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Biomedical subjects

M Fukunaga

Publications and source records attributed to M Fukunaga.

At least 19 recordsLinked to original sources

Vulval angiomyofibroblastoma. Clinicopathologic analysis of six cases.

Clinicopathologic, immunohistochemical, ultrastructural, and flow cytometric analyses were performed on vulvar angiomyofibroblastomas in six women (ages 32 to 46 years; average age, 41.3 years). The tumors were all well circumscribed, and measured 2 to 9 cm in greatest dimension. Five tumors were clinically diagnosed as Bartholin's gland cysts. At histologic analysis, the tumors were characterized by alternating hypercellular and hypocellular edematous areas with abundant blood vessels. The hypercellular areas showed a perivascular proliferation of spindle-shaped and round cells, which often formed small nests or epithelioid arrangements, and a short fascicular pattern of spindle cells. The proliferating vessels were thin-walled and capillary-sized. Cellular atypia and mitotic figures were absent. Two tumors contained an adipose element, and one showed a prominent vascular proliferation reminiscent of a capillary hemangioma. At immunohistochemical analysis, the tumor cells were strongly positive for vimentin and desmin. Some cells were weakly positive for HHF35 and alpha-smooth muscle actin. Ultrastructurally, one neoplasm showed fibroblastic differentiation. Flow cytometry revealed three tumors were DNA diploid and two were aneuploid. All tumors were excised, and none have recurred (average follow-up, 28.3 months). These results indicate that angiomyofibroblastomas contain heterogeneous components.

Adult

Treponema medium sp. nov., isolated from human subgingival dental plaque.

A new Treponema species, for which we propose the name Treponema medium, was isolated from subgingival plaque from an adult with periodontal disease. The morphological characteristics, differential biochemical characteristics, and protein profiles on sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels of this organism are described. The guanine-plus-cytosine content of the DNA of T. medium is 51 mol%. The levels of DNA-DNA relatedness of the new species to other Treponema species, including Treponema denticola, Treponema vincentii, Treponema socranskii, Treponema pallidum, and Treponema phagedenis, are less than 30%. A phylogenetic analysis based on 16S rRNA sequences distinguished the new Treponema strain from strains belonging to previously described Treponema species. The type strain of T. medium is strain G7201.

Bacterial Proteins

Homology of variable major protein genes between Borrelia hermsii and Borrelia miyamotoi.

Antigenic variation has been studied in detail for the etiological agent of relapsing fever, Borrelia hermsii. The variable major proteins (vmps) are found at its cell surface, enabling it to avoid the host's immune response. We have cloned and sequenced the vmp-gene (vmp)-like sequences from the Borrelia miyamotoi strains HT31 and FR64b and the deduced amino acid sequences were compared with the published vmp proteins vmp3, vmp24, and vmp33 of B. hermsii. The sequences were aligned and revealed pairwise sequence identities ranging from 45 to 51%, and differences were scattered throughout the sequences. Southern hybridization using the cloned vmp-like sequence of strain HT31 as a probe suggested that the vmp homologues reside on the linear plasmids of B. miyamotoi. The probe hybridized weakly with B. hermsii linear plasmids and restriction digests. These results suggest that B. miyamotoi has sequences resembling the vmp genes in B. hermsii.

Amino Acid Sequence

Choriocarcinoma in situ at a first trimester. Report of two cases indicating an origin of trophoblast of a stem villus.

Two cases of choriocarcinoma in situ arising in a first trimester placenta are reported in a 28-year-old gravida 2, para 1, Japanese woman and a 38-year-old gravida 2, para 0. Both had a dilation and curettage (D and C) for vaginal bleeding and the absence of intrauterine fetus. No macroscopic abnormalities were noted in either case. However, histologically, localized nodules of neoplastic trophoblastic proliferation measuring 5 mm in the first case, and 6 mm in the second appeared to arise directly from normal stem villi and project into the intervillous space. Both tumours were composed of biphasic cytotrophoblast and syncytiotrophoblast. Fetal elements were not observed in either case. Radiographic studies showed no metastatic lesions in either patient. Urinary human chorionic gonadotropin levels were within normal range in both patients. The first patient had a normal full-term spontaneous vaginal delivery 22 months after the D and C and was free from disease without therapy at 32 months. The second patient was free from disease without therapy with a limited follow-up. These tumours provide evidence for an origin of choriocarcinoma from trophoblast of a stem villus. This report illustrates the need to perform thorough microscopic examination of the products of conception especially in the absence of a fetus or fetal parts.

