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Biomedical subjects

M Fukunaga

Publications and source records attributed to M Fukunaga.

At least 55 records · Page 3Linked to original sources

Evaluation of disuse atrophy of rat skeletal muscle based on muscle energy metabolism assessed by 31P-MRS.

The purpose of this study was to evaluate disuse atrophy of skeletal muscle using a hind-limb suspension model, with special reference to energy metabolism. Twenty-four Sprague-Dawley rats were divided into four groups: control group (C), hind-limb suspended for 3 days (HS-3), for 7 days (HS-7) and for 14 days (HS-14). The gastrocnemius-plantaris-soleus (GPS) muscles in each group were subjected to the following measurements. After a 2-min rest, contraction of the GPS muscles was induced by electrical stimulation of the sciatic nerve at 0.25 Hz for 10 min, then the frequency was increased to 0.5 and 1.0 Hz every 10 min. During the stimulation, twitch forces were recorded by a strain gauge, and 31P-MRS was performed simultaneously. Maximum tension was measured at the muscle contraction induced at 0.25 Hz; the wet weight of the whole and each muscle in the GPS muscles was also measured. From the 31P-MR spectra during muscle contraction, the oxidative capacity was calculated and compared among the groups. The weights of the whole GPS muscles in C, HS-3, HS-7 and HS-14, were 2.66 +/- 0.09, 2.39 +/- 0.21, 2.34 +/- 0.21 and 2.18 +/- 0.14 (g) respectively. Thus, the muscle mass significantly decreased with time (p < 0.05). Among the GPS muscles, the decrease in weight of the soleus muscle was especially remarkable; in the HS-14 group its weight decreased to 60% of that in the C group. We evaluated maximum tension and oxidative capacity as the muscle function. The maximum tensions in C, HS-3, HS-7 and HS-14 were 519 +/- 43, 446 +/- 66, 450 +/- 23 and 465 +/- 29 (g), respectively. This was significantly greater in the C group than in any other groups, however there were no significant differences among the three HS groups. The oxidative capacity during muscle contraction in the C group was higher than in any HS group and it did not further decrease even if the suspension of the limbs was prolonged beyond 3 days. The present study showed that in disuse atrophy, muscle mass and muscle function did not change simultaneously. Thus, it is necessary to develop countermeasures to prevent muscle atrophy and muscle function deterioration independently.

Animals↗

Pseudopapillary solid cystic tumor arising from an extrapancreatic site.

A case of pseudopapillary solid cystic tumor arising in the omentum of a 46-year-old woman is presented. A well-defined, encapsulated tumor measuring 5.2 x 4.0 x 4.0 cm was histologically characterized by a combination of solid and pseudopapillary growth patterns of tumor cells with abundant pale-to-eosinophilic cytoplasm. No pancreatic tissue was observed within or adjacent to the tumor. Immunohistochemically, the tumor was positive for vimentin, epithelial membrane antigen, and alpha1-antichymotrypsin. Ultrastructurally, the tumor cells contained electron dense granules of variable sizes, most likely representing lysosomes. Flow cytometry showed a diploid DNA content with a high S-phase fraction. The patient was well without recurrence 3 months after diagnosis. It is important to include pseudopapillary solid cystic tumor in the differential diagnosis of omental tumors.

Cystadenoma, Papillary↗

[The efficacy of combination chemotherapy of 5'-deoxy-5-fluorouridine (5'-DFUR), cyclophosphamide (CPA) and medroxyprogesterone acetate (MPA) for bone metastasis in breast cancer patients].

5'-DFUR is a pro drug of 5-FU, which is known to be converted by thymidine phosphorylase (dThdPase). A recent pre-clinical study revealed that CPA upregulates dThdPase activity specifically in tumor cells. Furthermore, clinical trials have shown significant response rates in breast cancer patients, when using the chemotherapy combination of 5'-DFUR, CPA and MPA. The purpose of this study was to examine the efficacy of this regimen as a pain reduction therapy for breast cancer patients with bone metastasis. Ten patients who had bone metastasis with restricted ADL were included in the study. All of the patients had had previous exposure to such standard chemotherapy as CAF, CMF, taxol and oral 5-FU administration. The patients were administered daily oral doses of 5'-DFUR at 800-1,200 mg, CPA at 200 mg and MPA at 400-800 mg for two weeks as induction therapy, followed by two weeks rest (one to two cycles). Daily dose of 800 mg of 5'-DFUR, 100 mg of CPA, 400-800 mg of MPA was continuously administered thereafter. The main findings included a significant decrease in pain in eight patients, which continued for more than 6 months. In five patients, the effect lasted more than one year. As the pain decreased, the patients' QOL was improved. Hematological toxicity of more than grade 3 was observed in three patients but only during the induction therapy. One patient had pulmonary thrombosis and required hospitalization. In conclusion, oral administration of 5'-DFUR/CPA/MPA is well tolerated and useful in reducing pain.

