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Biomedical subjects

M Fukunaga

Publications and source records attributed to M Fukunaga.

At least 199 records · Page 11Linked to original sources
PubMed1996

Postmenopausal intra-abdominal desmoplastic small cell tumor.

Intra-abdominal desmoplastic small cell tumor (DSCT) usually occurs in infants and young male adults. A case of DSCT occurring in a 60 year old female is described. No other apparent primary origin was detected. A mesocolon tumor, measuring 23 x 12 x 10 cm, was composed predominantly of round to spindle cells which showed epithelioid- and focally sarcomatous arrangements. Immunohistochemically, the tumor cells showed perinuclear dot-like staining of CAM5.2, many cells expressed HHF35, and some cells contained vimentin, epithelial membrane antigen, desmin, alpha-smooth muscle actin, neuron-specific enolase, or Leu 7. Electron microscopic examination showed that the tumor cells had mesenchymal-fibroblastic features. The tumor had an aneuploid DNA content with high S-phase fraction. The patient, who was treated with adjuvant chemotherapy, was alive, having had three recurrences in 36 months. In the second and third recurrent lesions, increased cellular atypia and fascicular arrangements of spindle cells were observed. DSCT should be included in differential diagnoses of post-menopausal pelvic tumors which show light-microscopically and immunohistochemically divergent phenotypes.

Abdominal Neoplasms↗
PubMed1996

Effect of estriol on bone loss in postmenopausal Japanese women: a multicenter prospective open study.

OBJECTIVES: To assess the effects of oral estriol on the bone mineral density (BMD) and bone metabolism in postmenopausal women. METHODS: Seventy-five natural postmenopausal women with a BMD of more than 10% below the peak bone density were treated for 50 weeks with 2 mg/day estriol (E3) cyclically and 0.8 g/day of calcium lactate continuously. BMDs at L2-L4 were measured by dual energy X-ray absorptiometry (DXA). RESULTS: The BMD increased 1.79% (p < 0.01 vs. pretreatment) after 50 weeks, accompanied with decrease of biochemical markers of bone turnover. With regard to climacteric symptoms, Kupperman's menopausal index improved (p < 0.01 vs. pretreatment) after 5 weeks of treatment. As to the incidence of adverse events genital bleeding was observed in only 8.0% of the subjects. Endometrial histology and cytology showed neither abnormalities nor hyperplasia during and after the treatment. CONCLUSIONS: Estriol prevented postmenopausal bone loss and improved climacteric symptoms effectively with low incidence of genital bleeding.

Bone Density↗
PubMed1996

Characterization of spirochetes isolated from ticks (Ixodes tanuki, Ixodes turdus, and Ixodes columnae) and comparison of the sequences with those of Borrelia burgdorferi sensu lato strains.

Ixodes persulcatus serves as a tick vector for Borrelia garinii and Borrelia afzelii in Japan; however, unidentified spirochetes have been isolated from other species of ticks. In this study, 13 isolates from ticks (6 from Ixodes tanuki, 6 from Ixodes turdus, and 1 from Ixodes columnae) and 3 isolates from voles (Clethrionomys rufocanus) were characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, rRNA gene restriction fragment length polymorphism, partial sequencing of the outer surface protein C (OspC) gene, whole DNA-DNA hybridization, and 16S rRNA gene sequence comparison. All of the results revealed that these Borrelia strains clearly represent at least two new species. A third is also likely, although additional strains have to be isolated and characterized before a separate species is designated. We designated all isolates of I. tanuki and C. rufocanus as group Hk501 and all isolates of I. turdus as group Ya501. Phylogenetic analysis based on 16S rRNA gene sequences distinguished these Borrelia strains from those belonging to hitherto known Borrelia species. Furthermore, the genomic groups, each with its own tick vectors with enzootic cycles, were quite different from each other and also from those of Lyme disease Borrelia species known to occur in Japan. The results of 16S rRNA gene sequence comparison suggest that the strain Am501 from I. columnae is related to group Hk501, although its level of DNA relatedness is less than 70%.

Amino Acid Sequence↗
PubMed1996

Physical mapping of the Borrelia miyamotoi HT31 chromosome in comparison with that of Borrelia turicatae, an etiological agent of tick-borne relapsing fever.

We report the construction of physical maps of chromosomes for Borrelia miyamotoi HT31 (a new species of Borrelia) and Borrelia turicatae (relapsing fever agent) by pulsed-field gel electrophoresis of DNA fragments generated by digestion of chromosomal DNA with rare-cutting restriction endonucleases and reciprocal hybridization. The size of the B. miyamotoi HT31 chromosome was calculated to be approximately 925 kilobase pairs, and the chromosome for B. turicatae was estimated to be 951 kilobase pairs. The chromosomes of B. miyamotoi HT31 and B. turicatae consisted of single linear molecules. The locations of several genes have been assigned to the chromosome maps by Southern hybridization by using specific gene probes. Comparison of the genetic maps of the two species of Borrelia provided evidence that the gene order on the chromosomes is quite similar to that of Borrelia burgdorferi sensu lato strains and is highly conserved in the genus Borrelia.

