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Biomedical subjects

T Tsuda

Publications and source records attributed to T Tsuda.

At least 775 records · Page 43Linked to original sources

Inhibitory effect of peony root extract on pentylenetetrazol-induced EEG power spectrum changes and extracellular calcium concentration changes in rat cerebral cortex.

To elucidate the mechanism of anticonvulsant action of peony root and to determine the relative contributions of pure component substances, the water, water/acetone and methanol extracts of peony roots, paeoniflorin, albiflorin and pentagalloylglucose were studied in rats using the EEG power spectrum changes induced by pentylenetetrazol administration and the extracellular calcium and potassium concentration changes related to seizure activity. The water extract of peony roots, albiflorin and pentagalloylglucose given orally completely inhibited the EEG power spectrum changes as well as the extracellular calcium and potassium concentration changes related to seizure activity. The water/acetone and methanol extracts and paeoniflorin were relatively less potent. These findings suggested that the anticonvulsant action of peony roots is due primarily to albiflorin and the gallotannin fraction. Albiflorin and pentagalloylglucose appear to manifest their anticonvulsant action due to inhibition of the seizure-related decrease of extracellular calcium and consequent intracellular calcium increase.

Animals↗

Two novel mutations in a Japanese patient with the late-infantile form of metachromatic leukodystrophy.

Two novel mutations in the arylsulfatase A (ASA) gene from a Japanese patient with the late-infantile form of metachromatic leukodystrophy (MLD) were identified. One mutation was a G to C transversion at nucleotide 608 of the ASA gene (designated 608C) located at the 3' end of exon 2, which resulted in an amino acid substitution of Gln 153 to His. Although the 608 mutation resulted in a change in the exon-intron boundary consensus sequence, analysis of cDNA from the patient did not reveal the presence of aberrant splicing. The second mutation, a G to T transversion at nucleotide 1572 in exon 5 (designated 1572T), resulted in an amino acid substitution of Gly 308 to Val. This could potentially result in a conformational change in ASA protein structure. The patient was heterozygous for these two new mutations which were not present in 18 Japanese MLD alleles examined. A transient expression study in COS-1 cells showed no residual activity in either mutation. These results indicate that the 608C and 1572T mutations are responsible for the occurrence of the late-infantile form of MLD.

Cerebroside-Sulfatase↗

High-resolution computed tomography of Japanese summer-type hypersensitivity pneumonitis.

The high-resolution computed tomographic (CT) manifestations of Japanese summer-type hypersensitivity pneumonitis in eight patients were correlated with those of their chest radiography and with their histological findings. Histologically proven small granulomas were clearly demonstrated on CT as miliary opacities in five patients whose chest radiographic findings were normal. In two patients, these abnormalities were observed both by CT and chest radiography. High-resolution CT provides detailed morphological information about the lung parenchyma; it is an excellent means of following the clinical courses of hypersensitivity pneumonitis. CT is particularly useful for detecting persistent granulomas when symptoms subside and chest radiography becomes normal or nearly so.

Adult↗

No relationship between schizophrenic birth and influenza epidemics in Japan.

The finding that influenza epidemics are associated with an increased risk of adult schizophrenia has been controversial. Data was obtained from Japan's governmental statistics, the Patient Survey. Index years were defined as 1957/1958, 1962, and 1965, and comparison years were defined 2 years before and 2 years after the index year. Subjects were patients with schizophrenia who were born in the index years of influenza epidemics. Periods 5 months after the influenza epidemics were defined as exposed months. Proportions of patients born during the exposed period in the index years were compared with those of patients born in the corresponding months in the comparison years. The proportions of patients born in the exposed months in the index years were not significantly different from those born in the corresponding months in the comparison years, with odds ratios around 1 in the whole country, the Kanto area, and the Shikoku/Kyushu area where a remarkable influenza epidemic was observed in 1957. No difference was observed in analyses stratified by sex. In Japan, there was no relationship between influenza epidemics and schizophrenic birth.

Adult↗

Local spread of HDV infection transiently occurring in Japan.

