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Biomedical subjects

M Fujii

Publications and source records attributed to M Fujii.

At least 19 recordsLinked to original sources

Polyclonal activation of human lymphocytes and induction of cytotoxic lymphocytes by streptococcal preparations.

Polyclonal activation of human peripheral blood lymphocytes (PBLs) in vitro by preparations of Streptococcus pyogenes Su strain (OK-432) and other heat-killed strains was investigated. The streptococcal preparations tested induce a proliferative response of PBLs via interleukin-2 (IL-2)-independent pathways. The proliferative response is accompanied by the generation of lymphoblastic cells (LBCs), which consist of heterologous lymphocyte populations: CD4+ helper type of T cells, and CD4-CD8- double-negative (DN) lymphocytes, including both CD3+ TcR gamma + T cells and CD2+CD3- immature type of T or non-T cell type of lymphocytes. Almost all the LBCs express Leu19, TfR (transferrin receptor), LFA-1 and CD38 (OKT10) antigens, which are expressed on activated T cells, NK cells and some other lymphocytes. The proliferative response of human PBLs is also accompanied by the generation of potent cytotoxic activity against NK-sensitive and -resistant targets. C-dependent cytolysis and cell sorting experiments of OK-432-activated LBCs revealed that both CD3+ and CD3- types of CD4-CD8- DN lymphocytes, but not CD4+ helper T cells, may be major populations responsible for the cytotoxicity induced. On the other hand, CD4-CD8- T cells may be required for the proliferation of PBLs and generation of cytotoxic effector cells. These results suggest that the OK-432 and other streptococcal preparations stimulate the human PBLs in vitro to induce the proliferation/activation of CD4+ T cells, mediating the following generation of DN cytotoxic effector lymphocytes.

DNA Replication

Changes in the markers related to collagen synthesis in the liver of chronically alcohol treated rats.

In order to clarify the roles of Ito cells in the development of alcoholic fibrosis, markers related to collagen synthesis in the liver were analyzed in chronically alcohol treated rats. The livers were obtained from rats fed a diet containing alcohol (alcohol group) and those fed a control diet (control group) for 4 weeks. Prolyl hydroxylase (PH) activity in the whole liver tissue did not differ in the alcohol and control groups. However, the activity in the isolated Ito cells was significantly higher in the alcohol group than in the control group. Immunoreactive PH beta-subunit contents in the liver and serum were significantly higher in the alcohol group than in the control group. Hydroxyproline contents in the liver did not differ in either groups. Immunohistochemically, type IV collagen and laminin were clearly stained along with the sinusoid in the livers of the alcohol group. However, the staining reactions were very weak in the control group. Staining reactions to types I and III collagen were very weak or almost absent in the livers of both groups. Desmin-positive cells, along with the sinusoid, increased significantly in the alcohol group, especially at the centrilobular area, suggesting that the number of Ito cell increase in the centrilobular areas of the alcohol treated rats. These results suggest that type IV collagen and laminin synthesis increase in the Ito cells of chronically alcohol treated rats, although clear evidence of hepatic fibrosis was not obtained. This increase may be related to capillarization of the sinusoids and finally to the development of perisinusoidal fibrosis in alcoholics.

Animals

Time trends of HBsAg prevalence among blood donors in Fukuoka, Japan.

We examined time trends of the prevalence of hepatitis B surface antigen (HBsAg) among blood donors at the Fukuoka Red Cross Blood Center, Japan, during 1977-88. As was expected, a marked but artificial decrease in the HBsAg prevalence attributable to a notification program was detected. The seropositivities among males were uniformly higher than those among females. About 1% absolute rate decrease (approximately 50% relative rate reduction) was found among young donors aged 16-19 in seven years before the notification schedule. An age effect closely related to self-selection due to chronic hepatitis B virus (HBV) infection was demonstrated in the declining trends according to the advance of age. A remarkable birth cohort effect was also observed for both sexes. These data undoubtedly indicate that there were medical/iatrogenic factors as well as natural (sanitary/socioeconomic/nutritional) factors causing the reduction of chronic HBV infection.

