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Biomedical subjects

E Takeuchi

Publications and source records attributed to E Takeuchi.

At least 19 recordsLinked to original sources
PubMed1998

Soluble Fas ligand in the joints of patients with rheumatoid arthritis and osteoarthritis.

OBJECTIVE: To investigate the expression and function of Fas ligand (FasL),which can be in a membrane-bound or soluble form, in the joints of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: The concentration of soluble FasL (sFasL) in serum and synovial fluid (SF) from 24 OA and 38 RA patients was measured using an enzyme-linked immunosorbent assay. The expression of FasL on SF lymphocytes (SFL) and peripheral blood lymphocytes (PBL) was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. A cytotoxic killing assay of membrane-bound FasL and purified sFasL against cultured synovial cells was also performed. RESULTS: Soluble FasL was detected in the SF of patients with RA and OA, but not in their serum. The concentration of SF sFasL was remarkably higher in patients with severe RA than in patients with mild RA or with OA. RT-PCR showed that SFL, but not PBL, from RA patients expressed messenger RNA for FasL. Membrane-bound FasL induced apoptosis in cultured synovial cells from the RA and OA patients, but naturally processed human sFasL did not. CONCLUSION: SFL from RA patients expressed FasL, and cleaved sFasL accumulated in the SF of inflamed joints. The different killing activity of membrane-bound FasL and sFasL against synovial cells may regulate Fas-mediated apoptosis in synovial cells.

Aged↗
PubMed1998

Mesangiolytic glomerulopathy in severe congestive heart failure.

To study the glomerular morphological abnormalities in congestive heart failure (CHF), we analyzed 27 autopsy cases without other causes of renal disease. Their mean age was 59 years, and they showed mild prerenal azotemia. They had generally been treated with digitalis and diuretics, and a few of them with captopril or nifedipine. The abnormal glomerular findings of enlargement, hyperemia, and mesangial thickening were observed at high frequencies (61%, 64%, and 57%, respectively). They characteristically showed mesangiolysis (ML) by the findings of microaneurysms (81%) and mesangial degeneration (70%) such as loose reticular matrix and poor matrix area. In addition, glomerular infiltration of mononuclear leukocytes including macrophages was noted in 70% of the cases. Glomerular enlargement was not correlated with the grade of hyperemia, but it was correlated with the grade of ML index of % glomeruli with microaneurysms (F = 7.22, p < 0.004). There was an inverse relationship between the grades of mesangial thickening and of the ML index (P < 0.005). The number of glomerular leukocytes was positively correlated with mean glomerular size (P < 0.002) and with the ML index (P < 0.03). Notably, the glomerular macrophage-positive cases showed a prominently higher mean ML index than the negative cases (P < 0.005). There was an inverse correlation between the mean glomerular size and the partial oxygen pressure in arterial blood (PaO2; P < 0.01), and a positive correlation between the mean glomerular size and hematocrit (Hct) levels (P < 0.02). The cases positive for mesangiolytic mesangial degeneration showed significantly lower PaO2 values than the cases negative for this lesion (P < 0.04). In the analysis of the various causes of CHF, the patients with congenital cardiac anomalies showed mean levels of the lowest PaO2 (P < 0.02) and the highest Hct (P < 0.03) and histologically the largest mean glomerular size (P < 0.04). There was no difference in the ML index and the glomerular leukocyte number among the subgroups classified by the causes. These results indicate that ML associated with glomerular enlargement is the major glomerular abnormality characteristic in patients with severe CHF and suggest that glomerular infiltration of leukocytes, especially of macrophages, should play an important role in the progression of both ML and glomerulomegaly. The contributions of persistent hypoxia and up-regulated angiotensin II as the causative factors of these glomerular abnormalities in congestive heart failure are discussed.

Adult↗
PubMed1997

Interleukin-12-mediated killer activity in lung cancer patients.

