Biomedical subjects
Publications and source records attributed to J Taguchi.
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Twenty-six patients with histologically proven lung cancer, treated with carboplatin at the National Cancer Center Hospital between October 1985 and October 1986, were retrospectively analyzed to determine the hematologic toxicity of carboplatin (CBDCA) and to develop guidelines for dose modification. A total of 34 courses of CBDCA were administered, of which 21 were adequate for assessment of the myelosuppression in relation to the renal function. One of three doses of CBDCA was administered by iv drip infusion over one hour (450 mg/m2, 19 courses; 400 12; 300, 3). Myelosuppression was dose-limiting, with thrombocytopenia being more sensitive than leukopenia, neutropenia or anemia. No significant correlation of the absolute count of platelets, white blood cells, polymorphoneutrophils, or hemoglobin with patient's creatinine clearance (Ccr) and dose of CBDCA administered was found. However, the percent reduction in platelets, white blood cells, polymorphoneutrophils, or hemoglobin correlated well with the relative dose of CBDCA [RD = total dose of carboplatin administered (mg/m2)/pretreatment Ccr/m2]. As thrombocytopenia was dose-limiting, we have developed an equation for modification of the dose of CBDCA from the relationship between the relative dose and percent reduction at platelet count nadir: Dosage (mg/m2) = (Ccr/m2/5.34) x [(1-desired platelet count nadir/pretreatment platelet count) x 100-12.9]. After consideration of the range of thrombocytopenia, we have further developed a simple equation to use CBDCA easily and safely: Dosage (mg/m2) = (1/10) x Ccr/m2 x desired % reduction in platelet count nadir = 10 x Ccr/m2 x (1-desired platelet count nadir/pretreatment platelet count. The clinical validity of these two equations is now being evaluated in prospective studies.
A 56-year-old housewife was incidentally discovered to have an abnormal shadow in the right B6 area upon a chest X-ray film being taken. A transcutaneous lung biopsy of the mass revealed adenocarcinoma of the lung (WHO classification). A brain computed tomography (CT) scan demonstrated multiple brain metastasis. Following whole brain irradiation, carboplatin (CBDCA) (450 mg/m2) was administered by intravenous drip infusion on March 7, 1986. After three weeks of initial treatment with CBDCA, the size of the tumor in the primary site was found to have decreased on the chest X-ray film by more than 50%, following which, similar doses of CBDCA were administered twice, and reduced (330 mg/m2) doses three times every three to four weeks. She showed a partial response and, for seven months after the beginning of the CBDCA treatment, no progression was seen on the chest X-ray film. It is suggested that there is a need for further phase II studies of CBDCA against non-small cell lung cancer.
The purification of gamma-aminobutyric acid (GABA) and benzodiazepine receptors from the rat brain was employed by the affinity column using a new benzodiazepine, 1012-S, as immobilized ligand. The 1012-S has a aliphatic primary amino group and exhibited an extremely high potency for displacing [3H]flunitrazepam binding to solubilized benzodiazepine receptor preparation (IC50 = 6.0 X 10(-11) M). This benzodiazepine affinity gel retained almost all of the solubilized GABA receptors from synaptic membranes applied to the column, and 25.6% of the receptor was eluted bio-specifically following the application of 1 mM 1012-S. The highest purification fold thus obtained was 4576 (specific activity: 0.99 nmol/mg protein). Furthermore, the successive application of 1-2 M NaSCN also resulted the elution of a highly enriched GABA receptor (specific activity: 0.41 nmol/mg protein; purification fold: 1889). SDS-polyacrylamide gel electrophoretic profiles of the bio-specifically eluted fraction with 1012-S showed the existence of two major bands having the molecular weights of approximately 48,500 and 54,500, in which the former band was selectively photoaffinity-labeled with [3H]flunitrazepam. On the other hand, it was found that the non-specifically eluted fraction with NaSCN contained 4 additional minor bands having molecular weights of 41,000 to 51,000. These results indicate that GABA receptor of the rat brain is coupled, at least in part, with benzodiazepine receptor and is readily purified by the use of highly specific benzodiazepine affinity gel, 1012-S-acetamide adipic hydrazide Sepharose 4B. The present results also suggest that the purified GABA/benzodiazepine receptor complex may contain two different kinds of subunits having the molecular weights of 48,000 and 54,500, in which the former subunit may possess benzodiazepine binding sites.
