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Biomedical subjects

M Usami

Publications and source records attributed to M Usami.

At least 163 records · Page 9Linked to original sources

[Studies on the teratogenic potential of p-tert-butylphenolformaldehyde resin in rats].

p-tert-Butylphenolformaldehyde resin, an adhesive, was given orally to pregnant Wistar rats by stomach intubation at the dose levels of 250, 500 and 1000 mg/kg body weight during days 7 to 17 of gestation, and the effects of the compound on dams and fetal developments were examined. No changes in general conditions, maternal body weight, food consumption, numbers of corpora lutea and implantation ratio were observed. There was no evidence of an increase in fetal death or of malformation attributable to the treatment with p-tert-butylphenolformaldehyde resin in any of dose levels examined. It was concluded that p-tert-butylphenolformaldehyde resin has no teratogenic effect in rats.

Administration, Oral↗

[Therapeutic inventions of perioperative metabolic care in diabetic patients].

Perioperative metabolism was evaluated in diabetic patients and animal models. Experimental model of diabetes mellitus (DM) model was obtained by streptozotocine injection. Each 14C-labeled substrates and combination of carbohydrates mixture was administered intravenously in a dose of 1 g/kg before and after laparotomy and cumulative curves of expired 14CO2 was calculated. Biochemical analysis in the liver, blood and urine were performed following infusion of two different solutions, GFX (glucose, fructose, xylitol) solution, 4:2:1 ratio by weight vs. glucose solution, with 12% amino acids solution. In a clinical study, incidence of DM in digestive surgery was examined in 3481 cases. Retrospective evaluation of GFX solution was performed in cases after total gastrectomy. Incidence of DM was 14% and it has been increased recently, Glucose metabolism in DM rats was disturbed after surgery. Amino acids (alanine and valine) and lipid metabolism was slightly suppressed after surgery in DM rats. The best combination of carbohydrate mixture was determined as GFX solution in animal and clinical experiments. GFX solution improved not only glucose metabolism but also lipid and amino acid metabolism in DM rats. Decreased insulin requirement and increased total caloric intake were observed in DM and borderline DM cases treated by GFX solution.

Amino Acids↗

Long-term clinical study on luteinising hormone-releasing hormone agonist depot formulation in the treatment of stage D prostatic cancer. The TAP-144-SR Study Group.

The results of long-term administration of leuprorelin acetate depot (TAP-144-SR), a sustained-release preparation of luteinising hormone-releasing hormone (LH-RH) agonist, to 40 stage D prostate cancer patients who had had no previous hormonal therapy, have been analyzed. The drug was administered by subcutaneous injection once every four weeks at a dose of 3.75 or 7.5 mg. The mean duration of treatment was 480 (141-1,266) days, and treatment continued for more than one year for 60% of the 40 patients. Objective response was evaluated in accordance with Japanese Response Criteria. The best objective response in the overall evaluation was a partial response in 68.6% of the total patient group (3.75 mg, 64.3%; 7.5 mg, 71.4%). During the administration period, 21 patients were diagnosed as having progressive disease (PD), and the mean time to onset of PD was 308 days. The earliest diagnoses of PD were made on bone metastases (17 cases) and prostatic acid phosphatase levels (12 cases). The survival rate, as determined by Kaplan-Meier's method, was 81.2% (3.75 mg, 80.5%; 7.5 mg, 81.3%) two years after starting the regimen and 66.0% (3.75 mg, 65.1%; 7.5 mg, 66.0%) after three years. There was no dose dependency between either of the two drug doses, which we adopted as functions of the objective response rate, and patients' survival. Serum levels of testosterone, LH and follicle-stimulating hormone (FSH) were monitored from the first-dose until the 148th week of administration. In all patients receiving the drug as scheduled, the testosterone level was maintained at less than 1 ng/ml, and the LH and FSH levels were maintained at levels lower than their respective upper normal limits. There were no particular adverse reactions specific to the long-term administration subsequent to the foregoing 12-week administration study. In conclusion, LH-RH analogue treatment is thought to be a long-lasting, effective, palliative measure for patients with previously-untreated, advanced, prostatic cancer.

Aged↗

[Surgical treatment under extracorporeal circulation for renal cell carcinoma with tumor thrombus in inferior vena cava].

