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Biomedical subjects

M Kawakami

Publications and source records attributed to M Kawakami.

At least 289 records · Page 16Linked to original sources

[Roles of cytokines and growth factors in atherogenesis].

In lesions of atherosclerosis, various cytokines and growth factors, which are generally not expressed in the normal artery, are upregulated. Several of them including PDGF, bFGF, HB-EGF, IGF-1, IL-1 and TGF-beta and TNF play key roles in atherogenesis by stimulating chemotaxis and proliferation of vascular smooth muscle cells and production of extracellular matrix substances such as proteoglycans, collagen and elastic fibers by those cells. Endothelial cells and macrophages are also the targets as well as the sources of those cytokines and growth factors. The production of those cytokines or growth factors are regulated by molecules of each other or by themselves forming a complex cytokine network. Understanding and control of the roles of those cytokines in vascular walls will provide an insight on the mechanism of atherogenesis and contribute to the development of better ways to its prevention.

Arteriosclerosis↗

[A case of eosinophilic granuloma associated with a brain lesion].

A 32-year-old man was hospitalized due to right pneumothorax. Chest X-ray showed interstitial shadows predominantly in the upper and middle lung fields. Eosinophilic granuloma was diagnosed by transbronchial lung biopsy. He had a history of paraesthesia in the right arm for 6 months prior to the pneumothorax. Initially, head CT showed an iso-dense area enhanced with contrast medium in the left temporal lobe. Two weeks after the onset of paraesthesia, head CT showed an iso-dense lesion surrounded by low density area. Subjective symptoms disappeared in a month, and no abnormalities on head CT were seen at 2 months. It is highly suspected; therefore, that the present case of eosinophilic granuloma was associated with a brain lesion.

Adult↗

Changes in bone formation during experimental tooth movement after denervation of the rabbit inferior alveolar nerve.

The effects of nerve fibers on bone formation during tooth movement were examined using eight rabbits with denervation of inferior alveolar nerve (IAN). IAN on one side for all the animals was denervated and and sham operation was performed on the other side of denervation. The distance of tooth movement on the denervated and sham operated sides was very similar and 1.20 +/- 0.17 and 1.24 +/- 0.12 (mean +/- S.D. mm), respectively. From the fluorescent observations, the denervated and sham operated sides in the animals without tooth movement i.e. control group showed similar morphology. The animals with tooth movement i.e. experimental group showed significant new bone formation than the control group. However, the amount of new bone formation on the denervated side was less than the sham operated side. It was suggested that the nerve fibers might play some roles on bone formation during the tooth movement.

Alveolar Process↗

Assignment of the magnetic resonances of the imino protons and methyl protons of Bombyx mori tRNA(GlyGCC) and the effect of ion binding on its structure.

The magnetic resonances in the low-field H-NMR spectra of Bombyx mori tRNA(GlyGCC), corresponding to the hydrogen-bonded imino protons of the helical stems and tertiary base pairs, could be tentatively assigned by means of the sequential nuclear Overhauser effects. While B. mori tRNA(GlyGCC) does not contain the G19C56 tertiary base pair, the D20G57 base pair exists between the D and T loops, which was not found in the X-ray crystal structure of yeast tRNA(Phe). The effects of Mg2+, spermine and temperature on the conformation of this tRNA have also been examined based on the behavior of the assigned resonance signals. Mg2+ stabilize the D and T stems and the tertiary structure between the D and T loops. Spermine affects the resonances of the D and anticodon stems, and A23G9, but does not stabilize them. While the acceptor stem melts sequentially from both ends (G7C66 and G1C72) with increasing temperature, the anticodon stem melts from only one end (G39C31) and the G26C44 base pair is the most stable. In the tertiary structure between the variable loop and D stem, G10G45 melts first and G22G46 last. Yeast tRNA(Phe) has also been examined, and the results were compared with those for B. mori tRNA(Gly).

Animals↗

An ultrasensitive system to detect IL-4: enzyme-linked immunosorbent assay (ELISA) combined with an avidin-biotin and enzyme amplification system.