Hepatitis B virus (HBV) carriers and patients with acute hepatitis B living in the Kamigoto islands, a part of Japan with a high incidence of HBV carriage, were retrospectively tested for serum anti-hepatitis D virus (anti-HDV) and they were compared with the inhabitants of Oita City (an area with an average HBV carriage rate). The prevalence of anti-HDV in HBV-infected individuals was 8.3% (42/507) in Kamigoto and 0% (0/101) in Oita City. With one exception, all of the positive serum samples in Kamigoto were collected before 1986, and the mean age of the positive individuals was significantly younger than that of the negative individuals (P < 0.005). Among the 42 anti-HDV-positive patients, nine (21%) had definite liver disease. The route of infection was uncertain in most cases (i.e. sporadic), but two pairs of mothers and children were detected. Although the prevalence of anti-HDV positivity in Japan has been reported to be very low (about 1% or less), the present investigation showed that the local spread of HDV infection in Kamigoto occurred on a minor scale up to 1986. The infections presumably resulted from the closed environment and the high incidence of HBV carriage in these islands. Accordingly, there could be a considerable risk of the outbreak of HDV infection in the future under similar conditions, even in countries where the disease has never been detected previously.

Adolescent↗

Antifungal activity of D0870 against murine infections and its mechanism of action.

We evaluated the in vivo antifungal activity of D0870, a new triazole agent, in comparison with that of fluconazole in two murine infection models. The therapeutic mechanism of D0870 in these models was also investigated in vitro. In a pulmonary infection with Cryptococcus neoformans in immunosuppressed mice, D0870 at 10-100 mg/kg significantly reduced viable counts in lungs infected with C. neoformans to 1/10-1,000 of the control on day 14, whereas fluconazole, only at 100 mg/kg, showed a significant reduction in the viable counts and was less active than D0870 at 10 mg/kg. D0870 at 3-30 mg/kg also showed excellent therapeutic efficacy against murine vaginal candidiasis and completely eliminated viable yeasts from the vaginal cavity, whereas positive cultures were found in 20% of mice treated with 30 mg fluconazole/kg. At pH 7 and 37 degrees C, D0870 was active against C. neoformans in synthetic amino acid medium, fungal or sabouraud dextrose broth. By reducing the pH of the medium, the in vitro anticryptococcal activity of D0870 was enhanced and found to be fungicidal under all culture conditions at pH 4-5. D0870 also showed a stronger fungistatic activity against Candida albicans at pH 4. These results suggest that D0870 may exhibit a potent activity against these two murine infections by exerting an excellent antifungal activity at the infection sites thought to be acidic environments.

Amino Acids↗

Angiotensin-II-and endothelin-induced protein phosphorylation in cultured vascular smooth muscle cells.

In cultured vascular smooth muscle cells, angiotensin II and endothelin stimulate a variety of intracellular signals, including generation of inositol trisphosphate and diacylglycerol, mobilization of intracellular calcium, and activation of protein kinase C. These latter two events have been shown to mediate the phosphorylation of numerous proteins, but these substrates and the specific pathways mediating their phosphorylation have not been identified in vascular smooth muscle. Angiotensin II (100 nM, 10 min) induced a characteristic pattern of protein phosphorylation, which included the phosphorylation of many proteins, ranging in molecular mass from 20 to 76 kD. Three of these proteins have been identified as vimentin (M(r) 57,000), a specific protein kinase C substrate (M(r) 76,000) and the myosin light chain (M(r) 20,000). The 76-kD protein was one of the most highly phosphorylated proteins after agonist treatment. Endothelin-1 produced an identical pattern of phosphorylation. Five of these substrates were also phosphorylated by phorbol-12-myristate-13-acetate, and 5 were also phosphorylated after treatment with ionomycin. In general, the protein-kinase-C-dependent phosphorylations were sustained, while those mediated by calcium were rapid. Since these experiments were performed in cultured, phenotypically modulated cells stimulated with agents that promote cellular hypertrophy or hyperplasia, this pattern of phosphorylation may be representative of that seen during the growth response.