Three cases of renal cell carcinoma with tumor thrombus extending into the inferior vena cava are reported. Radical nephrectomy and thrombectomy were performed under extracorporeal circulation in all the cases. The level of tumor thrombus was preoperatively determined by computed tomography, magnetic resonance imaging or venacavography. The tumor thrombus extended into the right atrium in one, and above the hepatic vein in two cases. One patient whose thrombus reached the right atrium died of multiple metastasis of renal cell carcinoma 5 months after operation. Another patient with lung metastasis was given interferon-alpha and is alive 5 months after operation. The other patient is clinically free of disease and in good health 7 years after operation. We believe that extracorporeal circulation allows an opportunity to resect the tumor thrombus in a controlled situation, and makes the operation safer.

Aged↗

[Spontaneous peripelvic extravasation associated with primary ureteral tumor: a case report].

A case of spontaneous peripelvic extravasation associated with primary ureteral tumor is reported. A 56-year-old woman presented with left flank pain. Excretory urogram and abdominal computed tomographic (CT) scan demonstrated left hydronephrosis with extravasation of contrast materials around the renal pelvis. Retrograde pyelogram showed the filling defect in the left upper ureter. Under diagnosis of ureteral tumor, total nephroureterectomy was performed. Histological findings revealed transitional cell carcinoma. 80 cases of spontaneous peripelvic extravasation in Japan were reviewed and discussed briefly.

Carcinoma, Transitional Cell↗

[Assessment of myocardial viability by exercise stress myocardial tomography with 201Tl--the usefulness of 201Tl washout rate].

Exercise stress (Ex) and redistribution (RD) myocardial tomography with thallium-201 (Tl-201) has been widely used for evaluating myocardial viability. But recent studies have demonstrated that reinjection (ReI) study following RD study is necessary for detecting reversible ischemic myocardium. On the other hand, decreased myocardial washout of Tl-201 after Ex is an indicator of myocardial ischemia. So we have studied the usefulness of myocardial Tl-201 washout rate (WOR) for the evaluation of myocardial viability by comparing it with ReI images. Ex and RD myocardial tomographies were obtained immediately after Ex and 3 hours later. After RD study a small amount of Tl-201 was injected and ReI imaging was repeated. We studied 64 myocardial segments (in 58 patients with coronary artery disease) in which Ex-induced perfusion defects persisted in RD images. According to the changes of perfusion defects between Ex, RD and ReI images, they were classified into 3 types: Type I; perfusion defect on the RD image was identical to ReI image (75%) Type I was divided into 2 subgroups whether perfusion defect at Ex was unchanged (Ia, 42%) or improved (Ib, 33%) on the RD image. Type II; perfusion defect at Ex was reduced on the RD image and it improved furthermore at ReI image (17%). Type III; perfusion defect was the same at Ex and RD but it was reduced on the ReI image (8%). WOR less than 30% was defined as abnormal when Ex heart rate exceeded 120 bpm and lung-myocardial Tl-201 uptake ratio was less than 0.45.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[A case of complete remission of lymph nodes metastasis from esophageal cancer with combination treatment of UFT and radiation].

A 65 year old female patient, who had developed left atelectasis because of mediastinal lymph nodes metastasis after esophageal resection for esophageal cancer, underwent the combination treatment with UFT (300 mg/day) and radiation (1.5 Gy/day, total dosage: 70.2 Gy). The symptoms soon subsided, and mediastinal CT and bronchoscopy revealed a complete disappearance of metastatic lymph nodes after one month. During one year of CR she enjoyed her daily life, however the relapse occurred. It is suggested that the combination treatment is an effective and safe way even in a patient who went through a lot of invasive surgeries.

Aged↗

[Myocardial perfusion in patients with left bundle branch block and without coronary artery disease].

For the evaluation of myocardial perfusion in patients with left bundle branch block (LBBB), we performed exercise stress (Ex)-redistribution (RD) myocardial tomography with thallium-201 (201Tl) in 23 patients with LBBB and without coronary artery disease (CAD). Myocardial images in patients with LBBB were compared with those of 9 patients with CAD who showed Ex induced transient septal defect. Bull'-eye maps (201Tl distribution maps at Ex and RD and 201Tl washout rate [WOR] map) were made from myocardial tomograms. In 23 patients with LBBB, 15 patients (65%) developed myocardial perfusion abnormality. In 10 (67%) of these 15 patients, transient perfusion defect appeared in the entire septum (diffuse type). On the other hand in 5 patients (33%), localized fixed perfusion defect developed at the boundary between septum and anterior wall (focal type). In focal type, every patient had other disease such as hypertension, aortic stenosis or sick sinus syndrome. While in patients with diffuse type, other diseases were observed in 30% (p less than 0.05) and they were limited to hypertension or diabetes mellitus. These facts suggested that mechanisms of perfusion abnormalities might be different between these two groups. We compared the perfusion abnormality between LBBB diffuse type and CAD. The extent of the defects was not different between two groups. Although apex was included within the defect in 89% of CAD population, apical defect was observed in only 20% of diffuse type (p less than 0.05). Minimal 201Tl WOR and 201Tl uptake ratio of septum to lateral wall indicated that exercise induced septal defect was slighter in diffuse type than CAD.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Metabolic effects of GFX+BCAA solution in the old aged rats after operation].

