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Biomedical subjects

T Miki

Publications and source records attributed to T Miki.

At least 253 records · Page 14Linked to original sources
PubMed1998

A comparative study of FK506 granules and capsules in renal transplant recipients.

Nine renal transplant recipients in stable systemic condition on FK506 capsules were converted to FK506 granules in order to investigate the safety, efficacy, and pharmacokinetics of the granular formulation of FK506. The study period for the administration of FK506 granules was 4 weeks, and in principle, the oral dose was the same as that of the FK506 capsules. Renal graft function remained stable and no rejection signs were noticed while the patients were taking the granules. The area under the blood concentration-time curve (AUC), the maximum blood level (Cmax), and the time to reach Cmax (Tmax) after FK506 capsules and FK506 granules were, respectively, 93.1 +/- 66.4 and 97.0 +/- 89.1 ng.h/ml (P = 0.81), 12.7 +/- 7.1 and 15.2 +/- 11.7 ng/ml (P = 0.39), and 2.0 +/- 1.7 and 1.3 +/- 0.6 h (P = 0.29). The mean trough blood level during FK506 medication was 4.25 +/- 3.42 and 4.02 +/- 3.83 ng/ml, respectively, for the capsules and the granules. FK506 granules, a new formulation, showed an efficacy comparable to that of the FK506 capsular formulation.

Adult↗
PubMed1998

Low-dose tacrolimus (FK506)-based immunosuppressive protocol in living donor renal transplantation.

In order to avoid the side effects of tacrolimus (FK506), a lowdose FK506-based regimen was started from 1 June 1991. The dose was adjusted to maintain the FK506 whole blood trough level at 15-20 ng/ml for 7 days postoperatively, at 10-15 ng/ml for 2 months, and under 10 ng/ml thereafter. The graft survival rates at 3 years and 5 years were 87.8 and 82.3% (FK506) vs 86.8 and 86.8% [cyclosporine (CyA)]. The incidence of acute rejection within the first 90 days was 31.6% in the FK506 group which was lower than the 57.1% of the CyA group (P = 0.0585). Grades of acute rejection episodes over IIA in the FK506 group were 20%, which was lower than the 37% in the CyA group. The mean oral dosages of FK506 were 0.061 and 0.04 mg/kg per day at 3 and 5 years, respectively. The incidence of new onset diabetes was 27.8% in the FK506 group and 17.1% in the CyA group. However, insulin therapy was withdrawn in all patients of the FK506 group within 5 months. The percentage of patients who required an antihypertensive agent was 28.6% and 40% in the FK506 group and 73.2% and 88% in the CyA group at 1 and 3 years, respectively (P < 0.05). Nephrotoxicity was seen in 20% of the FK506 group and 14.3% of the CyA group. Hypercholesterolemia was less frequent in the FK506 group than the CyA group. The FK506-based regimen described here is a protocol with the potential to reduce its adverse effects. The Whole blood concentration of FK506 should be monitored and blood levels maintained in the range of 5-10 ng/ml after 90 postoperative days for optimal efficacy and minimal toxicity.

Cyclosporine↗
PubMed1998

Morphological findings in non-episode biopsies of kidney transplant allografts treated with FK506 or cyclosporine.

We conducted an analysis of biopsy specimens of non-episode renal allografts from patients treated with tacrolimus (FK506) or cyclosporine (CsA) to evaluate chronic drug-induced nephropathy in stable allografts. A total of 38 biopsy specimens from stable functioning renal allografts were examined. The patients had been treated with FK506 (n = 16) or CsA (n = 18) as main immunosuppressant for 0.3 to 7.4 years. Of the 38 biopsy specimens, 15 showed mild drug-induced arteriolopathy (hyalinosis or insudative change of arterioles and small arteries) with striped-form interstitial fibrosis, 10 showed minimum interstitial cellular infiltration (borderline rejection), 2 showed IgA nephropathy, 4 showed evidence of chronic rejection (transplant nephropathy) and 12 showed no abnormal findings. Of 34 renal allograft biopsy specimens with stable function, 22 (65%) showed pathological evidence of drug-induced nephropathy. There were no significant qualitative or quantitative differences between FK506- and CsA-associated nephropathy.