Blotting, Southern↗
PubMed1996

Alleviation of cisplatin nephrotoxicity: efficacy of local intra-arterial injection concomitant with hemodialysis.

Although cis-diamminedichloroplatinum (cisplatin) is widely used in the treatment of malignant tumors, the dose administered is limited because of side effects such as nephrotoxicity. The plasma levels of non-protein-bound platinum, which can be removed by dialysis, play an important role in the antitumor effects and the appearance of side effects. Selective intra-arterial injection of cisplatin during concomitant hemodialysis (HD) was performed in patients with gynecological malignancies. At a dose of 100 mg, about three times the non-protein-bound platinum excreted in the urine during the same period was removed by HD. The area under the time-concentration curve of plasma total platinum up to 5 h after intra-arterial injection was reduced by 46%. When doses of 200 or 250 mg were administered concomitantly with HD, the maximum plasma levels were suppressed to about the same degree as when 100 mg were injected without concomitant HD. A definite reduction in the incidence of side effects was seen, and a reduction in the severity of nephrotoxicity was also observed when 100 mg were given with HD. No severe side effects were found even when 200 or 250 mg were administered with concomitant HD. The antitumor effects were not reduced or possibly potentiated, but follow-up is still of short duration. These results indicate that chemotherapy with local intra-arterial injections of cisplatin using concomitant HD not only reduces systemic side effects, in particular nephrotoxicity, but also allows for increased doses at the tumor site and can be applied in patients with renal dysfunction.

Acetylglucosamine↗
PubMed1996

Influence of exercise and degenerative vertebral changes on BMD: a cross-sectional study in Japanese men.

The effects of recreational exercise and milk intake on BMD were assessed in Japanese men using analysis of covariance with significant predictor variables, selected from age, height, body weight and body mass index (BMI), as covariates. The influence of degenerative vertebral changes on these effects was also evaluated. Recreational exercise was found to be positively associated with BMD at the lumbar spine and the femoral neck, whereas milk intake, a possible indicator of calcium intake in the Japanese, was positively associated with BMD at the radius and the lumbar spine. Not only vertebral BMD but also radial and femoral neck BMD was higher in the subjects with osteophytosis or sclerosis in the lumbar vertebrae. Neither exercise nor lumbar pain was significantly related to these vertebral changes. These data suggest a protective effect of regular recreational exercise and milk intake on bone health in Japanese men.

Adult↗
PubMed1996

Clinicopathologic study of tetraploid hydropic villous tissues.

BACKGROUND: Because there are differences in the origin, morphology, and natural history of hydropic placental villous tissues, it is important to identify and document rare specimens that deviate from the diploid complete mole (CM), triploid partial mole (PM), or diploid hydropic abortion (HA). DESIGN: We clinicopathologically investigated 35 cytometric specimens of formalin-fixed, paraffin-embedded, tetraploid hydropic villous tissue. RESULTS: Of 35 cases, 25 were CMs, 10 were hydropic abortions, and none were partial moles. Assuming that the degree of molar change roughly correlates with the proportion of paternal chromosomes present, all chromosomes might be paternally derived in our 25 tetraploid CMs. Ten hydropic abortions, including two that were karyotypically either 92,XXYY or 90,XXYY,-13,14, were presumably due to two sets of chromosomes each from paternal and maternal origin. Of 14 tetraploid CMs for which follow-up data were available, two developed an invasive lesion and one developed choriocarcinoma with a diploid DNA content. However, as we reported previously, tetraploidy in CMs is not considered to be an independent predictor of persistent disease. CONCLUSION: These results indicate that patients with tetraploid CM require the same close follow-up given to diploid CM patients.

Abortion, Spontaneous↗
PubMed1995

The flagellin gene of Borrelia miyamotoi sp. nov. and its phylogenetic relationship among Borrelia species.

We have cloned and sequenced the flagellin gene from Borrelia miyamotoi strain HT31 and compared it with previously published flagellin sequences. Sequence similarity analysis demonstrated that strain HT31 is phylogenetically distant from the three species of Lyme disease borreliae is deeply branched into the relapsing fever borrelia cluster. The result was in full agreement with the classification of Borrelia strains using 16S tRNA sequences. This finding indicates that a phylogenetic analysis using flagellin gene sequences might be useful for classification of Borrelia strains.

Borrelia↗
PubMed1995

Flow cytometric and clinicopathologic study of 197 hydatidiform moles with special reference to the significance of cytometric aneuploidy and literature review.

