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Biomedical subjects

N Fujisawa

Publications and source records attributed to N Fujisawa.

At least 19 recordsLinked to original sources
PubMed2005

Human standing posture control system depending on adopted strategies.

Control of the standing posture of humans involves at least two distinct modes of operation to restore the body balance in the sagittal plane: the ankle strategy and the hip strategy. The objective of the study was to estimate the contribution of vestibular, visual and somatosensory feedbacks to these distinct strategies. The body dynamics was described as the motion of two linked rigid segments that represented the legs and the rest of the body. The posture controller received the inclination angles of the two body segments as inputs and regulated the moments around the ankle and hip joints. The controller had four feedback paths that were characterised by transfer functions connecting the two inputs and the two outputs. To evoke the distinct strategies, the floor conditions were varied by narrowing the support surface under the feet. A continuous pseudo-random external disturbing force was applied to the waist and the thigh independently. The inclination angles of the body segments and the ground reaction force were measured, and the transfer functions of the controller were estimated with the maximum-likelihood system identification procedure. Six healthy male adult subjects participated in the experiment. When the hip strategy became evident under the narrow support surface conditions, the transfer function relating the leg inclination angle and the ankle joint moment decreased its DC gain (16%), whereas the other three transfer functions increased the gains (20-140%) (ANOVA, p < 0.05). Based on a criterion for simplicity in the modification of the posture controller, these changes suggest a new hypothesis that, when posture control becomes difficult, the central nervous system selectively activates the somatosensory feedback paths from the hip joint angle to the moments around the ankle and hip joints.

Adult↗
PubMed2001

Homolytic carbostannylation of alkenes and alkynes with tributylstannyl enolates.

In the presence of AIBN, tributylstannyl enolates derived from aromatic ketones reacted with electron-deficient alkenes and a variety of alkynes to give the corresponding carbostannylated adducts. The reactions with methyl acrylate gave alpha-tributylstannylmethyl-gamma-ketoesters, unlike the known Michael-type reaction of stannyl enolates forming delta-ketoesters. The carbostannylation of alkynes proceeded in an anti addition mode to afford beta,gamma-unsaturated ketones. The reactivity of stannyl enolates as radical transfer agents could be utilized for radical cyclization of 1,6-enynes.

Journal Article↗
PubMed2001

Synthetic utility of stannyl enolates as radical alkylating agents.

[reaction: see text] The radical-initiated beta-ketoalkylation of haloalkanes with tributylstannyl enolates is described. Stannyl enolates derived from aromatic ketones are reactive toward the homolytic beta-ketoalkylation of simple haloalkanes as well as those activated by an electron-withdrawing group. The reactivity of stannyl enolates as radical alkylating agents can be utilized for an efficient three-component coupling reaction among stannyl enolates, haloalkanes, and electron-deficient alkenes.

Journal Article↗
PubMed2001

Allylstannylation of carbon-carbon and carbon-oxygen unsaturated bonds via a radical chain process.

In the presence of a radical initiator, allyltributylstannanes bearing an electron-withdrawing group at the beta-position smoothly reacted with electron-deficient terminal alkenes to give allylstannylated products in good yields. The stannyl group was introduced into the terminal carbon with high regioselectivity. The allylstannylation of homochiral 8-phenylmenthyl acrylate proceeded with moderate to good diastereoselectivity. Terminal and electron-deficient internal alkynes as well efficiently underwent the radical-initiated allylstannylation in an anti addition mode. The reaction of terminal alkynes showed the same regioselectivity as that of terminal alkenes. The present radical reaction was applicable to allylation of aromatic aldehydes and ketones.

Journal Article↗
PubMed2001

Fluid dynamics of a textured blood-contacting surface.