Angiotensin II↗

Growth of human gastric carcinomas and expression of epidermal growth factor, transforming growth factor-alpha, epidermal growth factor receptor and p185c-erbB-2.

We examined the expression of epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), epidermal growth factor receptor (EGFR) and p185c-erbB-2 immunohistochemically and correlated the expression with growth in 66 cases of human gastric carcinoma. To evaluate growth, we used the bromodeoxyuridine (BrdU) labeling index in 51 cases and the radiographic growth rate in 15 cases. Expression of EGF was detected in 41 cases (62.1%), TGF-alpha in 42 cases (63.6%), EGFR in 34 cases (51.5%), and p185c-erbB-2 in 37 cases (56.1%). The BrdU labeling index ranged from 1.5 to 32.0%. The BrdU labeling index was higher in tumors that coexpressed EGF and EGFR or TGF-alpha and EGFR than in tumors without expression or in tumors that expressed growth factors or the receptors (p < 0.01). The BrdU labeling index was also significantly higher in tumors with the expression of EGFR and/or p185c-erbB-2. Tumors with simultaneous expression of EGF, TGF-alpha, EGFR and p185c-erbB-2 had an association with a high BrdU labeling index. Moreover, all of these growth factors and receptors were expressed simultaneously in gastric carcinomas with rapid growth. These results suggest that the expressions of EGF, TGF-alpha, EGFR and p185c-erbB-2 are closely related and then play an important role in the growth of human gastric carcinomas.

Adult↗

Effects of bifemelane on calcium and magnesium deposition in the central nervous system tissues of rats maintained on low-calcium diets.

The effects of bifemelane [4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride] on the deposition of calcium and magnesium in central nervous system (CNS) tissues, heart, liver, kidney, muscle, abdominal aorta and bones were studied in rats maintained on standard and low-calcium diets. Rats were maintained for 90 days on the following diets: standard calcium (12.5 g/kg diet); standard with 100 mg/kg bifemelane; low-calcium (30 mg/kg diet); and low-calcium with bifemelane. The presence of bifemelane did not affect blood chemistry, but the magnesium concentration in the cerebellum was significantly (P less than 0.05) higher in rats receiving standard diet after bifemelane treatment. Magnesium concentrations in the pons, cerebellum, spinal cord, heart, liver and femur of bifemelane-treated rats fed low-calcium diets were significantly (P less than 0.05) higher compared with the corresponding controls, whereas the calcium concentration in the liver was significantly (P less than 0.05) lower. In general, bifemelane tended to decrease calcium deposition in the CNS and soft tissues of rats fed standard or low-calcium diets. Bifemelane may activate cerebral metabolism and maintain magnesium concentrations in the CNS and soft tissues, and be implicated in metal metabolism in rats fed low-calcium diets.

Animals↗

Isolated factor VII deficiency diagnosed after a life-threatening brain haemorrhage.

A 65-year-old man was admitted to another hospital with a life-threatening brain haemorrhage, and laboratory examinations on admission revealed prolonged prothrombin time with normal activated partial thromboplastin time. To establish the cause of his abnormal coagulation, he was referred to our clinic. Neither the patient nor his family had any previous history of bleeding symptoms. His liver function was within normal limits but coagulation tests showed increased plasma activities of factors II, VIII, IX, X, with reduced activities of factors V and VII. The activity of factor VII was less than 2% but no inhibitor of factor VII was detected in the plasma. We concluded that the patient had a rare congenital isolated factor VII deficiency although he had not shown earlier bleeding problems, presumably because of compensation for the factor VII deficiency by enhanced activities of components of the extrinsic coagulation pathway, factors II, VIII, IX and X.

Aged↗

The CAG regimen (low-dose cytarabine, aclarubicin hydrochloride and granulocyte colony-stimulating factor) for the treatment of elderly acute myelomonocytic leukaemia: a case study.