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The effect of cold and immobilization stress on presynaptic GABAergic autoreceptors was examined using the release of [3H]GABA (gamma-aminobutyric acid) from slices of rat striatum. It was found that in vitro addition of delta-aminolevulinic acid, as well as GABA agonists such as muscimol and imidazoleacetic acid, exhibited a significant suppression of the striatal release of [3H]GABA evoked by the addition of high potassium, whereas delta-aminovaleric acid had no significant effects on the evoked release. These suppressive actions were antagonized invariably by the GABA antagonists, bicuculline and picrotoxin, but not by the glycine antagonist, strychnine. Cholinergic agonists, such as pilocarpine and tetramethylammonium, also attenuated significantly the evoked release of [3H]GABA from striatal slices, while none of its antagonists, including atropine, hexamethonium and d-tubocurarine, affected the release. On the other hand, in vitro addition of dopamine receptor agents such as dopamine, apomorphine, and haloperidol, or the inhibitory amino acids, glycine, beta-alanine, and taurine failed to influence the evoked release of [3H]GABA from striatal slices. Application of a cold and immobilization stress for 3 h was found to induce a significant enhancement of the suppressive effects by muscimol and delta-aminolevulinic acid on the evoked release of [3H]GABA, without affecting that by pilocarpine and tetramethylammonium. These results suggest that the release of GABA from striatal GABA neurons may be regulated by presynaptic autoreceptors for this neuroactive amino acid, and may play a significant functional role in the exhibition of various symptoms induced by stress.
Twenty out-patients suffering from urinary tract infections (UTI) were treated with cefaclor. Cefaclor was administrated orally in daily doses of 1,500 mg for 7 days against 15 cases of simple UTI and 5 cases of complicated UTI. Of 20 cases with acute simple cystitis, acute pyelonephritis and complicated UTI, clinical responses were excellent in 10 cases, good in 6 cases and poor in 4 cases. The efficacy rate was 80%. No side effect was observed. The site of infection determined by the ACB detection method was in good agreement with that determined by clinical findings. Cefaclor appeared to be equally effective in the treatment of both ACB-positive and ACB-negative infections. The presence of absence of antibody-coated bacteria did not correlate with clinical symptoms or response to therapy.
Following results were obtained from intravenous single administration of cefotaxime 2 g by measuring its levels in uterine arterial blood, elbow venous blood, ovary, oviduct, several sites in uterine tissue, and in the fluid excreted in the dead space formed by radical hysterectomy. (1) Uterine artery and elbow vein blood levels revealed marked increase immediately after administration followed by gradual reduction at slow rate. (2) Peak levels in female internal genital organ tissue were achieved 12 approximately 19 minutes after cefotaxime administration, and ranged between 5 to 8 mcg/g independently from measurement site. In cervix uteri, portio vaginalis high concentration of 4.9 approximately 5.7 mcg/g was achieved within ten minutes after drug administration. (3) In the fluid excreted in the dead space formed by radical hysterectomy cefotaxime levels were maintained around 15 mcg/ml level throughout 5 approximately 6 hours following its administration, and gradually decreased at slow rate later.
Controlling the duration of hypnotic effect of pentobarbital by simultaneously administered bemegride, the relationship between the duration of hypnosis and the degree of developed tolerance after acute or chronic treatment was investigated in mice. Bemegride attenuated the hypnotic effect of pentobarbital, but neither the brain level of pentobarbital nor the development of tolerance was modified by bemegride, indicating that the brain level of pentobarbital is the primary determinant for the production of tolerance and full duration of hypnosis is not essential in this mechanism.
The data from the Veterans Administration Cooperative Study on Antihypertensive Agents Prevention of Morbidity Trial were reviewed from the point of view of the importance of normalizing the blood pressure in preventing cardiovascular complications. The treated group of patients was subdivided into three subgroups on the basis of the diastolic blood pressures recorded at the fourth month after randomization as follows: subgroup A, the poorly controlled patients whose diastolic blood pressures were 90 mm Hg or higher, an intermediate subgroup B with diatolic levels of 81 to 89 mm Hg, and subgroup C, the best controlled patients, all of whom exhibited diastolic blood pressures of 80 mm Hg or less. While the incidence of morbid events was slightly higher in subgroup A than in the other subgroups, the differences were not statistically significant. On the other hand, the incidence of morbid events in subgroup A was significantly lower (P less than 0.05) than in the untreated control patients (14.9% in subgroup A vs. 28.9% in the control group). While normalization of blood pressure is a desirable goal of treatment, even partial reduction appears to exert significant therapeutic benefit.
