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Biomedical subjects

M Togashi

Publications and source records attributed to M Togashi.

At least 19 recordsLinked to original sources

Characterization of 4-O-methyl-ascochlorin-induced apoptosis in comparison with typical apoptotic inducers in human leukemia cell lines.

Apoptosis can be induced by various stimuli such as the ligands of death receptors, chemotherapeutic drugs and irradiation. It is generally believed that chemotherapeutic drugs induce mitochondrial damage, cytochrome c release and activation of caspase-9, leading to apoptosis. Here, we found that an isoprenoid antibiotic, 4-O-methyl ascochlorin, significantly induces typical apoptotic events in Jurkat cells including the degradation of poly (ADP-ribose) polymerase, DNA fragmentation, activation of caspase-3, -9 and -8, and cytochrome c release from mitochondria. Similar to Fas stimulation, 4-O-methyl ascochlorin but not staurosporine, cycloheximide and actinomycin D, induced apoptosis in SKW6.4 cells, in which apoptosis is strongly dependent on death-inducing signaling-complex. Bcl-2 overexpression in Jurkat cells completely suppressed the apoptosis, but procaspase-9 processing was partially induced. A caspase-8 inhibitor, IETD-fmk, effectively suppressed poly (ADP-ribose) polymerase cleavage and cytochrome c release. However, 4-O-methyl ascochlorin induced apoptosis in Jurkat cells deficient of caspase-8 or Fas-associated death domain protein. These results suggest that 4-O-methyl ascochlorin induces apoptosis through the mechanism distinct from conventional apoptosis inducers.

Adaptor Proteins, Signal Transducing↗

A case of plasmacytic hyperplasia arising in a kidney allograft salvaged with immunosuppression reduction alone.

Post-transplant lymphoproliferative disorder (PTLD) is a well-known complication of organ transplantation. Plasmacytic hyperplasia (PH) is thought of as the mildest form of PTLD; however, a graftectomy is necessary in most situations. We experienced an interesting case of PH arising in a kidney allograft, which could be relieved with a reduction in immunosuppression. A 27-year-old female underwent a living-related kidney transplantation. A 3-month non-episode protocol biopsy unexpectedly showed the devastating appearance of polymorphic plasma cell infiltration into the graft intersitium, compatible with PH. The PH was located in the graft by radiographic examinations. The infiltration of plasma cell disappeared completely on the 6-month graft biopsy specimen following immunosuppression reduction and the graft is functioning, although it was damaged by a subsequent acute rejection. Our present case indicates that some PTLD can be completely cured with a reduction in immunosuppression alone. The diagnostic modality for the evaluation of PTLD cell extinction is necessary to maintain graft function with adequate immunosuppression thereafter.

Adult↗

Prevalence of A-to-G mutation at nucleotide 3243 of the mitochondrial tRNA(Leu(UUR)) gene in Japanese patients with diabetes mellitus and end stage renal disease.

The A-to-G mutation at nucleotide 3243 of the mitochondrial tRNA(Leu(UUR)) gene (mt.3243A>G) is associated with both diabetes mellitus and myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Recently, this mutation was found in three diabetic subjects with progressive kidney disease, suggesting that it may be a contributing factor in the development of kidney disease in patients with diabetes. The aim of this study was to evaluate the contribution of this mutation to the development of end stage renal disease (ESRD) in patients with diabetes. The study group consisted of 135 patients with diabetes and ESRD. The control group consisted of 92 non-diabetic subjects with ESRD who were receiving hemodialysis. The mt.3243A>G mutation was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). We found the mt.3243A>G mutation in eight patients (8/135; 5.9%), all of whom were initially diagnosed with type II diabetes. Five of the eight patients were subsequently also diagnosed with MELAS. We did not find the mutation in any of the 92 nondiabetic subjects with ESRD. The prevalence of this mutation was 6.5-fold higher in patients with diabetes and ESRD than in those with diabetes alone (8/135 vs 5/550, respectively; chi2 = 13.704; P = 0.0002). The mt.3243A>G mutation may be a contributing genetic factor in the development of ESRD in Japanese patients with diabetes.

Adult↗

Pre-emptive renal transplantation in children.