Adult

Retiform haemangioendothelioma.

A case of retiform haemangioendothelioma (RH), a recently described rare cutaneous low-grade angiosarcoma, is presented. A 75-year-old female had a 3.5 cm cutaneous nodule in her right lower thigh with 10 year preoperative duration. Microscopically, the dermis and subcutis contained a diffuse and infiltrative neoplasm which was characterized by long arborizing blood vessels arranged in a retiform pattern lined by cuboidal and flattened cells, occasional hobnail appearance of endothelial cells, and a prominent small lymphocytic infiltrate. Small solid areas were also found. Neither significant cellular atypia nor mitotic activity was observed. Immunohistochemically, the tumour cells reacted with endothelial markers (CD31, CD34, factor-VIII-related antigen) and bound Ulex europaeus agglutinin 1. There was no pericytic component within the tumour. The tumour was diploid by flow cytometry. The patient had a local recurrence 27 months after the excision. These findings support the view that RH is a low-grade angiosarcoma and indicate that RH must be distinguished from conventional angiosarcoma.

Aged

Low-grade fibromyxoid sarcoma.

A low-grade fibromyxoid sarcoma arising in the thigh of a 16-year-old Japanese girl is described. The patient had a well-circumscribed mass measuring 3.5 cm in its greatest diameter within her left vastus medialis muscle and a 6-month history of pain. Microscopically, the tumour was not encapsulated and filtrated into adjacent skeletal muscle. The tumour was characterized by poor to moderate cellularity, a proliferation of bland-appearing spindle tumour cells, and alternating fibrous and myxoid areas with a whorled pattern of the tumour cells. Neither cellular atypia nor mitotic figures were observed. There was no tumour necrosis. Immunohistochemically, the tumour cells were diffusely and strongly positive for vimentin and desmin. Some cells contained alpha smooth muscle actin. They were uniformly negative for CAM5.2, epithelial membrane antigen, muscle-specific actin (HHF35), factor-VIII-related antigen, S-100 protein, neurofilament, CD34, and CD31. The tumour had a diploid DNA content with S-phase fractions of 6.6% by flow cytometry. The patient was alive with no evidence of disease 11 months after excision.

Actins

Sex and age patterns of quantitative ultrasound densitometry of the calcaneus in normal Japanese subjects.

: The speed of sound (SOS), broadband ultrasound attenuation (BUA), and the stiffness index (stiffness), which was derived from SOS and BUA, were measured on the calcaneus using the Achilles ultrasound densitometer (Lunar) in normal Japanese woman (n = 473) and men (n = 218). Sex differences and age-related changes in these variables were investigated. In addition, the bone mineral density (BMD) of the lumbar vertebrae measured by dual X-ray absorptiometry (QDR-2000, Hologic) was compared with SOS, BUA, and stiffness. There were some decreases of ultrasound variables in both young adult men and women. BMD values were similar in young adults of both sexes. BMD was relatively stable in women from 20 to 49 years, then decreased at about 1.5%/year. Ultrasound variables were higher in males than females at all ages, and they decreased from age 20 onward in both sexes with an annual loss of about 0.6%. Age-related changes in SOS, BUA, and stiffness were different from those in BMD in normal Japanese subjects. The correlations between BMD and SOS and BUA and stiffness were higher in women (r = 0.51-0.64) than in men (r = 0. 43-0.49).

Absorptiometry, Photon

Prediction of bone mass in renal hyperparathyroidism by newly developed bone metabolic markers: evaluation of serum levels of carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen and carboxy-terminal propeptide of type I procollagen.

