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Biomedical subjects

T Sakamoto

Publications and source records attributed to T Sakamoto.

At least 469 records · Page 26Linked to original sources

Effects of MRI abnormalities on WAIS-R performance in solvent abusers.

OBJECTIVE: To clarify how chronic solvent abuse affects cognitive function using magnetic resonance imaging as an index of brain damage. MATERIAL AND METHODS: A total of 25 chronic solvent abusers underwent magnetic resonance imaging with quantitative neurometry and Wechsler Adult Intelligence Scales revised. RESULTS: The abusers with white matter change (n=10) showed significantly (P<0.05) lower performance IQ, especially in Digit Symbol subtest (P<0.01). Also, the severity of pontine atrophy was significantly correlated with PIQ (r=0.60, P<0.01). CONCLUSIONS: These data indicate that solvent abuse causes the decline in the test performance reflecting cognitive and fine motor dysfunction and that white matter changes and pontine atrophy may have some roles in this decline.

Adult↗

[A clinical study of skin flora in patients with MRSA colonization after introduction of preventive measures of hospital infection in a geriatric ward].

In early 1980's methicillin-resistant Staphylococcus aureus (MRSA) was reported as a major pathogenic organism of geriatric hospital infection in Japan. At the same time in the geriatric hospital MRSA infection was prevalent. To decrease nosocomial infections some active preventive measures against hospital infection were taken since Oct. 1991. After introduction of preventive measures of hospital infection in the geriatric ward (190 beds) nosocomial bacteremia and pneumonia were markedly decreased in comparison of episode number before introduction of prevention. However several patients with MRSA colonization were observed every month. The aim of this clinical study was to clear how frequent MRSA was isolated from skin. Consequently 3 strains (3.4%) of MRSA were observed in 86 cultured skin. In conclusion we considered frequency of MRSA colonization frequency of MRSA colonization on skin was not so high but rather very low under the preventive measures.

Aged↗

Characterization of a liver metastatic variant of murine colon 26 carcinoma cells.

Intraportal vein injection of highly metastatic L5 cells consistently resulted in liver metastases (increases in the number of tumor colonies in the liver), whereas inoculation of P cells rarely did. L5 cells invaded the basement membrane Matrigel in greater numbers than did P cells, suggesting that the metastatic potential of L5 cells is partly related to enhanced invasive properties. The enhanced adhesion of L5 cells to fibronectin-, laminin- and Matrigel-coated substrates, as well as their haptotactic migration to fribronectin, may be associated with the preferential expression of VLA-2 and VLA-4 integrins on the surface of these cells detected by flow cytometry. Gelatin zymograms showed that the degradative activity of 72-kD gelatinases was greater in L5 cells than P cells. These results indicate that, in addition to adhesiveness and motility, the invasive ability of L5 cells may also be attributed to enhanced gelatinolytic activity. L5 cells grew more rapidly than P cells in vitro. Thus, an experimental model using highly metastatic colon 26 L5 cells would be useful for analyzing the molecular mechanism of liver metastasis and for evaluating the efficacy of treatment of occult micrometastases which may already have been disseminated at the time of surgery.

Adenocarcinoma↗

Ocular gene therapy: experimental studies and clinical possibilities.

The Human Genome Project will identify, map and sequence all 50,000-100,000 human genes and will provide the tools to determine the genetic basis of both common and rare diseases. Understanding the genetic basis of human disease will allow for the development of highly specific drugs and for replacement of the altered gene through gene therapy. Gene therapy may also be used to introduce a new function into cells with resulting therapeutic benefit. Genes may be delivered into cells in vitro or in vivo utilizing viral or nonviral vectors. Viral vectors which have been used include retroviruses, adenoviruses, adeno-associated viruses and herpes viruses. Ocular disorders with the greatest potential for benefit of gene therapy at the current time include hereditary ocular diseases, including retinitis pigmentosa, tumors such as retinoblastoma or melanoma, and acquired proliferative and neovascular retinal disorders. We have demonstrated the feasibility of ocular gene therapy in a rabbit model of proliferative vitreoretinopathy, using retroviral vectors containing the herpes simplex virus thymidine kinase 'suicide' gene. Although in vivo transduction efficiency is low, the strong bystander effect results in prominent killing of proliferating cells in this model leading to inhibition of disease. In the future, gene therapy has the potential for the replacement of defective gene products or introduction of new gene products into ocular cells. The selection of appropriate target genes and cells will be critical, as will the development of a methodology for safe, targeted gene transfer.