We established an ultrasensitive interleukin-4 enzyme-linked immunosorbent assay by combining ELISA with an avidin-biotin and enzyme amplification system. The resultant system (AB-EA ELISA) was 250 times more sensitive than conventional ELISA and 2.5 times more sensitive than enhanced ELISA using an enzyme amplification system alone. The ultrasensitive assay was specific to IL-4 alone; there was no cross reaction with other cytokines. Using the ultrasensitive assay, we measured IL-4 synthesis in vitro by unstimulated and stimulated peripheral blood mononuclear cells (PBMC) from patients with allergic rhinitis. PBMC from patients spontaneously produced measurable amounts of IL-4, whereas IL-4 production from PBMC of normal controls, if any, was below detectable levels. Stimulation of the cultures with LPS significantly increased IL-4 production in two of six patient PBMC cultures but in none of the control cultures; stimulation with Con A markedly increased IL-4 production in all patient PBMC cultures but in only two of seven control cultures. These results suggest that the AB-EA ELISA is a useful method to study the mechanism of IL-4 synthesis in type-I allergic diseases.

Animals↗

cDNAs and deduced amino acid sequences of subunits in the binding component of mouse bactericidal factor, Ra-reactive factor: similarity to mannose-binding proteins.

The complement-dependent bactericidal factor, Ra-reactive factor, binds specifically to Ra polysaccharide, which is common to some strains of Gram-negative enterobacteria, and its is a complex of proteins composed of a polysaccharide-binding component and a component that is presumably responsible for the complement activation. The former component consists of two different 28-kDa polypeptides, P28a and P28b. We determined the partial amino acid sequences of P28a and P28b, and the results indicated that these polypeptides were similar to two species of mannose-binding protein, MBP-C and MBP-A (alternative names, liver and serum mannan-binding proteins, respectively), which have been isolated from rat liver and/or serum [Drickamer, K., Dordal, M. S., & Reynolds, L. (1986) J. Biol. Chem. 261, 6878-6887; Oka, S., Itoh, N., Kawasaki, T., & Yamashina, I. (1987) J. Biochem. 101, 135-144]. Thus, we cloned the respective cDNAs, using as probes synthetic oligonucleotides for which the sequences had been deduced from the amino acid sequences of P28a and P28b and of rat MBP cDNAs. The primary structures of P28a and P28b deduced from the cloned cDNAs are homologous to one another. They have three domains, a short NH2-terminal domain, a collagen-like domain, and a domain homologous to regions of some carbohydrate-binding proteins, as has been reported for rat MBPs. Southern and Northern blotting analyses using these cDNAs indicated that the P28a and P28b polypeptides are the products of two unique mouse genes which are expressed in hepatic cells.

Amino Acid Sequence↗

Increased interleukin 1 receptor, type I, at messenger RNA and protein level in skin fibroblasts from patients with systemic sclerosis.

Summary. To elucidate the mechanisms of the fibrosis in systemic sclerosis (SSc) through the action of a cytokine, interleukin 1 (IL-1), we studied the specific biologic and biochemical features of interleukin 1 receptor (IL-1R) as expressed on the surfaces of fibroblast cells in cultures from 3 SSc patients and 3 normal donors. 125I-IL-1 beta binding assays revealed a high density of IL-1R on the cell surfaces of SSc fibroblasts as compared to those of normal subjects. We also found an enhanced expression of IL-1R messenger RNA (mRNA) in SSc fibroblasts, using Northern blot or slot blot analysis. These findings indicate that the expression of IL-1R on SSc fibroblasts were spontaneously induced at the transcriptional level. It is suggested that SSc fibroblasts are more sensitive to IL-1, and that the signal transduction of IL-1 through IL-1R may be eventually involved in the fibrosis of SSc.

Cells, Cultured↗

Human mannose-binding protein is identical to a component of Ra-reactive factor.

Human Ra-reactive factor (RaRF) and mannose-binding protein (MBP) were isolated from sera by utilizing their affinity to Ra chemotype Salmonella typhimurium and yeast mannan, respectively. A predominant polypeptide of human RaRF with an Mr of 32 kDa (P32) has the same mobility as human MBP on SDS-PAGE gels. A monoclonal antibody against P32 of human RaRF, 3E7, was found to react not only with P32 but also with human MBP, as assessed by immunoblotting. In addition, 3E7 blocked the complement-activating capacity of human MBP. The NH2-terminal amino acid sequence of P32 of human RaRF was determined and found to coincide with that of human MBP. Based on these results, it is clear that human MBP is identical to a component of RaRF.