Biopsy↗
PubMed1998

Mild hypothermia reduces infarct size in the beating rabbit heart: a practical intervention for acute myocardial infarction?

The present study describes a method for rapidly cooling the whole body via its blood pool and tests whether cooling instituted after ischemia has begun can still limit infarction. We also evaluated whether the cardiac protection seen with cooling could be added to that from ischemic preconditioning. Recently it was reported that lowering myocardial temperature by only several degrees greatly slows the extent of myocardial infarction in the beating heart experiencing regional ischemia. To further explore the potential of hypothermia for myocardial protection, rabbits underwent either a 30-, 45- or 60-min coronary artery occlusion and 3-h reperfusion. Blood from a carotid artery was allowed to circulate through a heat exchanger immersed in ice water and return to a jugular vein until the blood temperature in the left atrium reached the target temperature of 35 or 32 degrees C. Furthermore, to elucidate the mechanism of hypothermia's protection, we also examined its effect on isolated cardiomyocytes. Rewarming began upon reperfusion in all protocols. Cooling to 32 degrees C before a 30-min ischemia reduced infarct size from 37.3 +/- 2.5% (n = 6) of the risk zone in normothermic controls to 3.6 +/- 0.3% (n = 6). When cooling was begun 10 or 20 min after the onset of ischemia infarct size was still significantly smaller [8.1 +/- 1.2% and 22.8 +/- 1.8%, respectively (n = 6 in each group)]. Less but significant protection was also seen with cooling to 35 degrees C. Cooling caused only mild bradycardia and hypotension and no apparent arrhythmias. Forty-five min of regional ischemia caused 50.7 +/- 3.3% (n = 6) of risk zone to infarct in untreated hearts. Preconditioning with 5-min ischemia/10-min reperfusion reduced infarct size to 27.5 +/- 2.5% (n = 6). Cooling to 32 degrees C starting 20 min after the onset of ischemia protected the heart (28.7 +/- 2.6% infarction, n = 8), and this protection could be added to the effect from ischemic preconditioning (6.3 +/- 2.3% infarction, n = 6). In the myocyte model, hypothermia and ischemic preconditioning delayed the progressive increase in osmotic fragility that occurs during simulated ischemia in an additive way, but only hypothermia delayed the appearance of contracture suggesting that different mechanisms are involved. Hence blood pool cooling was easily induced and well tolerated and protected the beating heart against infarction even when hypothermia was started after the onset of coronary occlusion. We conclude that hypothermia might be a simple and useful therapy for patients presenting with acute myocardial infarction.

Animals↗
PubMed1998

Recurrent dislocation of tibialis posterior tendon. A report of two cases.

We successfully treated two patients with recurrent dislocation of the tibialis posterior tendon by creating a bone block. Sudden resistive contraction of the tibialis posterior muscle is considered to be the mechanical cause of the initial traumatic injury, and a shallow tibialis posterior tendon sulcus may be the predisposing factor. Once the flexor retinaculum is torn during the initial trauma, recurrent dislocation is inevitable, and surgical treatment is mandatory. When treating patients with a complaint of long-standing pain around the medial malleolus, we must bear in mind the possible diagnosis of recurrent dislocation of the tibialis posterior tendon. If the patient can voluntarily dislocate the tendon by active plantar flexion and inversion of the ankle, the diagnosis is definitive.

Adult↗
PubMed1998

Choriocapillary changes and hyperfluorescence on indocyanine green angiography.

