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Biomedical subjects

K Hirabayashi

Publications and source records attributed to K Hirabayashi.

At least 19 recordsLinked to original sources

Clinical features associated with recurrence of tumours of the spinal cord and cauda equina.

STUDY DESIGN: Retrospective review of consecutive cases of recurrent spinal cord and cauda equina tumours. OBJECTIVES: We sought to identify factors and conditions resulting in re-operation to treat recurrences of spinal cord and cauda equina tumours. SETTING: Keio University Hospital, Tokyo, Japan. METHODS: Re-operation was performed in 39 patients with spinal cord and cauda equina tumours. Times of operation, interval between operations, affected spinal level, tumour site on cross section, configurations among dumb-bell tumours, and pathologic diagnoses were analysed. Recurrence rates were defined in terms of the number of cases with re-operation due to tumour recurrence relative to the total number of surgical cases for the same period at our institution. RESULTS: Recurrence rates were relatively high for intradural, extramedullary tumours and for tumours located anteriorly rather than laterally. Of patients with intradural, extramedullary plus extradural tumours who underwent initial surgery at our hospital, 75% (9/12) recurred; all tumours had dumb-bell-type configurations. The overall rate of re-operation due to tumour recurrence in 249 cases was 7.2% at our institution. By tumour types, 40% of malignant schwannomas recurred (2/5), as did 35.7% of neurofibromas (5/14), and 33.3% of ependymomas (6/18). CONCLUSION: Risk factors for tumour recurrence were anterior location, an intradural, extramedullary plus extradural site, extensive dumb-bell tumours, and pathologic diagnoses of neurofibroma, ependymoma, or malignant schwannoma.

Adolescent↗

Glycyrrhizin and some analogues induce growth of primary cultured adult rat hepatocytes via epidermal growth factor receptors.

We investigated the effects of glycyrrhizin (GL-1) and some analogues on DNA synthesis and proliferation in serum-free primary cultures of adult rat hepatocytes. The hepatocytes underwent DNA synthesis and proliferation in response to GL-1 and some analogues. The effects of these agents occurred in a time- and dose-dependent manner. The proliferative potency as judged by half-maximal effective concentrations was in the following order: 18-beta-H-glycyrrhetinic acid (GL-3; 4.5 x 10(-9) M)<18-beta-H-glycyrrhizin (GL-1; 4.4 x 10(-8) M)<18-alpha-H-glycyrrhetinic acid (GL-6; 6.0 x 10(-8) M). The analogue 18-alpha-H-glycyrrhetinic acid 3-O-beta-D-monoglucuronide (GL-5; 1.0 x 10(-7) M) weakly stimulated hepatocyte DNA synthesis and proliferation, whereas 18-alpha-H-glycyrrhizin (GL-4) and 18-beta-H-glycyrrhetinic acid 3-O-beta-D-monoglucuronide (GL-2) did not. The growth-promoting effects of GL-1, GL-3 and GL-6 were significantly inhibited at higher initial plating densities (7.0 x 10(4) and 10 x 10(4) cells/cm(2)). A monoclonal antibody against epidermal growth factor (EGF) receptor (1-100 ng/ml), but not that against EGF (1-100 ng/ml), dose-dependently inhibited glycyrrhizin- and analogue-induced hepatocyte DNA synthesis and proliferation. Specific inhibitors of growth-related signal transducers, such as genistein, PD98059 (2'-amino-3'-methoxyflavone) and rapamycin, completely blocked glycyrrhizin- and analogue-induced hepatocyte DNA synthesis and proliferation. Treatment of hepatocytes with GL-1, GL-3 and GL-6 rapidly stimulated tyrosine phosphorylation of the EGF receptor and p42 MAP kinase, which were inhibited by genistein and PD98059, respectively. These results suggest that glycyrrhizin and some analogues are primary hepatocyte mitogens that bind to EGF receptors and subsequently stimulate the receptor tyrosine kinase/mitogen-activated protein kinase pathway to induce hepatocyte DNA synthesis and proliferation.

Adenylyl Cyclase Inhibitors↗

Mizoroki-Heck type reaction of organoboron reagents with alkenes and alkynes. A Pd(II)-catalyzed pathway with Cu(OAc)2 as an oxidant.