The authors investigated the interleukin (IL)-12-inducible killer activity of blood mononuclear cells (MNC) from 30 untreated primary lung cancer patients and 24 control subjects. Cytotoxicity was assayed as 4-h 51Cr release from Daudi lymphoma cells or lung cancer cells (H-69, N-291 and PC-9). MNC from lung cancer patients exhibited similar killer activity to those from control subjects after in vitro incubation with IL-12 for 4 days. Effective killer induction by IL-12 was observed even in MNC from advanced lung cancer patients and patients with small cell lung cancer. IL-12 and a suboptimal dose of IL-2 had additive effects in inducing killer activity in MNC from both lung cancer patients and control subjects. On the other hand, with an optimal dose of IL-2, IL-12 suppressed killer induction. Addition of IL-12 alone or in combination with IL-2 resulted in interferon (IFN)-gamma production by MNC from lung cancer patients as well as control subjects. These observations suggest that IL-12 could be useful for immunotherapy of lung cancer in humans.

Adjuvants, Immunologic↗
PubMed1997

Intrapleural instillation of interferon gamma in patients with malignant pleurisy due to lung cancer.

The effect of intrapleural instillation of recombinant human interferon gamma (IFN gamma) at increasing doses of (1-12) x 10(6) U was examined in six patients with cytologically positive pleural effusion due to lung cancer. Intrapleural instillation was repeated up to three times. Clinically, no reaccumulation of pleural effusion was observed in one patient and disappearance of lung cancer cells from the pleural effusion was seen in two other patients. No severe side-effects were observed. Considerable levels of IFN gamma remained in the pleural effusion as well as in patients' serum up to 7 days after instillation of 2 x 10(6) U and higher doses. The total cell number showed a transient decrease on day 1 of therapy. Levels of pro-inflammatory cytokines, such as tumor necrosis factor alpha, interleukin(IL)-1 beta and IL-6, in the pleural effusion remained almost stable after IFN gamma instillation. On the other hand, intrapleural IL-1 receptor antagonist levels were remarkably elevated by the instillation of IFN gamma. IL-2- and IL-12-inducible killer activity of pleural mononuclear cells tended to increase slightly. Despite the inability of IFN gamma to control pleural effusion in this treatment schedule, IFN gamma instilled by an intrapleural route had a potential local antitumor activity. Moreover, since IFN gamma persists in pleural effusions for a long time after a single instillation, such a therapy in combination with other fibrogenic biological response modifiers can be promising.

Aged↗
PubMed1997

Aortic arch operation using selective cerebral perfusion for nondissecting thoracic aneurysm.

BACKGROUND: Risks of increasing mortality and disability in aortic arch operations using the selective cerebral perfusion method for nondissecting aneurysm have not yet been determined. A multicenter, retrospective study was employed. METHODS: The subjects were 143 patients who were admitted to one of the nine cardiovascular centers between January 1988 and December 1993, including 15 with ruptured aneurysm. A graft replacement of the transverse aortic arch or distal arch was performed in 80 patients, extensive aortic reconstruction comprising simultaneous replacement of the ascending or descending thoracic aorta (or both) in 46, and patch repair of involved arch in 17. The mean postoperative follow-up period was 19 months. RESULTS: Hospital mortality was 36/143 patients (25.2%). Univariate analysis revealed that age of 70 years or more, ruptured aneurysm, and renal dysfunction affected hospital mortality. Neurologic deficits were noted in 15 patients (10.5%). Reoperation was performed in 13 patients for residual distal aneurysm or false aneurysm. Late death occurred in 10 patients and were due to vascular complications in 6. Multivariate analysis confirmed that aneurysmal rupture and renal dysfunction were independent predictors for vascular death including hospital mortality. CONCLUSIONS: The present study confirmed that age, aneurysmal rupture, and renal dysfunction were significant predictors for mortality and disability in the aortic arch operation using selective cerebral perfusion for nondissecting thoracic aneurysm.

Aged↗
PubMed1997

Operation for nondissecting aneurysm in the descending thoracic aorta.

