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Biomedical subjects

T Taguchi

Publications and source records attributed to T Taguchi.

At least 199 records · Page 11Linked to original sources

Estimation of bloodstain age by rapid determinations of oxyhemoglobin by use of oxygen electrode and total hemoglobin.

Bloodstain age could be estimated from the ratio of oxyhemoglobin/total hemoglobin (fractional oxyhemoglobin) in the bloodstain by this present method, if the temperature at which the bloodstain had been kept was known. The oxyhemoglobin was determined with an oxygen electrode immersed in water in which the oxygen had been depleted, and the total hemoglobin was determined by conventional colorimetry (cyanomethemoglobin method). Ages of prepared bloodstain samples (within 24 h after bleeding) were estimated by this present method, which requires only 20 microliters of bloodstain and only 5 min for the whole analysis.

Adult

Preparation and biological activity of 24-epi-26,26,26,27,27,27-hexafluoro- 1 alpha,25-dihydroxyvitamin D2.

A new fluorinated analog of vitamin D2, 24-epi-26,26,26,27,27,27-hexafluoro- 1 alpha,25-dihydroxyvitamin D2, was efficiently synthesized starting from (R)-4-isopropyl-3-propionyl-2- oxazolidinone with high stereochemical control. In all four physiological test systems, the fluorinate vitamin D2 analog was found to be slightly less active than 1 alpha,25-dihydroxyvitamin D3.

Animals

Neurons with perineuronal sulfated proteoglycans in the human visual cortex, with special reference to their reactions to lectins.

The human visual cortex, especially its ganglionic lamina, was found to contain many neurons with perineuronal sulfated proteoglycans which were stained with cationic iron colloid and aldehyde fuchsin. It also contained many neurons with surface glycoproteins labeled with lectin Vicia villosa agglutinin (VVA) or Glycine max agglutinin (SBA). Double staining frequently showed that the neurons stained with cationic iron colloid were not labeled with lectin VVA or SBA. Hyaluronidase and chondroitinase ABC/heparitinase/keratanase digestions eliminated the perineuronal cationic iron colloid reaction, but never interfered with the cell surface lectin labeling. These findings indicate that the cell surface glycoproteins reactive to lectin VVA or SBA are neither structural elements nor adhesive molecules of the proteoglycans. Double staining further demonstrated that in some neurons with perineuronal sulfated proteoglycans, the cytoplasm was labeled with lectin Arachis hypogaea agglutinin (PNA). It was further noticed that the lectin VVA-labeled neurons were not always identical with the neurons labeled with lectin SBA or with lectin PNA.

Colloids

Perineuronal sulfated proteoglycans and dark neurons in the brain and spinal cord: a histochemical and electron microscopic study of newborn and adult mice.

Neurons of intracerebellar nuclei in the mouse brain were demonstrated to possess a marked surface coat, formed 3-4 weeks after birth, which was stainable with cationic iron colloid or aldehyde fuchsin. Neurons with a similar surface coat were noted as relay or local interneurons in rather restricted areas such as the occipital cortex, retrosplenial cortex, zona incerta, hippocampal subiculum and spinal posterior horn. Dark neurons with condensed cytoplasm were also shown to be covered with the surface coat. The surface coat was stained doubly with cationic iron colloid and aldehyde fuchsin. Digestion with hyaluronidase eliminated the stainability of the surface coat to both agents. Combined digestion with chondroitinase ABC, heparitinase and keratanase eliminated the cationic iron colloid staining of the surface coat, but did not interfere with the aldehyde fuchsin staining of the surface coat. Electron microscopy of ultrathin sections revealed that the iron particles indicating sulfated proteoglycans were preferentially deposited in the perineuronal tissue spaces. Many neurons in the hippocampal subiculum possessed cell surface glycoproteins which were labeled with lectin Vicia villosa or soybean agglutinin and formed 1-2 weeks after birth. Double staining revealed that these lectin-labeled neurons were identical in part with the neurons reactive to the cationic iron colloid. Dark neurons began to appear 3-4 weeks after birth. The formation of perineuronal sulfated proteoglycans and the appearance of dark neurons, both occurring during the weaning period, may reflect the morphological and physiological completion of the brain. Dark neurons are suggested to be exhausted cells that are restored to light or normal neurons after sleep.

