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Biomedical subjects

K Yoshikawa

Publications and source records attributed to K Yoshikawa.

At least 73 records · Page 4Linked to original sources
PubMed2001

Development of a high-temperature air-blown gasification system.

Current status of high-temperature air-blown gasification technology development is reviewed. This advanced gasification system utilizes preheated air to convert coal and waste-derived fuels into synthetic fuel gas and value-added byproducts. A series of demonstrated, independent technologies are combined to form the core of this gasification system. A high-temperature, rapid devolatilization process is used to enhance the volatile yields from the fuel and to improve the gasification efficiency. A high-temperature pebble bed filter is used to remove to the slag and particulates from the synthetic fuel gas. Finally, a novel regenerative heater is used to supply the high-temperature air for the gasifier. Component development tests have shown that higher gasification efficiencies can be obtained at more fuel-rich operating conditions when high-temperature air is used as the gasification agent. Test results also demonstrated the flex-fuel capabilities of the gasifier design. Potential uses of this technology range from large-scale integrated gasification power plants to small-scale waste-to-energy applications.

Biomass↗
PubMed2001

Stat3 in thymic epithelial cells is essential for postnatal maintenance of thymic architecture and thymocyte survival.

This study describes abnormalities of the thymus in mice in which the Stat3 gene has been specifically disrupted behind the keratin 5 promoter. In these mice, virtually all of the thymic epithelial cells (TEC) were deficient for Stat3 activation. Adult mutant mice developed severe thymic hypoplasia, which included alterations in the cortical TEC architecture that coincided with the loss of thymocytes. Even during the asymptomatic period of preadolescence, these mice exhibited a higher susceptibility of the thymus to suboptimal doses of dexamethasone or gamma-irradiation, while their thymocytes per se were no more sensitive than controls. These results indicate that Stat3 in TEC plays an essential role in maintaining thymic architecture and thymocyte survival.

Animals↗
PubMed2001

Tissue regeneration: hair follicle as a model.

The Cre-loxP strategy has allowed us to generate the mice whose keratinocytes are devoid of Stat3, which play a pivotal role in the signal transduction following the stimulation with various growth factors/cytokines, such as EGF, HGF, or IL-6. Although keratinocyte-specific Stat3-disrupted mice were born normal with intact skin and the first hair cycle, they exhibited retardation of wound healing and absence of the second hair cycle onward, leading to development of spontaneous skin ulcers and alopecia as they aged. Thus, analyses of these mice reveal that Stat3 in keratinocytes contributes to the regeneration of epidermis and hair cycle process.

Animals↗
PubMed2001

Impaired responses of peripheral blood mononuclear cells to T-cell stimulants in alopecia areata patients with a poor response to topical immunotherapy.

BACKGROUND: Topical immunotherapy with a contact allergen is effective in alopecia areata (AA). However, the mechanism of the effect is still unknown, and pretreatment prediction of the outcome of therapy in each patient remains difficult. OBJECTIVES: To predict the clinical effect of this therapy in AA patients, we investigated the relationship between clinical responses to topical immunotherapy and in vitro proliferative responses of peripheral blood mononuclear cells (PBMC) to T-cell stimulants. METHODS: PBMC were taken from 67 AA patients before or during diphenylcyclopropenone immunotherapy and from 14 healthy controls, and proliferative responses to phytohaemagglutinin and staphylococcal enterotoxin B were evaluated by measuring [3H]-thymidine incorporation. RESULTS: PBMC from the AA patients with a good clinical response to immunotherapy showed a normal level of proliferation, whereas PBMC from the poor responders showed a markedly suppressed proliferative response and interleukin (IL)-2 production, but increased IL-4 production compared with the controls. CONCLUSIONS: The proliferative response of PBMC to T-cell stimulants may be one of the indicators of the clinical effect of topical immunotherapy for AA.

Adolescent↗
PubMed2001

Self-assembled pearling structure of long duplex DNA with histone H1.

We report that complexes of giant DNA molecules with histone H1 proteins form a pearl necklace-like structure when the complexes are prepared by natural dilution from a high-salt solution (2 M NaCl) to a low-salt solution (0.2 M and 50 mM NaCl). We performed real-time observations on the conformational changes of individual T4 phage DNA (166 kb) molecules in bulk solution by fluorescence microscopy. To identify H1-binding regions on individual DNA molecules, we also performed immunofluorescence microscopic observations on the DNA-H1 complex spread on a glass surface. It was found that histone H1 binds DNA in a highly co-operative manner and is accompanied by local folding of the DNA. On the basis of the experimental observations and a theoretical simulation, we propose a self-assembling mechanism for the pearling structure.