BACKGROUND: Little is known about the risks of mortality and morbidity after descending thoracic aortic aneurysm repair using left heart bypass and temporary arterioarterial bypass. METHODS: A multicenter, retrospective study was performed on 120 patients who were admitted to one of nine cardiovascular centers between January 1988 and December 1993 and underwent operation for nondissecting thoracic aortic aneurysm. The present series included 10 patients with ruptured aneurysm. Graft replacement was performed in 95 patients, patch repair in 22, and suture of the ruptured aorta in 3. Venoarterial bypass was used in 45 patients, left heart bypass in 56, and temporary arterioarterial bypass in 19 as circulatory support. The mean postoperative follow-up period was 30 +/- 21 months. RESULTS: Hospital mortality occurred in 7 patients (5.8%). Univariate analysis revealed that only aneurysmal rupture was related to hospital mortality. Brain or cord injury was observed in 4. Of nine deaths that occurred after discharge, five were related to aneurysm and two were due to vascular event. No significant difference was noticed in probability of survival according to the circulatory supporting method. Only aneurysmal rupture affected probability of survival. Multivariate analysis revealed that aneurysmal rupture was the only independent predictor for vascular death including hospital mortality. CONCLUSIONS: The present study confirms that aneurysmal rupture is a significant predictor for mortality and morbidity in aortic operations for nondissecting descending thoracic aneurysm, and that a similarly good outcome would be expected when using left heart bypass, temporary arterioarterial bypass, or venoarterial bypass.

Aged↗
PubMed1997

Induced expression of Thy-1 molecules on dermal endothelial cells in skin allografts.

We obtained evidence in a foregoing study that inducible Thy-1 on vascular endothelial cells functions as a possible vascular permeability modulator in the rat. We now report on the regulation and function of endothelial Thy-1 in skin allograft rejection in the rat. While no obvious expression of Thy-1 antigen on the vasculature can be seen in normal organs, dermal endothelial cells do express Thy-1 during allogeneic skin graft rejection and Freund's complete adjuvant (FCA)-induced inflammation. The antigen was weakly induced on tubular epithelial, but not on endothelial cells during kidney allograft rejection, and not in FCA-induced inflammation of the kidney. In contrast, Thy-1 antigen was not induced in the rejected lung or in FCA-induced inflammation of the lung. This pattern of Thy-1 regulation was transcriptionally regulated. Administration of anti-Thy-1 antibodies generated increased vascular permeability in skin allografts, although this procedure did not modulate survival of the grafts.

Animals↗
PubMed1997

Early experience of retrograde cerebral perfusion.

Since 1990, retrograde cerebral perfusion has been applied in aortic arch surgery in the Nagoya University group to protect the brain. This study reviews the group's early clinical results, and especially of neurological outcome in patients undergoing aortic arch surgery via mid sternotomy by using retrograde cerebral perfusion only via the superior vena cava. Seventy-three cases (47 men, 26 women; mean age 62.3 (range 26-82 years)) participated in the study. True aneurysm was diagnosed in 17 cases and aortic dissection in 56. Emergency operations were performed in 49 cases (67%). The proximal aortic arch was replaced in 38 cases, the total aortic arch in 21, the distal arch in six, and the aortic root in two. Mean (s.d.) retrograde cerebral perfusion duration was 55(23) (range 12-115) min and superior vena cava flow rate 350(143) ml/min. Excluding four cases of early surgical death, a total of 10 patients (14.5%) showed neurological dysfunction. Symptoms were coma in eight cases and motor paralysis in two. Three of these 10 cases were recovered without symptoms and six died. The early mortality rate was 19.2%. Significant differences in retrograde cerebral perfusion duration (49(20) versus 83(18) minutes, P < 0.001), superior vena cava pressure (23.2(7.2) versus 28.2(7.4) mmHg, P = 0.046), and preoperative cardiac arrest P < 0.05) were evident between groups with and without neurological dysfunction. There were no neurological dysfunctions in patients undergoing retrograde cerebral perfusion for < 60 minutes at under 30 mmHg of superior vena cava pressure. In conclusion, retrograde cerebral perfusion may be used to extend the duration of safe cerebral circulatory arrest.

