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Biomedical subjects

T Shirai

Publications and source records attributed to T Shirai.

At least 325 records · Page 18Linked to original sources

Analysis of synergism in hepatocarcinogenesis based on preneoplastic foci induction by 10 heterocyclic amines in the rat.

The effects of simultaneous treatment with 5 or 10 heterocyclic amines at low dose levels on hepatocarcinogenesis in rats were investigated using a medium-term liver bioassay protocol based on the two-stage carcinogenesis hypothesis with diethylnitrosamine initiation (200 mg/kg, i.p.). Five carcinogenic heterocyclic amines in experiment 1 (Trp-P-1, Glu-P-2, IQ, MeIQ, MeIQx) and experiment 2 (Trp-P-2, Glu-P-1, MeAalphaC, AalphaC, PhIP) were administered together or individually in the diet at levels of 1/1, 1/5, or 1/25 carcinogenic doses, and all 10 chemicals were given at 1/10 or 1/100 levels in experiment 3. Induction of preneoplastic glutathione S-transferase placental form (GST-P)-positive foci in the liver was generally increased in the combination groups over the sums of the 5 or 10 individual effects. Thus, based on the heteroadditive concept, synergism was observed for each combination, being most obvious in the group given all 10 chemicals at the 1/10 dose levels. However, the values for the combined groups were generally close to the averages of the 5 or 10 data gained for the heterocyclic amines alone at the corresponding higher doses, indicating the possibility of isoadditivity. Based on these findings, we propose here a new statistical method for analysis of combined effects of multiple chemicals, and, using this, we demonstrated (true) synergism with some heterocyclic amine combinations. The importance of dose-response curves for evaluation of combination effects is discussed.

Amines↗

Establishment and characterization of three androgen-independent, metastatic carcinoma cell lines from 3,2'-dimethyl-4-aminobiphenyl-induced prostatic tumors in F344 rats.

Three stable carcinoma cell lines, designated PLS10, PLS20 and PLS30, have been established from 3,2'-dimethyl-4aminobiphenyl plus testosterone-induced carcinomas in the dorsolateral prostate of male F344 rats. The cells are keratin-positive and grow as typical epithelial monolayers in culture. When injected into intact male nude mice, PLS10 and PLS30 cells form well-differentiated adenocarcinomas with abundant connective tissue stroma, while PLS20 cells give rise to poorly differentiated adenocarcinomas. Growth of all PLS cell lines in nude mice is not affected by castration and the cells are immunohistochemically negative for androgen receptors. Tumor growth rates in nude mice were found to be PLS20 > PLS10 > PLS30, with significant in vitro stimulation by insulin/transferrin, but not epidermal growth factor, dexamethasone or basic fibroblast growth factor. Spontaneous lung metastases were observed in all cases. However, skeletal invasion including bone is essentially observed only with the PLS20 tumors. Gelatin zymography showed predominant secretion of the active form of gelatinase B (Mr 92,000 type IV collagenase) by all the cell lines. Karyotype analysis revealed PLS10, PLS30 and PLS20 to be diploid, hyperdiploid and hypertetraploid, respectively. The results demonstrate that the three PLS cell lines are androgen-independent and metastatic in common, but have different histology, growth potential and invasiveness. They may therefore be useful models for understanding progression and metastasis of human prostatic carcinomas.

Aminobiphenyl Compounds↗

Growth characteristics in the initial stage of micrometastasis formation by bacterial LacZ gene-tagged rat prostatic adenocarcinoma cells.

A micrometastasis model was established using a rat differentiated prostatic adenocarcinoma, designated PLS30lZ, transfected with the lacZ gene encoding a bacterial beta-galactosidase. The morphology, tumorigenicity and metastatic ability of PLS30lZ were comparable to those of the parental cells. Micrometastatic foci could be specifically detected at the single cell level after X-Gal staining with a dissecting microscope. After intravenous injection, the number of X-Gal positive foci in the lung decreased progressively to a steady-state level (less than 1% of injected cells) by 4-7 days, while the size of persisting positive foci started to increase from 4 days after inoculation, as demonstrated by image analysis. X-Gal and BrdU double staining revealed that BrdU labeling indices of X-Gal-positive cells decreased transiently at the 2-day time point and increased again from 4 days after inoculation. Type IV collagen immunostaining showed the tumor cells to be surrounded by a basement membrane intravascularly at the time point when they started new growth. Electron microscopy confirmed that, 2 days post injection, most tumor cells were degenerative or dead, but on day 4, persisting tumor cells formed multicellular clumps in contact with the vascular basement membrane inside vessels. These results indicate that PLS30lZ cells begin to grow intravascularly depending upon the presence of a basement membrane before extravasation at the initial stage of micrometastasis formation.