Elderly patients with acute myelomonocytic leukaemia (AMMoL) frequently have a poor quality of life after induction of remission using high-intensity treatment; we seek a more appropriate regimen for such patients. An 86-year-old man was hospitalized with a diagnosis of AMMoL (FAB classification M4), of abnormal karyotype, and complications of diabetes mellitus and complete right bundle branch block. He was treated with CAG therapy (cytarabine 10 mg/m2 subcutaneously every 12 h for 14 consecutive days; aclarubicin hydrochloride 10 mg/m2 per day, bolus intravenously for 4 consecutive days; granulocyte colony-stimulating factor 100 microg/day, subcutaneous injection for 14 consecutive days) every 3 months. White blood cell counts were at their lowest (around 600 - 800/microl) 12 days after the end of therapy, but returned to about 2000 - 2300/microl 30 days after stopping therapy. No symptoms of drug-related toxicity, except slight nausea, were found. Complete remission with a good quality of life was induced and lasted over 2 years suggesting that CAG therapy might prove effective in elderly patients with AMMoL.

Aclarubicin↗

Treatment of acute myeloblastic leukaemia in a patient with Bombay blood type: a case report.

A 62-year-old female was admitted to our hospital with suspected acute leukaemia and after investigation we diagnosed acute myeloblastic leukaemia (AML-M1). The patient's blood type was found to be the very rare Bombay type and surveillance of her relatives showed the same blood type in her male cousin on her mother's side. Alongside chemotherapy the patient received 4000 ml of frozen Bombay-type red cells, 1400 ml of concentrated red cells in manitol adenine phosphate solutions and 360 units of type O concentrated platelets without marked effects. The anti-H antibody was initially at 128 dilution but for unknown reasons increased to 2048 dilution after remission of AML-M1. About 3 months after hospitalization the patient died of Cryptococcus neoformans pneumonia despite strict precautions against infection. Although AML-M1 is a common adult leukaemia and is chemosensitive to anti-leukaemic drugs, neither AML-M1 in a patient with Bombay-type red cells nor its treatment with chemotherapy and transfusion with type Oh frozen red cells have previously been reported.

Antineoplastic Agents↗

A therapeutic strategy for isolated plasmacytoma of bone.

Two cases of solitary plasmacytoma of bone (SPB) were diagnosed. The first case was a 41-year-old woman, complaining of fatigue from her lumbar region to her legs. The second case was a 56-year-old man complaining of poor gait and severe lumbago with numbness in the toes of both feet. Magnetic resonance imaging showed the osteolytic lesion in the 12th thoracic bone in the first patient and around the 2nd, 3rd and 4th lumbar bones in the second patient. In both patients serum analysis revealed the monoclonal component of immunoglobulin G (IgG) protein with kappa-light chain, and considering this and other findings SPB was diagnosed. Both patients were first treated with irradiation around the involved bone and then with a course of chemotherapy. In the first patient the tumour region of the bone was surgically removed and replaced with a ceramic spacer. The symptoms of both patients were ameliorated, and the patients remained in good condition for around 3 years without conversion to multiple myeloma. In view of the overall effectiveness of treatments for SPB, our therapeutic strategy deserves careful evaluation.

Adult↗

Purpura due to aspirin-induced platelet dysfunction aggravated by drinking alcohol.

We report a rare case of prominent purpura induced by aspirin and enhanced by alcohol. A 44-year-old woman presented with a history of generalized purpura. She drank alcohol once or twice a week and regularly took an analgesic preparation, containing aspirin and acetaminophen, for alleviation of headaches. When purpura was evident the patient's liver function was within normal limits and her coagulation time was normal but her bleeding time was prolonged. Red blood cell, white blood cell and platelet counts were normal but a poor response to platelet agonists demonstrated platelet dysfunction. After stopping the analgesic and abstaining from alcohol for 5 days, platelet aggregation, in response to the agonists, returned to normal and purpura disappeared. When the patient took further doses of the analgesic preparation for 3 days for headache relief, but did not drink alcohol, platelet aggregation was again abnormal but purpura was only slight.