Aortic Dissection↗
PubMed1997

Human hepatocyte growth factor in bile: an indicator of posthepatectomy liver function in patients with biliary tract carcinoma.

We measured the concentration of hepatocyte growth factor (HGF) in bile obtained from patients after hepatectomy. The HGF concentrations in the bile samples were quantified using an enzyme-linked immunosorbent assay (ELISA). By immunoblotting, using a monoclonal antibody raised against the HGF alpha-subunit, the bile HGF, which was purified on a Heparin-Sepharose column, showed a band of the same size as the recombinant HGF alpha-subunit (69 kd). Bile samples were obtained from 24 patients with biliary tract disease before and after hepatectomy by means of biliary drainage. Before surgery, the bile HGF concentrations were minimal (0.8 +/- 0.1 ng/mL); however, after hepatectomy on postoperative day 1 in patients without posthepatectomy liver failure (20 of 24), they increased severalfold (4.1 +/- 0.4 ng/mL, P < .05). The patients with posthepatectomy liver failure (4 of 24) showed no significant increase in bile HGF after hepatectomy (less than 2 ng/mL on postoperative day 1). The volume of the remnant liver correlated positively with the bile HGF concentration. The bile HGF concentration on postoperative day 1 exhibited a significant negative correlation with the maximum concentration of serum total bilirubin after hepatectomy. The concentration of bile HGF was generally higher than that in serum (2.1-fold). Thus, the bile HGF concentration after hepatectomy may be useful for the early assessment of posthepatectomy liver function.

Adult↗
PubMed1997

Selective breeding for high serum IgA levels from noninbred ddY mice: isolation of a strain with an early onset of glomerular IgA deposition.

An outbred mouse strain known as ddY has been reported to spontaneously develop, late in life, mesangioproliferative glomerulonephritis with a severe glomerular immunoglobulin A (IgA) deposition that mimics human IgA nephropathy. However, the incidence of the disease in this strain is not very high, probably due to its heterogeneous genetic background. Therefore, we attempted to isolate a strain with a high incidence and an early onset of the disease through selection for high serum IgA from the outbred ddY mice. The selection procedure was successful in increasing the serum IgA level of the selected line and proved effective both in increasing the incidence and in accelerating the onset of the disease. We propose to designate this line of mice 'HIGA', denoting a line with high serum IgA levels. More than half of the mice from the HIGA strain showed a moderate to severe glomerular IgA deposition as early as 25 weeks of age. The severe deposition observed was comparable to that occasionally seen in the original nonselected ddY strain after 40 weeks of age. Thus, we have succeeded in generating a mouse model of IgA nephropathy with a high incidence and an early onset of glomerular IgA deposition. Using light microscopy, progressive and marked mesangial matrix accumulation was shown to develop in HIGA mice. However, they showed only mild proteinuria (100-300 mg/dl) and did not show hematuria.

Aging↗
PubMed1997

Effect of thoracic irradiation on hepatocyte growth factor in rats lung and in bronchoalveolar lavage fluid of patients with thoracic malignancies.

This study aimed to examine the physiological role of hepatocyte growth factor (HGF) after thoracic irradiation. We analysed the changes of HGF protein levels in rat lung following 12 Gy of whole thoracic irradiation. Bronchoalveolar lavage fluid (BALF) was then collected from 11 patients (10 lung cancer and one oesophageal cancer) after completion of radiation therapy. One month after irradiation, the HGF protein level in the lungs of irradiated rats decreased (p<0.05), followed by a remarkable elevation in HGF protein levels 2 (p<0.05) and 3 months (nonsignificant) after irradiation accompanied by the clinical appearance of radiation pneumonitis. Finally, HGF protein levels in the lung returned to their original level 6 months after thoracic irradiation. In humans, HGF protein levels in the BALF in the limited irradiated area were lower than those obtained from unirradiated areas (p<0.05). In conclusion, hepatocyte growth factor production is transiently suppressed in the irradiated area after irradiation.