[reaction: see text]. In contrast to the Pd(0)-catalyzed mechanism by Uemura, Mizoroki-Heck type reaction of boronic acids is found to proceed under a Pd(II)-mediated pathway using a catalytic amount of Pd(OAc)2 in the presence of Cu(OAc)2 as an oxidant. Treatment of a variety of alkenes with boronic acids, boronates, and sodium tetraphenylborate furnishes beta-arylated and alkenylated products in good to excellent yields. The reactions with norbornene, norbornadiene, and diphenylacetylene are also performed to give 1:2 or 2:1 coupling products.

Journal Article↗

Production of neuropeptide substance P by synovial fibroblasts from patients with rheumatoid arthritis and osteoarthritis.

We examined the production of substance P (SP) in synovial fibroblasts derived from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Immunoreactive SP was observed in non-stimulated RA fibroblasts. The expression of beta-preprotachykinin-A (beta-PPT-A) mRNA was confirmed by reverse transcription-polymerase chain reaction analysis. SP contents in culture medium were increased by treatment of RA fibroblasts with transforming growth factor-beta (TGFbeta) (10 ng/ml). Levels of SP release were elevated at 12 h after TGFbeta stimulation whereas the expression of beta-PPT-A mRNA was enhanced at 3 h. Furthermore, SP production in response to TGFbeta was dose-dependently enhanced by basic fibroblast growth factor (bFGF). OA fibroblasts also significantly released SP in the presence of TGFbeta (10 ng/ml) plus bFGF (50 ng/ml). These results suggest that SP produced by synovial fibroblasts may participate in joint diseases.

Arthritis, Rheumatoid↗

Long-term outcomes of standard discectomy for lumbar disc herniation: a follow-up study of more than 10 years.

STUDY DESIGN: A retrospective analysis of the long-term outcomes of standard discectomy for lumbar disc herniation. OBJECTIVES: To investigate the long-term outcomes of standard discectomy to address postoperative problems, including residual low back pain and recurrent herniation. SUMMARY OF BACKGROUND DATA: Most previous investigators found that favorable outcomes of standard discectomy were maintained for the long-term postoperative period. Although they observed postoperative complications such as residual low back pain and recurrent herniation, detailed analyses of these results have not been conducted. METHODS: The long-term follow-up results in patients who were observed for a minimum of 10 years after standard discectomy were evaluated by using the Japanese Orthopedic Association scoring system through direct examinations and questionnaires. Radiography also was used in patients who agreed to visit the hospital, and findings were compared with those on preoperative radiographs. RESULTS: The average recovery rate calculated by using Japanese Orthopedic Association scores was 73.5 +/- 21.7%. Even though residual low back pain was found in 74.6% of the patients, only 12.7% had severe low back pain. The majority of the patients with severe low back pain were under 35 years of age at the time of operation, with preoperative advanced disc degeneration. The final Japanese Orthopedic Association scores in the patients with decreased disc height were significantly lower than those in patients with no decrease. However, the disc height of patients with a recurrent herniation was preserved. CONCLUSION: The long-term outcome of standard discectomy in this series was favorable. Although patients with preserved disc height generally had favorable results, the risk of recurrent disc herniation was high in this population.

Activities of Daily Living↗

Detection of transgene in progeny at different developmental stages following testis-mediated gene transfer.

We recently reported that exogenous DNA injected into testis as a liposome complex can be transferred into the egg via sperm by natural mating and integrated in the genome (testis-mediated gene transfer: TMGT). Here, we studied the efficiency of each of the several liposomes in associating foreign DNA with sperm, the expression of an introduced gene in early embryos, and the presence of the DNA in fetuses and pups at different ages. The CMV/beta-actin/EGFP fusion gene, encapsulated with different liposomes, was injected into rat testis, and spermatozoa in the cauda epididymis were obtained 1, 4, and 14 days after injection. We tested each of the 8 liposomes, and found that only 2, DMRIE-C and SuperFect, led to the detection of foreign DNA on all of the days examined, with relatively higher ratios of rats having positive sperm. By means of TMGT using either of those two liposomes, more than 80% of morula-stage embryos expressed EGFP, as observed by fluorescence microscopy. Then we detected introduced DNA in the progeny by PCR and Southern dot blot, and found that the ratio of animals carrying the foreign DNA decreased as they developed, and that only a part of postpartum progeny were foreign-DNA-positive with high incidence of mosaicism. These results suggest that, although, the success rate is still limited, foreign DNA could be integrated into the genome of the progeny by TMGT at least under specific experimental conditions, the efficiency of which depends largely on the characteristics of the liposome. The results also suggest that TMGT could be applicable to fetal gene therapy as well as to the generation of transgenic animals.