Aging

Glomerular localization of interleukin-6 suppressed by steroid mini-pulse therapy in an IgA nephropathy patient.

A 16-year-old female with IgA nephropathy harboring histologically active lesions was treated with steroid mini-pulse therapy. Immunohistochemical examination revealed a diffuse distribution of interleukin-6 (IL-6) in the renal biopsy tissue. After treatment, her clinical factors and renal function improved, and renal biopsy showed reduced histological lesions and disappearance of the IL-6 distribution. Immunohistological studies of cytokines, such as IL-6, may be useful for evaluating the therapeutic effects in IgA nephropathy.

Adolescent

Elevation of cystathionine gamma-lyase activity in the serum of rats treated with a single dose of carbon tetrachloride.

Cystathionine gamma-lyase activity in the sera of rats subjected to experimental hepatotoxicity after intraperitoneal administration of carbon tetrachloride (CCl4) was measured and compared with activities of aspartate aminotransferase (GOT) and alanine aminotransferase (GPT), which have been clinically used for detecting liver damage. In the experimental subjects, serum levels of cystathionine gamma-lyase showed a similar behavior to GOT and GPT, increasing markedly with respect to the controls after administration of CCl4 and reaching a maximum at 24 hours. No such cystathionine gamma-lyase activity was detected immunochemically in the control subjects. These data suggest that measurement of serum cystathionine gamma-lyase activity could be used as a sensitive and specific marker of hepatic cytolysis.

Animals

Effect of magnesium on secretion of platelet-derived growth factor by cultured human umbilical arterial endothelial cells.

Conditioned media were prepared by incubating human cultured umbilical arterial endothelial cells for 48 h in magnesium (Mg) sufficient (900 microM) and deficient (100 microM) conditions. Minimum essential media (MEM) are designated as [900]- and [100]-MEM, respectively. After the incubation, a portion of the [100]-MEM media was adjusted from 100 to 900 microM magnesium ([100-900]-MEM). Smooth muscle cells were incubated with the three media and their growth rates were determined by [3H]-thymidine incorporation and cell counting. The growth rate in [100-900]-MEM was significantly higher than in [900]- or [100]-MEM. When platelet-derived growth factor (PDGF) was neutralized by the addition of a mixture of anti-PDGF-AA and -BB, [3H]-thymidine incorporation in [100-900]-MEM decreased by 12.5 per cent, but only by 4.9 per cent in [900]-MEM. These results indicate that magnesium deficiency increases the secretion of PDGF by endothelial cells. This is also supported by the results of the radioimmunoassay for PDGF-BB; the quantity of PDGF in the magnesium-deficient media was greater than in the magnesium-sufficient media.

Blood Proteins

[Clinical phase II study of tropisetron capsule in the treatment of nausea and vomiting induced by anti-cancer drugs].

A comparative clinical trial of tropisetron capsule was conducted in three dose groups to investigate its optimal dose on nausea and vomiting induced by anti-cancer drugs, including cisplatin. The doses were randomized by the central registration office. In the assessment of clinical efficacy, cases rated as "effective" or better accounted for 61.5% of the 2.5 mg group (16/26), 80.8% of the 5.0mg group (21/26) and 80.0% of the 10mg group (24/30), respectively; the ratings for the 5mg and 10mg groups were almost equivalent, which was higher than that for the 2.5mg group. Adverse events observed were fever, diarrhea, drowsiness, headache and/or facial erythema in 4 out of 97 cases. Abnormal laboratory findings noted were 6 cases of increased GOT, GPT, LDH, total bilirubin and/or creatinine, but none of these was serious or clinically problematic in particular. On the basis of the above results, the optimal dose of Tropisetron (capsule) is considered to be 5mg once daily.