This study examined the fluid dynamics of a textured blood-contacting surface using a computational fluid-dynamic modeling technique. The texture consisted of a regular array of microfibers of length 50 or 100 microm, spaced 100 microm apart, projecting perpendicularly to the surface. The results showed that the surface texture served as a flow-retarding solid boundary for a laminar viscous flow, resulting in a lowered wall shear stress on the hase-plane surface. However, the maximum wall shear stress on the fibers was much higher than the shear stress on the nontextured phase plane. At all fractions of fiber height down past 10 microm, the permeability of the textured region greatly exceeded the analytically predictable permeability of an equivalent array of infinite-height fihers. The lowered suiface shear stress appears to explain in part the enhanced deposition of formed blood elements on the textured surface.

Biocompatible Materials↗
PubMed2000

Acute cellular interaction with textured surfaces in blood contact.

Textured blood-contacting surfaces can promote the formation of a blood-compatible pseudo-neointima. We hypothesized that by controlling the surface texturing, the pseudo-neointima thickness could be controlled. The hypothesis was tested experimentally by fabricating the polyurethane textured surfaces with three different fiber lengths, and exposing them simultaneously to the flowing blood in an ovine ex vivo carotid-jugular series shunt for periods up to 4 h. The textured surface consisted of regularly spaced tapered micro-fibers of defined length on a smooth base-plane surface. Because of the simple surface topography, detailed computational fluid-dynamic modeling of the surface could be obtained as a parallel study. Experimental results showed that white cell was the predominant cell type deposited on the textured surfaces, whereas macroscopic thrombus formation occurred only in one of nine blood-contacting experiments. White cell density on the textured base-plane surface was subsequently quantified by image-analyzing the electron micrographs of blood-contacted textured surfaces. The statistical analysis of cell densities on individual textured surfaces showed effects of wall shear stress on the textured base plane (which was obtained from the fluid-dynamic modeling), the longitudinal position of the test section in the series shunt, and blood-contact time.

Animals↗
PubMed2000

alpha-Chemokine growth factors for adenocarcinomas; a synthetic peptide inhibitor for alpha-chemokines inhibits the growth of adenocarcinoma cell lines.

PURPOSE: The experiments aimed to determine if alpha-chemokine inhibitors are effective suppressors of the growth of adenocarcinomas, a neoplasm with a high mortality rate. METHODS: Expression of growth-related oncogene (GROalpha) and interleukin-8 (IL-8) was determined by enzyme-linked immunosorbent assay. Inhibition of alpha-chemokine binding to tumor cells was assessed in the presence and absence of the hexapeptide, antileukinate. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were performed to determine the effect of alpha-chemokines, monoclonal antibodies (mAb), and antileukinate on cell proliferation. Finally, antileukinate inhibition of human, lung adenocarcinoma tumor growth, was determined in BALB/c nude mice. RESULTS: All of the adenocarcinomas tested produced either GROalpha or IL-8 or both. Proliferation of lung, stomach and colon adenocarcinoma cells was inhibited by anti-GROalpha mAb and/or anti-IL-8 mAb while recombinant human GROalpha stimulated the proliferation of lung and stomach adenocarcinomas. Antileukinate inhibited GROalpha binding to specific receptors on adenocarcinoma cells and inhibited the proliferation of all adenocarcinomas tested. Colon-derived adenocarcinomas specifically bound IL-8 and this binding was also inhibited by antileukinate. Administration of antileukinate in vivo inhibited the tumor growth of adenocarcinoma A549. CONCLUSIONS: GROalpha and IL-8 are necessary for the growth of lung, stomach and colon adenocarcinomas, and can be inhibited by the hexapeptide, antileukinate. The findings suggest the possibility of using alpha-chemokine receptor inhibitors in the treatment of adenocarcinoma.

Adenocarcinoma↗
PubMed2000

Specific binding of IL-8 to rabbit alpha-macroglobulin modulates IL-8 function in the lung.