Effects of total parenteral nutrition (TPN) on the perioperative metabolism in old aged rats were evaluated. Extremely old rats (over 100 weeks old) and young rats undergoing laparotomy were treated with TPN (200 ml/kg/days, 182 cal/kg/day, 148 nonprotein cal/N ratio) consisting of carbohydrate mixtures (combination of glucose, fructose, and xylitol, 4:2:1 GFX solution) and 10% amino acids solution with 30% of branched chain amino acids (BCAA). Blood, liver, and urine samples were analyzed on 1, 3 postoperative days. Increased body weight, positive balance in daily nitrogen excretion, and decreased water content of the liver were observed in old rats. Protein, glycogen, and triglyceride contents of the liver tissue increased in old rats. However the young rats showed negative nitrogen balance and stronger catabolic effect than the old rats. It suggested negative nutritional balance in young rats with this decreased dosage of GFX+BCAA solution suitable for the old rats. In conclusion, decreased amounts of GFX+BCAA solution improved perioperative metabolism in the extremely old.

Age Factors↗

Mutation of Glu693 to Gln or Val717 to Ile has no effect on the processing of Alzheimer amyloid precursor protein expressed in COS-1 cells by cDNA transfection.

One of the features of Alzheimer's disease (AD) is the formation of senile plaques, of which the main component is a 42 amino acid beta-protein (beta P). Molecular cloning of beta P revealed the presence of a 90-130 kDa precursor, amyloid precursor protein (APP). Since APP is expressed in normal brain without producing beta P, some abnormal processing is the cause of the formation of beta P in AD. Two kinds of mutations of APP, Glu693 to Gln and Val717 to Ile, were reported in AD-related diseases. Site-directed mutagenesis was applied, and the mutated APPs were expressed in COS-1 cells by cDNA transfection. They showed apparently the same processing as wild APP. This means that these mutations might not be a direct cause for the abnormal processing of APP or the formation of beta P in AD.

Amino Acid Sequence↗

"Secretase," Alzheimer amyloid protein precursor secreting enzyme is not sequence-specific.

The major pathological change in Alzheimer's disease is the deposition of amyloid beta/A4-protein (beta P) in the brain. beta P is derived from a small part of the much larger amyloid protein precursor (APP). In the normal condition, APP is cleaved in the interior of beta P, preventing the formation of beta P, by a hypothetical proteinase "secretase". To characterize this enzyme, APP and mutated APPs were expressed by cDNA transfection in COS-1 cells, a monkey kidney fibroblast derived cell line. The mutant APPs with the mutations of the proposed cleavage site (Gln686-Lys687) were processed in the same way as wild APP. The deleted mutant APP (deletion of Arg676-Asp694) was also cleaved in a similar way to wild APP. The cleavage site of this deletion mutant was located at the 12 amino acid residues from the predicted membrane spanning domain. Hence, "secretase" cleaves APP, depending not on its specific amino acid sequence, but probably on the relative conformation with plasma membrane.

Alzheimer Disease↗

A novel brain-specific mRNA encoding nuclear protein (necdin) expressed in neurally differentiated embryonal carcinoma cells.

A novel DNA sequence has been isolated from a subtraction cDNA library of P19 embryonal carcinoma cells treated with retinoic acid which induces neural differentiation of the stem cells. The cDNA insert (4B) hybridized with a single 1.7 kb mRNA, whose abundance was markedly increased in P19 cells after retinoic acid treatment. The 1.7 kb mRNA was also expressed in the brain, but not in other non-neuronal tissues. A 1.6 kb cDNA insert (4BFL), which was cloned by screening another cDNA library with the 4B probe, encodes a novel protein sequence of 325 amino acids (Mr 36,831). The protein expressed in 4BFL-transfected COS cells was translocated into the nuclei as detected with antibodies against subsequences of the predicted protein. The antibodies stained the nuclei of neurally differentiated P19 cells but not of the undifferentiated stem cells. This novel mRNA encoding the nuclear protein, termed necdin, may represent a useful marker for the differentiation and development of brain cells.