Aged↗
PubMed1997

[Neoadjuvant CYVADIC (cyclophosphamide, vincristine, adriamycin and dacarbazine) therapy for retroperitoneal leiomyosarcoma: a case report].

Retroperitoneal leiomyosarcoma is often too large to be completely removed. We report a 67-year-old woman successfully treated with neoadjuvant CYVADIC (cyclosphosphamide, vincristine, adriamycin and dacarbazine). The tumor was removed with the right kidney and ureter and a part of the vena cava after 2 courses of CYVADIC. The tumor recurred at the duodenum 7 years later and was completely removed following neoadjuvant CYVADIC. Neoadjuvant chemotherapy could be helpful for the complete resection of advanced leiomyosarcoma.

Aged↗
PubMed1997

[A case of dyskeratosis congenita with acute interstitial pneumonia].

This is a rare case of Dyskeratosis Congenita (DC) with acute interstitial pneumonia. A 51-year-old man with DC was admitted to our hospital because of cough, sputum and fever. Chest X-ray film showed ground glass opacities in all lung fields for a while steroid's therapy proved effective, but about seven months later the patient's condition became serious. Methylprednisolone, cyclophosphamide and mechanical ventilation therapy were not effective. He died and an autopsy was performed. The lung specimen showed Organizing Diffuse Alveolar Damage, and some parts pointed to bacterial infection. But Pneumocystic carinii pneumonia and Fungal infections were not found. It is therefore necessary to conduct intensive examinations of lung involvement of patients with Dyskeratosis Congenita.

Acute Disease↗
PubMed1997

Ectopic bone formation after total hip arthroplasty.

Two hundred and forty consecutive Japanese patients with 280 primary total hip arthroplasties (THA) were analyzed to clarify the incidence of ectopic bone formation and its predisposing factors and to examine its effect on the clinical results. Ectopic bone formation after THA was found in 61 joints (22%). The predisposing factors were male patients and a hypertrophic type of osteoarthritis. It was revealed that extensive ectopic bone formation, class 3 according to Brooker's classification, restricted flexion and abduction motion of the hip joint.

Adult↗
PubMed1996

Ligation of portal vein branch induces DNA polymerases alpha, delta, and epsilon in nonligated lobes.

Ligation of a portal vein branch supplying 70% of the rat liver causes compensatory hypertrophy of the nonligated hepatic lobes with concomitant atrophy of the ligated lobes. To elucidate the mechanism of this response, the induction of the replication enzymes DNA polymerases alpha, delta, epsilon, as well as proliferating cell nuclear antigen (PCNA), were investigated in nonligated lobes after portal branch ligation. The induction patterns were compared with the well studied liver regeneration after 70% partial hepatectomy. DNA polymerases alpha, delta, and epsilon in the liver were extracted with 5 mM KCl (low-salt extract), then with 600 mM KCl (high-salt extract). DNA polymerases alpha, delta, and epsilon in low-salt extract were partially separated on a hydroxyapatite column and quantified. All enzyme activities in the nonligated lobes started to increase within 24 hr and reached maximum levels by 48 hr after portal branch ligation. These patterns were quite similar to those obtained with the remnant liver after partial hepatectomy. In low-salt extract, DNA polymerase delta and epsilon were prominent, while, in high-salt extract, largely DNA polymerases alpha and some activity of epsilon were recovered. PCNA was also induced after both portal branch ligation and partial hepatectomy, reaching maximum levels at 48 hr. From the similar changes in DNA polymerases and PCNA, our data indicate that portal branch ligation induces hepatocyte proliferation in the nonligated lobes in a way similar to partial hepatectomy.

Animals↗
PubMed1996

Enhanced production of glomerular extracellular matrix in a new mouse strain of high serum IgA ddY mice.

