Biomedical subjects

S Kishimoto

Publications and source records attributed to S Kishimoto.

At least 181 records · Page 10Linked to original sources

PubMed1991

Tumour necrosis factor/cachectin plays a key role in autoimmune pulmonary inflammation in lupus-prone mice.

The role of tumour necrosis factor-alpha (TNF-alpha) in the development of autoimmune pulmonary inflammation has been investigated in lupus-prone mice. An increase in TNF-alpha mRNA level from whole lung preparation of lupus-prone mice was evident, from 3 weeks to 12 weeks during growing process, as shown by Northern blot analysis, but not in control mice. Furthermore, it is also found that the major source of this increase in TNF-alpha mRNA was attributed to infiltrating mononuclear cells found within the lung. Treatment of lupus-prone mice with rabbit anti-mouse TNF-alpha IgG prevented the development of pulmonary inflammation lesions such as lung fibrosis and alveolitis. These results suggest that an increased TNF-alpha production by infiltrating mononuclear cells in the lungs of lupus-prone mice may play a role in the development of autoimmune pulmonary inflammation and in significant changes of cytokines and the immune responses in pulmonary inflammation lesions of lupus-prone mice.

Animals↗

PubMed1991

Effect of long-term L-threo-3,4-dihydroxyphenylserine administration on alpha 2-adrenergic receptors in platelet membranes in neurologic disorders.

The effects of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS), an unnatural norepinephrine precursor, on alpha 2-adrenergic receptors in platelet membranes were investigated in a patient with familial amyloidotic polyneuropathy, two patients with multiple system atrophy, and two patients with Parkinson's disease. Each patient was treated for at least six months. While L-threo-DOPS alone, or in combination with decarboxylase inhibitor benserazide hydrochloride, produced sustained increase in plasma norepinephrine and clinical improvement, it did not induce a change in the number of alpha 2-adrenergic receptors in platelet membranes.

Aged↗

PubMed1991

Increase of T-cell receptor gamma/delta-bearing T cells in cord blood of newborn babies obtained by in vitro stimulation with mycobacterial cord factor.

Cord blood T lymphocytes proliferated in vitro in response to mycobacterial organisms but did not proliferate in the presence of tuberculin purified protein derivative. Components recognized by cord blood T cells were resistant to protease digestion. In contrast, T lymphocytes derived from tuberculin-positive adult peripheral blood proliferated when stimulated by the protease-sensitive component of mycobacterial organisms or purified protein derivative, confirming that adult T cells respond to protein components whereas cord blood T cells respond to the nonpeptide component of mycobacteria. In vitro culture of cord blood lymphocytes stimulated by either mycobacterial lysates or the lipid fraction showed increases in the numbers of T-cell receptor (TcR) gamma/delta T lymphocytes with no changes in the numbers of TcR alpha/beta T lymphocytes in contrast to the in vitro cultures of adult blood lymphocytes stimulated with mycobacterial ligands in which no increase of TcR gamma/delta cells was observed. Interleukin-2 receptor (CD25) and Ia antigen (HLA-DR) analyses evidenced the activation of a large proportion of cord blood gamma/delta T cells which had increased after stimulation with mycobacteria in vitro. Further characterization of mycobacterial ligand suggested that the lipid fraction of mycobacterial lysate or trehalose dimycolate-cord factor was the most plausible cause for T-cell proliferation in cord blood. These results suggest that when the gamma/delta T cells in a newborn infant not yet sensitized to any pathogenic organisms are confronted by a mycobacterium, they respond nonspecifically to the mycobacterial organism or its lipid component (cord factor). gamma/delta T cells may therefore play a distinct role in forming the first line of the host defense system against certain microorganisms.

Cord Factors↗

PubMed1991

Phosphorylation in the carboxyl-terminal domain of the capsid protein of hepatitis B virus: evaluation with a monoclonal antibody.

The capsid protein of hepatitis B virus (p21c) is made of 183 amino acids coded for by the C gene. By using p21c isolated from Dane particles (hepatitis B virus) as an immunogen, a monoclonal antibody (no. 2212) which recognized an epitope dependent on the phosphorylation of p21c was raised. The binding of no. 2212 antibody to authentic p21c was completely inhibited by a synthetic undecapeptide with a sequence of RRRSQSPRRRR, representing amino acids 165 to 175 of p21c, only when the peptide was phosphorylated. Either or both of Ser-168 and Ser-170 were phosphorylated in p21c in vivo, therefore, and contributed to the manifestation of the epitope. No. 2212 antibody bound to p21c from core particles derived from Dane particles or hepatocellular carcinoma tissues (PLC/342) propagated in nude mice but did not bind to p21c from core particles expressed in Escherichia coli or yeast cells, indicating different states of phosphorylation in them. Nonphosphorylated p21c showed a higher affinity for the viral DNA than did phosphorylated p21c. Since the serum from an asymptomatic carrier, with a high titer for antibody to hepatitis B core antigen, specifically bound to phosphorylated undecapeptide (amino acids 165 to 175), the epitope would stimulate humoral antibody responses in the human host.

Amino Acid Sequence↗

PubMed1991

A novel antineuronal antibody in serum and CSF of a patient with motor neuron disease.