Bacteriophage T4↗
PubMed2001

Adenocarcinoma arising from the prostatic duct mimicking transitional cell carcinoma.

A 71-year-old man was first diagnosed with primary transitional cell carcinoma of the prostate with a skip lesion on the distal urethra. The patient received three courses of intra-arterial chemotherapy of cisplatin (CDDP) and pirarubicin (THP-ADM) followed by a radical prostatectomy. Histopathologic examination of the prostatectomy specimen revealed adenocarcinoma invasion along the prostatic duct extending to the peripheral acini, which was diagnosed as ductal adenocarcinoma. The clinical and histopathologic features of this case are entirely different from usual adenocarcinomas of the prostate. This rare histopathologic feature should be recognized as 'ductal carcinoma of the prostate', to distinguish it from papillary adenocarcinoma or adenocarcinoma with endometrioid features. The patient has had no sign of recurrence 14 months after the operation. CDDP-based chemotherapy followed by radical prostatectomy may be one of the promising therapeutic modalities for this rare entity.

Adenocarcinoma↗
PubMed2001

Secretion of non-helical collagenous polypeptides of alpha1(IV) and alpha2(IV) chains upon depletion of ascorbate by cultured human cells.

Our previous report showed that human fetal lung fibroblasts secreted non-disulfide-bonded, non-helical collagenous polypeptides of alpha1(IV) and alpha2(IV) chains depending on culture conditions [Connective Tissue (1999) 31, 161-168]. The secretion of non-helical collagenous polypeptides is unexpected from the current consensus that such polypeptides are not secreted under physiological conditions. The absence of interchain disulfide bonds among alpha1(IV) and alpha2(IV) chains was always correlated with the absence of triple-helical structure of the type IV collagen. The finding corresponds with the fact that the interchain disulfide bonds are formed at or close to the completion of the type IV collagen triple-helix formation. The present report shows that ascorbate is the primary factor for the triple-helix formation of the type IV collagen. When human mesangial cells were cultured with ascorbate, only the triple-helical type IV collagen was secreted. However, when the cells were cultured without ascorbate, the non-helical alpha1(IV) and alpha2(IV) chains were secreted. Relative amounts of the secreted products were unchanged with or without ascorbate, suggesting that ascorbate is required for the step of the triple-helix formation. The ascorbate-dependency of the triple-helix formation of the type IV collagen was observed in all the human cells examined. The non-helical alpha1(IV) chain produced by the ascorbate-free culture contained about 80% less hydroxyproline than the alpha1(IV) chain from the triple-helical type IV collagen. The evidence for the non-association of the non-helical alpha1(IV) and alpha2(IV) chains in the conditioned medium was obtained by an anti-alpha1(IV) antibody-coupled affinity column chromatography for the conditioned medium. Although all the non-helical alpha1(IV) chains were found in the bound fraction, all the non-helical alpha2(IV) chains were recovered in the flow-through fraction. The present findings suggest that ascorbate plays a key role in the trimerization step of three alpha chains and/or in the subsequent triple-helix formation of the type IV collagen.

Antibodies, Monoclonal↗
PubMed2001

Comparison of gadobenate dimeglumine with gadopentetate dimeglumine for magnetic resonance imaging of liver tumors.

RATIONALE AND OBJECTIVES: To compare gadobenate dimeglumine (Gd-BOPTA) with gadopentetate dimeglumine (Gd-DTPA) for magnetic resonance imaging of the liver. METHODS: The contrast agent Gd-BOPTA or Gd-DTPA was administered at a dose of 0.1 mmol/kg to 257 patients suspected of having malignant liver tumors. Dynamic phase images, spin-echo images obtained within 10 minutes of injection, and delayed images obtained 40 to 120 minutes after injection were acquired. All postcontrast images were compared with unenhanced T1-weighted and T2-weighted images obtained immediately before injection. A full safety assessment was performed. RESULTS: The contrast efficacy for dynamic phase imaging was moderately or markedly improved in 90.9% (110/121) and 87.9% (109/124) of patients for Gd-BOPTA and Gd-DTPA, respectively. At 40 to 120 minutes after injection, the cor- responding improvements were 21.7% (26/120) and 11.6% (14/121) for spin-echo sequences and 44.5% (53/119) and 19.0% (23/121) for breath-hold gradient-echo sequences, respectively. The differences at 40 to 120 minutes after injection were statistically significant (P < 0.02). Increased information at 40 to 120 minutes after injection compared with information acquired within 10 minutes of injection was available for 24.0% (29/121) of patients with Gd-BOPTA and for 14.5% (18/124) of patients with Gd-DTPA (P < 0.03). Adverse events were seen in 4.7% (6/128) and 1.6% (2/127) of patients receiving Gd-BOPTA and Gd-DTPA, respectively. The difference was not statistically significant. CONCLUSIONS: The efficacy of Gd-BOPTA is equivalent to that of Gd-DTPA for liver imaging during the dynamic phase and superior during the delayed (40-120 minutes) phase of contrast enhancement. Both agents are safe for use in magnetic resonance imaging of the liver.