Animals↗

Captopril reduced plasminogen activator inhibitor activity in patients with acute myocardial infarction.

Recent clinical trials have demonstrated that the administration of angiotensin-converting enzyme (ACE) inhibitors to patients with myocardial infarction reduces the incidence of recurrent myocardial infarction. It has also been reported that an elevated level of plasminogen activator inhibitor (PAI) appears to constitute a marker of the risk of recurrent coronary thrombosis. To determine whether the ACE inhibitor captopril reduces plasma PAI inhibitor activity, we measured changes in plasma PAI activity (IU/ml), tissue plasminogen activator (t-PA) antigen (ng/ml), and serum ACE activity (IU/L) in 14 survivors of myocardial infarction receiving captopril therapy (37.5 mg daily) and compared them with the values in 15 placebo-treated patients chosen at random. Blood sampling was performed at 07.00 h. In the captopril-treated group, serum ACE activity decreased significantly, from 14.0 +/- 0.8 to 11.5 +/- 1.2 IU/L 24 h after captopril therapy (p < 0.01), and those of PAI activity and t-PA antigen also decreased significantly-from 11.9 +/- 2.8 to 5.5 +/- 2.2 IU/ml (p < 0.02) and from 9.9 +/- 1.0 to 7.5 +/- 0.9 ng/ml (p < 0.05), respectively 48 h after captopril therapy. However, the levels of ACE activity, PAI activity, and t-PA antigen remained unchanged during the study period in the placebo group. Thus, our data indicate that the administration of captopril to patients with acute myocardial infarction may result in a reduced frequency of recurrent coronary thrombosis by increasing fibrinolytic capacity.

Aged↗

Increased plasma soluble intercellular adhesion molecule-1 levels in patients with acute myocardial infarction.

Intercellular adhesion molecule-1 (ICAM-1) is a major ligand for 2 members of the CD18 family of leukocyte integrin adhesion molecules and mediates adhesion between leukocytes and stimulated endothelial cells. We examined plasma soluble ICAM-1 (sICAM-1) levels in 30 patients with acute myocardial infarction (AMI) within 6 h of symptom onset, 21 patients with unstable angina (UA), 35 patients with stable exertional angina (SEA) and 21 control subjects. Plasma sICAM-1 levels (ng/ml) were significantly higher in both the acute and chronic phases of AMI and in the UA group than in the SEA and the control groups (195 +/- 14, 198 +/- 16 in the acute and chronic phases of AMI, 188 +/- 11 in the UA group vs 142 +/- 7 in the SEA group, 141 +/- 10 in the control group, p < 0.01). Plasma sICAM-1 levels were significantly higher in AMI patients when preceded by unstable angina than when not preceded by unstable angina at any point over the time course except 1 week after admission (p < 0.01 vs admission, 12 h, 2 days, 3 days, 5 days, 2 weeks, 3 weeks. p < 0.05 vs 24 h). These results suggest that the increase in sICAM-1 is associated with repeated episodes of myocardial ischemia and reperfusion not leading to myocardial necrosis. The increase in sICAM-1 may play an important role as an inflammatory component in the pathogenesis of the ischemic myocardium.

Adult↗

Difference of virus populations in HIV carriers in relation to AZT treatment.