Adenocarcinoma↗

Dose-dependent induction of 8-hydroxyguanine and preneoplastic foci in rat liver by a food-derived carcinogen, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, at low dose levels.

Male F344 rats were administered 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in the diet at doses of 200, 50, 12.5, 3.2, 0.8, 0.2 and 0.05 ppm for six weeks, and partially hepatectomized 1 week after the beginning of MeIQx administration. Quantitative values for glutathione S-transferase placental form (GST-P)-positive foci in the liver were dose-dependently increased by the MeIQx treatment. 8-Hydroxyguanine (8-OHG) levels assessed after 1 week of dietary MeIQx administration were also dose-dependently increased, although the effect was no longer observed at the end of the treatment period. The correlation between numbers of GST-P-positive foci at week 6 and 8-OHG levels at week 1 was linear, values for both parameters being higher than the control levels even in the 0.8 ppm dose group. These findings indicate that, in addition to the previously reported MeIQx-DNA adduct formation, DNA modifications due to oxidative damage may play an important role in MeIQx liver carcinogenesis in rats.

Animals↗

Bullous pemphigoid associated with internal malignancies: identification of 180-kDa antigen by western immunoblotting.

We report three cases of bullous pemphigoid associated with internal malignancies. Two cases were associated with gastric cancer and one with rectal cancer. Immunoblot analysis, using epidermal extract of normal human skin, revealed that these patients' sera reacted only with bullous pemphigoid antigen with a molecular weight of 180 kDa (BP180). The relationship of BP180 to malignant tumours is discussed.

Adenocarcinoma↗

Biotin deficiency in an infant fed with amino acid formula and hypoallergenic rice.

An amino acid formula produced in Japan is not supplemented with biotin since biotin is not permitted as a food additive. Biotin deficiency developed in an 11-month-old Japanese infant who had been diagnosed as a neonate with cow milk and soy bean allergy and fed with an amino acid formula and hypoallergenic rice processed by protease. Serum levels of zinc, essential fatty acids and biotinidase were within the normal range while that of biotin was below the normal range. Urinary 3-hydroxy-isovalerate and slightly elevated levels of plasma branched-chain amino acids disappeared 1 week after oral supplementation with 1 mg day-1 of biotin as did the symptoms of orificial skin lesions, lethargy, hypotonia and alopecia later. In summary, to prevent biotin deficiency, biotin should be added to the Japanese amino acid formula.

Biotin↗

[Incidence and duration of febrile episodes in a hospitalized geriatric cohort].

Fever is a common and important clinical symptom observed among hospitalized geriatric patients. To investigate the frequency and duration of fever episodes, we surveyed fever episodes in a hospital where the frequency of patients over 60 years of age exceeds 90 per cent of the patients. Fever episodes with body temperature of over 37.5 degrees C were registered from May in 1991 to December in 1994, and 6809 episodes were subjected to analysis. The average incidences per month were 157.1, 165.3, 158.0, and 139.3 in 1991, 1992, 1993, and 1994, respectively. The numbers of episodes per month did not show any significant correlation with temperature or humidity. Average duration of the episodes were 8.0, 6.5, 7.6, and 6.7 days for 1991, 1992, 1993, and 1994, respectively. Episodes of one day duration were the most frequent in all months, and the frequencies of that ranged from 37.1% to 58.6% with a mean of 47.8%. The average duration of episodes and the frequency of one day episodes did not change significantly irrespective of a notable decrease in the total incidence. The high frequency of one day episodes and their consistency through the observed period suggest that fevers with one day duration are one of the characteristic features of the febrile symptoms in geriatric patients. Causality and prevention methods for these one day fever episodes should be investigated.

Aged↗

Effect of recombinant human granulocyte colony-stimulating factor on combination therapy with aztreonam and clindamycin for infections in neutropenic patients with hematologic diseases.

