Search PubMed⌕ Search

Biomedical subjects

T Imamura

Publications and source records attributed to T Imamura.

At least 559 records · Page 31Linked to original sources

Why do frontal lobe symptoms predominate in vascular dementia with lacunes?

We studied 30 necropsy cases of vascular dementia with a lacunar state. Manifestations included dementia, lack of volition, emotional lability, small-stepped gait, dysarthria, urinary incontinence, grasp reflex, pyramidal signs, paraplegia in flexion, and akinetic mutism. Pathologically, there was diffuse incomplete softening of white matter in all cases. Both lacunes and diffuse softening were found predominantly in the frontal lobes. The prominent clinical features were therefore frontal lobe symptoms, with good correlation between the symptoms and the distribution of pathologic lesions.

Aged↗

Effects of digitalis on cardiopulmonary baroreflex in man.

We examined whether digitalis augments cardiopulmonary baroreflex control of forearm vascular resistance in normal young men. Cardiopulmonary baroreceptor input was reduced with lower body negative pressure (LBNP) at 10 and 20 mmHg which decreased central venous pressure (CVP) but did not alter blood pressure (BP) or heart rate (HR). Decreases in forearm blood flow and increases in forearm vascular resistance with LBNP were greater after cedilanid than before and the slope of the regression line relating changes in central venous pressure and those in forearm vascular resistance was steeper after cedilanid. Vasoconstrictor responses to a cold pressor test did not differ before and after cedilanid, which suggested that augmented responses to LBNP after cedilanid were not due to a generalized change in reflex control. These results suggest that cedilaniid augments the tonic inhibitory influence of cardiopulmonary baroreceptors in normal men.

Adult↗

Werner's syndrome associated with cholangiocarcinoma.

A 38-year-old Japanese man had cholangiocarcinoma in association with typical features of Werner's syndrome. The replicative capacity of fibroblasts in culture was characteristically reduced, and the in vitro natural killer cell activity was deficient. He died of massive G-I tract bleeding 8 months after admission.

Adenoma, Bile Duct↗

[Successful chemotherapy in undescended testicular and extragonadal germ cell tumors: report of 2 cases].

Two patients with advanced germ cell tumor who entered complete remission following intensive combination chemotherapy, radiation therapy and surgical intervention are reported. A 28-year-old businessman presented with abdominal pain and masses associated with an elevated HCG level for which he underwent exploratory laparotomy. Large retroperitoneal masses were found and microscopical examination of the masses were revealed seminoma. Three courses of combination chemotherapy consisting of CDDP, VLB and PEP were given to the patient followed by radiation therapy to the parailiac, paraaortic, mediastinal and supraclavicular lymph nodes with boost irradiation to the paraaortic lymph nodes where the large masses were located. The other patient was a 21-year-old student who developed sharp precordial chest pain which proved to be due to a large mediastinal mass accompanied by an elevated AFP level. He was treated with radiation therapy to the mediastinum, surgical resection and combination chemotherapy. However, he showed recurrence in the lungs associated with rising AFP levels, and was given a salvage chemotherapy consisting of 3 courses of CDDP, ADR, PEP and Etoposide. Both patients were successfully treated with combined modalities of treatment including intensive chemotherapy and have been off therapy without recurrence for over 12 and 4 months, respectively.

Adult↗

Influence of aging and poly IC treatment on xenobiotic metabolism in mice.

Cytochrome P-450-dependent and independent metabolism of xenobiotics in the liver of C57BL/10ScSn male mice was investigated in relation to age and the age-related differences in response to treatment with polyriboinosinic-polyribocytidylic acid (poly IC), an interferon inducing agent. Young (3 months), middle-aged (15 months) and old (27 months) animals were studied. Mean survival time of males of this strain is 30-33 months. Age-related changes in the metabolism of xenobiotics included significant decreases between middle and old age in activities of the microsomal P-450-dependent mixed function oxidases (MFO), aryl hydrocarbon hydroxylase (AHH) and p-nitroanisole (p-NA) O-demethylase, but not 7-ethoxycoumarin (7-Ec) O-deethylase. Analysis of P-450-independent enzymes revealed a significant decrease in the epoxide hydrolase activity in the microsomes and cytosol from old compared to middle-aged or young mice. Glutathione S-transferase activity towards 1-chloro-2,4-dinitrobenzene (CDNB) was lower in cytosols of middle-aged and old than young mice. Carboxylesterase activity was not altered by age. Hepatic microsomal protein content was significantly higher in middle-aged and old than in young mice. Intraperitoneal treatment with a single dose of 5 mg/kg poly IC 24 hours before sacrifice resulted, for mice of all age groups, in a marked inhibition of activities of all 3 microsomal cytochrome P-450-dependent enzymes, without any changes in activities of the P-450-independent enzymes. The inhibition of AHH by poly IC was much higher in old and middle-aged than in young mice, averaging 87.1%, 74.5%, and 41.9%, respectively, in the 3 age groups. Poly IC treatment increased lipid peroxidation in liver homogenates of all groups of mice. Body and liver weights were not altered in animals of the 3 age groups by poly IC treatment, but hepatic microsomal protein contents were significantly decreased.

