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Biomedical subjects

T Fukumoto

Publications and source records attributed to T Fukumoto.

At least 55 records · Page 3Linked to original sources
PubMed1998

Pretransplant virological markers hepatitis C virus genotype and viremia level are not helpful in predicting individual outcome after orthotopic liver transplantation.

BACKGROUND: Recurrence of hepatitis C viremia after orthotopic liver transplantation (OLT) is nearly universal, leading to variable outcome from no to severe recurrent disease. In the present study, the prognostic relevance of hepatitis C virus (HCV) genotypes and viremia for the development and severity of graft hepatitis was investigated. METHODS: A total of 79 patients with chronic hepatitis C who could be followed for 1 to 78 months (mean: 30 months) after OLT were included in this study. HCV RNA concentrations were measured before OLT, 1 month after OLT, as well as in the long-term follow-up after OLT in 54 of the 79 patients. RESULTS: Graft hepatitis could be documented in 40 of the 79 patients (51%), and 7 of them (9%) progressed to liver cirrhosis. More severe forms of graft hepatitis predominated in patients with subtype 1b infection, and all seven patients with progression to liver cirrhosis had subtype 1b (P=NS). Neither the pretransplant nor the posttransplant HCV RNA levels were significantly associated with the occurrence of graft hepatitis. However, there was a trend of more severe recurrent disease in subtype 1b-infected patients with high level viremia in the early course after OLT. CONCLUSIONS: Pretransplant HCV virological markers are not helpful to predict the outcome after OLT. However, it should be further investigated whether estimation of HCV genotype and viremia levels very early after OLT, i.e., within the first weeks, may be a better approach to recognize high-risk patients.

Adult↗
PubMed1998

Polymorphisms of HLA class II genes and autoimmune responses to Ro/SS-A-La/SS-B among Japanese subjects.

OBJECTIVE: To investigate HLA class II allele associations with autoantibody responses to Ro/SS-A and La/SS-B among Japanese subjects. METHODS: Haplotype and allele distributions, along with molecular polymorphisms, of HLA class II genes were analyzed by polymerase chain reaction-restriction fragment length polymorphism in 41 Japanese women with precipitating autoantibodies to Ro/SS-A and/or La/SS-B. RESULTS: Among women with both Ro/SS-A and La/SS-B antibodies, the HLA class II haplotype DRB1*08032/DQA1*0103/DQB1*0601 and DRB1*08032 allele showed significantly increased frequencies compared with patients with anti-Ro/SS-A alone or with normal controls. All women with both anti-Ro/SS-A and anti-La/SS-B, but not those with anti-Ro/SS-A alone, carried DRB1 alleles that shared the same amino acid residues at positions 14-31 and 71 of the hypervariable regions of the DRB1 chain. All anti-Ro/SS-A positive women carried 1 or 2 alleles of DQB1*06 and DQB1*03 subtypes that shared the same amino acid residues at positions 71-77 of the DQB1 chain. HLA class II allele distributions did not differ among 3 anti-Ro/SS-A positive groups with different disease expressions, i.e., patients with systemic lupus erythematosus, patients with primary Sjögren's syndrome, and women with no apparent symptoms of rheumatic disease. CONCLUSION: HLA class II allele distributions differ among anti-Ro/SS-A positive subjects according to the presence or absence of coexisting anti-La/SS-B antibodies, but not according to disease expression. Our findings suggest that different HLA class II molecules might control the development of anti-Ro/SS-A and/or anti-La/SS-B antibodies in the autoimmune response to the Ro/SS-A-La/SS-B complex.

Adolescent↗
PubMed1998

IL-8 is an essential mediator of the increased delayed-phase vascular permeability in LPS-induced rabbit pleurisy.

We investigated the involvement of IL-8 in the delayed vascular permeability (VP) in rabbit lipopolysaccharide (LPS)-pleurisy. Maximal level of interleukin-8 (IL-8) was detected in pleural fluid at 2 h after LPS injection and anti-IL-8 inhibited the delayed VP by 90%. Injection of homologous IL-8 induced VP, the time-course of which preceded that of LPS-induced delayed VP. Production of IL-8 in LPS-pleurisy was inhibited with anti-tumor necrosis factor alpha (TNF-alpha), whereas the production of TNF-alpha was not affected with anti-IL-8. Injection of IL-8 did not induce TNF-alpha production and anti-TNF-alpha had no effect on IL-8-induced VP. Injection of homologous TNF-alpha induced IL-8 production and VP, and TNF-alpha-induced delayed VP was blocked with anti-IL-8. These results indicate important roles of IL-8 in LPS-induced delayed VP and that TNF-alpha causes the delayed VP through the production of IL-8.