Serum levels of the carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) and the carboxy-terminal propeptide of type I procollagen (PICP) were measured in 95 patients with renal hyperparathyroidism who had undergone a total parathyroidectomy and autotransplantation of a small portion of the resected gland. The results were compared with the serum levels of other bone metabolic markers and bone mineral densities in the distal radius (R-BMD) and lumbar vertebrae (L-BMD), which were measured by dual energy x-ray absorptiometry and converted to the percentage of the mean value of sex- and age-matched healthy controls. The preoperative mean values of ICTP and PICP were 142.4 ng/ml and 187.8 ng/ml, respectively. Although the serum levels of PICP levels exceeded the normal range in 42.1% of the patients, those of ICTP exceeded it in all of them. The serum levels of ICTP correlated positively not only with those of tartrate-resistant acid phosphatase (TRACP), total alkaline phosphatase (ALP), and osteocalcin but also negatively with the values of %R-BMD and %L-BMD and seemed to manifest specifically the disturbance of bone metabolism. On the other hand, the serum levels of PICP correlated with those of ALP and TRACP but not with values of %BMDs. After surgery, the serum levels of ICTP decreased gradually, but those of PICP increased immediately up to peak values at 7 days and then decreased gradually after 14 days, reaching the normal range at 3 months. These changes in the bone metabolic markers seemed to reflect the change in bone metabolism that was converting from bone resorption to bone formation. The percent change in the PICP/ICTP ratio at 7 days correlated significantly with the percent change in R-BMD at 12 months, and it was suggested that postoperative bone gain might be predicted using a combination of postoperative changes in PICP and ICTP.

Absorptiometry, Photon

Anti-inflammatory lymphokine mRNA expression in antibody-induced glomerulonephritis.

T-helper subset 2 (Th2) lymphocytes produce interleukin 4 (IL-4) and IL-10, which exert anti-inflammatory actions on monocytes and macrophages. Th1 lymphocytes, on the other hand, secrete interferon-gamma (IFN gamma) which promotes tissue inflammation. The functional dichotomy between TH1 and Th2 lymphocyte subsets suggests that these cells play a regulatory role in inflammatory disease. The participation of Th subpopulations and their lymphokine products in experimental glomerulonephritis (GN) has not been previously evaluated. In this study, we examined renal expression of Th1 and Th2-type lymphokines in the first 48 hours of passive anti-glomerular basement membrane (anti-GBM) GN in the rate. Using the reverse transcriptase-polymerase chain reaction (RT-PCR) method, apparent increase in expression of both TH1-type (IL-2 and IFN gamma) and Th2-type (IL-4 and IL-10) lymphokine mRNA was observed in glomerular-enriched renal tissue obtained from nephritic rats. Induction of monocyte-derived IL-1 alpha and IL-1 receptor antagonist (IL-1RA) mRNA expression was also detected shorted after initiation of GN. Evidence for influx of mononuclear cells including T lymphocytes into the kidney was noted during the same time period as cytokine mRNA expression. Utilizing a monoclonal anti-rat IL-4 antibody, we also detected interleukin 4-producing cells in the renal cortex 24 hours following induction of GN. these experiments demonstrate for the first time anti-inflammatory lymphokine (IL-4 and IL-10) mRNA expression and IL-4 protein production in the kidney during antibody-mediated GN. WE hypothesize that Th lymphocyte subsets modulate glomerular inflammation by producing lymphokines with opposing actions.

Animals

Mixed tumour of the vagina.

A 33-year-old Japanese woman presented with a polypoid 2.5 x 2.5 x 1.9 cm mass located in the posterior wall of the lower vagina. Microscopically, the tumour was composed of benign epithelial and stromal-type elements. Predominant epithelial elements were mucinous glands with squamous metaplasia and islands of mature squamous epithelium. The stromal-type cells showed reticular or short fascicular patterns with a transition to the epithelial elements. There was no dual epithelial-myoepithelial combination in the glands as seen in so-called mixed tumours (pleomorphic adenomas) of the salivary gland. Immunohistochemically, the epithelial elements were strongly positive for cytokeratin, PKK1 and epithelial membrane antigen, while the stromal-type cells co-expressed PKK1 and vimentin. Staining for S-100 protein, muscle actin, alpha-smooth muscle actin, desmin, and CD34 was uniformly negative in the tumour cells. The DNA pattern was diploid. The patient is alive and well without recurrence for 50 months after excision. These results indicate that an epithelial cell proliferation, probably of the remnant vestibular gland, plays a major role in the development of mixed tumours of the vagina.