In order to evaluate the significance of cytometric aneuploidy in molar placentas, we analyzed 197 hydatidiform moles by flow cytometry using formalin-fixed, paraffin-embedded tissues. Of 150 complete moles (CMs), 110 were diploid, 26 were tetraploid, and 14 were aneuploid (non-triploid/tetraploid aneuploid). Of 47 partial moles (PMs), 44 were triploid and 3 were diploid. We could not find any histologic differences among the diploid, tetraploid, and aneuploid CMs. We found that flow cytometric DNA analysis was very helpful to differentiate CM from PM. Persistent diseases developed in 12 of 69 CMs (17.4%) (9 of 47 diploid and 3 of 14 tetraploid CMs) and in none of 26 PMs (0%). Four diploid and 2 tetraploid CMs were invasive and one each with diploid and tetraploid CM developed choriocarcinoma and none of 8 aneuploid CMs had sequelae; however, there was no correlation between DNA ploidy and clinical outcome in the CMs. These results suggest that cytometric aneuploidy (non-diploidy) in CMs is not an independent predictor of persistent disease.

Aneuploidy↗
PubMed1995

Increased plasma levels of soluble thrombomodulin in patients with sepsis and organ failure.

The fact that thrombomodulin (TM) is released into the bloodstream from damaged vascular endothelial cells led us to hypothesize that plasma levels of soluble TM could be an indicator of the development of organ failure. In this study, we examined the changes in plasma levels of TM in 60 septic patients and 13 postsurgical patients, and investigated the circulating levels of interleukin 6 (IL-6) and polymorphonuclear leukocyte elastase (PMN-E) to determine the mechanism causing the excess liberation of TM. The arterial ketone body ratio (AKBR) was also measured as an indicator of the hepatocyte energy state. Of the 60 septic patients, 26 developed organ failure, 10 of whom died. In contrast, none of the postsurgical patients developed organ failure. The mean plasma level of TM was significantly higher in the septic patients who developed organ failure compared to those without organ failure (P < 0.001) or the postsurgical patients (P < 0.001). Furthermore, those patients whose plasma TM values became elevated over 6.0 ng/ml frequently developed complications. A positive correlation was also observed between the plasma TM levels and the IL-6 (P < 0.01) and PMN-E levels (P < 0.01). In contrast, a negative correlation was seen between the plasma TM levels and the AKBR (P < 0.01). These findings show that plasma TM could be a useful indicator of impending organ failure during sepsis.

Adult↗
PubMed1995

Evaluation of bone loss and the serum markers of bone metabolism in patients with hyperparathyroidism.

Bone loss and the serum markers of bone metabolism were studied in 22 patients with primary hyperparathyroidism and 108 patients with renal hyperparathyroidism. The parameters of bone loss were bone mineral density in the distal radius and lumbar vertebrae, measured by dual energy X-ray absorptiometry, and bone mass index (sigma GS/D) and the metacarpal index, in the second metacarpal bone, measured by the digital image processing method. Alkaline phosphatase (AIP), intact osteocalcin (OC), and the carboxyterminal propeptide of type I procollagen (PICP) were measured as serum markers of bone formation, while tartrate-resistant acid phosphatase (TRACP) and the carboxyterminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) were measured as serum markers of bone resorption. Bone loss and elevated markers of bone metabolism were observed both in patients with skeletal symptoms and in those without. Furthermore, the decrease in the cortical bone mass was more predominant than that of the trabecular bone. As markers of bone formation, AIP and OC seemed to be more sensitive than PICP, and as markers of bone resorption, ICTP appeared to be more sensitive than TRACP. Thus, a close correlation was observed between bone loss and the markers of bone formation and resorption.

Acid Phosphatase↗
PubMed1995

Incidence of hydatidiform mole in a Tokyo hospital: a 5-year (1989 to 1993) prospective, morphological, and flow cytometric study.

This prospective study reports the incidence of hydatidiform mole (HM) in a population of 13,510 pregnancies in a Tokyo hospital over a 5-year period between 1989 and 1993. During this period all "products of conception" from first- and second-trimester abortions were histologically reviewed, and 76 hydropic placentas were retrieved and analyzed by flow cytometry (FCM). Of 23 specimens originally diagnosed as complete hydatidiform mole (CM), 21 were diploid, and two were aneuploid (nontriploid/tetraploid). Of 22 partial hydatidiform moles (PMs), 20 were triploid, and two were diploid. Of 31 hydropic abortions (HAs), 20 were diploid, nine were triploid, one was tetraploid, and one was aneuploid. As to the correlation between morphology and data of FCM, two PMs were reclassified as HA, and eight HAs as PM, giving a ratio of 1 CM to 1.22 PM (23:28 cases). The incidence of HM was 1:265 pregnancies, (CM, 1:587; PM, 1:483). Only one case (3.6%) of PM was suspected clinically. One specimen of persistent disease occurred following a diploid CM. In our retrospective histological and FCM study in which 172 cases diagnosed as HM were retrieved from surgical pathology files between 1981 and 1991, there were 129 CMs and 43 PMs (CMs:PMs = 3:1). These findings indicate that PM is a common but underdiagnosed condition. Almost all studies in the literature may have severely underreported the incidence of PM. It is suggested that during routine delivery and pathology examination only the most florid PMs are recognized, whereas most with subtler changes go undiagnosed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Urinary excretion of type I collagen crosslinked N-telopeptides in healthy Japanese adults: age- and sex-related changes and reference limits.

