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Biomedical subjects

Yasufumi Hayashi

Publications and source records attributed to Yasufumi Hayashi.

At least 19 recordsLinked to original sources

Vanishing White Matter Disease With EIF2B2 c.254 >A Variant: Mild Clinical and MRI Findings.

OBJECTIVES: Typical MRI findings of vanishing white matter disease (VWM) include diffuse white matter lesions with cystic degeneration. However, mild cases may lack these typical features, posing diagnostic challenges. METHODS: We describe 2 of 3 individuals carrying the homozygous c.254T >A variant in EIF2B2 identified at our hospital, excluding 1 previously reported case.1 Genetic analyses were performed using whole-genome sequence or whole-exome sequence analysis, and detected variants were confirmed by direct nucleotide sequence analysis. Brain MRI findings and clinical features were reviewed for the 2 individuals along with other cases in the literature with the same variant. RESULTS: A 69-year-old woman presented with recurrent transient dizziness and secondary amenorrhea. MRI of the brain revealed small T2-hyperintense lesions confined to the subcortical white matter with hyperintensities on diffusion-weighted images and mildly elevated apparent diffusion coefficient values. A 28-year-old woman presented with transient dizziness and secondary amenorrhea. MRI of the brain showed mild T2-hyperintense lesions in the cerebral white matter with frontal predominance. DISCUSSION: This report highlights the clinically mild cases of VWM with subtle abnormalities on brain MRI who had the homozygous c.254T >A in EIF2B2, further expanding the clinical spectrum of VWM and underscoring the importance of genetic assessments in the diagnosis of individuals with mild clinical and MRI findings.

Journal Article↗

A new active vitamin D, ED-71, increases bone mass in osteoporotic patients under vitamin D supplementation: a randomized, double-blind, placebo-controlled clinical trial.

CONTEXT: ED-71 has been shown to increase lumbar bone mineral density (BMD) in osteoporotic subjects. However, vitamin D insufficiency might have influenced the effect of ED-71 on BMD. OBJECTIVE: Our objective was to examine whether ED-71 can increase BMD in osteoporotic patients under vitamin D supplementation. DESIGN, SETTING, AND PATIENTS: We conducted a randomized, double-blind, placebo-controlled clinical trial of 219 osteoporotic patients (49-87 yr of age). INTERVENTIONS: Subjects were randomly assigned to receive placebo or 0.5, 0.75, or 1.0 microg/d ED-71 for 12 months. All the subjects received 200 or 400 IU/d vitamin D(3). MAIN OUTCOME MEASURES: We assessed changes in lumbar and hip BMD and bone turnover markers from baseline. RESULTS: Lumbar BMD increased with ED-71 treatment for 12 months (2.2, 2.6, and 3.1% from baseline and 2.9, 3.4, and 3.8% vs. placebo group in subjects receiving 0.5, 0.75, and 1.0 microg ED-71, respectively). Total hip BMD also increased with 0.75 and 1.0 microg ED-71 (-0.8, 0.6, and 0.9% from baseline and 0.1, 1.5, and 1.8% vs. placebo group in the 0.5, 0.75, and 1.0 microg ED-71 groups, respectively). Bone formation and resorption markers were suppressed by approximately 20% after 12 months of 0.75 and 1.0 microg ED-71 treatment. Transient hypercalcemia over 2.6 mmol/liter occurred in 7, 5, and 23% of subjects in the 0.5, 0.75, and 1.0 microg ED-71 groups, respectively, but none of them developed sustained hypercalcemia. CONCLUSIONS: These results demonstrate that ED-71 treatment at around 0.75 microg/d can effectively and safely increase lumbar and hip BMD in osteoporotic patients with vitamin D supplementation.

Absorptiometry, Photon↗

[Active vitamin D metabolite and prevention of falls].