Animals↗

Expression of ovarian 20alpha-hydroxysteroid dehydrogenase in rat thymus.

Ovarian 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD), which converts progesterone to a derivative devoid of biological activity, plays a crucial role in achieving the short estrous cycle in rats. Although 20alpha-HSD activity has also been demonstrated in the thymus, its molecular nature, function, and regulation of expression have yet to be determined. In the present study we investigated if 20alpha-HSD activity in the thymus originates in a transcript identical to that expressed in the ovary. RT-PCR analysis indicated the expression of 20alpha-HSD mRNA in rat thymus, and sequencing of the PCR product showed 100% identity to ovarian 20alpha-HSD cDNA. Immunohistochemical study using anti-rat ovarian 20alpha-HSD antibody demonstrated the expression of 20alpha-HSD protein in the thymus. The 20alpha-HSD-expressing cells in the thymus seemed to be some type of lymphocyte by their morphology. These results suggest that the same molecular species as ovarian 20a-HSD is expressed in thymic lymphocytes. Therefore, 20alpha-HSD may play a role in T-lymphocyte proliferation and differentiation processes.

20-Hydroxysteroid Dehydrogenases↗

Tsutsugamushi disease in Kanagawa Prefecture, Japan: clinical report of two cases and survey of other incidences in 1998.

Tsutsugamushi disease is characterized by the early appearance of a black crust at the bitten area and the subsequent development of macular or macropapular rush on the whole body with high fever. While treatment with tetracycline derivatives and chloramphenicols is effective, delayed diagnosis or inappropriate treatment will lead to fatality. In this report, we describe two typical cases of tsutsugamushi disease and discuss other incidences in Kanagawa Prefecture, Japan, in 1998. One of the present two patients was diagnosed to be a case of the new type by Kawasaki strain of Rickettsia tsutsugamushi, while responsible strain was not identified for the other case. Since the disease is spreading widely even to suburban areas, we emphasize the need to consider the possible diagnosis of tsutsugamushi disease in patients with generalized eruption and high fever.

Anti-Bacterial Agents↗

Impact of longitudinal distance of the cervical spine on the results of expansive open-door laminoplasty.

STUDY DESIGN: A retrospective study in patients who underwent expansive open-door laminoplasty (ELAP) for cervical myelopathy and in whom the cervical alignment was nonlordotic at the final follow-up to analyze the correlation between the longitudinal distance of the cervical spine and surgical results. OBJECTIVES: To determine the impact of longitudinal distance of the cervical spine on surgical results of ELAP and to propose a new concept, the redundant spinal cord, that may influence patient selection for ELAP. SUMMARY OF BACKGROUND DATA: Results in many studies have demonstrated that postoperative cervical alignment has significant effect on surgical results, and spines that are malaligned are thought to deteriorate. The current surgical data showed that not all patients with postoperative malalignment had poor surgical results. Patients with cervical spondylotic myelopathy (CSM) tended to have better clinical results than those with ossification of the posterior longitudinal ligament (OPLL). METHODS: Results in 70 patients who underwent ELAP for cervical myelopathy with postoperative cervical malalignment were investigated. The longitudinal distance index (LDI) was defined as the length of a vertical line between the posteroinferior edges of C2 and C7 divided by the anteroposterior diameter of C4 and was measured on lateral neutral radiographs at final follow-up. Correlation between LDI and surgical results represented by Japanese Orthopedic Association scores and percentage of recovery were analyzed statistically in each patient. RESULTS: Patients with CSM had smaller LDI and better surgical results than those with OPLL. Weak but significant negative correlation was detected between LDI and percentage of recovery, indicating that longitudinal distance of the cervical spine may have some degree of impact on the surgical results of ELAP. CONCLUSION: A decrease in LDI represents shortening of the cervical spine caused by multiple disc degeneration and may influence surgical results of ELAP by inducing redundancy of the spinal cord in patients with postoperative malalignment.