A new immunoassay for measuring urinary excretion of type I collagen crosslinked N-telopeptides (NTx) has been reported to be a specific and sensitive method for assessing bone resorption. We have studied factors affecting biological variations in urinary NTx excretion in a population of 452 healthy Japanese adults, comprising 238 men and 214 women, 20-79 years of age. Urinary NTx excretion increased significantly with age in women (> or = 25 years of age) (r = 0.55, p < 0.0001) and modestly correlated with lumbar bone mineral density (L-BMD) in both sexes (> or = 25 years of age) (r = 0.31, p < 0.0001 for men; r = 0.50, p < 0.0001 for women). Urinary NTx levels in women were significantly higher than in the corresponding male age groups after the fifth decade (p < 0.0001). None of the anthropometric variables (weight, height, and body mass index) showed a linear effect on the urinary NTx excretion independent of age and L-BMD. In women, menopause was reflected by a twofold increase in urinary NTx excretion, from a mean of 28-59 pmol bone collagen equivalents (BCE)/mumol creatinine, and this menopause-related increase persisted for the entire postmenopausal period. In postmenopausal women, the interindividual variations of urinary NTx excretion were much more marked than in men and in premenopausal women. Moreover, in the subgroups of pre- and postmenopausal women, urinary NTx excretion correlated with neither age nor L-BMD. These data show that the major biological factor that modifies urinary NTx level is menopause and suggest that the bone turnover rates in the elderly women are increased, on average, irrespective of bone mineral density.

Absorptiometry, Photon↗
PubMed1995

Coexpression of cdk2/cdc2 and retinoblastoma gene products in colorectal cancer.

The retinoblastoma gene (Rb gene) is a tumour-suppressor gene and its product (pRB) is known to act as a negative regulator of the cell cycle. Although lack of pRB expression resulting from gene alterations is considered to be responsible for the genesis of several human malignancies, increased expression of pRB has been demonstrated in a majority of colorectal cancer cases. In the present study, we investigated the expression of pRB as well as that of its related kinases, cdk2 and cdc2, in colorectal cancer, since these kinases have been reported to phosphorylate and inactivate pRB. Western blot analysis revealed that colorectal cancer expressed higher levels of cdk2 and cdc2 than did normal mucosa and that the ratio of the hyperphosphorylated form of pRB was higher in colorectal cancer. Furthermore, immunohistochemical studies showed that cdk2/cdc2 was expressed exclusively in the cancer cells positive for pRB. These results suggest that an increase in the expression of cdk2/cdc2 in colorectal cancer may have prevented pRB from braking the cell cycle through phosphorylation.

Blotting, Western↗
PubMed1995

Atypical and malignant variants of ossifying fibromyxoid tumor. Clinicopathologic analysis of six cases.

Ossifying fibromyxoid tumor (OFMT) of soft parts is a recently defined fibro-osseous neoplasm, the biologic behavior of which is generally regarded as benign. We report six variant cases of OFMT with histologic features of malignancy, two of which behaved aggressively. All these tumors arose in the extremities of adults (aged 36-76 years), and five of the six were subcutaneous. Four patients were men. Macroscopically, all the tumors were well circumscribed and somewhat lobulated. Cardinal morphologic features included lobules of round to spindled cells within a fibromyxoid matrix and randomly distributed, often centrally located osteoid within which were plump neoplastic cells. In contrast to typical OFMT, a hypocellular, cytologically benign, lamellar bony shell was observed only focally; cellularity was increased (four cases), and mitotic activity was frequent, exceeding two mitotic figures per 10 high-power fields (three cases). One case associated with metastases was morphologically bland. Immunohistochemically, positivity for S-100 protein was observed in the primary tumors of three cases and in the pulmonary metastasis of a fourth. Desmin was positive in one case. Ultrastructural features in three cases were very similar to usual OFMT. Clinical follow-up revealed local recurrence in two cases; one patient has developed recurrent pulmonary metastases. We believe these findings support the view that some atypical cases of OFMT exhibit morphologic patterns that might predict more aggressive behavior.

Adult↗