BACKGROUND: Renal transplantation is a definitive therapeutic modality in end-stage renal disease (ESRD). Most ESRD patients in Japan experience dialysis prior to renal transplantation. The present study was undertaken to examine the usefulness of pre-emptive renal transplantation (PET). METHODS: Between 1987 and 1998, 255 renal transplantations were carried out by the authors. Among those consecutive cases, 10 were cases of PET. In nine pediatric cases, demographics, graft and patient survival, height growth and benefits from successful transplantation were studied and compared with age-matched dialyzed transplantation controls. RESULTS: All transplantation was living-related. There was a disparity of causes of ESRD between the two groups. In PET, acquired renal deterioration due to a congenital lower urinary tract disorder was the major cause. Graft and patient prognosis was favorable in both groups. Growth retardation in PET patients under 15 years of age was significantly less apparent at the time of transplantation and after 3 years compared to the control. The benefits from transplantation were different in the two groups. Most PET patients felt an improvement of their physical condition; however, all of the control patients felt that the major boon was the freedom from the restriction of the daily diet and time for dialysis. CONCLUSION: In pediatric renal transplantation, short-term preceding dialysis does not have a detrimental effect, but PET could benefit ESRD patients by maintaining their quality of life. Moreover, PET minimizes the production of renal dwarfism in prepubertal children. Thus, PET should be taken into consideration in the choice of renal replacement therapy.

Acute Disease↗

Intravenous digital subtraction angiography and helical computed tomography in evaluation of living renal donors.

OBJECTIVES: The present study was carried out to evaluate the accuracy of helical computed tomography (CT) and intravenous digital subtraction angiography (IV-DSA) on anatomical assessment of renal vasculature for living renal donors. METHODS: Forty-two healthy potential renal donors were prospectively evaluated and 35 subsequently underwent donor nephrectomy after helical CT and IV-DSA evaluation. The vascular and non-vascular findings were compared between the findings on helical CT, IV-DSA and surgery. RESULTS: Ten prehilar branches and five accessory renal arteries were found at nephrectomy. Overall, operative findings agreed with the findings by IV-DSA in 89% and by helical CT in 83%. In delineating accessory arteries, IV-DSA had a sensitivity of 60% and specificity of 97%, whereas helical CT had a sensitivity of 40% and specificity of 100%. In delineating prehilar branches, IV-DSA had a sensitivity of 90% and specificity of 100%, whereas helical CT had a sensitivity of 70% and specificity of 100%. Accessory arteries and prehilar branches that were not detected by helical CT or IV-DSA, were less than 2 mm in diameter and did not require vascular reconstruction. Renal veins were delineated in 63% by IV-DSA, whereas they were clearly imaged by helical CT in all cases, including a case with a circumaortic renal vein. Non-vascular findings were obtained in 64% by helical CT, including two renal tumors. None of these findings were obtained by IV-DSA. CONCLUSION: Helical CT and IV-DSA provide comparably sufficient information on renal artery vasculature. However, helical CT provides significantly more information on venous and non-vascular findings as a single-imaging modality.

Adult↗

Asynchronous (heterochronic) bilateral renal infarction associated with primary antiphospholipid syndrome.

We report the rare case of a 51-year-old man with asynchronous (heterochronic) bilateral renal infarction associated with primary antiphospholipid syndrome. He was treated for right renal infarction, but 2 months later, while under anticoagulant treatment, he had a recurrence on the other side of the renal infarction. The laboratory work-up confirmed antiphospholipid syndrome. Six months later the patient has not experienced any new thrombotic episodes and is receiving oral anticoagulants and antiplatelet therapy.

Anticoagulants↗

Renal arteriovenous malformation with thrombus in the inferior vena cava.

BACKGROUND: Thrombus formation in the inferior vena cava (IVC) is usually seen in cases with malignancy. In contrast, vascular anomalies hardly ever accompany this disorder. Herein, a case of thrombus formation in the IVC associated with renal arteriovenous malformation (AVM) is reported. METHODS/RESULTS: A 50-year-old woman who received transarterial embolization (TAE) for AVM in the right kidney noticed right flank pain with macrohematuria 12 months later. Because radiographic evaluation could not rule out malignancy in the kidney, nephrectomy was performed. During nephrectomy, a palpable thrombus was found in the IVC, so thrombectomy was performed simultaneously. Histopathologic examination revealed an old infarction due to the TAE, circumferential arteriovenous thrombi and a large organized thrombus up to the IVC, but neither renal cell carcinoma nor transitional carcinoma in the kidney. CONCLUSIONS: Careful observation may be required, even after treatment for renal AVM, such as TAE, to avoid the formation of an IVC thrombus.