Cervical Vertebrae↗

Non-Sonogashira-type palladium-catalyzed coupling reactions of terminal alkynes assisted by silver(I) oxide or tetrabutylammonium fluoride.

Palladium-catalyzed reaction of aryl and alkenyl halides with terminal alkynes in the presence of silver(I) oxide as an activator furnishes various arylated or alkenylated alkynes in good to excellent yields. The similar coupling reaction is also found to proceed using tetrabutylammonium fluoride (TBAF) or tetrabutylammonium hydroxide (TBAOH) as an activator.

Journal Article↗

Palladium-catalyzed cross-coupling of silanols, silanediols, and silanetriols promoted by silver(I) oxide

Palladium-catalyzed cross-coupling of aryl- or alkenylsilanols, silanediols, and silanetriols with a variety of iodoarenes by the catalysis of palladium(0) and in the presence of silver(I) oxide furnished the coupling products in good to excellent yields. The reactions of silanediols or silanetriols under similar conditions proceeded much faster than those of silanols to afford the corresponding coupling products in excellent yields within shorter reaction periods (5-12 h). The measurement of the X-ray diffraction (XRD) pattern of the silver residue after the reaction revealed that silver(I) oxide was converted to silver(I) iodide.

Journal Article↗

Coupling Reactions of Alkynylsilanes Mediated by a Cu(I) Salt: Novel Syntheses of Conjugate Diynes and Disubstituted Ethynes.

Reaction of 1-trimethylsilylalkyne with copper(I) chloride in a polar solvent, DMF, at 60 degrees C under an aerobic conditions smoothly undergoes homo-coupling to give the corresponding symmetrical 1,3-butadiynes in 70-99% yields. In addition, (arylethynyl)trimethylsilanes are found to couple with aryl triflates and chlorides in the presence of Cu(I)/Pd(0) (10 mol %/5 or 10 mol %) cocatalyst system to give the corresponding diarylethynes in 49-99% yields. The cross-coupling reaction is applied to a one-pot synthesis of the corresponding unsymmetrical diarylethynes from (trimethylsilyl)ethyne via sequential Sonogashira-Hagihara and the present cross-coupling reactions using two different aryl triflates. The reactions of (arylethynyl)trimethylsilanes with aryl(chloro)ethynes in the presence of 10 mol % of CuCl also yield the corresponding unsymmetrical 1,3-butadiynes in 43-97% yields.

Journal Article↗

Progesterone is a cell death suppressor that downregulates Fas expression in rat corpus luteum.

In female rats, apoptotic cell death in the corpus luteum is induced by the prolactin (PRL) surge occurring in the proestrous afternoon during the estrous cycle. We have previously shown that this luteolytic action of PRL is mediated by the Fas/Fas ligand (FasL) system. During pregnancy or pseudopregnancy, apoptosis does not occur in the corpus luteum. Progesterone (P4), a steroid hormone secreted from luteal steroidogenic cells, attenuated PRL-induced apoptosis in cultured luteal cells in a dose-dependent manner. P4 significantly decreased the expression of mRNA of Fas, but not FasL, in cultured luteal cells prepared from both proestrous and mid-pseudopregnant rats. These data indicate that P4 suppresses PRL-induced luteal cell apoptosis via reduction of the expression level of Fas mRNA in the corpus luteum, suggesting that P4 acts as an important factor that can change the sensitivity of corpus luteum to PRL.

Animals↗

A phase II trial of docetaxel in platinum pre-treated patients with advanced epithelial ovarian cancer: a Japanese cooperative study.