Adult

[Clinical phase III study of tropisetron capsule in the treatment of nausea and vomiting induced by anti-cancer drug; a placebo-controlled, multicenter, double-blind comparative study].

A placebo-controlled, double-blind comparative study of tropisetron capsule was conducted to assess its clinical usefulness for nausea and vomiting induced by the anticancer drug, cisplatin, at a single dose of 50 mg/m2 or higher. Either 5mg tropisetron capsule or its placebo was given orally to patients 2 hours prior to cisplatin administration; the clinical efficacy was determined the severity of nausea and the number of emesis that occurred during 24 hours after cisplatin. Tropisetron significantly exceeded the placebo in the assessment of clinical efficacy. The ratings for the tropisetron group and the placebo group were 91.7% (22/24 cases) and 25.9% (7/27 cases), respectively. Adverse events observed were one case of headache in the tropisetron group and one diarrhea in the placebo group, while neither case was serious nor clinically problematic in particular. The above results reveal that tropisetron 5 mg capsule is significantly effective in the treatment of anticancer drug-induced nausea and vomiting. It has also been confirmed that tropisetron is a useful agent without any safety problems.

Administration, Oral

[Clinical phase III study of tropisetron capsule in the treatment of nausea and vomiting induced by carboplatin or non-platinum anti-cancer drugs].

A clinical phase III study of tropisetron capsule was conducted to assess its efficacy, safety and usefulness on nausea and vomiting induced by carboplatin or non-platinum anti-cancer drugs. The study was conducted in patients who experienced vomiting on previous chemotherapy. Tropisetron 5 mg capsule was given to patients once 2 hours prior to the first administration of either carboplatin or non-platinum anti-cancer drugs; the patients were then observed for nausea and/or vomiting during 24 hours after the first administration. Some 56.7% (17/30) of the patients did not vomit after tropisetron administration, and the frequency of vomiting was significantly reduced compared with that during the previous chemotherapy. Further, in the clinical efficacy ratings, in which the efficacy was assessed on the basis of the nausea and vomiting data, 83.3% (25/30) of cases were rated as "effective or better". Adverse events observed were 3 cases of mild headache, but these were not clinically problematic. The above results reveal that tropisetron capsule is significantly effective and safe in the treatment of nausea and vomiting induced by carboplatin or non-platinum anti-cancer drugs; in addition, tropisetron proved to be highly useful for its convenience as an oral agent.

Adult

A case of acute renal failure due to ethylene glycol intoxication.

We describe an 18-year-old man with acute renal failure due to inadvertent ingestion of antifreeze that contained ethylene glycol (EG). A relatively small amount of EG was ingested, but nausea and vomiting were observed soon after ingestion. During admission to a local hospital, consciousness became impaired and generalized convulsion was noted. He was transferred to our hospital because of rapid deterioration of renal function. Emergency hemodialysis was begun. The patient underwent one treatment session of hemodialysis each day, for a total of 8 hemodialytic sessions before his renal function recovered. Examination of the renal biopsy specimen revealed degeneration of the renal tubular epithelium and presence of intratubular calcium oxalate crystals. The clinical features of the patient were mild except for acute renal failure. These findings suggest that even a small amount of EG will have toxic effects on the kidney.

Acute Kidney Injury

[Phase I study].

Criticisms and proposals were presented from the standpoint of implementation with regard to the objectives, person in charge, test facilities, patients tested and test design in the first phase cited in the "Guidelines For Methods To Evaluate Drugs for Malignant Tumors at the Clinical Level." Moreover, it was proposed that the public be informed as to the need and importance of scientific, theoretical and highly cost-efficient clinical trials.

Clinical Trials, Phase I as Topic

[Early phase II trial of l-leucovorin and 5-fluorouracil in advanced colorectal cancer. l-Leucovorin and 5-FU Study Group].