Angiography↗

[Epidemiological evaluation of Serratia marcescens isolates in one Japanese hospital during the two years from April 1997 to March 1999].

One hundred fourteen isolates of Serratia marcescens from different patients in Showa University Fujigaoka Hospital during the 2 years from April 1997 to March 1999 were investigated in this study. The isolation frequency(37%, 43 of the isolates) of O-serotype 14(O14) was highest among the 16 different serotypes, and that(24%, 27 of the isolates) of O2 was secondarily highest, while these types were frequently isolated from patients in the surgical ward. O14 with major bacteriocin types 4 and 9(B4 and B9, respectively) showed resistance to piperacillin, the third and fourth generation cephems, new quinolones and aminoglycosides except gentamicin tested. However, O2 with major B1 and B5 showed much greater sensitivity to the antimicrobial agents tested than O14. Furthermore, O2 and O14 were frequently isolated from patients' sputa(41%, 11 of the 27 isolates) and urine(72%, 31 of the 43 isolates), respectively. These findings suggested that S. marcescens O14 with B4 and B9, more resistant to various agents, and O2 with B1 and B5, more sensitive to various agents, show a tendency to inhabit the urinary and respiratory tracts in the hospital patient's body, respectively, having a high risk of hospital infection.

Anti-Bacterial Agents↗

Effect of recombinant human granulocyte colony stimulating factor (lenograstim) on chemotherapy induced neutropenia in patients with urothelial cancer.

BACKGROUND: A multicenter cooperative study to evaluate clinical usefulness of recombinant human granulocyte colony stimulating factor (rG-CSF; lenograstim) in the treatment of neutropenia associated with cancer chemotherapy was conducted in patients with urothelial cancer. METHODS: Therapeutic responses were compared within each patient between the observation and study treatment phases. RESULTS: Treatment with rG-CSF raised the nadir of the neutrophil count (343 to 3015/mm3), reduced the duration of neutropenia (6.2 to 0.4 days) and hastened recovery from the neutropenic state (23.5 to 5.5 days). Febrile neutropenia was encountered in 12 patients during the observation phase alone and in only one patient during the study treatment phase alone. The mean duration of febrile neutropenia was also shortened (0.39 to 0.12 days). In addition, the duration of antibiotic therapy was significantly reduced during treatment. The percentage of patients completing the chemotherapeutic regimens of combination M-VAC therapy was markedly increased to 81.0% as a result of rG-CSF therapy compared with 44.8% in the observation phase. Adverse reactions were observed in four patients and abnormal laboratory values were found in nine patients. None of these adverse events was of a serious nature. CONCLUSIONS: These results indicate that rG-CSF is a useful drug for the treatment of neutropenia associated with chemotherapy in urothelial cancer.

Adjuvants, Immunologic↗

Arg260-Cys mutation in severe factor XIII deficiency: conformational change of the A subunit is predicted by molecular modelling and mechanics.

To explore the implications of the structure/ function relationships in factor XIII. a patient with severe A subunit deficiency was examined at the DNA and RNA levels. Nucleotide sequence analysis of the patient's DNA amplified by PCR revealed that the patient had a replacement of C by T in the codon for Arg260. RT-PCR analysis demonstrated that only one kind of mRNA coding for the Arg260-Cys mutation was expressed in the patient at a normal level. Another possible defective allele of the A subunit gene with a G-A polymorphism was not expressed (null allele). The substitution of Arg260 by Cys located on the interface of two A subunits would preclude the reciprocal ionic interaction (salt bridge) between Arg260 and Asp404. Molecular modelling and, for the first time, molecular mechanics calculated that Cys260 changed the local conformation of the A subunit and reduced the electrostatic interaction between two monomers, suggesting destabilization of the molecule's dimer.

Amino Acid Substitution↗

[Clinical study of long graft survival in renal transplantation recipients].

