Thyroid hormone promotes neurogenesis in the Xenopus spinal cord.

Three phases of neurogenesis can be recognized during Xenopus spinal cord development. An early peak during gastrulation/neurulation is followed by a phase of low level neurogenesis throughout the remaining embryonic stages and a later peak at early larval stages. We show here that several genes known to be essential for early neurogenesis (X-NGNR-1, XNeuroD, XMyT1, X-Delta-1) are also expressed during later phases of neurogenesis in the spinal cord, suggesting that they are involved in regulating spinal neurogenesis at later stages. However, additional neuronal determination genes may be important during larval stages, because X-NGNR-1 shows only scant expression in the spinal cord during larval stages. Thyroid hormone treatment of early larvae promotes neurogenesis in the spinal cord, where thyroid hormone receptor xTRalpha is expressed from early larval stages onward and results in precocious up-regulation of XNeuroD, XMyT1, and N-Tubulin expression. Similarly, thyroid hormone treatments of Xenopus embryos, which were coinjected with xTRalpha and the retinoid X receptor xRXRalpha, repeatedly resulted in increased numbers of neurons, whereas unliganded receptors repressed neurogenesis. Our findings show that thyroid hormones are sufficient to up-regulate neurogenesis in the Xenopus spinal cord.     

Morphometric comparison of human nerve cells: pyramidal motor system

We compared morphological and morphometric data on various motor neurons in the human pyramidal system using the modified Klüver-Barrera staining method with extremely minimized shrinkage ratio and an image-analyzer. We classified motor neurons in the human pyramidal system into three groups according to the measurement data. This report may be of interest to better understand the process of nerve conduction in the human pyramidal system.     

Suppressive effect of leflunomide metabolite (A77 1726) on metalloproteinase production in IL-1beta stimulated rheumatoid synovial fibroblasts

Leflunomide, an isoxazol derivative structurally unrelated to other immunomodulatory drugs, has proven to be efficacious in the treatment of rheumatoid arthritis (RA). This study was conducted to elucidate the mechanism by which leflunomide mediated antirheumatic effects. We investigated the effects of A77 1726, leflunomide's active metabolite, on mitogen-activated protein kinase (MAPK) activation in IL-1beta-stimulated rheumatoid synovial fibroblasts. The effects of A77 1726 on the secretion of matrix metalloproteinases (MMPs) from rheumatoid synovial fibroblasts were also examined. A77 1726 partially suppressed IL-1beta-induced ERK1/2 and p38 kinase activation. In contrast, A77 1726 efficiently suppressed IL-1beta-stimulated JNK1/2 kinase activation. Although no suppressive effect was demonstrated on MMP-2, A77 1726 markedly inhibited MMP-1, 3, and 13 secretions from IL-1beta-stimulated rheumatoid synovial fibroblasts. Tissue inhibitor of metalloproteinases-1 (TIMP-1) was constitutively produced from rheumatoid synovial fibroblasts and the suppressive effects of A77 1726 on TIMP-1 production were minimal. Our results suggest that the suppression of the MAPK signalling pathway and MMP synthesis in rheumatoid synovial fibroblasts is a possible mechanism for the inhibitory activity of leflunomide against rheumatoid arthritis.     

Effects of an erbium:YAG laser on ocular structures

We evaluated the effects of the erbium:YAG laser (2.9 m wavelength) on ocular structures. Energy was successfully transmitted through a fiberoptic bundle for intraocular and extraocular applications. The wavelength was strongly absorbed by ocular tissues, producing ablations with minimal thermal damage. Our results indicated that the erbium: YAG laser may have potential uses as a photoablative tool to reshape the corneal surface and as a surgical knife.     

Determination of diquat in biological materials by electron spin resonance spectroscopy

Summary An electron spin resonance (ESR) method already in use for the quantitative analysis of paraquat was applied to the analysis of diquat in blood, serum, urine, tissue homogenates and several drinks without purification of the samples. The diquat radical produced with ascorbic acid at alkaline pH was much more stable than that produced with the commonly used sodium dithionite. Radical decay in solutions covered with n-hexane was less than 5% after 60 min over a wide range of ascorbic acid concentrations. In 0.2N NaOH solution 85% of the radicals was present even after 24h. The limit of detection was 0.3 g/ml and the required amount of sample was 0.1 ml. When both diquat and paraquat were present in a sample the diquat was first extracted with 1-butanol prior to the ESR measurement, because both species were converted to the radicals.     

