWMC), and compare the results with reports of other countries. METHODS: A retrospective study of 482 cases of DM pregnancies were included over a 13-year period in a tertiary care hospital in Tokyo. Information were obtained from medical records of both mothers and babies. RESULTS: The prevalence of pregnancies complicated with DM was 5.1%. Preeclampsia developed in 124 cases at a rate of 25.8%. Incidence of preterm delivery was 16.6%. Caesarean sections were performed in 36.7% patients. There were significant differences of caesarean section rates between diabetic complication group (retinopathy and nephropathy) and non-complication group (69.5% vs 30.5%, p < 0.0001), and between preterm and term deliveries (60.0% vs 32.1%, p < 0.0001). Maternal backgrounds significantly involved with preterm delivery were DM nephropathy and severe preeclampsia. Babies with heavy for gestational age (HGA) were observed at a rate of 21% in all. There were 3 perinatal deaths (intrauterine fetal deaths, IUFD) with the perinatal mortality rate of 6.1/1,000 births. The incidence of caesarean section and perinatal mortality rate of non-DM pregnancies in our center during the same study period were 16.3% and 7.7/1,000 births respectively. CONCLUSIONS: The perinatal outcome in our study was better compared to other worldwide reports. With accurate perinatal management, perinatal mortality rate of DM pregnancies in the current study was almost same as that of non-DM pregnancies in our center. The main factors to promote adverse perinatal outcomes were presence of DM nephropathy and severe preeclampsia.

Adult↗

The fetal aortic pressure pulse waveform in normal and compromised pregnancy.

OBJECTIVE: To study the arterial pressure waveform in the descending thoracic aorta during pregnancy in both normal and compromised fetuses. DESIGN: The pressure pulsation waveform propagated along the vascular tree, and acting laterally on the arterial wall, produces a corresponding change in the vessel diameter. The distance between diametrically opposite points of the aortic lumen was followed using a phase locked loop echo tracking system coupled to a B-mode ultrasonic imager (central frequency 3.5 MHz). SETTING: Tertiary referral unit, teaching hospital. PARTICIPANTS: A cross-sectional study of 80 normal fetuses between 20 and 40 weeks yielded normal data. We studied 58 women with evidence of potential fetal compromise (high umbilical artery systolic: diastolic ratio). MAIN OUTCOME MEASURES: From the aortic diameter waveform we measured the maximum systolic and minimum diastolic dimension and calculated pulse amplitude. The first derivative of the aortic diameter waveform identified the incisura of aortic and pulmonary valve closure and was used to time the end of ventricular ejection and systole. RESULTS: In normal pregnancy there was an increase in systolic and diastolic diameter and pulse amplitude with advancing gestation. Ventricular ejection time was constant. In the fetal compromised group the absolute systolic and diastolic diameters were within the normal range, but diastolic diameter per unit fetal weight was increased. There was a decrease in pulse amplitude as a percentage of diastolic diameter and an increase in the diastolic systolic diameter ratio. Fetal outcome was examined in relation to the diastolic systolic diameter ratio. Those with a high ratio (above 90th centile of normal group) exhibited significantly more adverse indices of fetal outcome. CONCLUSIONS: The fetal aortic pressure pulse waveform was represented by the vessel diameter waveform. In fetal compromise reduced pulse amplitude and increased diastolic to systolic diameter ratio suggest corresponding changes in arterial pressure pulse. We suggest these are the response of the cardiac pump to increased afterload imposed by the high umbilical placental vascular resistance.

Aorta, Thoracic↗

[Isolation of verotoxin-producing Escherichia coli from cattle and characterization of the isolated strains].

Attempts to isolate Verotoxin-producing Escherichia coli (VTEC) from 53 dead baby cattle were made during a period from January 1989 to July 1991. From 6 cattle of 5 farms, VTECs were isolated. Further examination of cattle from 2 farms with dead baby cattle and from 1 farm with an outbreak of diarrhea among baby cattle, from 8 of 26 cattle with diarrhea and from 9 of 58 healthy cattle, VTECs were isolated. Several serotypes which caused food poisoning in Japan as well as in the US and Europe were included in the isolated strains. VTECs were also isolated from several cattle imported from the US suggesting that these VTECs were from outside the country together with the imported cattle.

Animals↗

Examination of diarrheagenicity of cytolethal distending toxin: suckling mouse response to the products of the cdtABC genes of Shigella dysenteriae.