Adolescent

Preliminary evidence for a postsynaptic action of beta-bungarotoxin in mammalian skeletal muscle.

Two hours after treatment with beta-bungarotoxin (0.34-0.4 microM), when there was complete neuromuscular block, the peak contracture response to 50 microM succinylcholine was significantly reduced by about 35% in the mouse phrenic nerve-diaphragm preparation. Additionally, significant phospholipase A2 activity was detected on primary cell cultures from skeletal muscle which were incubated for 2 hr with concentrations of beta-bungarotoxin greater than or equal to 0.1 microM. Thus, beta-bungarotoxin appears to have pharmacologically and biochemically detectable postsynaptic actions in mammalian muscle systems.

Animals

Axons from the olfactory bulb transplanted into the cerebellum form synapses with dendrites in the granular layer, as demonstrated by mouse allelic form of Thy-1 and electron microscopy.

Transplant-to-host axon projection and synapse formation from the olfactory bulb (OB) transplant to the host cerebellum were studied using the mouse allelic form of Thy-1 (AKR strain of Thy-1.1 was used as host and BALB/c strain of Thy-1.2 as graft). Thy-1.2 immunohistochemical and ultrastructural examination showed that numerous OB axons elongate into the cerebellar granular layer and form asymmetrical synapses there with dendrites of host origin (perhaps of the host granule neuron). Factors which support this mismatched synapse formation are discussed.

Animals

Interaction of HTLV-1 Tax1 with p67SRF causes the aberrant induction of cellular immediate early genes through CArG boxes.

Tax1 of human T-cell leukemia virus type 1 (HTLV-1) is a transcriptional activator for viral gene expression and is also a transforming protein through inducing the expression of several cellular genes under the control of mitogenic signals. We identified the CArG boxes as a Tax1-responsive cis-acting element for the cellular immediate early genes c-fos, egr-1, and egr-2. Using a chimeric protein consisting of the CArG-binding factor p67SRF and the heterologous DNA-binding domain of a yeast transcription factor GAL4, we demonstrated that Tax1 activates the transcriptional activity of p67SRF through the GAL4-binding site. The carboxy-terminal half of p67SRF, which lacks domains for DNA-binding, dimerization, and ternary complex formation with p62TCF, was sufficient for the activation by Tax1. Tax1 produced in Escherichia coli bound p67SRF in vitro. The complex formation in vivo was also indicated by the finding that the acidic activation domain of VP16, by fusion to p67SRF, can complement the transcriptional activation function of a mutant Tax1 in trans. Thus, Tax1 activates CArG-mediated transcription without mitogenic signals through interaction with a CArG-binding factor, p67SRF. This must be one of the primary steps by which Tax1 causes aberration in growth control of the infected cells.

Base Sequence

Marked eosinophilia induced by nafamostat mesilate, an anticoagulant in a hemodialysis patient.

A 61-year-old Japanese female on hemodialysis developed marked eosinophilia induced by nafamostat mesilate as an anticoagulant for hemodialysis. This is the first case of hypereosinophilic syndrome induced by nafamostat mesilate in a hemodialysis patient. The elevated eosinophil counts (51,900/mm3) are the highest for hemodialysis-associated eosinophilia. This eosinophilia was eliminated after cessation of nafamostat mesilate. We confirmed that the cause of this eosinophilia was nafamostat mesilate by using the challenge test.

Anticoagulants

Effect of hypertension and hypertrophy on coronary microvascular pressure.

We tested the hypothesis that transmural differences in coronary microvascular pressures may be greater in the setting of hypertension and left ventricular hypertrophy. Epicardial and endocardial microvascular pressures were measured in isolated lidocaine-arrested hearts during adenosine vasodilation. In both normotensive (n = 19) and hypertensive (one clip, one kidney, n = 10) dogs, microvascular pressures in endocardial arterioles at 60, 70, 80, 90, and 100 mm Hg of left main coronary perfusion pressures were lower than in epicardial arterioles (p less than 0.05 at all perfusion pressures). The pressures in epicardial arterioles as a percentage of the left main coronary perfusion pressure were similar in normotensive versus hypertensive hearts at all perfusion pressures. In contrast, the pressures in endocardium at 90 and 100 mm Hg of perfusion pressure were significantly (p less than 0.05) lower in dogs with hypertension and hypertrophy than in the controls (41 +/- 4 versus 50 +/- 2 and 40 +/- 4 versus 50 +/- 3 mm Hg at 90 and 100 mm Hg of perfusion pressure, respectively). Thus, there is a greater transmural resistance to microvascular perfusion in hearts with myocardial hypertrophy secondary to hypertension. This is likely due to differences in the vascular anatomy, secondary to hypertension and hypertrophy, and may contribute to vulnerabilities in subendocardial ischemia encountered in this condition.