BACKGROUND: The purpose of this study is to examine the relationship between pathological changes of the choriocapillaris (CC) and the finding of bright fluorescence on indocyanine green (ICG) angiography. METHODS: An animal model was used, with chorioretinal lesions produced by injecting sodium iodate 3 h, 24 h, 7 days or 14 days previously. The ICG angiographic findings were compared with histology. RESULTS: Three hours after injection, many spots of bright fluorescence were scattered at the posterior pole. Histologically, variable changes in CC endothelial cells were observed. In some regions, the cells remained almost normal morphologically. In other regions, the endothelial cytoplasm was thickened with decreased fenestrations, or precipitation of fibrin in the choroidal interstitium was observed. Twenty-four hours after injection, the area of bright fluorescence had extended beyond that observed after 3 h. Histologically, the cytoplasmic structure of CC endothelial cells was unclear, and the endothelial walls were detached from the basement membrane. When ferritin was administered as a tracer, many ferritin granules were observed in Bruch's membrane. Seven days after injection, the degree of bright fluorescence was reduced as compared with 3 and 24 h after injection. Histologically, the cytoplasm of CC endothelial cells was thinned, but contained few fenestrations. The endothelial walls were detached from the basement membrane. Fourteen days after injection, normal diffuse ICG fluorescence was observed. Histologically, CC endothelial cells exhibited almost normal structure. CONCLUSION: These findings indicate that changes in CC endothelial cells and bright fluorescence on ICG angiography are closely related. ICG angiography should enable clinical evaluation of increased permeability of CC endothelial cells to relatively large molecules.

Animals↗
PubMed1998

Retinal sensitivity measurement over drusen using scanning laser ophthalmoscope microperimetry.

BACKGROUND: Retinal sensitivity over drusen was examined using a scanning laser ophthalmoscope to confirm a previous report of no change in sensitivity over drusen. METHODS: Microperimetry was performed using a scanning laser ophthalmoscope in 23 eyes of 19 subjects. Subject age ranged from 42 to 86 years (mean 68.5 years). Fifty-four drusen bigger than the diameter of a major retinal vein at the optic disc rim were examined, and drusen were classified as soft drusen and other large drusen. RESULTS: Nine eyes of eight subjects showed a decrease in retinal sensitivity over drusen. The decrease in retinal sensitivity was more than 5 dB less than the sensitivity at a peripheral non-drusen area peripheral to the measurement point. The sensitivity decrease was noted over 15 of 29 large drusen and the decrease was statistically significant (P < 0.02). However, no relationship between the size of the drusen and the amount by which sensitivity decreased was found. Nevertheless, a decrease in retinal sensitivity was not seen over any of 25 soft drusen. CONCLUSION: Large drusen may influence retinal sensitivity and function.

Adult↗
PubMed1998

Agenesis of the right lobe of the liver: report of a case.

A case of congenital agenesis of the right lobe of the liver detected in a patient with gastric cancer is reported. The diagnosis of this rare anatomical variant was established by a combination of computed tomography, abdominal angiography, and operative findings. The importance of accurately recognizing this condition is stressed, and the clinical presentation, radiographic appearance, and differential diagnosis are also discussed.

Aged↗
PubMed1998

Further evidence for a major ancient mutation underlying myotonic dystrophy from linkage disequilibrium studies in the Japanese population.

The myotonic dystrophy (DM) mutation is an unstable (CTG)n repeat, present at a copy number of 5-37 repeats on normal chromosomes but amplified to 50-3000 copies on DM chromosomes. Previous findings in Caucasian populations of a DM founder chromosome raise a question about the molecular events involved in the expansion mutation. To investigate whether a founder chromosome for the DM mutation exists in the Japanese population, we genotyped families using polymorphic markers near the (CTG)n repeat region and constructed haplotypes. Six different haplotypes were found and DM alleles were always haplotype A. To find an origin of the (CTG)n repeat mutation and to investigate the mechanism of the expansion mutation in the Japanese population we have studied 90 Japanese DM families comprising 190 affected and 130 unaffected members. The results suggest that a few common ancestral mutations in both Caucasian and Japanese populations have originated by expansion of an ancestral n = 5 repeat to n = 19-37 copies. These data support multistep models of triplet repeat expansion that have been proposed for both DM and Friedreich's ataxia.