The present multicenter study was performed to evaluate the effect of recombinant human granulocyte-colony stimulating factor (rhG-CSF) on combination therapy using aztreonam (AZT) and clindamycin (CLDM) to treat severe infection in neutropenic patients with hematologic diseases. Forty-three neutropenic patients with infections (rhG-CSF group) were treated with AZT (2 g) and CLDM (600 mg) 2-3 times daily as well as rhG-CSF (Lenograstim or Filgrastim: 2-5 mu/kg/day). The clinical efficacy of this regimen was compared to that obtained in 44 febrile neutropenic patients, with hematologic diseases, who received only AZT and CLDM in a previous study (historical control group). The overall efficacy rate was 69.8% (30/43) in the rhG-CSF group and 65.9% (29/44) in the historical control group. Although the neutrophil count was significantly increased and C-reactive protein tended to be lower in the rhG-CSF group, the daily maximum body temperature profiles of the 2 groups were nearly the same. These results suggest that rhG-CSF is of little benefit in the treatment of single infectious episodes in neutropenic patients, and that appropriate antibiotic therapy is more important.

Acute Disease↗

[Serum albumin level as a predictor of incidence of febrile episodes and mortality in hospitalized geriatric patients].

To investigate the relationship between serum albumin level and incidence of febrile episodes and mortality in the elderly, we studied 748 patients hospitalized for over one year. The subjects included 123 males and 355 females with a mean age 81.2 years. The average serum albumin level was 3.79 g/dl and levels of serum albumin decreased with advancing age. The incidence of febrile episodes was 1.8 per year in patients with serum albumin levels over 4.1 g/dl, increasing with decline of serum albumin levels. The incidence of febrile episodes was 5.3 per year in patients with serum albumin levels under 3.0 g/dl. Patients with serum albumin levels under 3.0 g/dl displayed a high incidence of febrile episodes irrespective of age. Age adjusted in-hospital mortality was 40.4% during the observed period in patients with serum albumin levels under 3.0 g/dl, significantly higher than that of the patients with serum albumin levels over 3.1 g/dl. Relative risk of febrile episode and mortality calculated using the patients with serum albumin levels over 4.1 g/dl as a control was 2.9 and 2.1, respectively, in the patients with serum albumin levels under 3.0 g/dl. These results indicate that serum albumin level is a simple, but strong, predictor of susceptibility of febrile episode and death. Patients with serum albumin levels under 3.0 g/dl may constitute a high risk group for febrile episode and death.

Aged↗

Morphological study of vagal innervation in human semilunar valves using a histochemical method.

To determine the innervation of human semilunar valves, we examined the pulmonary and aortic valves of the normal autopsied hearts of 3 men (53 to 71 years old). Whole valve tissues with the aorta or pulmonary trunk were stained for acetylcholinesterase by a histochemical method. Acetylcholinesterase-positive nerve fibers with a diameter of 2 to 20 mm were located on the ventricular side of the semilunar valves. Innervation of the semilunar valves was extremely sparse compared with that of the atrioventricular valves and that of the aortic or pulmonary arterial wall. The nerves originated from the subendocardium of the ventricles and the adventitia of the arterial walls. The nerves were more distributed in the basal site than in the marginal site of the semilunar valve. The nerve fibers formed a network in basal two-thirds of the leaflet. Thick nerves ramified in the thin nerve plexus. The thick nerves had a varicose-like structure. Thin nerves had a dot- and brush-like ending. The nerves in human semilunar valves may play a role in valve motion.

Aged↗

A novel differentiation factor for PC12 cells from culture supernatant of mouse hepatocyte cell line MLE-15A2.

We have found a factor that induces neurite outgrowth of rat PC12 cells in the culture supernatant of the cell line MLE-15A2. This factor was designated as MDDF. The factor was sensitive to protease, dithiothreitol, and high-temperature treatments. The apparent molecular mass was 80 kDa on Superdex 200 gel filtration. No significant tyrosine phosphorylation was detected after MDDF stimulation in Western blotting analysis with anti-phosphotyrosine antibody, suggesting that the signal transduction may not be mediated by a tyrosine kinase cascade that is involved in signaling of most of the known factors. Activation of MAP kinase was very weak and was seen only 5 min after stimulation, suggesting that prolonged activation of MAP kinase was not required for neurite outgrowth induced by MDDF. Because the biochemical characteristics of MDDF are different from those of any known peptide factors that induce neurite outgrowth of PC12 cells, MDDF may be a novel differentiation factor for PC12 cells.

Animals↗

Varicella pneumonia in a healthy adult presenting with severe respiratory failure.