Animals

Effect of pH and guanidine hydrochloride on the conformation of 57 kDa rat liver nuclear thyroid hormone binding protein measured by fluorescence.

The denaturation of the 57 kilodalton (kDa) rat liver nuclear thyroid hormone binding protein (NTHB) by pH and guanidine hydrochloride (GdnHCl) has been investigated with the fluorescence method. The acid and alkaline fluorescence quenching suggests that the structure of NTHB is invariant in the relatively narrow pH region of approximately pH 7-9. A cooperative conformational transition occurred in GdnHCl concentrations of 1.5-2.5 m. The apparent free energy of unfolding of NTHB, delta G(appH2O) was evaluated as 6.31 (+/- 0.12) kcal.mol-1 at pH 7.7, 25 degrees C.

Animals

Lysinuric protein intolerance presenting deficiency of argininosuccinate synthetase.

A 35-yr-old woman, who suffered from relapsing coma with hyperammonemia for 17 yr, was diagnosed to have lysinuric protein intolerance (LPI). Increased urinary dibasic amino acids (lysine, arginine and ornithine) and impaired absorption of orally administered lysine and arginine proved the defects of renal tubular and intestinal transport of dibasic amino acids. These defects are the primary cause of impaired urea cycle metabolism in LPI. Further, the level of argininosuccinate synthetase (ASS), a urea cycle enzyme, was analyzed and it was found to be below the normal level. This is the second reported case of LPI presenting ASS deficiency.

Adult

[A phase II clinical study of cis-diammine glycolato platinum, 254-S, for primary lung cancer].

A phase II clinical study of 254-S, a new anticancer platinum complex, for primary lung cancer was conducted by the 254-S Lung Cancer Study Group consisting of 15 institutions nation-wide. Considering the results of the phase I clinical study, 254-S was administered at 100 mg/m2 by intravenous drip infusion and this administration was repeated at least 2 times at 4-week intervals. Of 75 patients registered, 61 patients consisting of 22 with small cell lung cancer (SCLC) and 39 with non-small cell lung cancer (NSCLC) were evaluable for complete tumor response. Partial response (PR) was obtained in 17 patients, for a 27.9% response rate. The response rate for SCLC was 40.9% (9 PR in 22 patients) and that for NSCLC was 20.5% (8 PR in 39 patients). In SCLC patients with no prior chemotherapy, a 50.0% (5 PR in 10 patients) response rate was obtained. In those with prior chemotherapy, the response rate was 33.3% (4 PR in 12 patients). In NSCLC patients with no prior chemotherapy, a 22.6% (7 PR in 31 patients) response rate was obtained. In hose with prior chemotherapy, the response rate was 12.5% (1 PR in 8 patients). Major toxic effects observed were hematotoxicity such as thrombocytopenia and leukopenia, and gastrointestinal toxicity such as nausea, vomiting and anorexia. Nephrotoxicity observed was mild and infrequent in spite of the low-volume hydration performed. Based on these results, it was concluded that 254-S is a useful anticancer agent for the treatment of primary lung cancer.

Adult

[Inhibitory effect of somatostatin analog, SMS 201-995, on exocrine secretion from isolated rat pancreatic acini].