Adult↗

Studies on mechanisms of low emetogenicity of YM976, a novel phosphodiesterase type 4 inhibitor.

YM976 is a novel and selective inhibitor of phosphodiesterase type 4 (PDE4) with a different chemical structure from rolipram. Orally administered YM976 showed anti-inflammatory activity (ED(50) = 2.8 mg/kg) similar to rolipram (3.5 mg/kg). On the other hand, the emetogenicity of YM976, one of the main adverse effects of PDE4 inhibitors, was lower (maximal non-emetic dose = 10 mg/kg) than that of rolipram (1 mg/kg). The reasons for this low emetogenicity of YM976 remain unclear, and the present study endeavored to elucidate the mechanisms. Candidates for the possible mechanisms included 1) PDE4 subtype selectivity, 2) binding affinity for HAR-conformation, and 3) brain penetration. YM976 exhibited affinity for high affinity for rolipram-conformation (HAR-conformation) (IC(50) = 2.6 nM) identical to that of rolipram (1.2 nM), and failed to show significant selectivity for the individual PDE4 subtype. These results suggested that neither subtype selectivity nor the affinity for HAR-conformation may be related to the low emetogenicity of YM976. YM976 showed a minor effect on reserpine-induced hypothermia, in contrast to rolipram. To estimate brain penetration, we then measured cAMP contents in peripheral tissues (peritoneal macrophages) and in the brain. YM976 increased the cAMP content of peritoneal macrophages, but caused no significant increase in brain cAMP levels, while rolipram elevated the cAMP content of both tissues at the same dose. In conclusion, YM976 shows an apparent dissociation between its anti-inflammatory effects and emetogenicity, perhaps because of the poor brain penetration.

3',5'-Cyclic-AMP Phosphodiesterases↗

[Whole-body MR imaging for evaluation of bone marrow cellularity in aplastic anemia].

The aim of this study was to investigate the usefulness of whole-body MRI(WB-MRI) in the evaluation of cellularity in bone marrow and the distribution of fatty marrow in aplastic anemia. WB-MRI was performed on five patients with aplastic anemia who ranged in age from 62 to 70 years of age, and on four controls with malignant lymphoma who ranged in age from 59 to 67 years. Coronal images were obtained using a body coil with an FOV of 48 cm x 48 cm, and with both fast short T1 inversion recovery(STIR) and spin-echo T1-weighted(T1-WI) in three regions: (1) head to thorax, (2) abdomen to pelvis, and (3) lower extremities. The findings on WB-MRI were compared with those of histological studies of bone marrow at the sternum and the posterior iliac crest. The results were as follows: (1) there was a correlation between the cellularity of histological studies of bone marrow and signal intensity on WB-MRI; (2) WB-MRI could detect the activity of bone marrow; and (3) in a comparison of signal intensity in aplastic anemia and control subjects, there were differences of signal intensity in the central marrow.

Aged↗

[Diagnosis with bone mass].

In diagnostic criteria of osteoporosis proposed by WHO, the severe osteoporosis is defined as a patient with a value for BMD or BMC more than 2.5SD below the young adult mean value in the presence of one or more fragility fractures. When severe fragility fracture occurs from the second to forth lumbar vertebra, the lumbar BMD could be over-estimated. On the other hand, when the lumbar BMD is markedly low, the demarcation of bone contour is incomplete, and the precision of the BMD measurement decreases. Thus, in the severe osteoporosis it is necessary to be careful in the diagnosis with bone mass using DXA.

English Abstract↗

[Diagnostic imaging of osteoporosis: special reference to diagnosis by radiography and DXA].