We describe a case of varicella pneumonia in a 24-year-old healthy man presenting with severe respiratory failure. A chest radiograph showed diffuse, bilateral airspace consolidation; additional complications included liver dysfunction and thrombocytopenia. However, treatment with intravenous acyclovir and gamma-globulin improved his clinical symptoms and signs. A greater than four-fold change in paired titers of the varicella-zoster virus antibody was observed. Bronchoalveolar lavage performed during the recovery phase revealed increased total cell and lymphocyte counts and a decreased CD4:CD8 ratio of T lymphocytes. Transbronchial lung biopsy findings were compatible with a diagnosis of interstitial pneumonia.

Acyclovir↗

Large right ventricular myxoma in a 79-year-old male.

A 79-year-old male, admitted because of severe dyspnea on exertion, showed echocardiographic findings of a large tumor in the dilated right ventricle. The right ventricular outflow tract was nearly occluded by the tumor mass, and the mass was attached to the interventricular septum by a pedicle. The tumor removal operation was successful. The size of the tumor was 40 mm x 90 mm, and the weight 70 g. Microscopic findings showed typical myxomatous tissue with high cellularity, and no malignancy was observed. This is the oldest reported patient with right ventricular myxoma which was cured by operation.

Aged↗

The effect of Helicobacter pylori on gastric acid secretion by isolated parietal cells from a guinea pig. Association with production of vacuolating toxin by H. pylori.

BACKGROUND: One of the features of Helicobacter pylori infection in the human stomach seems to be disordered gastric acid secretion. The effect of vacuolating toxin (VT) produced by H. pylori on gastric acid secretion was examined. METHODS: VT(+)(toxigenic) and VT(-)(nontoxigenic) strains of H. pylori were cultured in brucella broth. The culture supernatant was added to isolated parietal cells, and acid secretion and intracellular adenosine 3'5'-cyclic phosphate (cAMP) and Ca2+ levels were measured with the 14C-aminopyrine (14C-AP) method, with 125I radioimmunoassay (RIA), and with the fura-2 fluorescence method, respectively. RESULTS: In the VT(+) strain a considerable inhibitory effect on 14C-AP accumulation was observed. However, the VT(-) strain had no significant effect on intracellular c-AMP and Ca2+. CONCLUSIONS: The VT(+) strain of H. pylori has an inhibitory effect on gastric acid secretion, whereas the VT(-) strain does not. This inhibitory effect was not associated with the response of second messengers. It is speculated that VT produced by H. pylori has a direct action on H(+)-K+ adenosine triphosphatase in parietal cells.

Animals↗

Recombinant human growth/differentiation factor 5 stimulates mesenchyme aggregation and chondrogenesis responsible for the skeletal development of limbs.

We have expressed and biologically characterized recombinant human growth/differentiation factor 5 (huGDF5). This protein is composed of a mature homodimer consisting of 15 kD subunits. Using recombinant expressed protein, we have demonstrated that huGDF5 in vitro stimulated mesenchyme aggregation and chondrogenesis in rat limb bud cells. In vivo, partially purified huGDF5 induced cartilage and bone formation in muscular tissues of rodents. However, in contrast to the effects of other BMPs, as for example BMP-2, the osteoblastic MC3T3-E1 cells did not respond to huGDF5 as measured by alkaline phosphatase activity. These results suggest that the action of GDF5 may be relatively specific for chondrogenesis during the entire process of the endochondral bone formation. GDF5 may control the morphogenesis of cartilaginous tissue, including joints, in the skeletal development of limbs.

Alkaline Phosphatase↗

[Highly effective preoperative intraarterial infusion chemotherapy with CDDP for progressive uterine corpus cancer with a Sister Mary Joseph's nodule].

A 57-year-old female patient complained of atypical genital bleeding and a noxious emanation from her navel. A histological examination of the uterine body and the navel area confirmed a diagnosis of adenocarcinoma. We diagnosed it as IVb stage of uterine corpus cancer with a Sister Mary Joseph's nodule. We selectively administered intraarterial injection chemotherapy (Cisplatin 120 mg, Pirarubicin 40 mg) in the uterus and navel area (three times, once every three weeks) prior to surgery. The isolated uterus showed that the cancerous tissue had been eradicated, and we judged the cancer to be grade 3 following histopathological effective grading standards. The metastasis exhibited extreme shrinkage, but affirmed changes in the tumor quality. Currently, the patient is receiving maintenance therapy of 600 mg of Hysron H, and 600 mg of UFT. There are no indications of recurrence, and the patient is progressing well.