Aging↗

Isolation and characterization of an activated C-H-ras-1 gene from a squamous-cell lung carcinoma cell line.

We determined a complete nucleotide sequence of an activated form of the c-H-ras-1 proto-oncogene cloned from the human cell line (QG56), using the DNA transfection technique and NIH3T3 cells as recipients. This cell line was established from a squamous-cell lung carcinoma of a Japanese patient, and the activated gene had 2 nucleotide substitutions. One substitution of a thymidine for an adenosine was found at position 1069 of the 2898 nucleotide sequence in a restriction endonuclease (SacI) fragment, which corresponds to the second base of the 61st codon of the gene encoding P21 protein. This nucleotide replacement was assumed to be responsible for the transforming activity. Another substitution of a guanosine for an adenosine which was detected at position 746 in the first intron was thought to be a genetic polymorphism unassociated with the transforming activity. Comparison of the various lengths of restricted fragments suggested that the activity was markedly influenced by certain sequences flanking the c-H-ras-1 gene.

Animals↗

Interaction of O,O,S-trimethyl phosphorothioate and O,S,S-trimethyl phosphorodithioate, the impurities of malathion with supercoiled PM2 DNA.

The interaction of O,O,S-trimethyl phosphorothioate and O,S,S-trimethyl phosphorodithioate, the impurities found in malathion, with DNA at pH 8.0, was investigated. Supercoiled PM2 DNA was incubated with these compounds at pH 8.0 at 37 degrees C and then the superhelicity of the modified DNA was determined by gel electrophoresis. Both compounds caused unwinding of supercoiled DNA in dose- and incubation time-dependent manner. O,S,S-trimethyl phosphorodithioate was a more potent agent than O,O,S-trimethyl phosphorothioate. At 37 degrees C following 2.0 hours incubation, 100 mM O,S,S-trimethyl phosphorodithioate produced fully unwound DNA, whereas at 200 mM O,O,S-trimethyl phosphorothioate produced 80% unwound DNA following 12 hours' incubation. At the same condition, 5 mM methyl methanesulfonate, a potent alkylating mutagen, produced fully unwound DNA following 1 hour incubation at 5 mM. These results indicated that there were chemical interactions between these agents and DNA. The possibility of the interaction of OOS-TMP being as a covalent intercalation as well as strand nicking was discussed.

Animals↗

Cellular responses to O,O,S-trimethyl phosphorothioate-induced pulmonary injury in rats.

O,O,S-Trimethyl phosphorothioate (OOS-TMP), an impurity of many organophosphorus insecticides, causes a delayed toxicity in rats and mice which is associated with morphological and biochemical changes in the lung. Oral administration of doses as low as 20 mg/kg alters bronchiolar epithelial morphology and causes an increase in bronchopulmonary lavage lactate dehydrogenase levels. In the present study, the effects of OOS-TMP on alveolar and bronchiolar cells were examined by determining the patterns of cellular regeneration in rats at periods of 12 hr, 24 hr, 3 days, and 7 days after treatment. Dividing cells were labeled with tritiated thymidine and studied with autoradiographic techniques. The results showed that OOS-TMP treatment initiated proliferation of alveolar type II cells within 24 hr. The proliferative response of type II cells continued to increase in 3-day and 7-day treatment groups. Labeled alveolar type I cells began to appear after 3 days, indicating that type II cells were dividing to replace damaged type I cells. Cells of the alveoli were thickened and showed vacuolization. In the bronchioles, labeled Clara cells were increased on Day 3 and Day 7 while the number of labeled ciliated cells remained near control levels throughout all time points, indicating that in bronchiolar epithelium, OOS-TMP stimulates the proliferation of Clara cells but does not damage ciliated cells. The binding of tritiated OOS-TMP to lung tissue was also examined by autoradiography. It was found that [3H]OOS-TMP binds to all regions of lung tissue.

Animals↗

Effects of subchronic treatment with O,O,S-trimethyl phosphorothioate on cellular and humoral immune response systems.