OBJECTIVE AND DESIGN: The purpose of this study was to compare chemotactic activity of IL-8 alone with that of IL-8 reacted with rabbit alpha-macroglobulins (alphaM) in vivo. METHODS: Initially the binding of recombinant human IL-8 (rhIL-8) to rabbit alphaM was studied. 125I-labeled rhIL-8 was incubated with alphaM, and electrophoresed on native 5% gels or SDS-polyacrylamide 4-20% gradient gels. Next, rhIL-8 or rhIL-8 bound to alphaM was administered via an endotracheal tube to rabbit's lungs. TREATMENT: An endotracheal tube was wedged into a segment of the lobe of each lung, and a sample instilled through the tube into this segment. After 4 h the lungs were lavaged. RESULTS: rhIL-8 bound to alphaM retained its full chemotactic activity in vitro but exhibited a diminished ability to induce the influx of neutrophils into the rabbit lung. CONCLUSIONS: The data suggest that alphaM may facilitate IL-8 clearance from the lung.

Animals↗
PubMed1999

Inhibition of GROalpha-induced human endothelial cell proliferation by the alpha-chemokine inhibitor antileukinate.

GROalpha, an autocrine mitogenic factor for melanoma cell lines, belongs to the superfamily of alpha-chemokines. Here, we report that GROalpha stimulates the growth of human umbilical vein endothelial cells (HUVEC) in vitro, with proliferation being significantly stimulated by 100 nM recombinant human (rh) GROalpha. Proliferation was significantly inhibited by 100 microg/ml anti- human GROalpha monoclonal antibody (mAb), while excess GROalpha restored the growth. The addition of rhIL-8, rhIP-10, anti-human IL-8 or anti-human ENA-78 mAbs did not alter HUVEC proliferation. [125I]IL-8 binding to HUVEC was saturable and inhibited by non-radioactively iodinated IL-8, but not non-iodinated IL-8. [125I]GROalpha binding was also inhibited by iodinated IL-8. Since these data suggested specific binding sites for alpha-chemokines on HUVEC, we tested the effect of antileukinate, a potent alpha-chemokine receptor inhibitor, on [125I]GROalpha binding. Antileukinate inhibited GROalpha binding and suppressed HUVEC proliferation in a dose-dependent manner. Antileukinate was not cytotoxic, with no decrease in cell viability in the presence of 100 microM antileukinate. These findings suggest that GROalpha is essential for HUVEC growth factor and that antileukinate inhibits growth by preventing autocrine GROalpha receptor binding. This raises the interesting possibility of alpha-chemokine receptor inhibitors, such as antileukinate, in the treatment of cancer where angiogenesis is an important factor for tumour growth.

Antibodies, Monoclonal↗
PubMed1999

Historical survey of carcinoma of the pancreas.

The ancient Egyptians probably recognized cancerous lesions on the surface of the body. Hippocrates described cancers of the skin, larynx, breast, inguinal region, uterus, and vagina. For centuries, the treatments were excision, cauterization, ointment application, and fomentation. The development of anesthesia, antisepsis, and disinfection, and the discoveries of X-rays and radium in the nineteenth century, have greatly promoted advances in surgery in the twentieth century. At the beginning of this century, it became possible for surgeons to extirpate tumors from previously inaccessible body interiors, and today surgeons are able to remove affected organ systems and even entire regions of the body with safety because of advances in physiology, anesthesia, transfusion, and anti-infective agents. The surgical results for most gastrointestinal cancers have improved markedly in recent years, only with pancreatic cancer showing no improvement in results. Drastic extensive surgery has not led to better results. A small carcinoma less than 1 cm in diameter may not always be an early carcinoma. Early cancer in duct cell carcinoma may be one localized in the mucous membrane of the pancreatic duct. There is now an expectation that early diagnosis will be possible by using magnetic resonance cholangiopancreatography and cytological diagnosis of the pancreatic juice.

History, 17th Century↗
PubMed1999

Castleman disease presenting with ophthalmic signs and symptoms.