Adult↗
PubMed2001

Cutaneous wound healing: an update.

Our understanding of wound-healing mechanisms has progressed over the past decade. Wound healing is traditionally divided into three phases--the inflammatory phase, the proliferation phase, and the remodeling phase--and involves a well-orchestrated interaction among blood vessels (platelets, macrophages, neutrophils, endothelial cells, and smooth muscle cells), epidermis (keratinocytes, melanocytes, and Langerhans cells), adnexal structures (outer root sheath cells and hair dermal papilla cells), dermis (fibroblasts and myofibroblasts), nervous system (neurons), and subcutaneous fatty layers (adipocytes). We review recent discoveries of basic and clinical aspects of wound healing including several revolutions that occurred in wound management: occlusive dressing therapy, use of living skin equivalents, and topical administration of growth factors. As we previously proposed, the use of tissue substitutes and autologous epidermal sheets led to a new concept of skin grafting through the keratinocyte activation phase in the graft healing mechanism. In this review, we also discuss a representative patient who presented with plantar wounds caused by calcaneal osteomyelitis and healed by the coverage of epidermal grafting.

Humans↗
PubMed2001

A case of lichenoid purpura possibly caused by diltiazem hydrochloride.

A 65-year-old Japanese man presented with itchy purpuric lichenoid papules of six months' duration on his legs and buttock. A topical glucocorticoid ointment was not effective. The biopsy specimen histologically showed a dense lichenoid infiltration of lymphocytes and histiocytes into the dermoepidermal junction; red blood cells were seen in the infiltration. Based on the clinical and pathological findings, we diagnosed this case as lichenoid purpura of Gougerot-Blum. The lesions disappeared when the diltiazem hydrochloride that he had been taking was discontinued.

Aged↗
PubMed2001

Churg-Strauss syndrome involving medium-sized arteries.

A 69-year-old Japanese man suffered from bronchial asthma, atrial fibrillation, general fatigue, high fever, and weight loss of about 5 kg within a month. He also had intermittent claudication, a tingling feeling in his fingers and toes, and an ulcer on his toe. His laboratory data revealed leukocytosis with absolute eosinophilia. The patient was treated with predonisolone 30 mg daily. Although the ulcers healed once, the lesions recurred with tapering predonisolone. The patient visited us because of the ulcer on his toe. Physical examination showed a 2 cm ulcer surrounded by slight erythema on his right fourth toe. Magnetic resonance angiography detected tapering stenosis of the medium-sized arteries in both legs. A biopsy from his myocardium showed the infiltration of eosinophils into the myocardium. The neuron conduction rate of his lower leg was slower than that of the normal control, demonstrating mononeuritis. From these findings, we diagnosed this patient as Churg-Strauss syndrome.

Aged↗
PubMed2001

Targeting hyperthermia for renal cell carcinoma using human MN antigen-specific magnetoliposomes.