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PURPOSE: The purpose of this study was to clarify characteristics of combined hepatocellular and cholangiocarcinoma (HCC-CC) on CT and clinicopathological examinations. METHODS: Dynamic incremental CT was performed on 15 combined HCC-CC patients. CT of the early phase was started at 30 s and of the late phase at 120-140 s, after the start of contrast medium injection at a rate of 3 ml/s. The images and clinicopathological findings were retrospectively compared. RESULTS: Lesions grossly resembling HCC (HCC type, n = 6) were well enhanced in the early phase and changed to low attenuation areas in the late phase. In lesions grossly resembling CC (CC type, n = 9), 8 of 9 lesions were enhanced only at the peripheral portions in the early phase and changed to low attenuation areas or had only central portions enhanced in the late phase. The other CC-type lesion was not enhanced in either the early or the late phase. In all 15 cases, there was no dilatation of the intrahepatic bile ducts. Hepatitis B virus surface antigen was positive in five cases. Hepatitis C virus antibody was positive in 10 cases. Serum alpha-fetoprotein (AFP) levels were > or = 200 ng/ml in seven cases. CONCLUSION: In the CC type, enhanced CT images were compatible with CC, but positivities for virus markers and serum AFP levels were almost equivalent to those in HCC. Therefore, the CC type can be diagnosed as combined HCC-CC by evaluating virus markers and serum AFP levels with CT. In addition, no association of intrahepatic bile duct dilatation was considered to be a characteristic feature of combined HCC-CC.
One of the proteins belonging to the transmembrane 4 superfamily, T-cell acute lymphoblastic leukemia-associated antigen 1 (TALLA1), behaves like a potential tumor-associated antigen. Furthermore, its mRNA is expressed in normal brain. We examined here the histochemical localization of the protein and its mRNA in human brain tissues. Both nonneurological and Alzheimer disease (AD) brains showed astroglial staining for the TALLA1 molecule. In AD brain tissues, globular dystrophic neurites were positively stained. In damaged white matter showing leukoaraiosis by CT scan there was varicose axonal staining with the anti-TALLA1 antibody. In situ hybridization histochemistry using a RNA probe demonstrated neuronal expression of the mRNA. These results suggest that TALLA1, like amyloid precursor protein or chromogranin A, is produced in neurons and transported by axonal flow.
We clinicopathologically studied 6 resected cases of cholangiolocarcinoma (CLC) including 2 referred cases from other hospitals. The frequency of CLC was 0.56% of the 708 consecutively resected cases of primary liver cancer and the mean age of CLC cases was 66 years. Three of the 6 cases (50%) were hepatitis C virus antibody (HCVab) positive, one (17%) was hepatitis B virus surface antigen (HBsAg) positive, and 2 (33%) were negative to both HCVAb and HBsAg. Serum levels of alpha-fetoprotein were slightly elavated only in 1 case. Clinically, 4 cases were diagnosed as hepatocellular carcinoma (HCC) and 2 cases as cholangiocellular carcinoma (CCC). Grossly, CLCs were whitish in color and solid, not encapsulated, and resembled CCC. Histologically, the tumor cells had eosinophilic cytoplasm with ovoid nuclei, and mild atypia. The tumor proliferated in an anastomosing pattern of Hering's canal-like small glands with an abundant fibrous stroma. Four of the 6 tumors (83%) consisted of only CLC and other 2 tumors contained CCC-like area and HCC-like area in a part of the nodules, respectively. Immunohistochemically, all tumors were positive to cytokeratin (CK) 7. CK8 were also positive in all of 6 cases. These results revealed that CLC had the clinical features resembling HCC but the morphologic features resembling CCC. It is suggested that CLC cells might be derived from Hering's canal or stem cells which have the intermediate features between hepatocytes and bile duct epithelium.