Amino Acid Sequence↗

Changes of serum bilirubin fraction in postoperative liver failure cases treated by plasmapheresis: an effective marker for evaluation of bilirubin removal.

Utility of a new method of bilirubin fractionation was evaluated in monitoring the effectiveness of plasma exchange (PE) performed in 10 postoperative cases with liver failure. Fractionation of serum bilirubin by high-performance liquid chromatography demonstrated a higher delta bilirubin (B delta) peak against lower conjugated bilirubin peaks [monoconjugated bilirubin (MCB) and diconjugated bilirubin (DCB)] in the three recovered cases. The calculated ratio of MCB/B delta and the ratio of B delta/(MCB + DCB + B delta) in the recovered cases showed statistically significant different against seven unrecovered cases (p less than 0.01). These results suggest that the recovered cases had a different quality hyperbilirubinemia and a different disease entity before PE as well as a different response to PE, and this novel method for serum bilirubin subfraction is considered a useful marker in selecting a patient responsive to PE.

Aged↗

[A study on the usefulness of the OECD Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test (ReproTox)].

We studied the usefulness of the OECD combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test (ReproTox) using cyclophosphamide (CP), which is well known for its toxicological properties. CP was given daily by gavage to groups of 12 male and 12 female 8-week-old Sprague-Dawley rats at doses of 0, 2, 3, 4.5 or 6.7 mg/kg. Significant decreases in body weight and food consumption were observed in males given 6.7 mg/kg and in all treated females. One, 3 and 12 females died during pregnancy in the groups given 3, 4.5 and 6.7 mg/kg, respectively. In males 2 died in the 6.7 mg/kg group. Leukopenia and anemia were evident in treated males. The thymus and spleen weights were significantly decreased in treated rats. Histopathologically, atrophy of the thymus, spleen and bone marrow was observed. With respect to the reproductive/developmental toxicity, dose-dependent increases in postimplantation loss and postnatal death of pups were found in treated dams. The body weight of pups from treated dams was significantly lowered. Thus, most of the known toxicological properties of CP regarding systemic toxicity and reproductive/developmental toxicity were clearly demonstrated in this study. Therefore ReproTox can be considered a useful screening test for assessing repeat dose and reproductive/developmental toxicity of existing chemicals of high production volume, although teratogenic potential and adverse effects on spermatogenesis and fertility were not detected under the present experimental conditions.

Administration, Oral↗

[Studies on the teratogenic potential of 2,2'-isobutylidene-bis (4,6-dimethylphenol) in rats].

2,2'-Isobutylidene-bis(4,6-dimethylphenol), an antioxidant, was given orally to pregnant Wistar rats by stomach intubation at the dose levels of 5, 15 or 45 mg/kg body weight during days 7 to 17 of gestation, and the effects of the compound on dams and fetal developments were examined. In the dams at the two higher dose levels of 15 and 45 mg/kg, toxic signs (tremor, startle reflex, salivation, involuntary urination, wheezing and nostril discharge) were observed. Moreover, at the highest dose level, additional toxic signs (lacrimation and vaginal bleeding), suppression in maternal body weight gain and food consumption were observed. However, there was no evidence of an increase in malformations attributable to the treatment with 2,2'-isobutylidene-bis(4,6-dimethyl-phenol) in any of the treated groups. It was concluded that 2,2'-isobutylidene-bis(4,6-dimethylphenol) has no teratogenic effect in rats, though toxic signs were observed in treated dams of the 15 and 45 mg/kg groups.

Administration, Oral↗

[Combination chemotherapy with ifosfamide (or cyclophosphamide), adriamycin, cis-platinum and peplomycin (IAPP) for hormonally resistant metastatic prostatic cancer].

From January, 1986 to April, 1990, combination chemotherapy with ifosfamide (or cyclophosphamide), adriamycin, cis-platinum and peplomycin was performed in 15 patients with hormonally resistant metastatic adenocarcinoma. Three patients had partial response (PR) and 9 remained objectively stable (ST). The median response duration of PR + ST (12) was 5.7 months (range 2.8 to 18.0+). Three patients progressed while on this therapy. Of 8 patients with prior treatment of chemotherapy or chemo-hormonal therapy, 6 achieved an objective response (2 PR, 4 ST). Severe toxicities occurred in 2 patients. One died of lung fibrosis induced by peplomycin and the other received urinary diversion for persistent hemorrhagic cystitis. These results compare favorably with previous reports of chemotherapy treatment of metastatic prostatic cancer patients who failed on hormonal manipulation. However, careful treatment is needed for lung fibrosis and hemorrhagic cystitis.

Aged↗