The effect of a 14-day treatment with low doses of O,O,S-Trimethyl phosphorothioate (OOS-TMP), an impurity in technical malathion, on the generation of cell-mediated and humoral immune responses was examined in female C57B1/6 mice. At a dose of 0.5 mg/kg/day OOS-TMP, the generation of antibody-secreting cells to sheep red blood cells (SRBC), the production of interleukin 2 (IL-2), and proliferative responses to the mitogens concanavalin A (Con A) and lipopolysaccharide (LPS) were elevated. In contrast, the cytotoxic T-lymphocyte (CTL) response to alloantigen was unchanged. At 5.0 mg/kg/day OOS-TMP, both the CTL and specific antibody response were unchanged, but all other immune parameters examined were elevated. Data from cell separation and reconstitution experiments indicated that both macrophages and B cells were affected by this treatment regime. These data suggest that long-term exposure to low amounts of OOS-TMP may enhance the ability of an animal to generate an immune response.

Administration, Oral↗

Investigations into the mechanism of immunosuppression caused by acute treatment with O,O,S-trimethyl phosphorothioate. I. Characterization of the immune cell population affected.

Acute administration of O,O,S-trimethyl phosphorothioate (OOS-TMP), an impurity in technical formulations of malathion, to female C57B1/6 mice was previously shown to suppress the generation of both cytotoxic T lymphocyte to alloantigen and antibody-secreting cells to sheep red blood cells. In this report, macrophages were shown to be the immune cell population most affected by acute OOS-TMP pretreatment by cell separation and reconstitution experiments. Macrophages from OOS-TMP-treated animals had increased levels of nonspecific esterases. In addition, the size distribution of macrophages from treated animals was slightly larger and more heterogeneous than macrophages from control animals. However, macrophages from OOS-TMP-treated animals did not exhibit tumoricidal activity. These data suggest that macrophages from OOS-TMP-treated animals were similar to those located in nonimmune inflammatory sites.

Animals↗

Investigations into the mechanism of immunosuppression caused by acute treatment with O,O,S-trimethyl phosphorothioate. II. Effect on the ability of murine macrophages to present antigen.

Acute administration of 10 mg/kg O,O,S-trimethyl phosphorothioate (OOS-TMP) for 24 h has been shown to suppress the in vitro generation of cytotoxic T lymphocyte responses and antibody-secreting cells to sheep red blood cells and to increase interleukin-2 production. Macrophages were shown to be the splenic cell population most affected by OOS-TMP pretreatment. In this report, the ability of macrophages from OOS-TMP-treated animals to function in antigen presentation was shown to be significantly decreased. In addition, macrophages from treated animals had increased phagocytic capability and interleukin-l production. However, the percentage of Ia-positive macrophages present in splenic populations was decreased following OOS-TMP treatment. A decrease in antigen presenting ability and the number of Ia-positive macrophages may explain the reversible suppression in cytotoxic T lymphocytes and antibody responses reported previously.

Animals↗

Alterations of alveolar macrophage function and level of bronchopulmonary protease inhibitors in O,O,S-trimethyl phosphorothioate-induced lung injury.

O,O,S-Trimethyl phosphorothioate (OOS-TMP), an impurity present in widely used organophosphorus insecticides, has been shown to induce pneumotoxicity after oral administration. To date very little is known about the pathogenesis of the injury. Protease-anti-protease imbalance has been proposed as a mechanism of various lung injuries; thus, the effect of OOS-TMP on alpha 1-protease inhibitor capacity, pulmonary alveolar macrophage (PAM) esterases, cytotoxic activity and on specific esterase inhibitors in the bronchopulmonary lavage fluid and serum were measured. OOS-TMP (20 mg/kg) administered orally to rats produced a 27% increase in PAM esterase activity 6 h after treatment. The activity then declined to 63% of control value on day 3 and had not recovered to any significant extent on day 7. The cytotoxic activity of PAM was significantly increased at 6 h and 24 h following treatment. Chymotrypsin inhibitory capacity (CIC) of the lavage fluid was decreased by 45% at 6 h but recovered rapidly and reached control levels by 24 h. Trypsin inhibitory capacity (TIC) of serum was affected to a lesser extent such that no change was detected after 6, 12 or 24 h. These data, early elevation of PAM esterase levels with a concomitant increase in cytotoxic activity and decreased TIC and CIC in bronchopulmonary lavage fluid, support the view that pathogenesis of OOS-TMP produced lung injury could be due to increased protease levels.

Administration, Oral↗