Magnetoliposomes (MLs) conjugated with an antibody fragment to give specificity to a tumor were applied to hyperthermia for cancer. The Fab' fragment of the G250 antibody, which binds to MN antigen on many types of human renal cell carcinoma, was cross-linked to N-(6-maleimidocaproyloxy)-dipalmitoyl phosphatidylethanolamine (EMC-DPPE) in liposomal membrane. The targetability of the G250-Fab' fragment-conjugating MLs (G250-FMLs) was investigated using the mouse renal cell carcinoma (mRCC) and MN antigen-presenting cell, MN-mRCC. The amount of G250-FMLs uptake reached 67 pg / cell against MN-mRCC cells in an in vitro experiment using plastic dishes and this value was about 6 times higher than that in the case of MLs. In an in vivo experiment using MN-mRCC-harboring mice, 1.5 mg of the FMLs per carcinoma tissue accumulated (tumor weight was 0.19 g), which corresponded to approximately 50% of the total injection. This value was 27 times higher than that of the MLs. After injection of the FMLs, mice were exposed to intracellular hyperthermia using alternating magnetic field irradiation. The temperature of tumor tissue increased to 43 degrees C and the growth of the carcinoma was strongly arrested for at least 2 weeks. These results indicate the G250-FMLs could target renal cell carcinoma cells in vitro and in vivo, and are efficiently applicable to the hyperthermic treatment of carcinoma.

Animals↗
PubMed2001

Structure, expression and chromosome mapping of MLZE, a novel gene which is preferentially expressed in metastatic melanoma cells.

We isolated a novel gene, termed MLZE, from a B16-BL6 cDNA library after subtraction of B16-F10 mRNA. Expression levels of mouse MLZE (mMLZE) increased in accordance with metastatic ability of B16 melanoma sublines. Human homolog of mMlze (hMlze) contained one leucine zipper structure and two potential nuclear localizing signals. Northern blot analysis of multiple human tissues showed that hMLZE was expressed primarily in trachea and spleen. We mapped the hMLZE gene (by fluorescence in situ hybridization) to 8q24.1 - 2, which contains the c-myc gene and is often amplified in malignant melanoma. Immunohistochemistry revealed that the number of hMlze-positive cases was significantly larger in Clark levels III, IV and V melanomas (6 / 11 = 55%) than in Clark levels I and II melanomas (2 / 15 = 13%). In two cases of hMlze-positive melanomas, the strength of hMlze staining increased substantially in the deep component of the tumor. Considering that melanomas above Clark level II are more metastatic than those below Clark level III, these findings suggested that MLZE is one of the genes whose expression is upregulated during the course of acquisition of metastatic potential in melanoma cells.

Adult↗
PubMed2001

Inhibition of lung natural killer cell activity by smoking: the role of alveolar macrophages.

BACKGROUND: It is known that natural killer (NK) cell activity in the lung of smokers (SM) is lower than in non-smokers (NS). However, little is known about the underlying mechanisms. OBJECTIVE: The purpose of this work was to investigate the mechanisms of the inhibition of NK cell activity by alveolar macrophages (AM) in SM. METHODS: Lung effector cells and AM were obtained using bronchoalveolar lavage. The NK cell activity was assayed by 51Cr release method after incubation of 4 and 24 h, using K562 as target cell. AM were added at a concentration of 25% to effector cells. RESULTS: Following 24-hour culture, NK cell activity significantly increased in the NS but not in the SM. Lung NK cell activity was significantly augmented by interleukin-2 in the NS but not in the SM. Addition of AM to the NK cell preparation from SM exerted a significantly greater suppressive effect on autologous blood NK cell activity than in the NS. Indomethacin, catalase or thiourea did not prevent AM-mediated suppression of NK cell activity, in contrast to superoxide dismutase. CONCLUSIONS: These results suggest that the suppression of NK cell activity by AM in SM may be caused by O2- release rather than by prostaglandins, H2O2 or OH release from AM.

Adult↗
PubMed2001

Extract from Serenoa repens suppresses the invasion activity of human urological cancer cells by inhibiting urokinase-type plasminogen activator.

We used three human urological cancer cell lines, PC-3, LNCaP and SKRC-1, to investigate the effects of the extract from Serenoa repens (Palmae) on tumor cell invasion. The invasion activity of these cell lines was determined in vitro using a Transwell cell-culture chamber. The invasion activity of PC-3 cells into Matrigel was effectively suppressed by the extract at the concentration range of 1-10 microg/ml, while that of LNCaP and SKRC-1 cells was unaffected by the extract. The extract did not affect the viability, adhesion ability, or motility of the cell lines. uPA is more strongly expressed on the membrane fraction of PC-3 cells than that of LNCaP or SKRC-1 cells. The purified uPA activity is inhibited by the extract from S. repens in a dose-dependent manner, suggesting that the suppression of PC-3 cell invasion by the extract is based on an inhibition of the uPA activity which is necessary for tumor cell invasion. These data suggest that the extract from S. repens specifically inhibits the uPA activity and may therefore be useful for the therapeutic treatment of prostate cancer.

Enzyme Inhibitors↗