Animals↗
PubMed1998

Percutaneous isolated liver chemoperfusion for treatment of unresectable malignant liver tumors: technique, pharmacokinetics, clinical results.

We have developed a single-catheter technique for percutaneous isolated liver chemoperfusion (PILP) with hepatic venous isolation and charcoal hemoperfusion (HVI-CHP) for the treatment of malignant liver tumors. We report here the surgical technique, pharmacokinetics, and effectiveness of PILP in multiple advanced liver tumors. Twenty-eight patients with hepatocellular carcinoma (HCC) and 18 with metastatic liver tumors underwent a total of 61 PILPs with HVI-CHP. HVI-CHP was accomplished mainly by the single-catheter technique using a novel four-lumen, two-balloon catheter; it was used to isolate and capture total hepatic venous outflow and, at the same time, to direct the filtered blood to the right atrium. Under HVI-CHP, either doxorubicin 960-150 mg/m2) or cisplatin (150-200 mg/m2) was infused via the hepatic artery. The PILP was completed successfully in all 61 trials. Two of forty-six patients died early; one of necrotizing pancreatitis and the other of hepatic arterial thrombosis. Both deaths were related directly to the hepatic arterial catheter. Excluding these two deaths, the treatments were well tolerated. The major side effects were mild to moderate chemical hepatitis and reversible myelosuppression. Of the 27 evaluable HCC patients, 17 (63%) had an objective tumor response (5 complete and 12 partial responses). In 15 patients with colorectal hepatic metastases (CHM), 7 had a sharp decrease in serum carcinoembryonic antigen (CEA) levels (to < 50% of their pretreatment levels) after treatment. However, a single PILP had limited efficacy in terms of the durability of remission (< or = 6 months in most CHM patients, as assessed by CEA levels). These results indicate that PILP with HVI-CHP has high efficacy in most patients with multiple advanced liver tumors. In addition, the results suggest a role of multiple treatment courses of PILP in the induction of long-term remission, especially for patients responsive to the first treatment.

Antineoplastic Agents↗
PubMed1998

Activation of polymorphonuclear leukocytes in oleic acid-induced lung injury.

OBJECTIVE: Oleic acid (OA) can produce a lung injury similar to the adult respiratory distress syndrome (ARDS). Elastase and superoxides are thought to have an effect in ARDS. However, the effect that elastase and superoxide have in OA lung injury is unclear. To examine their involvement in OA lung injury, we tested the effects of methoxysuccinyl-alanyl-alanyl-prolyl-valyl chloromethyl ketone (MAAPVCK), an elastase inhibitor, and N-acetyl-L-cysteine (NAC), an active oxygen scavenger, on the increase in pulmonary vascular permeability caused by OA. We also examined whether OA stimulated elastase and/or superoxide release from polymorphonuclear leukocytes (PMNs). DESIGN: Prospective trial. SETTING: University laboratory. INTERVENTIONS: (1) Guinea pigs were anesthetized. MAAPVCK (2.5 mg/ kg) or NAC (150 mg/kg) was infused over OA (15 microl/kg) injection. Evans blue was used to measure vascular permeability. (2) PMNs were isolated from the blood of guinea pigs and rats. Elastase release was measured with MeO-Suc-Ala-Ala-Pro-Val-7-amino-4-methylcoumarin. Superoxide production was measured by the ferricytochrome c reduction method. MEASUREMENTS AND RESULTS: OA caused pulmonary hemorrhage and an increase in vascular permeability. MAAPVCK and NAC significantly attenuated the increase in vascular permeability in distal bronchus and trachea, respectively. OA induced superoxide production from PMNs in guinea pigs, but elastase release from PMNs was not detected. CONCLUSIONS: These results suggest that elastase and superoxide are involved in OA lung injury.

Acetylcysteine↗
PubMed1998

Diffusely infiltrative squamous cell carcinoma of the esophagus.