PURPOSE: To describe a patient with multicentric Castleman disease who was initially examined with ophthalmic signs and symptoms. METHODS: Case report. A 71-year-old man was initially examined with swelling of both upper eyelids and diplopia of 2 months' duration. RESULTS: Medical evaluation and right axillary lymph node biopsy disclosed Castleman disease. Systemic corticosteroid treatment temporarily resolved signs and symptoms, but the patient died of recurrence with cytomegalovirus and Aspergillus infection 10 months after initial examination. CONCLUSIONS: Multicentric Castleman disease is a rare but distinct disorder that may present initially with ocular signs and symptoms. This disease must be included in the differential diagnosis of orbital pseudotumor and lymphoma.

Aged↗
PubMed1999

A novel textured surface for blood-contact.

Blood-contacting surface modifications aimed at reduction of thromboembolic complications have included the texturing of surfaces so as to promote the formation of a stable pseudo-neointima. A technique has been developed whereby a textured surface consisting of regularly spaced micro-fibres was produced on a smooth base plane. Polyurethane vascular patches with and without the textured luminal surface were fabricated and implanted bilaterally in ovine carotid arteries for 1- and 3-week implantation periods (n = 6 per period). One of 6 arteries with textured patches in the 1-week group was occluded. All other arteries were patent. At 1 week, all patent textured patches had adherent thrombus covering the entire patch surface. By 3 weeks, the thrombus had organised to form a stable pseudo-neointima. Non-textured patches at 1 week had only partial surface coverage of thrombus. At 3 weeks, 4 of 6 non-textured patches had significant red thrombus in the lumen. At 3 weeks, there was also evidence of cellular migration from artery onto both textured and non-textured patches. These findings suggest that the major role of the textured surface was as a promoter of a stabilised thrombus base onto which subsequent cellular migration and tissue healing occurred more rapidly than onto a smooth polyurethane surface.

Animals↗
PubMed1999

Three cases of pustulotic arthro-osteitis associated with episcleritis.

Three cases of pustulotic arthro-osteitis (PAO) associated with episcleritis were described. In each patient, the episcleritis developed more than 10 years after the onset of PAO. These episcleritis were treated with topical corticosteroids. PAO is classified as a member of the seronegative spondylarthritis group of diseases. Though complications of seronegative spondylarthritis include uveitis and episcleritis. PAO associated with episcleritis was not reported. Episcleritis should be considered as a complication of PAO.

Adult↗
PubMed1999

A synthetic peptide inhibitor for alpha-chemokines inhibits the tumour growth and pulmonary metastasis of human melanoma cells in nude mice.

Growth-related oncogene-alpha (GROalpha) was first described as an autocrine mitogen and growth factor for melanoma cells. More recent studies show that GROalpha, interleukin-8 (IL-8) and other members of the alpha-chemokine superfamily are also angiogenic. Therefore, we sought to determine if inhibitors of the alpha-chemokine receptor would be effective in inhibiting the tumour growth and pulmonary metastasis of human melanoma cells. We determined that melanocytes and 12 human melanoma cell lines produce both GROalpha and IL-8. The proliferation of A375SM, a highly metastatic cell line, and C8161-C were significantly increased by human recombinant GROalpha and inhibited by anti-human GROalpha monoclonal antibody. Antileukinate, a potent inhibitor of alpha-chemokine receptor binding, inhibited the binding of GROalpha to its receptors in melanocytes and all 12 melanoma cell lines tested. Antileukinate also suppressed proliferation of A375SM and C8161-C cells in a dose-dependent manner, and the suppression was not due to cytotoxic effects. Furthermore, continuous administration of antileukinate inhibited the tumour growth and pulmonary metastasis of A375SM cells in athymic BALB/c nude mice. These findings suggest that antileukinate inhibits the growth of melanoma cells by preventing GROalpha from binding to its receptors. This suggests a possible use of alpha-chemokine receptor inhibitors such as antileukinate in the treatment of malignant melanoma.

Animals↗