Expression of vascular endothelial growth factor isoforms and their receptors Flt-1, KDR, and neuropilin-1 in synovial tissues of rheumatoid arthritis

Angiogenesis is an indispensable process in the chronic proliferative synovitis and pannus formation of rheumatoid arthritis (RA). This study examined the expression of vascular endothelial growth factor (VEGF) isoforms and VEGF receptors, Flt-1, KDR and neuropilin-1, in RA and osteoarthritis (OA) synovia, and studied the relationship between their expression and the synovial angiogenesis. By RT-PCR analysis, the isoform VEGF(121) was constitutively expressed in all the RA (17/17 patients) and OA (8/8 patients) synovia. In contrast, the expression of the isoform VEGF(165) was observed in 41% of the RA synovia (7/17 patients), but was undetectable in the OA samples (0/8 patients). The receptor Flt-1 was almost constitutively expressed in RA (15/17 patients) and OA (8/8 patients) synovia, while the expression of KDR was detected in the synovia of six RA patients (6/17 patients; 35%) but none of the OA patients (0/8 patients). The expression of neuropilin-1, an isoform-specific receptor for VEGF(165) which enhances the binding of VEGF(165) to KDR, was also up-regulated in the same RA synovia that expressed KDR. Furthermore, there was a close correlation between the expression of isoform VEGF(165) and that of its receptors KDR and neuropilin-1. Morphometric analysis demonstrated that the vascular density is significantly higher in the RA synovial tissues with expression of VEGF(165), KDR, and neuropilin-1 than in those without their expression (p<0.01). In situ hybridization and immunohistochemical studies indicated that the cells expressing VEGF are macrophage-like synovial lining cells and spindle-shaped cells in the sublining cell layer. These results suggest that the selective up-regulation of the isoform VEGF(165) and its signalling via KDR and neuropilin-1 play an important role in the synovial angiogenesis which occurs in RA.     

Study on the mechanism of the appearance of noise effects

Summary This study was undertaken to investigate the dose-response relationship between the biological effect and noise exposure, and to consider the mechanism of the appearance of noise effects. Rats were exposed to noise at intensities of 60 dB (A), 80 dB (A) and 100 dB (A) for 240 min and examined for the change of activities of dopamine--hydroxylase (DBH) in serum and adrenal glands. Plasma cyclic adenosine 3,5-monophosphate (c-AMP) levels were also measured. Some rats were given 6-hydroxydopamine (6-OHDA) as a chemical sympathectomyzing agent 20 h before noise exposure in order to consider the mechanism of the appearance of noise effects. By noise exposure, serum DBH activity was significantly (P<0.01) increased at each intensity compared with the control group, but there were no remarkable changes in adrenal DBH activity. Plasma c-AMP level was also significantly elevated in response to the noise stress. When the rats, which had been pretreated with 6-OHDA, were exposed to noise with an intensity of 100 dB (A), the response of serum DBH activity was no longer observed. Therefore it is suggested that the effect due to noise exposure appears through the post-ganglionic sympathetic nerve fiber.     

Fermented grain products, production, properties and benefits to health

Fermented foods such as Japanese traditional food “miso (fermented soy bean paste)” have been shown to be rich source of micronutrients with the potential to prevent various human diseases. We have introduced effects of a new dietary supplement of fermented grain foods mixture containing extracts from wheat germ, soybeans, rice bran, tear grass, sesame, wheat, citrus lemon, green tea, green leaf extract and malted rice under the trade name of antioxidant biofactor (AOB). Chemical analysis of AOB shows the presence of various phenolic compounds (catechins, rutin, genistin, daidzin, etc.). AOB has strong antioxidant properties and additional biological effects, which might be of importance in context with the prevention of degenerative diseases. This paper focuses on the effect of supplementing AOB in various animal models and humans.     