Adult↗
PubMed1998

Choroidopathy after blunt trauma to the eye: a fluorescein and indocyanine green angiographic study.

PURPOSE: To describe the uses of fluorescein angiography and indocyanine green angiography in highlighting traumatic choroidopathy. METHODS: In a prospective study, 21 patients (21 eyes) who presented with traumatic retinal opacity ophthalmoscopically underwent fluorescein angiography and indocyanine green angiography. With indocyanine green angiography, the subtraction method was used for detailed examination. RESULTS: In 11 of 21 eyes, fluorescein angiography showed no abnormalities. On indocyanine green angiography, delayed filling in the choroid was found locally in nine of these 11 eyes. Delayed filling of the choroidal veins was clearly visualized by the subtraction method. In six eyes, intrachoroidal indocyanine green leakage around the choroidal vessels, including vortex veins, was found. In the remaining 10 of the 21 eyes, fluorescein angiography showed fluorescein leakage or a salt-and-pepper appearance in the region of retinal opacity. On indocyanine green angiography, a triangular-shaped area of delayed filling of the choroidal arteries was observed in four eyes. Delayed filling of the choroidal veins was visualized in all 10 eyes, intrachoroidal indocyanine green leakage was found in eight, and dilation and/or narrowing of the choroidal veins and changes in choroidal vasculature were visualized in five eyes. Furthermore, in regions with fluorescein leakage, indocyanine green leakage or hypofluorescence was observed, suggesting damage to the choriocapillaris. CONCLUSION: Indocyanine green angiography allows the analysis of various degrees of choroidal vascular damage. Because the choroidal circulation nourishes the outer retinal layer, traumatic choroidopathy may play a role in the prognosis for visual recovery in eyes affected by contusion retinal opacities.

Adolescent↗
PubMed1998

Acute retinal necrosis late in the second trimester.

PURPOSE: To report treatment of a patient with acute retinal necrosis during pregnancy. METHODS: A 24-year-old woman in her twenty-third week of gestation was diagnosed with acute retinal necrosis. A combination of acyclovir and interferon therapy was started at 25 weeks. Pars plana vitrectomy was performed during the 26th week of gestation. RESULTS: The necrotizing retina became gliotic within 3 weeks of surgery. The patient's visual acuity improved to LE, 20/40. A healthy baby was delivered at 39 weeks of gestation. CONCLUSION: Combination therapy of acyclovir and interferon followed by surgery partially restored the patient's vision without affecting fetal development.

Acyclovir↗
PubMed1998

Effects of epidermal growth factor on the invasion activity of the bladder cancer cell line.

PURPOSE: Epidermal growth factor (EGF) is excreted in high concentrations in the urine and stimulates urothelial cell growth. The cultured bladder cancer cell line KU-1 was used to study the molecular mechanisms by which EGF affects urothelial tumor growth and invasion activity. MATERIALS AND METHODS: KU-1 cells were grown in cell culture in the presence or absence of EGF. Anchorage-independent cell growth assays and Matrigel invasion assays were performed. Expression of cytokeratins was examined by Northern and Western blot analyses. Chloramphenicol acetyltransferase assays were used to determine whether EGF stimulated matrix metalloproteinase expression. RESULTS: EGF enhanced anchorage-independent growth in soft agar and increased the number of cells penetrating into a Matrigel membrane. A transient transfection assay revealed that EGF increased the promoter activities of the matrix metalloproteinase 1 and 9 genes in KU-1 cells. Moreover, the morphology of KU-1 cells changed after the addition of EGF to the culture medium. Western and Northern blot analyses demonstrated that EGF decreased cytokeratin 19 expression, but did not affect expression of cytokeratin 8 or 18. CONCLUSION: EGF increased the invasive activity of KU-1 bladder cancer cells in part by increasing the secretion of matrix metalloproteinases. Morphologic changes may result from altered composition of cytoskeletal proteins.