Adult↗

Autologous peripheral stem-cell transplantation after intensive chemotherapy in a case of CD30 (Ki-1)-positive anaplastic large-cell lymphoma.

Simultaneous treatment with peripheral blood stem-cell (PBSC) transplantation and intensive chemotherapy was evaluated in a case of non-Hodgkin's lymphoma (NHL) with poor prognosis. A 59-year-old male diagnosed with a high-grade, anaplastic large-cell (Ki-1) NHL, involving fractures in the left hip, underwent computed tomography and gallium scintigram surveillance. The patient received chemotherapy with epirubicin hydrochloride, cyclophosphamide, vincristine and prednisolone, and the fractured hip bone was repaired following the first course of chemotherapy. After the second and third courses of chemotherapy, PBSCs were harvested and cryopreserved. The patient then received a further course of chemotherapy and PBSC transplantation was conducted using infused cells consisting of 9.63 x 10(6)/kg CD34 cells and 2.24 x 10(5)/kg granulocyte macrophage colony-forming units. Recovery of platelet and white blood cell counts occurred 10 and 8 days, respectively, after PBSC infusion and the patient remains well.

Antineoplastic Combined Chemotherapy Protocols↗

Lymphocytic infiltrations in the lung of two autopsy cases with HTLV-I-associated myelopathy.

Pulmonary involvement in two autopsy cases with HTLV-I-associated myelopathy (HAM) was observed histopathologically and immunohistochemically. Case 1 was a 59-year-old woman who fell ill after having a blood transfusion, and died immediately of acute heart failure. Case 2, a 55-year-old man, died of pelvic tumor after a long period of steroid medication for the myelopathy. Histologically, in case 1, the submucosal stroma of bronchioles was thickened with T-lymphocyte infiltration. In addition, clusters of B-lymphocytes were aggregated beneath the epithelial layer of respiratory bronchiole; the alveolar septum was infiltrated with a few T-lymphocytes. Furthermore, many B-lymphocytes were aggregated in the submucosal stroma of large bronchi. On the other hand, obvious pathological changes were not seen in the lung tissues of case 2. The long period of steroid medication may account for the fewer findings in case 2. These results present the possibility that latent inflammatory changes develop in the lung of HAM patients, although clinical manifestations are not obvious, and that steroid therapy can modify those inflammatory changes.

Abdominal Neoplasms↗

In vitro angiotensin-converting enzyme and interleukin-1 production by epithelioid cells isolated from induced rabbit lung granuloma.

We attempted in this experiment to culture epithelioid cells isolated from granuloma induced in the lung of female rabbits that had been injected intravenously with Freund's complete adjuvant. The morphologic findings of isolated cells included abundant rough-surfaced endoplasmic reticulum, mitochondria, Golgi complexes, electron-dense lysosomes, and numerous cytoplasmic processes on the cell surface. Enzymatically these cells were positive for acid alpha-naphthyl acetate and beta-galactosidase staining. These findings coincided with the expected morphologic and enzymatic characteristics of epithelioid cells examined in vivo. Cells isolated from this granuloma are thought to be more than 86% epithelioid cells. Additionally, 14.4 +/- 4.3% of the epithelioid cells showed phagocytosis of latex beads, low when compared with the 83.9 +/- 5.2% value of alveolar macrophages obtained from rabbits injected with adjuvant 4 weeks before sacrifice. The isolated epithelioid cells were incubated for 24 h without decrease in cell population. Their culture supernatants showed 1.86 +/- 0.38 units/ml of angiotensin-converting enzyme (ACE) activity, which was inhibited by cycloheximide. The culture supernatants also showed interleukin-1 (IL-1) activity levels of 6411 +/- 914 cpm without lipopolysaccharide (LPS) stimulation. This increased to 21,766 +/- 3026 cpm with LPS stimulation. In view of these results, we believe it is possible to incubate epithelioid cells for up to 24 h during which time they will produce ACE and IL-1 in the culture supernatants.

Animals↗