BACKGROUND: This phase II study was conducted to evaluate the efficacy and toxicity of docetaxel in Japanese patients with advanced ovarian cancer. PATIENTS AND METHODS: Docetaxel was administered at a dose of 70 mg/m2 intravenously to patients with platinum pretreated advanced ovarian cancer. Treatment was repeated every three weeks. No routine corticosteroid premedication was given. RESULTS: Ninety patients with advanced ovarian cancer were entered and sixty were assessable for response. The overall response rate was 28% in the assessable patients (95% confidence interval (95% CI): 17.54%-41.4%). CA125 responses were seen in 8 (24%) of 34 assessable patients for CA125 criteria. The 36 platinum-refractory patients had a response rate of 25% compared with 33% in the platinum-sensitive patients. The predominant toxicity was neutropenia, with 86% of the patients experiencing grade 3 or 4. Hypersensitivity reactions occurred in 37% of the patients and were not life threatening. Edema was mild and infrequent. CONCLUSION: Docetaxel at 70 mg/m2 demonstrated effectiveness as a treatment of both platinum-sensitive and platinum-refractory ovarian cancer patients, with a low incidence of severe hypersensitivity reactions and edema.

Adult↗

Inhibition of apoptosis in human tumour cells by the tumour-associated serpin, SCC antigen-1.

The squamous cell carcinoma antigen (SCC Ag) is a tumour-associated protein and a member of the serine protease inhibitor (serpin) family. The SCC Ag has been used as a serologic tumour marker for SCC progression, and its elevated serum levels are a risk factor for disease relapse. However, the biologic significance of this intracytoplasmic protein in cancer cells remains unknown. In this report, we demonstrated that apoptosis induced by 7-ethyl-10-hydroxycamptothecin, tumour necrosis factor-alpha (TNF-alpha) or interleukin (IL)-2-activated natural killer (NK) cells was significantly inhibited in tumour cells transduced with the SCC Ag-1 cDNA, as compared to control cells in vitro. Also, inhibition of the SCC Ag-1 expression in tumour cells by transfection of antisense SCC Ag-1 cDNA was accompanied by significantly increased sensitivity of these cells to apoptosis induced by etoposide or TNF-alpha. The mechanism of protection of tumour cells from apoptosis involved inhibition of caspase-3 activity and/or upstream proteases. In vivo, tumour cells overexpressing the SCC Ag-1 formed significantly larger tumours in nude mice than the SCC Ag-1-negative controls. Thus, overexpression of the SCC Ag-1, a member of the serpin family, in human cancer cells contributed to their survival by mediating protection from drug-, cytokine- or effector cell-induced apoptosis.

Antigens, Neoplasm↗

Development of obesity in transgenic rats with low circulating growth hormone levels: involvement of leptin resistance.

BACKGROUND: Human growth hormone (hGH) transgenic (TG) rats have been produced in our laboratory. These TG rats are characterized by low circulating hGH levels, virtually no endogenous rGH secretion, and massive obesity. OBJECTIVE: To elucidate how energy balance and leptin sensitivity contributed to the establishment of this obesity. DESIGN AND METHODS: Food intake, locomotor activity and leptin concentrations in serum and cerebrospinal fluid were measured in TG rats and their non-transgenic littermates (control). The effect of intraperitoneal and intracerebroventricular injection of leptin on food intake and body weight gain was also examined. RESULTS: An increase in food intake and a decrease in locomotor activity were observed from 4 and 7 weeks of age, respectively, in the transgenic rats compared with control. Serum leptin concentrations of the transgenic rats were more than twice as high as those of control rats and were associated with an increased white adipose tissue mass and ob gene expression. Intraperitoneal injection of leptin significantly decreased food intake and body weight gain in control rats, but not in transgenic rats. Leptin concentration in the cerebrospinal fluid of transgenic rats was not different from that of control rats, and intracerebroventricular injection of leptin was similarly effective in reducing food intake and body weight gain as it was in control rats. CONCLUSIONS: These results suggest that the transgenic rats, whose GH secretion is suppressed, develop obesity due to early onset of an increase in food intake and a decrease in locomotor activity with leptin resistance resulting from deteriorating leptin transport from peripheral blood to cerebrospinal fluid.

Adipose Tissue↗