BACKGROUND: A total of 110 patients, in whom kidneys from 95 living related and 15 cadaver donor, had experienced renal transplantation between February 1985 and October 1996 in our clinic. This study was conducted to evaluate the influence of the various pre-operative factors to the graft survivals and clinical course of patients in living related renal transplantation. METHODS: In 95 recipients, 17 adult patients had long term graft survivals over 5 years including 6 recurrent or denovo nephritis without chronic allografts nephropathy. Eight failed to graft loss attributed to chronic allografts nephropathy diagnosed within 5 years. Retrospective analysis were performed to elucidate the differences of these recipients. RESULTS: Donors of long graft survival recipients were younger (49.1 +/- 12.1 v.s. 58.9 +/- 10. 2) and had a better renal function evaluated by preoperative creatinine clearance in living related donors (115.5 +/- 37.0 v.s. 79.7 +/- 22.0 1/day). Graft long survival recipients had experienced less frequencies of acute rejection within 6 months (0.53 +/- 0.62: 8 patients, 9 times) compared with chronic allografts nephropathy recipients (1.00 +/- 0.53: 7 patients, 8 times). Long graft survival recipients had better responses to the antirejection therapy. Additionally acute rejection over 6 months were experienced only in chronic allografts nephropathy recipients. Higher serum creatinine level was revealed in recipients with chronic allografts nephropathy at 1 year after transplantation (1.27 +/- 0.27 v.s. 1.88 +/- 0.42 mg/dl). CONCLUSIONS: We concluded that donor age and renal function are related to the graft long survival as background factors. Long graft survival recipients had less frequency of acute rejection and good response to the antirejection therapy. In recipients with of acute rejection and good response to the antirejection therapy. In recipients with chronic allografts nephropathy, serum cretine level had already increased gradually within 1 year.

Adult↗

Experience with revascularizing renal artery aneurysms: is it feasible, safe and worth attempting?

PURPOSE: We retrospectively evaluated the feasibility and efficacy of surgical revascularization for renal artery aneurysms. MATERIALS AND METHODS: Beginning in 1984, 12 patients with renal artery aneurysm underwent renal revascularization regardless of clinical features. Postoperative results were analyzed regarding split renal function, patency of the revascularized arteries, blood pressure control and surgical complications. RESULTS: Postoperative renal function was stable or improved in all but 1 case and patency in branched arteries was preserved in 86%. Hypertension in 8 patients was cured in 7 (88%), including 2 with renovascular hypertension, and improved in 1 (12%). Complications were minimal with only 1 ureteral stricture that required reoperation. CONCLUSIONS: The majority of renal artery aneurysm cases are amenable to surgical repair. Carefully performed renal revascularization is rewarding in that high blood pressure is better controlled, renal function is improved and the potential risk of rupture is obviated.

Adult↗

[Clinical evaluation of donor renal artery reconstruction in kidney transplantation].

UNLABELLED: This retrospective study describes the experience of arterial reconstruction of donor kidney in our institute since 1982. MATERIALS AND METHODS: Of total 56 living related kidney transplantations 15 required renal arterial reconstruction or ligation of donor kidneys. Renal arterial reconstruction was employed for 11 cases (end to side anastomosis [4 cases], conjoined anastomosis [3], hypogastric artery graft interposition [3], other [1], while simple ligation was employed for 4. Bench surgery with microsurgical techniques was employed for the repair. Elective surgery was done for preoperatively defined multiple renal arteries [10] and aneurysm [1], while imperative surgery for intraoperatively detected accessory arteries [2] and surgical injuries [2]. Postoperative patency of arteries and renal function (GFR) and evaluated by 99mTc-DTPA renoscintigraphy. RESULTS: The mean total ischemic time of reconstructed cases was 135 min., while that of ligated ones was 67 min. None of them required hemodialysis due to acute tubular necrosis. Postoperative graft arterial patency was impaired in 2 of 11 reconstructed cases (18%), while it was impaired in 3 of 4 ligated cases (75%). Two failure attempts of arterial reconstruction cases were all imperative ones. Postoperative GFR of the graft was well preserved in all cases. CONCLUSION: We conclude that (1) Ligation and imperative surgery tend to be associated with renal infarction, although it does not affect GFR. (2) Renal artery reconstruction was highly successful in preserving renal mass (or normal cortical image), albeit longer ischemic time than simple ligation. (3) Considering importance of preserved nephron mass in clinical renal transplantation every attempt should be made to repair the donor arterial anomalies when expected (elective) or found (imperative). (4) Thorough preoperative evaluation of donor renal arteries is mandatory.

Adult↗

The proportion of free to total prostate specific antigen: a method of detecting prostate carcinoma.