Reduction of voltage-dependent magnesium block of N-methyl-D-aspartate receptor-mediated current by in vivo axonal injury

The post-traumatic change of the voltage-dependent Mg(2+) block of N-methyl-D-aspartate response was investigated using nystatin perforated patch recording mode under the voltage-clamp condition. Motor neurons of the dorsal motor nucleus of vagus nerve were freshly dissociated from rat brain at 2h to 10 days after receiving axonal crush injuries in vivo at the neck. The reduction of voltage-dependent Mg(2+) block of N-methyl-D-aspartate response became evident at more than 12h after the injury, sustained for at least five days and recovered within 10 days. Other characteristics examined such as reversal potentials, the Hill coefficient and EC(50) of N-methyl-D-aspartate-induced current were not affected by axonal injury. The Mg(2+) block of N-methyl-D-aspartate response was not affected at all by local application of colchicine onto the vagal axon in in vivo condition, suggesting that axonal injury, but not the blockade of the axonal flow, is responsible for the change of the sensitivity of N-methyl-D-aspartate response to extracellular Mg(2+). In addition, the reduction of Mg(2+) block by the nerve injury persisted regardless of the presence of protein kinase C modulators, such as 10(-6)M chelerythrine and 10(-7)M calphostin C. Therefore alteration of protein kinase C activity after axonal injury is not responsible for the maintenance of the reduced Mg(2+) block.These findings suggest that injured neurons acquire immature characteristics of plasticity with respect to the sensitivity of N-methyl-D-aspartate receptors to extracellular Mg(2+) or a long-term increase in the susceptibility to Ca(2+) excitotoxicity.     

Pump for accurate mixing of three gas components with predetermined fractions

A mixing pump that creates an accurate mixture of three gases at predetermined fractional ratios that can be set in steps of 10 ppm is described. A nearly continuous flow of each of the three component gases is produced by pistons driven by stepping motors; the gas mixture is forwarded by a fourth piston. The flow of each component gas is adjusted by the stepping frequency of the motor and a microcomputer system is used to adjust the three frequencies according to the desired fractional concentrations. The total flow of the gas mixture is adjustable between 0.1–500 ml/min and is nearly independent of the after-load. The accuracy of the pump was tested by mixing the respiratory gases, O₂ and CO₂, with various carrier gases (N, He or Ar) at various fractional ratios and total flow rates. The fractions of O₂ and CO₂ in the mixture were analysed with the Scholander technique. In the physiological range, the mixing error in the gas fractions was less than 4%. The pump is, thus, suited for producing calibration mixtures.     

C cell hyperplasia and carcinoma developing in sheep with experimentally-induced lymphosarcoma.

Two cases of C cell hyperplasia and one case of C cell carcinoma of the thyroid glands were bilaterally recognized in 11 sheep with experimentally-induced lymphosarcoma. The serum calcium concentration in the C cell carcinoma case was slightly increased above the normal concentration of around 9 mg per dl. Bilateral C cell hyperplasia also developed in the thyroid lobes of the C cell carcinoma case. Immunohistochemically, hyperplastic C cells and tumour cells were positive for calcitonin, calcitonin gene-related peptide, chromogranin A and neurone-specific enolase. No amyloid deposition nor multiple endocrine neoplasia was demonstrated in any of the cases. Ultrastructurally, many secretory granules were observed in the cytoplasm of neoplastic cells constituting the C cell carcinoma and in the hyperplastic C cells.     

Contribution to the morphology of mitochondria with prismatic cristae in astrocytes of the inferior olivary nucleus of the cat

The internal structure of mitochondria with prismatic cristae in astrocytes of the inferior olivary nucleus of the adult cat was examined. The interior of the mitochondria with prismatic cristae cut in cross-section can be divided into 2 areas: (1) a peripheral, rather structureless area, and (2) a central, highly organized area. The former is composed of the inner mitochondrial membrane and a small number of peripheral cristae protruding from the membrane and scattered dots. The latter is composed of numerous prismatic cristae arranged in almost hexagonal spacing and many dots which probably represent the transverse configuration of filaments oriented parallel to the cristae embedded in the matrix. For future comparative analysis, various quantitative observations on the fine structure of the central, highly organized area are described and discussed.