Recently, vitamin D metabolites have been internationally recognized to be effective for osteoporosis. The beneficial trend of the drugs for osteoporosis has been more in the prevention of fracture than in the increase of bone mineral density, and more in the prevention of fractures of four extremities compared to spinal fractures. The reason to reduce the fracture frequency of four extremities is due to increase the muscle power, the decrease of body sway and the reduction of falls by the action of the vitamin D. In the study of Japanese, it was declared that administration of active vitamin D significantly reduced the frequency of femoral neck fracture.

Accidental Falls↗

Enhancement of pleural dissemination and lymph node metastasis of intrathoracic lung cancer cells by vascular endothelial growth factors (VEGFs).

The expression of vascular endothelial growth factors (VEGFs) in tumors including lung cancer is considered to be associated with tumor development via capillary and lymph vessel neogenesis. Dissemination of the tumor cells to the pleura or regional lymph nodes is a critical poor prognostic factor for lung cancer patients. To investigate how VEGFs expressed in the intrathoracic infiltrating lung cancer cells participate in disease progression, we established stably VEGF-A-, VEGF-C-, VEGF-D-, VEGF-A and VEGF-C-, and VEGF-A and VEGF-D-expressing large cell lung cancer clones (TKB5/VEGF-A, TKB5/VEGF-C, TKB5/VEGF-D, TKB5/VEGF-A/C, and TKB5/VEGF-A/D), orthotopically inoculated these into the right thoracic cavity (i.t.) of nude mice, and evaluated the subsequent development of lung lesion, pleural effusion, pleural dissemination, and lymph node metastasis. While there were no significant differences either in culture or in subcutaneous tumor cell growth between the empty vector-transfected group (TKB5/empty) and each transfectant, the i.t. model demonstrated significantly different biological properties between the transfectants. TKB5/empty-inoculated mice frequently developed a large tumor on the pleura without pleural effusion, dissemination, or lymph node (LN) metastasis. In contrast, VEGF-A promoted a bloody pleural effusion (6/14), and VEGF-A and VEGF-D frequently generated pleural dissemination (11/14 and 9/11, respectively). Although both VEGF-C and VEGF-D generated LN metastasis (6/10 and 8/11, respectively), the locations of the metastasized LNs were quite different. TKB5/VEGF-C metastasized on the same side of axillary LNs as i.t. (right axillary LNs), whereas TKB5/VEGF-D metastasized to the mediastinal and left axillary and/or cervical LNs. Since the TKB5/VEGF-A/C or TKB5/VEGF-A/D co-transfectants revealed overlapping tumor progression patterns of VEGF-A and VEGF-C or VEGF-D, the metastatic LNs had abundant new capillaries and were larger than those of TKB5/VEGF-C or TKB5/VEGF-D-inoculated mice. Our results clearly demonstrate that VEGF-A secreted from intrathoracic lung cancer cells plays important roles in producing pleural effusion, dissemination, and capillary neogenesis, that VEGF-C is involved in LN metastasis, and VEGF-D in pleural dissemination and LN metastasis. It is most likely, however, that the mechanisms by which VEGF-C promotes LN metastasis are different from those of VEGF-D. The regulation of the expression of VEGFs in intrathoracic lung cancer cells might be a useful therapeutic approach to inhibiting tumor development and improving patient prognosis.

Animals↗

Correlation between lymph node micrometastasis and histologic classification of small lung adenocarcinomas, in considering the indication of limited surgery.

The validity of limited surgery for lung carcinomas have not been clearly established. Several reports suggest that not only tumor size but also the histological findings may be of importance in this role. By conducting immunohistochemical examinations of lymph node micrometastases from small lung adenocarcinomas, we considered the suitability of limited surgery for especially localized bronchioloalveolar carcinoma (LBAC) without active fibroblastic proliferation (Noguchi's histologic classification types A and B). In this study, we enrolled 54 patients with lung adenocarcinoma smaller than 2 cm in diameter. Lymph node involvement was demonstrated in 11 (20.4%) patients. Lymph node micrometastasis was present in 11 (25.6%) of the 43 patients at pN0 disease. However, 13 patients with LBAC without active fibroblastic proliferation (types A and B) had neither lymph node involvement nor micrometastasis. Our results indicate that limited pulmonary resection may be acceptable procedure for LBAC without active fibroblastic proliferation.