Some strains of Escherichia coli, Shigella spp., and Campylobacter spp. that have been implicated in diarrheal disease produce cytolethal distending toxin (CDT). CDT induces unique morphological changes in Chinese hamster ovary cells, but its association with diarrheal disease is unclear. We studied the diarrheagenicity of CDT using the cdt genes that we originally cloned from Shigella dysenteriae. The cdt genes were subcloned into a high-copy-number plasmid in E. coli JM109 to achieve high-level CDT production into the culture supernatant. An isogenic CDT- derivative was constructed by deletion of the 0.9-kb sequence internal to the cdt genes. A suckling mouse model was established, in which the intragastrically administered culture supernatant of the CDT+ E. coli strain induced excretion of loose and/or watery feces more often than did that of the CDT- strain in 24 h. The partially purified CDT preparation induced profuse watery diarrhea by 12 h in this model. High-level intestinal fluid accumulation in 4 h appeared to be related to the watery diarrhea. The results indicate that CDT is diarrheagenic to suckling mice and suggest that diarrheagenicity is dependent on CDT level. The preparations containing wild-type CDT induced tissue damage (necrosis and reparative hyperplasia) in the descending colon, whereas the tissues of the small intestines remained apparently intact. Association between the colonic damage and diarrhea is unclear and needs further investigation.

Animals↗

Emergence of a unique O3:K6 clone of Vibrio parahaemolyticus in Calcutta, India, and isolation of strains from the same clonal group from Southeast Asian travelers arriving in Japan.

Active surveillance of Vibrio parahaemolyticus infection among hospitalized patients in Calcutta, India, was initiated in January 1994. The incidence of cases of V. parahaemolyticus infection suddenly increased in February 1996 and has remained high since then. One hundred thirty-four strains of V. parahaemolyticus isolated from January 1994 to August 1996 were examined for serovar, the presence of the thermostable direct hemolysin gene (tdh) and tdh-related hemolysin genes (trh1 and trh2), production of urease, and antibiogram. Strains of the O3:K6 serovar appeared for the first time in February 1996. The O3:K6 serovar strains accounted for 50 to 80% of the strains isolated during the high-incidence period (February to August 1996). All of the serovar O3:K6 strains carried the tdh gene but not the trh genes and did not produce urease. All of the isolates except two were sensitive to all of the antibiotics tested. These and the results of analysis by an arbitrarily primed PCR method indicated that the O3:K6 serovar strains belong to a unique clone. When the O3:K6 serovar strains, isolated from travelers arriving in Japan from Southeast Asian countries, were compared by the arbitrarily primed PCR method, the strains isolated between 1982 and 1993 were distinct from Calcutta O3:K6 while the strains isolated in 1995 and 1996 were indistinguishable from the Calcutta O3:K6 strains. The results suggest that this unique O3:K6 clone may have become prevalent not only in Calcutta but also in Southeast Asian countries very recently. Not only the O3:K6 strains but also the non-O3:K6, tdh-bearing strains isolated in 1996 produced thermostable direct hemolysin at high levels, and thus the level of hemolysin produced does not appear to have influenced the high incidence of serovar O3:K6 strains.

Asia, Southeastern↗

A novel antifolate, MX-68, inhibits the development of autoimmune disease in MRL/lpr mice.

We compared a novel unpolyglutamable antifolate, MX-68, with polyglutamable antifolate, methotrexate (MTX), for treatment of an autoimmune kidney disease which develops spontaneously in MRL/Mp-lpr/lpr (MRL/lpr) mice. Oral administration of either MX-68 or MTX was commenced in 8-week-old female mice and continued 3 times a week until they reached 30 weeks of age. MX-68 delayed the onset of proteinuria and prolonged life span dose-dependently. Furthermore, it suppressed the elevation of serum blood urea nitrogen and cholesterol levels. MX-68 was as effective as MTX at ameliorating events which accompany the development of lupus nephritis, despite that MX-68 did not undergo polyglutamation. These ameliorative effects of MX-68 and MTX did not occur via inhibition of either autoantibody production or cell proliferation. Neither compound suppressed age-dependent elevation of immune complexes or antibodies for single-stranded DNA and TNP in serum nor did they influence the associated enlargement of lymph nodes and spleen. We conclude that MX-68 is beneficial for the treatment of autoimmune kidney disease in mice and may be useful for other related diseases such as systemic lupus erythematosus.

2-Aminoadipic Acid↗