This study was designed to clarify the clinical and pathologic features of diffusely infiltrative squamous cell carcinoma of the esophagus. Diffusely infiltrative squamous cell carcinomas were classified grossly into two types, namely, scirrhous carcinoma and nonscirrhous carcinoma. There were seven patients with the former type and three with the latter type. Scirrhous-type carcinoma was associated with a prominently thickened esophageal wall with strictures, whereas nonscirrhous-type carcinoma demonstrated thickening of the esophageal wall without strictures. Microscopically, all patients had lymph node metastases and lymphatic invasion. Blood vessel invasion was found in seven patients and extranodal invasion was found in seven. The prognosis of patients with both types of carcinoma was extremely poor. Only two patients who underwent curative surgery as well as chemoradiotherapy survived for more than 1 year. Therefore, further morphological studies on the early stages of diffusely infiltrating esophageal carcinoma should be performed. New treatment strategies such as intensive preoperative chemoradiotherapy based on sensitivity tests in individual patients will be required for treating the advanced stages of this disease.

Aged↗
PubMed1998

Peptide mimics of the CTLA4-binding domain stimulate T-cell proliferation.

Phage library clones selected by a conformational epitope-recognizing and inhibitory monoclonal antibody may display moieties that mimic a receptor/ligand-like three-dimensional structure. This pseudoreceptor/ligand should be able to bind to natural ligand/receptor molecules. We tested this idea using anti-T cell costimulatory molecule antibodies and successfully isolated phage clones with costimulatory effects on T-cell proliferation. This strategy facilitates the designing of regulatory peptide molecules in the absence of precise information about the structure-function relationships in receptor/ligand interactions.

Abatacept↗
PubMed1998

Detection of lymph node metastasis using desmoglein 1 expression in superficial esophageal cancer in relation to the endoscopic mucosal resection.

Endoscopic mucosal resection (EMR) has recently been standardized for mucosal cancer of the esophagus. It may be hypothesized that EMR may be considered to be curative for superficial esophageal cancer (SEC), if the possibility of lymph node metastasis can be excluded beforehand. Ninety patients with p-T1 tumours who underwent esophagectomy were studied. Their primary lesions were stained with anti-Desmoglein 1 antigens using the ABC method. The p-T1 tumors were subdivided into three categories: carcinoma limited to the lamina propria mucosae (19 patients, SEC1), carcinoma invading the lamina muscularis mucosae or with invasion just into the submucosa (27 patients, SEC2), and carcinoma definitely invading the submucosa (44 patients, SEC3). Lymph node metastasis was not observed in the SEC1 patients but was observed in 19% of the SEC2 patients and 41% of the SEC3 patients. None of the SEC1 or SEC2 patients had lymph node metastasis when preserved Desmoglein 1 expression was obtained. The EMR appears to be appropriate therapy for SEC1. Our findings indicate that, for SEC2, preserved expression of Desmoglein 1 may be a helpful aid to exclude the possibility of lymph node metastases. Transthoracic esophagectomy with lymphadenectomy should be selected in the SEC3 patients.

Aged↗
PubMed1998

Induction of long-term remission in advanced hepatocellular carcinoma with percutaneous isolated liver chemoperfusion.

OBJECTIVE: The aim of this study was to report the long-term results of percutaneous isolated liver chemoperfusion with hepatic venous isolation and charcoal hemoperfusion (HVI-CHP) in patients with multiple advanced hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: The results of conventional chemotherapy including regional and systemic chemotherapy in patients with HCC remain dismal, and long-term survivors after treatment are rare among patients with multiple advanced HCC. In an effort to improve this situation, we previously developed a novel system of percutaneous isolated liver chemoperfusion with HVI-CHP. METHODS: Doxorubicin (60 to 150 mg/m2) was administered via the hepatic artery, under conditions of extracorporeal drug elimination by HVI-CHP in 28 consecutive patients with advanced HCC (39 total treatments). Hepatic venous isolation and charcoal hemoperfusion was accomplished mainly by the single catheter technique using a newly developed 4-lumen-balloon catheter, which was used to isolate and capture total hepatic venous outflow and, at the same time, to direct the filtered blood to the right atrium. RESULTS: Complete remission was achieved in five patients, of which four received repeated treatments (two or three times). Although 1 of 5 patients with complete remission died of pulmonary metastases at 8 months, the other 4 remain healthy and free of disease at 20, 24, 27, and 42 months after the first treatment. Partial responses were observed in 12 patients. Duration of response in responders (complete and partial) with repeated treatments was significantly longer than that with a single treatment (p = 0.01). The overall survival rate by the Kaplan-Meier method was 39.7% at 5 years. The treatments were well-tolerated, and the primary side effects were mild to moderate chemical hepatitis and reversible myelosuppression. CONCLUSIONS: The results suggest that percutaneous isolated liver chemoperfusion with HVI-CHP is an effective palliative treatment in the majority of patients and yields long-term complete remission in some patients with multiple advanced HCC.