We report the results of a multicenter clinical trial comparing three combination chemotherapeutic regimens including 5-fluorouracil (5-FU) and l-leucovorin (l-LV). One hundred and twenty-two patients were randomized to three regimens comprising 5-FU (600 mg/m2) plus high-dose l-LV (250 mg/m2) in six doses given weekly by i.v. injection midway during a 2-hr infusion of l-LV (regimen A), 5-FU (370 mg/m2) plus high-dose l-LV (100 mg/m2) given simultaneously for 5 consecutive days and a 23-day interval between treatments (regimen B) and 5-FU (370 mg/m2) plus low-dose l-LV (10 mg/m2) with the same dose administration schedule as regimen B (regimen C). The response rates were 32.4% (12/37 cases) in Regimen A, 20.0% (8/40) in regimen B and 11.1% (4/36) in regimen C. The most prominent side effects observed in regimen A were diarrhea (53.8%) and leukopenia (53.8%); however, they were within permissible levels. The combinations of high-dose l-LV and 5-FU (regimen A and B) had higher response rates than that of low dose l-LV and 5-FU (regimen C). Weekly administration of high-dose l-LV and 5-FU (regimen A) is now being expanded to late phase II trials.

Aged

[A controlled study of AO-90, a methionine-free intravenous amino acid solution, in combination with 5-fluorouracil and mitomycin C in advanced gastric cancer patients (surgery group evaluation)].

The results of recent preclinical and clinical studies suggest that AO-90, a methionine-free intravenous amino acid solution (7.43%), potentiates the antitumor effect of 5-fluorouracil (5-FU). In the present multi-center, randomized, controlled study conducted at the surgery departments of 53 institutions between July 1991 and March 1993, patients with advanced gastric cancer were randomly allocated to receive either AO-90 (500-750 mL/day, AO/MF group) or Amiparen, a commercial intravenous amino acid solution (600-800 mL/day, C/MF group) by total parenteral nutrition for 14 days. Both groups received MF therapy which consisted of a continuous infusion of 5-FU at 350 mg/m2/day for 14 days and an i.v. push of mitomycin C 7 mg/m2 on days 7 and 14 (one course). Additional treatment courses were initiated after a withdrawal period when appropriate. Of the 138 subjects enrolled, 129 (93.5%) were eligible and 119 (86.2%) completed the scheduled treatment (AO/MF group: 57, C/MF group: 62). The overall clinical response rates in the completed cases were 26.3% (15/57) in the AO/MF group and 8.1% (5/62) in the C/MF group, and the difference between the groups was significant (p = 0.015). In particular, the response rate in the postoperative recurrent patients with measurable lesions was 42.9% (12/28) in the AO/MF group versus 12.0% (3/25) in the C/MF group (p = 0.016). Further, in the patients who were previously treated with fluoropyrimidine drugs, 29.0% (9/31) responded to the AO/MF therapy versus 8.6% (3/35) in the C/MF group (p = 0.053). The treatment-related adverse reactions observed were mainly hematologic and subjective/objective symptoms, such as decreased leukocyte count and hemoglobin level, nausea/vomiting and stomatitis. The differences in the incidence were not significant between the groups. Based on these results, AO-90 in the MF regimen appears to be effective in the treatment of patients with advanced gastric cancer by significantly potentiating the effects of 5-FU.

Adolescent

[A cooperative late phase II trial of l-leucovorin and 5-fluorouracil in the treatment of advanced gastric cancer. l-Leucovorin and 5-FU Study Group (Japan Western Group)].