Epidermal Growth Factor↗
PubMed1998

Translocation (3;16)(q27;p11) in a patient with diffuse large B-cell lymphoma associated with the BCL-6 gene rearrangement.

A patient with B-cell lineage diffuse large-cell lymphoma carrying the t(3;16)(q27;p11) and BCL-6 rearrangement is described. Cytogenetic studies showed 46,XY,t(3;16)(q27;p11.2)[.11]/46,idem,add(18)(q21)[7]/46,XY[2]. The chromosomal translocation involving the 3q27 locus was associated with the BCL-6 gene rearrangement identified by Southern blot analysis. This case involved systemic lymph nodes, as large as 3 cm in diameter, bilaterally in neck, axilla, and inguinal regions. The patient obtained complete remission with chemotherapy.

Antigens, CD↗
PubMed1998

Angiotensin II type 1 receptor gene polymorphism is associated with increase of left ventricular mass but not with hypertension.

A genetic epidemiologic approach is useful to elucidate the genes responsible for hypertension. Genetic analyses of the components of the renin-angiotensin system have succeeded in showing an association between their polymorphism and hypertension. Recently, two types of angiotensin II receptor were cloned and characterized. To examine the genetic contribution of angiotensin II type 1 receptor (AT1) and type 2 receptor (AT2) genes in human essential hypertension, a case-control study was performed in Japanese subjects. The study comprised 321 subjects with hypertension who satisfied the criteria for essential hypertension, together with 215 age and sex matched controls. The significance of the differences in genotype distribution between hypertensive and normotensive subjects was examined by chi2 analysis. Neither AT1 nor AT2 gene variants were associated with human essential hypertension in the Japanese subjects. However, the AT1 receptor gene polymorphism was associated with left ventricular mass index in normotensive subjects. The study results suggest that gene polymorphisms of both angiotensin II receptors are not directly involved in the increase of genetic risk for hypertension, but that the AT1 receptor gene might contribute genetically to the increase of left ventricular mass.

Aged↗
PubMed1998

Methylenetetrahydrofolate reductase gene polymorphism: relation to blood pressure and cerebrovascular disease.

Hyperhomocysteinemia is reported to be associated with an increase in the incidence of ischemic heart disease and cerebrovascular disease. Genetic aberrations in methylenetetrahydrofolate reductase (MTHFR) may account for reduced enzyme activity and elevated plasma homocysteine level. A recent report revealed that a common mutation (677C to T; Ala to Val) in the MTHFR gene is associated with decreased specific MTHFR activity and with increased risk for coronary artery disease in the homozygous state (Val/Val). In the present study, we investigated whether the MTHFR gene is a genetic risk factor for cerebrovascular disease (CVD). To undertake a case-control study, we selected the patients with cerebral infarction (n = 48) or cerebral hemorrhage (n = 35) and examined the association between MTHFR gene polymorphism and CVD. The genotype distribution of the MTHFR gene was not significantly different between cases and controls. Because the possibility of matching the morbidity of the effects of hypertension, the lack of association could not be excluded in the first study; however, we also examined whether the MTHFR mutation was associated with any clinical risk factor for CVD or with hypertension. It turned out that the subjects with the Val allele of the MTHFR gene had significantly lower blood pressure than the subjects with other genotypes in the general population (P = .02), and that the frequency of the Val/Val genotype in hypertensive subjects (n = 173) was significantly lower than in control subjects (n = 184) (P = .03). From these results, we conclude that the Val/Val homozygous state of the MTHFR gene increased the risk of thrombosis, but reduced the blood pressure, which resulted in the lack of increased risk for CVD.

Cerebrovascular Disorders↗