Calcaneus Bone Mineral Density is Lower Among Men and Women with Lower Physical Performance

Fracture risk is influenced by both bone strength and by falls. Measures of physical function and performance are predictors of falls. However, the interrelationships among bone mineral density (BMD), regular physical activity, and measures of physical performance are not well known. We studied 447 community-dwelling Japanese people aged 40 years and over (96 men and 351 women) to examine the association of calcaneus BMD with measures of physical performance (grip strength, walking speed, chair stand, and functional reach) and regular physical activity. Calcaneus BMD decreased with age by approximately 25% in men and 42% in women. Measures of physical performance decreased with age by approximately 30% in both genders, however, performance on the chair stand test declined by approximately 60%. There were only minimal differences in performance measures and calcaneus BMD between people with and those without regular physical activity in both genders, and most differences were not significant. However, there were significant BMD increases of 3–6% per standard deviation (SD) increase in all performance measures for women and a 7% increase in BMD per SD increase in grip strength for men, after adjusting for age. These associations remained after additional adjustment for body mass index and regular physical activity. These findings suggest that bone density and physical function decline markedly in both men and women with age, and that low BMD and poor function tend to occur together, which would increase fracture risk more than either risk factor alone. Received: 9 August 1999 / Accepted: 4 February 2000     

An angiogenesis inhibitor E7820 shows broad-spectrum tumor growth inhibition in a xenograft model: possible value of integrin alpha2 on platelets as a biological marker.

We reported previously that an angiogenesis inhibitor, E7820, inhibits in vitro tube formation of human umbilical vein endothelial cell through the suppression of integrin alpha2 expression. Here we describe the antiangiogenic and antitumor effects of E7820 in mice and discuss the feasibility of using platelet integrin alpha2 expression on platelets as a biological marker of the efficacy of E7820. Oral administration of E7820 significantly inhibited basic fibroblast growth factor-induced angiogenesis in Matrigel implants and human colon WiDr tumor-induced angiogenesis in a dorsal air sac model. Twice-daily treatment with E7820 clearly inhibited the s.c. tumor growth of seven tumor cell lines derived from human colon, breast, pancreas, and kidney, and completely suppressed the growth of human pancreatic KP-1 and human colon LoVo cell lines. Moreover, E7820 significantly inhibited the growth of KP-1 and human colon tumor Colo320DM cells orthotopically implanted in the pancreas and cecum, respectively. The efficacy of E7820 was comparable in the s.c. and orthotopic transplantation models. Immunohistochemical analyses using anti-CD31 antibody showed that E7820 significantly reduced microvessel density in orthotopically implanted KP-1 tumor. E7820 reduced integrin alpha2 expression on a megakaryocytic cell line, Dami cells, induced by phorbol 12-myristate 13-acetate treatment. It also decreased the expression level of integrin alpha2 on platelets withdrawn from mice bearing s.c. KP-1 tumor at a dosage close to that affording antitumor activity. These data demonstrate that E7820 showed a broad-spectrum antitumor effect in mice through inhibition of angiogenesis and indicate that the decrease of integrin alpha2 on platelets might serve as a biological marker for the antitumor efficacy of E7820.     

Coronary artery bypass surgery in a patient with myasthenia gravis

A 73-year-old man with myasthenia gravis required quadruple coronary artery bypass grafting due to triple-vessel disease. Anesthetic management was performed with general anesthesia using a reduced dose of muscle relaxant with the aid of a neuromuscular transmission monitor. He was extubated 14 hrs after surgery without difficulty under this monitor. His postoperative course was uneventful. A patient with myasthenia gravis who required coronary artery bypass surgery was successfully performed by the deliberate preoperative evaluation of patient's myasthenic and cardiac status, and by the careful perioperative management.     

Morphological change in the MNNG-treated rat gastric mucosa

To investigate the process of carcinogenesis in gastric cancer, we studied the histological features of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-treated rats. Samples of the gastric mucosa from both MNNG-treated and control rats were histologically examined every 2 months, for 10 months. In 40% of the MNNG-treated rats, atrophy in the gastric mucosa was observed after 2 months, and regenerative epithelium was observed after 4 months, followed by adenomatous proliferation and disappearance of the tight junction electron microscopically after 6 months. A small intestinal cancer had developed in 2 rats at 6 months. While gastric cancer had developed in 3 rats at 8 months, and in one of these 3 rats, peritoneal dissemination was observed macroscopically and histologically. These results suggested that adenomatous proliferation and disappearance of the tight junction observed electron microscopically were characteristic pathological features of precancerous lesions in the stomach in MNNG-treated rat.