BACKGROUND: Prostate specific antigen (PSA) is the most useful marker for prostate carcinoma (CaP). However, the sensitivity and specificity for PSA are not sufficient for the diagnosis of organ-confined prostate carcinoma. Recent studies have revealed that anti-PSA antibody identifies both PSA complexed to alpha-1-antichymotrypsin and free PSA, whereas anti-gamma-seminoprotein antibody recognizes free PSA exclusively. To enhance the ability of PSA to detect CaP in patients with total PSA levels of 10 ng/mL or lower, we developed the ratio of gamma-seminoprotein and PSA (free/total PSA index). METHODS: We measured free/total PSA indices for 285 patients who had serum PSA levels of 10 ng/mL or lower and who were diagnosed pathologically. RESULTS: Of the 285 patients, 228 had no prostate carcinoma (NC) and 57 had CaP. The mean total PSA level for CaP (5.137 +/- 2.483 ng/mL; mean +/- standard deviation) was significantly greater (P < 0.0001) than that for NC (3.251 +/- 2.129). The mean free/total PSA index for CaP (0.774 +/- 0.468 was significantly lower (P < 0.0001) than that for NC (1.563 +/- 0.938). The sensitivity for the free/total PSA index was similar to that for total PSA (78.9% vs. 75.4%). However, the specificity, positive predictive value, and overall accuracy for the free/total PSA index (75.9%, 45%, and 76.5%, respectively) increased by 15-20% compared with those for total PSA (56.6%, 30.3%, and 60.4%, respectively). CONCLUSIONS: The free/total PSA index improved the specificity of PSA without impairing the sensitivity in detecting CaP among patients with serum PSA levels of 10 ng/mL or lower.

Humans↗

Surgical revascularization in children with renovascular hypertension.

Two boys, 11 and 10 years of age, respectively, having renovascular hypertension are reported. Diagnostically, captopril test and renal scintigraphy were useful as pharmacologic probes of the renal arterial stenosis and to determine its laterality, as well for examination of the operative outcome. Both children were rendered normotensive after renal revascularization, one by renal autotransplantation and the other by aortorenal bypass procedure. Renovascular hypertension in children is also discussed.

Aortography↗

Anterior ischemic optic neuropathy in a patient with positive antinuclear antibody and lupus anticoagulant findings.

A 64-year-old woman complained of blurred vision in her right eye. A pale optic disc with a blurred nasal margin was found in the right fundus. An inferior altitudinal defect in the right eye was observed on Goldmann perimetry. Her right visual acuity deteriorated to 0.1. Her antinuclear antibody and lupus anticoagulant test results were positive. Intravenous methylprednisolone (1,000 mg/day) improved her right visual acuity to 1.0. We believe that the anterior ischemic optic neuropathy in our patient may be associated with the presence of positive antinuclear antibody and lupus anticoagulant findings.

Antibodies, Antinuclear↗

[Tumor size and DNA ploidy changes in renal cell carcinomas--flow cytometric analysis of DNA content in renal cell carcinomas associated with von Hippel-Lindau disease].

BACKGROUND: Renal cell carcinomas (RCCs) develop in 8-63% of von Hippel-Lindau disease (VHL) patients, and loss of 3p segments, chromosome aberrations found in 90% of sporadic RCCs, has also been observed in RCCs associated with VHL. In fact, comparative analysis showed that the chromosome aberrations in RCCs associated with VHL are similar to those found in sporadic RCCs. VHL patients have the whole spectrum of tumors from small early lesions to large ones in the same kidney, providing a unique opportunity to analyze tumors in different stages of development. Subsequently deoxyribonucleic acid (DNA) content in RCCs of VHL patients was examined and correlated to their tumor size to gain some insight in the progression of sporadic RCCs. METHODS: From 1988 to 1991, we have experienced 6 cases of RCCs associated with VHL who underwent partial or radical nephrectomy. A total number of 52 paraffin-embedded samples from 33 RCCs from 6 patients with VHL was analyzed by flow cytometry. RESULTS: The sizes of tumors ranged from 0.2 to 8.2 cm. DNA aneuploid patterns demonstrated in none of 9 tumors less than 1.6 cm, 4 of 14 tumors (29%) as large as 1.6 to 2.5 cm, and 5 of 10 tumors (50%) larger than 2.5 cm (p < 0.05). Twelve tumors less than 1.8 cm showed DNA diploid, so the smallest size of aneuploid tumors was 1.8 cm. CONCLUSION: These data suggest that DNA ploidy change (diploid to aneuploid) in RCCs probably takes place as tumors grow approximately 1.8 cm in size.

Adult↗