To analyse the appearance of AZT-resistant HIV in HIV carriers after AZT treatment and compare the mutations responsible for resistance employing cloned HIV DNA derived from provirus and free virions in plasma, serial blood specimens were taken before and after AZT treatment. RNA in virions in plasma, proviral DNA and RNA from virus isolates by coculture of PBMCs of HIV carriers and healthy blood donors were cloned and sequenced. DNA clones were compared for their nucleotide sequences responsible for AZT resistance. AZT resistance was acquired as early as 2 months after the start of the treatment and follow-up study was performed for 16 months of the treatment. Population of DNA clones was different according to the origin of the DNA or RNA, which indicated that the provirus population in PBMC was different from that in virions in plasma. These data demonstrated the possibility of selective activation of provirus or activation of provirus in organs other than peripheral blood, although the number of cases was small.

Anti-HIV Agents↗

Clinical results of treatment of advanced esophageal carcinoma with hyperthermia in combination with chemoradiotherapy.

Chemoradiotherapy combined with hyperthermia was administered to 35 patients with advanced esophageal carcinoma who either required preoperative treatment or had nonresectable disease. As a rule, each patient received a total dose of 30 Gy in 15 daily fractions of 2 Gy, 5 d/wk. Bleomycin or cisplatin, in combination with fluorouracil, was employed as chemotherapy. Hyperthermia was applied by intraluminal heating twice a week for a total of six sessions using an apparatus (IH-500T; Japan Crescent Co Ltd; Tokyo, Japan) (radiofrequency, 13.56 MHz) with an intraesophageal applicator and two extracorporeal applicators placed on the chest and back. This treatment method obtained a response rate of 80%, consisting of a complete response rate of 22.9% and partial response of 57.1%. In 15 cases, the tumor became resectable (resectability rate, 42.9%) following treatment. The histologic study of the resected specimens revealed absence of viable tumor cells in five patients (33.3% of the resected cases) (markedly effective), and in six patients (40.0%), the combined therapy was considered to be moderately effective. No complications considered due to hyperthermia itself were recognized. The overall 5-year survival rate was 11.8%. In conclusion, chemoradiotherapy combined with hyperthermia was locally effective, yielding an overall response of 80.0%. However, the prognosis of the patients remains unfavorable. Advanced esophageal carcinoma requires treatment taking into account lymphatic and hematogenic metastasis at the beginning of treatment.

Aged↗

[Reproductive and developmental toxicity studies of landiolol hydrochloride (ONO-1101) (2). Teratogenicity study in rats].

A teratogenicity study of landiolol hydrochloride (ONO-1101), a novel ultra short acting beta-blocker, was conducted in Sprague-Dawley (SD) rats. ONO-1101 was administered intravenously at a dose level of 0 (control), 25, 50 or 100 mg/kg/day to pregnant rats from day 7 to 17 of gestation, and effects of ONO-1101 on dams, fetuses and their offspring, were examined. In the 100 mg/kg/day group, hypoactivity, bradypnea, reddish lacrimation, clonic convulsion and loss of righting reflex were observed and 2 animals died. Food consumption in the 100 mg/kg/day group decreased during the treatment period. No drug-related changes were observed in dams for their body weights, necropsy findings or organ weights. Decrease in placental weight was seen in the 100 mg/kg/day group, but no effect was found in fetal weight. ONO-1101 had no effects on delivery and lactation. On day 4 after birth, viability of offspring were decrease in the 50 or 100 mg/kg/day group, and body weight of males were decreased in the 100 mg/kg/day group, but no change caused by the treatment was observed in growth of offspring thereafter. On skeletal examination in offsprings culled on day 4 after birth, increase in the incidence of unossificated talus were seen in the 50 or 100 mg/kg/day group. But no drug-related anomalies were observed in external, skeletal or visceral findings in fetuses. It was not also found any influence of ONO-1101 on external differentiations, functional, behavioral or learning abilities or reproductive performance in offspring. From the above results, it is estimated that the no-toxic dose level of ONO-1101 under these experimental conditions is 50 mg/kg/day for dams, and 25 mg/kg/day for their offspring.

Adrenergic beta-Antagonists↗

[Reproductive and developmental toxicity studies of landiolol hydrochloride (ONO-1101) (3). Teratogenicity study in rabbits].