A multicenter cooperative study was conducted to evaluate the clinical efficacy of l-leucovorin (l-LV) and 5-fluorouracil (5-FU) treatment in 69 cases of advanced gastric cancer. l-LV was administered intravenously by a 2-hour infusion at a dosage of 250 mg/m2 and 5-FU at a dosage of 600 mg/m2, intravenously via bolus one hour after administration of l-LV had been started. The combination was given weekly for 6 weeks followed by a 2-week rest period. Patients were evaluated for response after the sixth dose. Nineteen PRs were noted in the 55 patients for an overall response rate of 34.5%. Median survival time was 190 days for eligible cases, and 448 days for PR cases. Age and performance status (PS) appeared to influence clinical response. Patients aged 49 years or younger showed a significantly higher PR rate than those aged 50 years or older. The PR rate was significantly higher in the patients of PS 0-1 than those of PS 2. Diarrhea and leukopenia were experienced in 46.7% and 65% of patients, respectively. Patients who had severe toxicities required discontinuity of treatment. After recovery, treatment was repeated. The clinical results are promising for patients with advanced gastric cancer, particularly middle-aged patients. However, whether the l-leucovorin and 5-FU combination therapy will ultimately produce superior results in middle-aged patients awaits the results of Phase III trials.

Adult

[Quality of life in patients with advanced gastric cancer receiving AO-90, a methionine-free intravenous amino acid solution, with 5-fluorouracil and mitomycin C].

We conducted a randomized, multicenter, controlled trial of AO-90, a methionine-free 7.43% intravenous amino acid solution, in patients with advanced recurrent gastric cancer. The regimen used in the study was comprised of two-week treatment cycles, with a withdrawal period between cycles. During treatment, patients were given either AO-90 (500-750 ml/day; AO/MF group) or a commercial amino acid solution (600-800 ml/day; C/MF group) by total parenteral nutrition (TPN) for 14 days concomitantly with MF therapy (5-fluorouracil 350 mg/m2/day, iv continuously for 14 days and mitomycin C 7 mg/m2, iv push on days 7 and 14). We interviewed 118 eligible and evaluable patients (72 men and 46 women; 59 cases in the AO/MF group and 59 in the C/MF group) about their quality of life immediately before the start of treatment, one week and two weeks after the start of treatment, and one week and two weeks after treatment. A 11-item questionnaire was used to interview the subjects: nine questions using a five-point scale, one question using a 100-mm linear visual analog scale, and one question using a five-grade face scale. Changes in the grades compared with baseline data were scored as 1 point (improvement of one grade or more, or 20 mm or more), 0 points (no changes), and-1 point (decline of one grade or more, or 20 mm or more). Before analyzing the significance, quality of life score data were adjusted by the Mantel-Haenszel method due to uneven distribution of subjects concerning baseline performance status and complications. Among the items questioned, subjects receiving AO-90 showed significantly higher scores in appetite, nausea, and ambulation at some evaluation time points than those receiving a methionine-containing TPN. The results show that AO-90 improved the quality of life of patients with advanced recurrent gastric cancer.

Adolescent

[A late phase II trial of l-leucovorin and 5-fluorouracil in advanced colorectal cancer. l-Leucovorin and 5-FU Study Group (Japan Western Group)].

A multicentral cooperative study was conducted to evaluate the clinical efficacy and toxicity of l-Leucovorin (l-LV) and 5-fluorouracil (5-FU) in advanced colorectal cancer. The administration schedule was a two-hour intravenous infusion of l-LV (250 mg/m2) and an intravenous bolus injection of 5-FU (600 mg/m2), given one hour after the beginning of the l-LV infusion. Sixty-four patients were treated weekly for six weeks followed by two-weeks rest, and then evaluated for response. Complete response and partial response were obtained in 21 patients (32.8%). The median survival time was 12.8 months. The most prominent side effects were anorexia (57.8%), nausea and vomiting (56.3%), diarrhea (48.4%) and myelosuppression such as leucopenia (54.7%), thrombocytopenia (18.8%) and decreased hemoglobin (40.6%). These side effects, however, were within permissible levels. Severe toxicity was prevented by discontinuance of the treatment. From the present study, l-LV and 5-FU combination therapy seems to be a very promising and useful treatment for patients with advanced colorectal carcinoma.

Adult