Adenoma, Pleomorphic

Carcinosarcoma of the uterus with extensive neuroectodermal differentiation.

A case of uterine carcinosarcoma with extensive neuroectodermal differentiation occurring in a 54-year-old woman is described. Microscopically, the endometrial tumour was predominantly composed of a sheet-like proliferation of small- and medium-sized cells. These cells were characterized by fibrillary cytoplasmic processes, rosette-like formations, perivascular palisading patterns, and immunoreactivity for glial fibrillary acidic protein, synaptophysin, leu 7 and neuron-specific enolase. In limited areas, features of conventional carcinosarcoma, including squamous cell carcinoma, leiomyosarcoma and islands of the above mentioned small- to medium-sized cells that were intermingled, were observed. The tumour was aneuploid by flow cytometry. The patient is alive with tumour for three months. It is suggested that at least some cases of uterine primitive neuroectodermal tumour may be explained by one-sided neuroectodermal development within a carcinosarcoma.

Biomarkers

I-123 iodoamphetamine scintigraphic detection of bone metastases from malignant melanoma.

Widely used for cerebral perfusion imaging, I-123 iodoamphetamine (I-123 IMP) is also known to accumulate in malignant melanomas. A case of malignant melanoma is presented, in which I-123 IMP scintigraphy was useful to visualize the bone metastases. During the period of postoperative follow-up, multiple foci of increased I-123 IMP uptake appeared in the skeleton. Conventional bone scintigraphy was less striking, showing cold defects or irregular radionuclide uptake.

Amphetamines

Alterations in coagulation and fibrinolysis during sepsis.

Circulating levels of thrombin-antithrombin III complex (TAT) and plasmin-alpha 2 plasmin inhibitor complex (PIC) in 49 septic patients (23 patients with organ dysfunction (OD), 26 without OD) and 11 postgastrectomy patients were measured to determine the significance of the coagulation-fibrinolytic systems in the development of OD. Tissue plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), and thrombomodulin were also measured. The mean level of TAT on the day when OD occurred was significantly higher compared with the maximum level of TAT in septic patients without OD (P < .01) or postoperative patients (P < .01). There was no difference in PIC levels between the three groups. The TAT/PIC ratio was significantly higher in septic patients with OD compared with the other groups (P < .001). Septic patients with OD showed higher levels of PAI-1 (P < .001) but not of t-PA. Thrombomodulin levels were significantly higher in the septic patients with OD compared with the others (P < .001). We conclude that suppression of the fibrinolytic system contributes to the imbalance between coagulation and fibrinolysis, and that this hypercoagulable millieu on the endothelial surface leads to the onset of OD.

Adult

A phylogenetic analysis of Borrelia burgdorferi sensu lato isolates associated with Lyme disease in Japan by flagellin gene sequence determination.

We determined nearly complete flagellin gene sequences for Borrelia burdgdorferi sensu lato isolates (11 isolates obtained from Ixodes persulcatus ticks and patients in Hokkaido, Japan, and 1 European isolate) representing six different restriction fragment length polymorphism (RFLP) ribotype groups following cloning of the PCR-amplified genes. These sequences were aligned with those of representatives of the three Borrelia species associated with Lyme disease, and a phylogenetic tree was constructed by the Clustal method. On the Lyme disease borrelia portion of the tree, the species were clearly delineated into three different phylogenetic groups, in complete agreement with the division of B. burgdorferi sensu lato into three species. A phylogenetic analysis revealed that the representatives of RFLP ribotype groups IV, V, and VI clustered tightly with each other and belonged on the same branch as Borrelia garinii. We used the criteria that are currently used to delineate bacterial species and determined the levels of DNA relatedness for these Borrelia isolates. For the RFLP ribotype group IV, V, and VI isolates, the levels of DNA relatedness ranged from 79 to 88%, and the levels of relatedness to the reference strain of B. garinii ranged from 70 to 80%. The levels of DNA relatedness of the RFLP ribotype group IV, V, and VI isolates to the representatives of other species associated with Lyme disease ranged from 53 to 66%. All of these findings indicate that the RFLP ribotype group IV, V, and VI isolates should be included in the species B. garinii.

Bacterial Typing Techniques