A teratogenicity study of landiolol hydrochloride (ONO-1101), a novel ultra short acting beta-blocker, was conducted in KAR:NZW rabbits. ONO-1101 was administered intravenously at a dose level of 0 (control), 25, 50 or 100 mg/kg/day to pregnant rabbit from day 6 to 18 of gestation to examine the effects on dams and fetuses. Death occurred on 3 animals in the 100 mg/kg/day group and one animal in the 50 mg/kg/day group during the treatment period. Hypoactivity, bradypnea/apnea and clonic convulsion after administration was observed in animal dosed 100 mg/kg/day. No maternal effects were seen on body weight, food consumption, necropsy findings or organ weights. External, skeletal and visceral findings revealed no adverse effects of ONO-1101 on fetuses. From the above results, it is estimated that the no-toxic dose level of ONO-1101 under these experimental conditions is 25 mg/kg/day for dams and 100 mg/kg for fetuses.

Adrenergic beta-Antagonists↗

[Reproductive and developmental toxicity studies of landiolol hydrochloride (ONO-1101) (4). Perinatal and postnatal study in rats].

A perinatal and postnatal study of landiolol hydrochloride (ONO-1101), a novel ultra short acting beta-blocker, was conducted in Sprague-Dawley(SD) rats. ONO-1101 was administered intravenously at a dose level of 0 (control), 25, 50 or 100 mg/kg/day from day 17 of gestation to day 20 after parturition to examine the effects on pregnancy, delivery, lactation and the effects on postnatal growth and development of offspring. In the 100 mg/kg/day group, hypoactivity, reddish lacrimation, clonic convulsion and bradypnea/apnea were observed after administration and 5 animals died in the treatment period, and body weight on day 21 and food consumption on day 14-21 of dam at weaning were lower than control group. In the 50 mg/kg/day group, reddish lacrimation was occasionally seen in some animals. ONO-1101 had no effects on pregnancy, delivery, lactation and necropsy findings or organ weights of dams. In the 100 mg/kg/day group, viability of offspring on day 4 after birth decreased and body weight gain of the suckling suppressed, but those changes recovered after weaning. On the skeletal examination of offspring culled on day 4 after birth, decrease in the mean number of osiffied phalanges of hindpaw and increase in the incidence of unossified talus bone were seen in the 100 mg/kg/day group, however, no delay of ossification was found form the weanling. There were no influence of ONO-1101 on external differentiation, functional, behavioral or learning abilities or reproductive performance in offspring. From the above results, it is estimated that the no-toxic dose level of ONO-1101 under these experimental conditions is 50 mg/kg/day for dam and offspring.

Adrenergic beta-Antagonists↗

Combination chemotherapy for malignant paraganglioma.

Treatment with a combination chemotherapeutic regimen consisting of cyclophosphamide, vincristine, and dacarbazine for malignant paraganglioma with hepatic metastasis is reported. A 51-year-old male presented with tumors in the retroperitoneal space and liver. The patient was diagnosed as having paraganglioma based on elevated levels of serum neuron-specific enolase, urinary catecholamine and vanillylmandelic acid, and on histological findings of the liver specimen. The patient was treated with this combination chemotherapy in repeated 21-day cycles. Temporary improvement in laboratory findings and a 20% reduction in the size of the hepatic masses were observed without severe adverse effects.

Antineoplastic Combined Chemotherapy Protocols↗

Hybrid logistic characterization of isometric twitch force-time curve of intact blood-perfused canine right ventricular papillary muscle.

We previously found that a ventricular isovolumic pressure-time curve could be well fitted by the difference between two S-shaped logistic curves for the pressure rising and falling components, and called it "hybrid logistic" function: P(t)=A/[1+exp[-(4B/A)(t-C)]]-D/[1+exp[-(4E/D)(t-F)]]+G. We reported that the parameters of this hybrid logistic function are useful to characterize left ventricular contraction and relaxation comprehensively. In this study, we investigated how well this hybrid logistic function could fit the isometric twitch force-time curves of cross-circulated right ventricular papillary muscles of 7 dogs. This function precisely fitted the isometric force curves with correlation coefficients above 0.9996, much better than another fitting function (F(t)=C(t/A)(B)exp[1-(t/A)(B)]) proposed by Nwasokwa. The present results indicate that our hybrid logistic function can also reasonably express the canine right ventricular papillary muscle isometric twitch force-time curve. We suggest the possibility that the parameters of this hybrid logistic function are also useful to comprehensively characterize right ventricular papillary muscle twitch contraction and relaxation.