Abdominal Neoplasms↗

[A 78-year-old man with young onset parkinsonism and sudden death].

We report a right-handed 78-year-old man with early onset parkinsonism. The patient had an onset of micrographia at 23 years of the age in 1939. Seven years later he started to drag his right foot, and at 38 years of age, he walked with small steps with festination. Tremor was also present in his right hand. His daily life was independent as a otorhinolaryngologist. He visited our clinic on March 24, 1977 when he was mentally sound and showed mild parkinsonism consisting of masked face, stooped posture, small step gait, bradykinesia, and right side dominant rigidity and tremor. He showed good response to trihexyphenidyl and amantadine HCl. Two month later, he developed dyskinesia and some worsening of parkinsonism, and was admitted to our hospital for the first time. He was treated with 400 to 600 mg/day of levodopa/ carbidopa. He showed marked improvement, however, dyskinesia remained in his mouth. He was doing well until 77 years of age (June of 1993) when he developed hallucination and motor fluctuations. He was admitted again to our hospital on June 22, 1993. On admission, he was alert and appeared mentally sound. However, Hasegawa dementia scale was 18/30. Upward gaze was slightly restricted (3/5). Voice was somewhat small but no masking was noted. His posture was stooped and the gait was of small step. Dyskinesia was noted during walk. No rigidity nor tremor was noted. Deep tendon reflexes were lost but no sensory loss or motor weakness was noted. Routine laboratory studies were unremarkable. A cranial CT scan revealed only mild to moderate cortical atrophy. Motor and sensory conduction velocities were within normal limits, however, motor action potentials could not be obtained with stimulation to the right common peroneal nerve. He was treated with 600 mg/day of levodopa with carbidopa, 100 mg of amantadine HCl, 300 mg of Dops, and 25 mg of tiapride. He continued to show motor fluctuations, and was discharged on July 23, 1993. Since then his motor functions had become progressively worse with frequent falls, but he was still able to walk without support. On October 3 of 1994, he went to bed as usual. On the next morning, he was found dead in his bed at 9: 30. The patient was discussed in neurological CPC, and the chief discussant arrived at the conclusion that the patient had young-onset Parkinson's disease with Lewy bodies in the substantia nigra. Opinions were divided between Parkinson's disease and Lewy body negative young onset parkinsonism. Postmortem examination revealed obstruction of the trachea by aspirated foods, and the cause of death appeared to have been suffocation by the foods. Macroscopically, the external appearance of the brain was unremarkable except for slight frontal atrophy. The substantia nigra showed depigmentation in the lateral part, but the pigmentation of the medial part was well preserved. Upon histologic examination, the number of pigmented neurons in the dorsomedial part was well preserved. In the lateral part, pigmented neurons were well preserved in the dorsal area, however, in the ventral area, only non-pigmented neurons were seen; they appeared to be neurons in the pars reticulata. No gliosis was seen in any of the nigral areas. No Lewy bodies were seen in the remaining neurons. So-called immature neurons with rounded shape without neuromelanin could not be detected. The locus coeruleus neurons were well preserved. The putamen and the other basal ganglia structures were also intact. Slight myelin pallor was noted in the subcortical white matter, however, otherwise cerebral cortices were normal. The histology of this patient is unique in that only the ventrolateral part of the substantia nigra showed abnormal finding consisting of lack of pigmented neurons without gliosis. It is not clear whether the nigral change represents degeneration or a congenital "hypoplasia'. To our knowledge, such a unique pathology of the substantia nigra has not been reported in the literature. Our patient ma

Age of Onset↗

Hypergammaglobulinaemic purpura of Waldenström and Ro/SSA autoantibodies.

Seven out of nine patients (78%), seen over a 13-year period with hypergammaglobulinaemic purpura of Waldenström were found to have antibodies to Ro/SSA. Over this period we saw 175 patients who had antibodies to Ro/SSA. In six of the seven patients, associated diseases were recognized. Five had Sjögren's syndrome, and one had systemic lupus erythematosus with Sjögren's syndrome and thyroiditis (and died 19 years after initial presentation from cerebral infarction). Screening for antibodies to Ro/SSA is important in the diagnosis of patients with hypergamma-globulinaemic purpura, and is helpful in predicting prognosis.

Adult↗