Adenocarcinoma↗

[Clinical practice guidelines for diagnosis and treatment of osteoporosis].

The Japanese Society for Bone and Mineral Research organized a committee to make a new criteria of diagnosis for osteoporosis in 2000. In the criteria, cases who show atraumatic fractures in demineralized bone are made a diagnose of osteoporosis. In the cases who show no atraumatic fractures, patients whose bone mineral densities are less than 70% of mean density of young adult persons or whose X-ray films indicate coarse or unclear longitudinal trabeculae in vertebral body, are also made a diagnose of osteoporosis. A guideline for treatment of osteoporosis had been present in 1998, and another committee make ready for a new guideline in 2002. The new guideline is presenting as (1) increase in oral calcium intake and inpact exercise, prevention of fall, and wearing of external hip protector are recommended in addition to pharmacological agents, (2) in pharmacological agents, estrogens, calcitonins and bisphosphonates are effective to the patients with rapid bone loss, and (3) vitamin D3 derivatives and vitamin K2 are recommended for the patients with diminished bone formation.

Humans↗

Hepatoid adenocarcinoma in the lung.

We have experienced a very rare case of hepatoid adenocarcinoma in the lung. A 55-year-old male with a history of smoking was diagnosed as adenocarcinoma of the right S2, and underwent resection of the right upper lobe and dissection of the hilum and mediastinal lymph nodes (complete resection). Pathological examination revealed cuboid atypical cells arranged in a papillary or trabecular fashion, and a proliferating pattern in most part of the tumor resembling that of hepatocellular carcinoma. Immunohistochemistry study showed alpha-fetoprotein (AFP)-positive tumor cells, hence the diagnosis of hepatoid adenocarcinoma was confirmed. Postoperative pathological staging classified the patient as having as p-T2NOMO, p-stage I B disease. The serum AFP level was not determined before surgery, but the value decreased gradually after surgery and has since remained within the normal range. At present, 32 months after the operation, no signs of recurrence have been observed. Hepatoid adenocarcinoma in the lung has been reported in eight patients with the present one being the ninth case. All were males, the tumor diameter was large and the patient prognoses were mostly poor, but at early stage two cases of long-term survival have been reported indicating that the stage is the most important prognostic factor also for rare tumor.

Adenocarcinoma↗

[Bone and joint diseases in the elderly].

As a current attention of the medical treatment has been paid to improve guality of the life rather than to save the life of the patient, so the treatment of bone and joint diseases, which are not ordinarily fatal and deteriorate quality of the life of the patient, would become important in the aged society of 21 century. In a strategy to improve the quality of life in the patient with osteoarthritis, disease modifying anti-osteothritis drugs are investigated for primary prevention and complete recovery of osteoarthritis. In osteoporosis, a characteristic bone disease of the aged, aims of the treatment have been changed from freeing of pain in the nineteen sixties, increase of bone mass in the nineteen eighties and reduction of the fracture rate in the nineteen nineties to improve of quality of the life through decrease of pain and fracture in 21 century. In conclusion, current management for bone and joint diseases in the elderly is finally designed to enjoy a healthy life of long span by medical intervention.

Aged↗

[Economical efficacy of physical exercises for osteoporosis].

From mean 12.5% increase of lumbar bone mineral density by one year's physical training, it is calculated to reduce the frequency of femoral neck fracture by 80% and the rate of falls by 50%. And 60% reduction of femoral neck fracture by physical exercise gains about 200 billion yen of medical and care costs annually, because a patient with femoral neck fracture consumes mean 1,320,000 yen for medical treatments and about 19% of the patients become bed-ridden state after the treatments for mean 5 years.

English Abstract↗