Animals↗

Subacute and chronic prurigo effectively treated with recombination interferon-gamma: implications for participation of Th2 cells in the pathogenesis of prurigo.

Subacute and chronic prurigo is notoriously resistant to usual therapies. Four of five patients with a subacute or chronic form of prurigo responded well to daily intravenous injections of recombinant interferon-gamma (rIFN-gamma) (0.25-2 x 10(6) Japan Reference Unit (JRU; 1 JRU roughly corresponds to 4 NIH units) daily, for 10-14 days). In one patient examined, the dermal portion of lesional skin before the treatment contained considerable amounts of mRNA for interleukin (IL)-4, IL-5, and IL-10, indicative of infiltration of Th2 cells. Furthermore, the administration of rIFN-gamma selectively down-regulated mRNA for Th2 cytokines, IL-4 and IL-10 in peripheral blood mononuclear cells. These findings suggest that Th2 cells play a pathogenic role in these types of prurigo and that rIFN-gamma exerts its efficacy by inhibiting Th2 cells. Our pilot study suggests that the systemic administration of rIFN-gamma is a therapeutic alternative for the treatment of recalcitrant prurigo.

Adult↗

Treatment of sleep apnea with a new separated type of dental appliance (mandibular advancing positioner).

We investigated a new separated type of dental appliance (mandibular advancing positioner: MAP) that is mobile and allows free adjustment of mandibular advancement. In 8 adult male patients with sleep apnea syndrome (SAS), the mean apnea index (AI) decreased from 31.1 to 4.2, and the mean apnea hypopnea index (AHI) decreased from 44.2 to 11.7. The distance of mandibular advancement using the Flankfort horizontal plane as a standard ranged in the 8 SAS patients from 1.8 to 5.0 mm by lateral cephalograms. A high positive correlation was observed between the distance of mandibular advancement and the rate of improvement in AI (R2 = 0.878), or the rate of AHI (R2 = 0.861), showing a higher improvement rate with more marked mandibular advancement.

Adult↗

[Lipid and lipoprotein profile of Japanese centenarians--high prevalence of hypo beta lipoproteinemia].

To study the relationship between lipids and longevity, we examined the level of serum lipids and apolipoproteins, and the susceptibility of low density lipoprotein (LDL) to oxidation of 45 centenarians (15 men, 30 women, mean age 101.1 +/- 1.4) living in the Tokyo metropolitan area. The average levels of total cholesterol (TC), of LDL-C of high-density lipoprotein cholesterol (HDL-C), and of apolipoproteins A1 and B were significantly lower in centenarians than in healthy middle-aged controls. The frequency of hypobeta-lipoproteinemia (apoB < 60 mg/dl) in centenarians was almost ten times as high as in controls. The time course of copper-mediated LDL, oxidation (assessed by monitoring 234 nm diene absorption (lag time)) did not significantly differ between the two groups. Analysis of LDL subfractions by non-denaturated gradient-gel electrophoresis showed a predominance of large, buoyant LDL particles (pattern A) in 75%, and a predominance of small dense LDL particles (pattern B) in 25% of centenarians. We also assessed activities of daily living (ADL) and cognitive function in the centenarians. Centenarians were divided into two groups according to the median ADL score, and were classified into five groups with a scale clinical dementia. In subjects with good ADL scores, the mean concentration of HDL-3-C was significantly higher than in those with poor ADL scores. Average levels of HDL-C were also significantly lower in subjects with moderate or severe dementia than in those with normal cognitive function. These findings suggest that centenarians have protective phenotypes of lipids and lipoproteins that protect them from atheroscierosis.

Activities of Daily Living↗