Primary osteoporosis is diagnosed by diagnostic criteria, eg. whether non-traumatic vertebral body is or not, or the severity of low bone mass. As a diagnostic imaging of osteoporosis, grading of radiographic osteopenia, and Singh index in the upper end of femur are well-known. Vertebral fracture associated with osteoporosis shows wedge, fish or flat deformity, but it is necessary to differentiate from Schmorl node and so on. DXA is a main stream of bone mineral quantification method, and its image is expressed the distribution of bone mineral density per unit area.

English Abstract↗

[Bone metabolic markers and diagnosis of abnormal bone and calcium metabolism].

Bone metabolic markers increase in blood or urine, when bone formation or bone resorption accelerates. Reference values of bone metabolic markers are determined in male or female, and in pre- or post-menopause, respectively. Values of bone metabolic markers in most patients with primary osteoporosis were distributed within a reference value, mean+/-1.96 SD. When measured values exceeded a reference values, we should survey a possibility of abnormal calcium or bone metabolism such as primary hyperparathyroidism, renal osteodystrophy, hyperthyroidism and Paget's disease of bone or bone metastasis associated with malignant tumor.

English Abstract↗

[Blood concentrations and secretory capacity of calcitonin in blood in osteoporosis].

The deficiency of calcitonin, CT, which has an inhibitory effect of bone resorption might be related to the pathogenesis of osteoporosis. Therefore, in this paper, in regard to the sex difference, the changes with aging, and the comparison with patients with osteoporosis and normal controls, the basal value and the secretion capacity of CT concentrations in the blood, and the metabolic clearance rate, MCR, and the production rate, PR, of CT have been reviewed.

English Abstract↗

Precipitation of Zinc Sulfide Particles from Homogeneous Solutions.

Zinc sulfide particles were homogeneously precipitated by thermal decomposition of thioacetamide in acidic aqueous solutions in a one-step process. The influence of the operating conditions (initial concentration of zinc ion and TAA) on the nucleation time and number concentration of the generated particles was investigated. The experimental results show that the model of homogeneous nucleation previously developed and successfully tested for silver particle generation by a chemical reduction method can also be applied to the formation of zinc sulfide particles by homogeneous precipitation. Furthermore, in the particle formation method in which the nucleation time t* can be measured, the particle number concentration n* can be predicted by the simple relation n*=1/(4pir*Dt*) (r* is the critical nucleus radius, and D the monomer diffusion coefficient). Thus the particle number concentration can be easily predicted even if the rate expression and the critical supersaturation concentration are unknown. Copyright 2000 Academic Press.

Journal Article↗

A Model for Simultaneous Homogeneous and Heterogeneous Nucleation in the Case of Slow Reaction Rate.

Our previous model for simultaneous homogeneous and heterogeneous nucleation, which was successfully tested for silver particle generation by a chemical reduction method, is extended to the case of slow reaction rate. Nucleation in a system containing seed particles in the case where the reaction rate is slow occurs according to the following rule: homogeneous nucleation is predominant when n(p)/n(0)(*),>1 (n(p) is the seed number concentration, and n(0)(*) the number concentration of homogeneously nucleated particles without seed particles), and heterogeneous nucleation is predominant when n(p)/n(0)(*)<1. This theoretical prediction is in good agreement with the experimental results obtained for zinc sulfide particles generated by homogeneous precipitation. Copyright 2000 Academic Press.

Journal Article↗

Frequent genetic heterogeneity in the clonal evolution of gynecological carcinosarcoma and its influence on phenotypic diversity.

Carcinosarcomas of the uterus, ovaries, and fallopian tubes are highly aggressive neoplasms with incompletely understood histogenesis. Although recent immunohistochemical, cell culture, and molecular genetic studies all favor these cancers to be monoclonal in origin, the extent of intratumoral genetic heterogeneity in these tumors with divergent histology has not been reported previously. For this study, we microdissected a total of 172 carcinomatous or sarcomatous foci from 17 gynecological carcinosarcomas and analyzed allelic status with 41 microsatellite markers on chromosomal arms 1p, 1q, 3p, 4q, 5q, 6q, 8p, 9p, 10q, 11p, 11q, 13q, 16q, 17p, 17q, 18q, and 22q. With the exception of a single case with microsatellite instability, we found shared allelic losses and retentions among multiple individually dissected foci of each case, strongly supportive of the concept of a monoclonal origin for these neoplasms. In eight of these cases, we also found heterogeneous patterns of allelic loss at limited numbers of chromosomal loci in either the carcinomatous or sarcomatous components of the neoplasms. These heterogeneous patterns of allelic losses were consistent with either genetic progression or genetic diversion occurring during the clonal evolution of these neoplasms. In two cases, we found the specific patterns of genetic progression to be consistent with sarcomatous components of the neoplasms arising from carcinomatous components. We conclude that most of the gynecological carcinosarcomas have a monoclonal origin, and that genetic progression and diversion parallel the development of divergent phenotypes in these tumors. Because phenotypically divergent areas of the tumors share numerous genetic alterations, this divergence most likely occurs relatively late in the evolution of these tumors.