Adult↗
PubMed1998

Primary Sjögren's syndrome followed by chronic myelogenous leukemia: a case report with a ten year history.

We describe a female patient with primary Sjögren's syndrome who subsequently developed chronic myelogenous leukemia. The patient received a bone marrow transplant (BMT) from a genotypically HLA-identical brother after pre-transplant preparation with busulfan and cyclophosphamide. Eighteen weeks later, cutaneous and mucosal chronic graft-versus-host disease developed, followed by death 11 months after transplantation. Anti-Ro/SS-A antibodies disappeared within 6 months post-BMT, but antinuclear antibodies remained positive through the post-transplant course.

Adult↗
PubMed1998

Clinical suppression of bradycardia dependent premature ventricular contractions by the potassium channel opener nicorandil.

OBJECTIVE: To assess the clinical antiarrhythmic effect of nicorandil, a potassium channel opener; on premature ventricular contractions. DESIGN AND PATIENTS: The effect of oral nicorandil (15 to 60 mg daily for four weeks) on premature ventricular contractions was investigated in 20 patients (11 female, nine male, mean (SD) age 63 (17) years) who underwent 24 hour ambulatory ECG. Patients were classified into two groups based on the relation between the frequency of premature ventricular contractions and heart rate: (1) those with a positive correlation (n = 9); and (2) those with a bidirectional correlation (n = 11), characterised by an increased frequency of premature contractions at low heart rates and a decreased frequency at high heart rates. RESULTS: Nicorandil reduced the frequency of premature ventricular contractions by 75% in five patients in group 2, but was not effective in any patient in group 1. The heart rate at which the frequency of premature ventricular contractions peaked was significantly lower in the five responders in group 2 than in the six non-responders (63.2 (3.7) v 76.3 (12.4) beats/min, p < 0.05). CONCLUSIONS: Nicorandil may suppress premature ventricular contractions when they occur mainly at a low heart rate.

Adult↗
PubMed1998

[Carotid blood flow volume measurement using an ultrasonic Doppler flowmeter--predictive diagnosis of ischemic cerebrovascular diseases].

BACKGROUND: It is difficult to predict ischemic cerebrovascular diseases by noninvasive methods before overt symptoms develop. Advanced carotid and cerebral atherosclerosis reduce common carotid blood flow volume due to increased resistance of peripheral circulation. According to a study in which clinical and pathological specimens were compared, the lower threshold for the flow volume in normal individuals has been confirmed to be 6.5 ml/s. We investigated the possibility that the development of ischemic cerebrovascular diseases can be predicted based on blood flow volume. METHOD: We conducted a retrospective study on 314 patients who were available for determination of common carotid blood flow volume with an ultrasonic quantitative flowmeter. RESULTS: Thirty-three patients developed ischemic cerebrovascular attacks during the observation period (onset group), while the remaining 281 did not develop attacks (non-onset group). The discriminating value for common carotid blood flow volume between the onset and non-onset groups was 6.8 ml/s. Based on an odds ratio of 6.7, it was concluded that a common carotid blood flow volume of less than 6.8 ml/s is highly likely to predict the onset of ischemic cerebrovascular accidents.

Aged↗
PubMed1998

Quality of life following esophagectomy with three-field lymphadenectomy for carcinoma, focusing on its relationship to vocal cord palsy.