In vitro effect of somatostatin analog, SMS 201-995 (SMS), on pancreatic exocrine secretion was investigated using isolated rat pancreatic acini. SMS had no effect on basal, cholecystokinin octapeptide (CCK-8)- or secretin-stimulated amylase release. SMS inhibited pancreatic amylase release in response to simultaneous stimulation with secretin and CCK-8 in a dose-dependent manner. Significant inhibition was observed with 10 nM SMS and maximal inhibition with 0.1-1 microM SMS. Amylase release in response to the combination of 100 pM CCK-8, 1 nM secretin and 0.1-1 microM SMS was similar to that to 100 pM CCK-8 alone. Secretin significantly increased acinar cell cAMP content. SMS partially inhibited an increase in cAMP content induced by secretin. The present study has demonstrated, therefore, that SMS directly inhibits the potentiating effect of secretin on exocrine secretion in part by inhibiting an increase in secretin-induced cAMP accumulation in rat pancreatic acinar cells.

Amylases

[Clinical evaluation of intra-arterial methotrexate, vinblastine, doxorubicin and cis-platinum for bladder cancer].

Chemotherapy regimens including Methotrexate, Vinblastine. Doxorubicin and Cis-platinum (M-VAC) have shown objective responses in more than 50% of uroepithelial tumors. And intra-arterial chemotherapy can theoretically increase the drug concentration delivered to the tumor with maximum efficacy and less toxicity. In this report we review our experience at Matsuyama Red Cross Hospital between September 1987 and February 1991 using intra-arterial M-VAC in 21 evaluable patients with bladder cancer. Response was observed in 62% of the treated patients, two with complete remission and eleven with partial remission. WBC nadir and platelet nadir were mild to moderate. Other adverse effects such as mucositis, hair loss and creatinine elevation were seen in a small number of patients. Intra-arterial M-VAC can be one of the most useful forms of chemotherapy for patients with bladder cancer.

Adult

[Clinical examination of acetated Ringer solution in patients with normal liver function and those with liver dysfunction].

Acetated Ringer solution (AR) was studied clinically to find its usefulness in patients with liver dysfunction compared with lactated Ringer solution (LR). The thirty-eight patients scheduled to be operated were divided into four groups (Group I: with normal liver function and AR infused, Group II: with normal liver function and LR infused, Group III: with liver dysfunction and AR infused, Group IV: with liver dysfunction and LR infused). AR or LR was administered to each group at a speed of 10 ml.kg-1.h-1, and we investigated the differences of these four groups clinically. L-lactic acid increased significantly in all groups after administration of AR or LR. D-lactic acid increased in LR groups, and acetic acid increased in AR groups. However, the other parameters, including the acid-base balance, electrolytes and liver function, showed no significant changes in any group. Therefore the status of liver dysfunction did not affect the metabolism of lactic acid in this study. These findings indicate that as an intraoperative fluid, AR is just as useful as LR. However, there was no significant difference between the data of AR groups compared with those of LR groups. In conclusion, AR is not necessarily a better fluid compared with LR as an intraoperative fluid in patients with liver dysfunction.

Adult

[A case of hematuria associated with cefem group antibiotics].

The patient was a 76-year-old male with disturbance of consciousness due to cerebral infarction. He was found lying in his garden on July 30, 1990 and was immediately hospitalized. Central venous alimentation was started on the same day, because the patient was incapable of oral nutritional intake. Aspiration pneumonia developed on August 3. As Pseudomonas aeruginosa and Candida were detected by sputum cultures on August 20, antibiotics were changed to latamoxef (LMOX), 6 g/day, tobramycin, 180 mg/day, and fluconazole, 200 mg/day, from August 30. Macroscopic hematuria was noted after exchange of the urethral catheter. Hematuria gradually worsened, bladder tamponade occurred, and anemia had exacerbated with Hb decreasing from 13.4 to 8.7 g/dl and Hct from 39.1 to 26% on September 14, when the patient was referred to our department. Corresponding marked increases were observed in PT from 11.5 to 50.1 seconds and in APTT from 33.7 to 107.6 seconds. As the hematuria was suspected to be due to vitamin K deficiency hypoprothrombinemia induced by LMOX, its administration was discontinued on the day of the referral. Hematuria was alleviated from the next day, and PT normalized to 12.1 seconds and APTT to 36.6 seconds 3 days after discontinuation. The administration of vitamin K was started on this day, and hematuria disappeared 7 days after discontinuation of LMOX administration.

Aged