Carcinosarcoma↗

Early partial hydatidiform mole: prevalence, histopathology, DNA ploidy, and persistence rate.

The widespread use of ultrasound in the diagnosis and management of intrauterine fetal death has resulted in moles being evacuated earlier than before. In order to clarify clinicopathologic features of early partial mole (PM), morphology and DNA ploidy of early (< or =12 gestational weeks) and late (>12 gestational weeks) partial PM were studied. A total of 80 early and 20 late PMs (37 from 1981-90; 63 from 1991-98) were analyzed. Mean gestational ages were 9.6 weeks for early PMs and 14.8 weeks for late PMs. Early PM was more common in 1991-1998 (57/63, 90%) than in 1981-1990 (23/37, 62%). Pre-evacuation diagnosis of hydatidiform mole was achieved in only 4 early and 1 late PMs. There were no significant differences in histology between early and late PMs, except that villi were smaller in early PMs and there was extensive stromal fibrosis in late PMs. Ploidy was as follows: 70 of 80 early PMs and 19 of 20 late PMs were triploid, 5 early PMs were aneuploid, and 5 early and 1 late PM were diploid. None of 45 patients with early PM and 1 of 11 with late triploid PM developed persistent gestational trophoblastic disease. Early PM is now more prevalent than it was previously. This may be a result of greater awareness of the entity of PM, its increased recognition by pathologists and the widespread use of ultrasound in the diagnosis and management of intrauterine fetal death. The diagnosis of PM should be based on pathological examination, since most PMs still elude clinical detection. DNA ploidy analysis is useful in the evaluation of problem cases. The risk of persistent disease seems to be very low in the case of early PMs.

Adult↗

Standard radial bone mineral density and physical factors in ordinary Japanese women.

To prevent osteoporosis, which is expected to increase in incidence in this rapidly aging society, in recent years bone mineral density (BMD) has frequently been measured as a predisposition index. However, these measurements are made on different sites with different apparatus, and the results are independently studied by different institutions. In our present investigation, to establish the standard radius BMD as determined by dual-energy X-ray absorptiometry (DXA), we carried out a general population survey in 29 municipalities and prefectures on 11,252 locally residing females aged 15 to 83 years (mean, 35.61 +/- 12.85 years). Their YAM (young adult mean) BMD was estimated at 0.664 +/- 0.054 g/cm2, which was almost the same as the figure given in the 1996 version of the diagnostic criteria for primary osteoporosis. We further studied the relationships of BMD to age and physical factors known to be influential to BMD. It was found that BMD was correlated negatively to age and positively to body mass index (BMI). The average values we obtained for age and physique groups appeared to have provided reliable indices for the primary prevention of osteoporosis.

Adolescent↗

Mitochondrial genetic code in cestodes.

The flatworm mitochondrial genetic code, which has been used for all species of the Platyhelminthes, is mainly characterized by AUA codon for isoleucine, AAA codon for asparagine and UAA codon for tyrosine. In eight species of cestodes (Echinococcus multilocularis, Echinococcus granlosus, Taenia solium Taenia saginata, Taenia hydatigena, Taenia crassiceps, Hymenolepis nama and Mesocestoides corti), the cytochrome c oxidase subunit I (COI) genes were partially sequenced to verify this genetic code. Comparison of the COI-encoding nucleotide sequences with those of human, sea urchin, fruit fly, nematode and yeast indicated that the assignments of AUA and AAA codons are adequate for cestodes. In addition, the nucleotide sequences of ATPase subunit 6 (ATP6) gene and its flanking region were compared to examine initiation and stop codons. In the related species of T. solium and T. saginata, the deduced amino acid sequences of ATP6 were homogeneous; however, the conversion of initiation codon AUG into GUG was observed in T. saginata. We also found the similar conversion in T. crassiceps. The C-terminal sequences of putative ATP6 proteins were highly conserved among the eight species and the stop codon UAG was altered to UAA in all Taenia species. The features of the gene-junctional region between NADH dehydrogenase subunit 4 (ND4) and glutamine tRNA (tRNAGln) genes also supported that UAA serves as a stop codon. Based on these results, we propose that the flatworm mitochondrial code should be modified for cestodes, particularly, in an initiating methionine codon (GUG) and a terminating codon (UAA).