To investigate the relationship between high serum levels of IgA and glomerular lesions, selective mating was performed in high serum IgA ddY mice, a murine model of spontaneously developing mesangioproliferative glomerulonephritis mimicking human IgA nephropathy. The selection and mating of high IgA ddY mice were accomplished when the mice were three to four months old. In the 12th generation of high IgA ddY (HIGA) mice, significantly higher levels of serum IgA from 10 age weeks to 60 weeks (P < 0.0002 to 0.0001) were observed in comparison with BALB/c mice. Relatively high proteinuria was observed at 40 weeks of age, although hematuria was consistently negative. Microscopic observations of renal tissue disclosed a marked glomerular mesangial matrix increase and a reduction of cell proliferation with age by both semiquantitative and morphometric analyses with moderate tubulointerstitial damage. These mesangial matrices were stained markedly by antisera for collagen type IV and by fibronectin, but not by collagen type I. Localization of TGF-beta protein was also detected in the mesangium of the HIGA mice. The positive mesangial IgA deposition was maintained consistently by this mating procedure and became more marked with age. Size analysis of IgA from ten pooled HIGA mice aged 50 to 60 weeks revealed dominant polymeric IgA in sera and dimeric IgA in glomerular eluates. Clonal analysis of serum IgA disclosed heterogeneous spectrotypes in a wide pH range (4.5 to 6.5), in contrast to very limited spectrotypes in the acidic pH range (4.5 to 5.2) of IgA in the glomerular eluates from these mice. The analyses of retroviral gp70 antigen involvement in the HIGA mice disclosed a significant increase of serum levels of gp70 anti-gp70 immune complexes with age, with no relationship to the severity of glomerular gp70 deposition. Northern blot analysis of renal tissue revealed markedly high mRNA expression of collagen type I, IV, fibronectin and TGF-beta even in 10-week-old HIGA mice in comparison with BALB/c mice. The expression became more significant in 60-week-old animals. The genetic background required to induce the expansion of IgA-producing B-cell clones is suggested to be closely related to the increased gene expression of TGF-beta, which induces enhanced glomerular extracellular matrix (especially fibronectin) accumulation in HIGA mice, being possibly mediated by the mesangial deposition of dimeric and highly acidic IgA. This newly established strain may provide a model for investigating the relationship between progressive glomerular sclerotic lesions and the induction of pathogenic IgA in human IgA nephropathy.

Aging↗
PubMed1996

Induction by interleukin-15 of human killer cell activity against lung cancer cell lines and its regulatory mechanisms.

Interleukin (IL)-15 is a novel cytokine with IL-2-like activity. In the present study, we examined IL-15-mediated induction of killer activity of peripheral blood mononuclear cells (MNC) against lung cancer cell lines, and the regulatory mechanisms of this induction by IL-15. Cytotoxic activity was measured by 51Cr release assay. IL-15 at concentrations of more than 10 ng/ml induced significant killer activity of blood MNC against a small cell lung cancer cell line (SBC-3), as well as Daudi cells, and 50 ng/ml was considered its optimal concentration. A time course study revealed that an incubation period of 4-6 days was optimal for induction of killer activity. MNC cultured with IL-15 also exhibited killer activity against other lung cancer cell lines (H-69, N-291 and PC-9 cells). IL-15 and IL-12 had additive effects on induction of killer activity against SBC-3 cells. On the other hand, IL-15 had no synergistic or additive effect on induction of killer activity by IL-2. Fresh human monocytes isolated by centrifugal elutriation augmented the development of killer activity of lymphocytes stimulated by IL-15. As a humoral regulatory factor, IL-4 had a suppressive effect on induction of killer activity by IL-15. IFN-gamma, IL-1beta, TNF-alpha, IL-6 or IL-10 had no effect on induction of killer activity by IL-15 at the optimal concentration. These results suggest that IL-15 has potential for the immunotherapy of lung cancers.

Antibody-Dependent Cell Cytotoxicity↗