Antibodies, Monoclonal↗

Serum granulocyte colony-stimulating factor in patients with repeated infections.

We have already reported significant elevation of serum granulocyte colony-stimulating factor (G-CSF) in the acute phase of infection. In this study, we compared the responses to infection between patients with frequently repeated infection (repeaters) and others (non-repeaters). We examined the clinical data and serum G-CSF levels in 48 patients with acute infections. Serum G-CSF levels were significantly lower in repeaters than in non-repeaters (197.7 +/- 370.0 vs. 1014.1 +/- 924.4 pg/ml. P less than 0.001). There were no significant differences in age, serum total protein, or cholinesterase between the groups, but serum albumin was significantly lower in repeaters than in non-repeaters (2.87 +/- 0.5 vs. 3.31 +/- 0.4 g/dl. P less than 0.005). It is suggested that administration of recombinant G-CSF may be useful for patients with repeated infections.

Aged↗

On the variability of the 3' terminal sequence of the turnip mosaic virus genome.

The sequence of the 3'-terminal 1223 nucleotides (nts) of a Japanese isolate of turnip mosaic virus (TuMV-Jap) RNA has been determined. The sequence reveals a single open reading frame (ORF) which terminates at a position 212 nts upstream of the 3' poly(A)-tract. Determination of the N-terminal amino acids of TuMV-Jap coat protein (CP) mapped the CP cistron within this ORF and revealed a Glu-Ala dipeptide sequence as the putative cleavage site by which the CP is released from the viral polyprotein. The predicted amino acid sequence of the TuMV-Jap CP shows 97.2% identity with that of a Canadian isolate of TuMV (TuMV-Can) and 99% with a second, Chinese, isolate (TuMV-Chi). However, the 3'-terminal non-translated region (NTR) of TuMV-Jap RNA is significantly shorter (212 nts) than the 3'-NTR of TuMV-Can RNA (668 nts), but of equal length as the 3'-NTR of the TuMV-Chi isolate which also measures 212 nts. The 3'-NTRs of both the TuMV-Jap and TuMV-Chi RNAs show homology with the first 201 nucleotides of the TuMV-Can RNA 3'-NTR. A search in the EMBL nucleotide sequence database revealed that the 467 nt-long unique extension of the 3'-NTR of TuMV-Can RNA has 89.8% homology to a part of the chloroplast ribosomal protein 12 gene (rsp12-gene). Irrespective of the origin of this extra sequence in the reported TuMV-Can sequence, which may have been introduced by a genuine RNA recombination event, it is concluded that the standard TuMV genome has a CP gene of 864 nts and an conserved 3'-NTR of approximately 212 nucleotides in length.

Amino Acid Sequence↗

Presence of autoantibodies to peptidyl-prolyl cis-trans isomerase (cyclosporin A-binding protein) in systemic lupus erythematosus.

Several autoantibodies against cytoplasmic or nuclear components of cells have been reported in autoimmune diseases. We report here a previously unrecognized autoantibody to peptidyl-prolyl cis-trans isomerase (PPIase) in patients with systemic lupus erythematosus (SLE). PPIase, which catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides, has recently been found to be identical to cyclophilin, a specific binding protein of a potent immunosuppressant, cyclosporin A. IgG and IgM anti-PPIase antibodies were detected in 40 and 20% of unselected patients with SLE, respectively, by ELISA. The reactivity of these sera was confirmed by immunoblotting experiments. Sera from rheumatoid arthritis patients showed no reactivity and 1 of 8 sera from systemic sclerosis patients and 1 of 25 sera from normal controls showed only weak reactivity. Unexpectedly, the anti-PPIase antibody was unable to inhibit PPIase activity, indicating that the autoantibody recognizes an epitope of PPIase which is different from the active site of PPIase. The levels of the anti-PPIase antibody in SLE patients correlated with remissions and flares of the disease. The anti-PPIase antibody was higher in patients with active SLE than those with inactive disease. The prevalence of the active stage of the disease was significantly higher in IgG anti-PPIase antibody-positive SLE patients as compared to antibody-negative SLE patients. These data define the presence of a new autoantibody against PPIase and its association with the activity and certain clinical manifestations in SLE.