Animals↗

A new approach for glomerular lesions: evaluation of scanning acoustic microscopy (SAM) for experimental glomerular disease in rats.

Most pathological evaluations using ordinary optical microscopy are usually qualitative and subjective. The beneficial properties of scanning acoustic microscopy (SAM) include not only observation of microstructure but also quantitative measurement of acoustic propagation speed, indicating the tissue elasticity. In this study, we examined the capability of SAM to evaluate pathological findings in glomeruli using anti-Thy.1 glomerulonephritis. Light microscopic observations of the glomeruli showed severe cell proliferation and mesangial matrix expansion at 10 days after induction of glomerulonephritis and, yet, to a lower extent at day 21 with onset of healing. C-mode scanning of SAM enabled imaging of glomerular structure compatible to findings of ordinary light microscopy. In addition, glomerular propagation speed in nephritic rats was significantly increased at day 10, and then decreased at day 21. These results indicate that SAM evaluation may be a new, useful technique for quantitative evaluation of proliferative glomerular lesions.

Animals↗

Intravenous tufted angioma.

A case of a rare vascular tumor, intravenous tufted angioma, is described. A 51-year-old Japanese man presented with a 12x8 mm solitary reddish nodule on the right foot, which had been found at birth. Histologically, the tumor was confined to a malformed vein and was characterized by nodular aggregates of plump cells. The aggregates showed a compact proliferation of round cells, including capillary-forming cells. Venous angiomatous areas were also observed. No multinucleated giant cells were seen. Immunohistochemically, the capillary-forming cells in the aggregates and the endothelial cells in the angiomatous areas were positive for endothelial markers (factor VIII-related antigen, CD31, CD34). Pericyte-like cells expressing alpha-smooth muscle actin and muscle actin, and macrophage-like cells, which stained for factor XIIIa, were intermingled in the cellular aggregates. Flow cytometric analysis showed diploidy. The tumor may be a hamartomatous lesion modified by secondary reactive changes, and it may represent a distinctive clinicopathological entity that is closely related histogenetically and perhaps pathologically to tufted angioma and the recently described "giant cell angioblastoma".

Antigens, CD34↗

Smooth muscle metaplasia in ovarian endometriosis.

AIMS: Little is known about smooth muscle metaplasia (SMM) in ovarian endometriosis. The clinicopathological significance of SMM in ovarian endometriosis is analysed. METHODS AND RESULTS: Three hundred and twenty-seven consecutive cases of ovarian endometriosis, including 58 cases associated with malignant ovarian epithelial tumour, between 1987 and 1996 were retrieved from hospital files and clinicopathologically analysed. The ages of the patients who showed SMM in ovarian endometriosis ranged from 28 to 70 years (average, 43. 8 years). SMM was observed in 58 cases (17.7%); in 51 of 269 cases without tumour (19.0%) and in seven of 58 with tumour (12.1%). The differences in the incidence of SMM in cases with and without tumour were not statistically significant. SMM was a focal, microscopic change and there was neither smooth muscle tumour nor uterus-like mass. Sixteen cases had short fascicles or stellate foci of SMM in the endometriotic stroma, an incomplete rim of SMM surrounding the endometriotic cysts was present in 32 cases, and 10 cases showed SMM in both the endometriotic stromal and incomplete rim of the endometriotic cysts. There was no significant histological difference in SMM between cases with and without malignant ovarian epithelial tumour. CONCLUSIONS: SMM in ovarian endometriosis is not an uncommon phenomenon. SMM may be explained in two ways. First, smooth muscle originates from metaplastic endometrial stromal cells in endometriotic foci. Second, it originates from metaplastic ovarian stromal cells in the rim of endometriosis.

Adult↗