To clarify the quality of life of patients who underwent esophagectomy for carcinoma by right thoracotomy, laparotomy and cervical anastomosis, 116 patients who were cancer free at the time of mailing a questionnaire were analyzed. A significant decrease in vital capacity for 3 years postoperatively, as well as in the percentage of ideal body weight, between 3 and 5 years were observed in 57 patients with three-field lymphadenectomy. Patients' quality of life undergoing three-field dissection was worse than those with less radical lymphadenectomy (59 cases) in terms of the performance status and difficulty in talking at 60 months or more postoperatively. Around 20% of all patients reported severe hoarseness due to permanent recurrent nerve paralysis, resulting in poor quantity of food intake at 24 months or less postoperatively and restricted daily activity and difficulty in talking at 60 months or more after the operation. When a patient suffers from vocal cord insufficiency caused by permanent paralysis of the recurrent nerve, early treatment before discharge from the hospital should be performed to improve the quality of life of such a patient.

Aged↗
PubMed1998

Bidirectional blockade of CD4 and major histocompatibility complex class II molecules: an effective immunosuppressive treatment in the mouse heart transplantation model.

BACKGROUND: Anti-CD4 monoclonal antibodies (mabs) are powerful immunosuppressive agents. However, in experimental models anti-CD4 treatment alone is not always completely effective. Anti-major histocompatibility complex (MHC) class II mabs may have a synergistic effect with anti-CD4 mab therapy by blocking the function of both antigen-presenting cells and T cells. METHODS: C3H/He mice (H-2k: I-Ak, I-Ek) received a vascularized cardiac graft from C57BL/10 (H-2b: I-Ab) or BALB/c (H-2d: I-Ad, I-Ed) mice and were treated with a depleting anti-CD4 or a depleting anti-MHC class II antibody either alone or in combination. RESULTS: Anti-CD4 treatment alone prolonged graft survival in both strain combinations but was only minimally effective when BALB/c donors were used. However, when anti-CD4 and anti-MHC class II mabs were administered together, graft survival was significantly prolonged in both strain combinations. The ratio of interleukin-4 (IL-4)/interferon-gamma (IFN-gamma) expressed in both C57BL/10- and BALB/c-transplanted hearts 7 days after transplantation was significantly higher after combined treatment with anti-CD4 plus anti-MHC class II mabs compared with that found after either treatment alone. Twenty-one days after transplantation, the ratio of IL-4/IFN-gamma in BALB/c hearts after combined mab therapy was significantly lower than at 7 days after transplantation, but in contrast, the cytokine ratio in C57BL/10 hearts remained at an elevated level during the first 21 days after transplantation. CONCLUSIONS: These data demonstrate that bidirectional blockade of the antigen-presenting cell and T-cell interaction by use of anti-CD4 and anti-MHC class II mabs in combination is more effective than either treatment alone. Graft survival in this model seems to correlate with a prolonged elevation of the IL-4/IFN-gamma ratio in the transplanted heart, suggesting that in this model the induction of unresponsiveness may be associated with a shift toward a Th2-type T-cell response.

Animals↗
PubMed1998

[The long-term results of percutaneous isolated hepatic perfusion for patients with advanced hepatocellular carcinoma].

We studied the long-term outcome of percutaneous isolated hepatic perfusion (PIHP) for patients with hepatocellular carcinoma. This study included 31 patients with Stage IVA and 5 with IVB disease treated by PIHP until December, 1997. The mean age and tumor diameter were 55 and 7.7 cm, respectively. Twenty-two had portal vein invasion, 13 had hepatic vein invasion, and all patients had multiple intrahepatic metastases of more than 5 tumor foci. The PIHP with adriamycin or cisplatin was undertaken in a total of 50 treatments in these 36 patients. CR was observed in 6 and PR in 13 with an overall response rate of 59%, excluding 4 patients who were not evaluable. Five of 6 patients with CR remain free of disease at 7 to 54 months after the first treatment. The overall survival rate was 67% at 1 year and 32% at 5 years. The survival rates of Stage IVA patients (1-year = 71%, 5-year = 36%) were higher than Stage IVB patients (1-year = 20%, 5-year = 0%). The 5-year survival rates of patients with vascular invasion (Vp1-3 = 23%, Vv1-3 = 8%) were lower than those without it (Vp0 = 47%, Vv0 = 51%). These results indicated that PIHP achieved a 5-year survival rate of approximately 40% in patients with multiple advanced hepatocellular carcinoma in the absence of distant organ metastases and marked vascular invasion, and yielded complete long-term remission in some of these patients.

Antibiotics, Antineoplastic↗