Adult↗

Influence of the electrical stimulation of the hypothalamus on adrenocortical steroidogenesis in hypophysectomized rats.

The electrical stimulation of the ventromedial hypothalamus (VMH), lateral hypothalamic area (LHA), periventricular arcuate nucleus (ARC), and posterior hypothalamus (PHY), on 14C transfer rates from 14C-1-acetate into adrenocortical steroids in adrenal slices of hypophysectomized rats were investigated. The 14C transfer rates into corticosterone and cortisol were increased by the stimulation of the VMH, ARC, and PHY, but decreased by the stimulation of the LHA. From these results, it might be suggested that these hypothalamic structures were involved in the regulation of adrenocortical steroidogenesis without participation of the pituitary.

Acetates↗

The role of limbic-hypothalamic systems in metabolic responses of phenylalanine to repeated cold exposures in rabbits.

In this study we examine the effects of lesions to limbic or hypothalamic structures on the metabolic responses of phenylalanine in liver slices prepared from rabbits exposed to cold stress (-20 degrees C) for 12 hours at a fixed time once a day. The results were as follows: 1. The 1st cold exposure (cold exposure on the 1st day) had marked and various effects on phenylalanine metabolism, and the metabolic responses of phenylalanine to cold exposure gradually decreased and then completely disappeared with repetitions of exposure in intact rabbits. 2. The metabolic patterns and responses of phenylalanine to the 1st cold exposure were altered by lesioning the periventricular arcuate nucleus (ARC), ventromedial hypothalamus (VMH), stria terminalis (ST) or dorsal fornix (FX). 3. The complete abolishment of the metabolic responses to cold exposure by its repetition was observed in rabbits with lesions in the ARC or VMH as well. 4. In contrast, metabolic responses of phenylalanine to cold exposure in rabbits with lesions in the ST or FX remained even after six exposures. These results suggest that the ARC, VMH, amygdala (AMYG)-ST system and dorsal hippocampus (HPC)-FX system played a role in the metabolic regulation of phenylalanine and in the metabolic responses of phenylalanine to the 1st cold exposure and that the AMYG-ST and HPC-FX systems, but not the ARC or VMH, participated in the process of the metabolic adaptation of phenylalanine to cold exposure.

Amygdala↗

Influence of the electrical stimulation of the medial amygdala on adrenocortical sensitivity to adrenocorticotrophin in hypophysectomized rats.

The effects of electrical stimulation of medial amygdala on the adrenocortical sensitivity to adrenocorticotrophin (ACTH) were investigated in hypophysectomized rats. The intravenous injection of ACTH increased the rates of 14C transfer from 14C-l-acetate into corticosterone and cortisol in the adrenal slices of hypophysectomized rats. The electrical stimulation of the medial amygdala produced a further increase in the rates of 14C transfer from 14C-l-acetate into corticosterone and cortisol. From these results, it might be suggested that the medial amygdala was capable of enhancing the adrenocortical steroidogenesis in response to ACTH.

Acetates↗

Morphologic and quantitative changes in neurotransmitters in the lumbar spinal cord after acute or chronic mechanical compression of the cauda equina.

Changes in the neurotransmitters associated with pain transmission and regulation in the lumbar spinal cord were studied after acute or chronic mechanical compression of the cauda equina in rats. Using glyoxylic acid histofluorescence and immunohistochemical methods, it was morphologically apparent that substance P-containing nerve ending were decreased after chronic compression of the cauda equina. Somatostatin nerve terminals were reduced, and aminergic fibers and serotonin were enhanced after both acute and chronic mechanical compressions. In addition, quantitative analysis revealed that the levels of norepinephrine and serotonin remained elevated after mechanical compression of the cauda equina. It is suggested that pain in the lower back and extremities after mechanical compression of the cauda equina is controlled by these complicated changes of neurotransmitters in the lumbar spinal cord.

Animals↗