A patient with motor neuron disease and tonic pupil who had an antinuclear antibody (Ab) in the serum and oligoclonal pattern in IgG in the CSF is described. Sera and CSF from this patient and controls (37 sera and 30 CSF) were screened for an antineuronal Ab using immunoblotting. Only the serum and CSF from this patient contained an Ab to a 70-kD protein in the human spinal cord but not in the human muscle or cerebellar cortex. This patient's serum immunohistochemically stained human and Japanese monkey anterior horn cells but not Japanese monkey dorsal root ganglion.

Animals↗

PubMed1991

Spontaneous activation of transforming growth factor-beta gene transcription in broncho-alveolar mononuclear cells of individuals with systemic autoimmune diseases with lung involvement.

The spontaneous elevation of the transcription of the transforming growth factor-beta (TGF-beta) gene in broncho-alveolar mononuclear cells (BMC) of individuals with autoimmune diseases with lung involvement, by nuclear run-on transcription assay, is shown in this study. In quantification analysis of TGF-beta gene transcription, we found more than 10 times the enhanced transcription of the TGF-beta gene in BMC of individuals with autoimmune diseases with lung involvement, in comparison to normal healthy subjects or patients with bronchial asthma used as controls. Our observation suggests that TGF-beta, a potent mitogen for fibroblasts, may be produced in BMC during an active immune response in individuals with systemic autoimmune diseases with lung involvement, and may be involved in autoimmune-related pathophysiological changes of cytokine networks in lung involvement such as lung fibrosis.

Autoimmune Diseases↗

PubMed1991

Synthesis and biological activity of (S)-2-amino-3-(2,5-dihydro-5-oxo-4-isoxazolyl)propanoic acid (TAN-950 A) derivatives.

(S)-2-Amino-3-(2,5-dihydro-5-oxo-4-isoxazolyl)propanoic acid (TAN-950 A (1)) is a novel amino acid antibiotic which shows a high affinity for glutamate receptors of the central nervous system. To improve the affinity for glutamate receptors, the structure-activity relationships of TAN-950 A derivatives 6a--o, 15a--o were investigated. Optically active TAN-950 A analogs 15a--h were synthesized starting with methyl (S)- and (R)-N-Boc-pyroglutamate (8) via acylation at the C-4 position followed by isoxazolone formation with hydroxylamine and subsequent deprotection reactions. The lactam 16, prepared from (RS)-aminoadipic acid, and dimethyl esters 19 of (R)- and (S)-aspartic acid were converted to (RS)-3-methyl-homo-TAN-950 A (15i) and optically active nor-TAN-950 A derivatives 15j--o, respectively, utilizing a similar sequence of reactions. Most of TAN-950 A derivatives 6a--o, 15a--o showed an affinity for glutamate receptors. The 3-alkyl derivatives 15b, d--g, especially, showed a high affinity for the quisqualate subtype-receptor and had a strong activating effect on the hippocampal neurons (glutamate agonistic activity). The (R)-enantiomer 15a of TAN-950 A had increased selectivity for the N-methyl-D-aspartate (NMDA) subtype-receptor. This selectivity was further enhanced by removal of the methylene group in the amino acid moiety of 15a. The most potent and selective NMDA agonistic activity was observed with (R)-3-methyl-nor-TAN-950 A (15m).

Animals↗

PubMed1991

Interaction of vitamin D-binding protein with immobilized cibacron blue F3-GA.

An interaction of vitamin D-binding protein to immobilized Cibacron Blue F3-GA was studied under urea containing buffers. In these buffers, this protein was adsorbed to the immobilized dye and was eluted with salt gradients as in the same buffer without urea. The protein was also adsorbed to immobilized diethylaminoethyl but not to immobilized carboxymethyl. It is implicated that a combination of pseudo-ligand affinity and/or hydrogen bonding interaction plays a large role whereas ionic, hydrophobic and lipophilic interactions act little between the protein and the immobilized blue dye.

Buffers↗

PubMed1991

[Respiratory tract infection and immunodeficiency].

Many defense mechanisms are located in the respiratory tract, since they are constantly exposed to a variety of pathogens from both inside and outside the body. Among the various defense mechanisms, the immune system is so potent that immunodeficiency results in proneness to infections and repeated and/or intractable infection. It is not uncommon to encounter patients with congenital immunodeficiency in clinical practice because of recent advances in supportive therapy. This paper describes cases of primary immunodeficiency that developed respiratory infections, together with the results of investigations of their immune status. Doctors should suspect the possibility of immunodeficiency in patients with repeated or intractable respiratory infections. Intractable respiratory infections, however, have been seen with increasing frequency in the elderly because of the increase in the elderly population. One reasons for this is the physiologic immunodeficiency associated with aging, which is characterised by decreased antigen-induced lymphocyte proliferation, IL-2 production, IL-2R expression, hsp 70 mRNA production, and demethylation of T lymphocytes, and delayed degradation of c-myc mRNA.

Aging↗

PubMed1991

Release of a suppressor cell-inducing factor by monocytes from patients with pulmonary tuberculosis.

We observed that blood monocytes from tuberculous patients secreted a factor which induced suppressor cells. Monocyte-enriched adherent cells were prepared from peripheral blood mononuclear cells (PBMC) of 14 patients with active pulmonary tuberculosis or nine healthy tuberculin skin reactors and were cultured without any stimulus for 5 days. For induction of suppressor cells, PBMC from a healthy tuberculin reactor were cultured with the monocyte culture supernatants (MN SUP). After 2 days, those cells were washed and irradiated, then tested for their ability to suppress blastogenesis in autologous PBMC stimulated with purified protein derivative (PPD). Mean activity of suppressor cell induction in MN SUP of patients with pulmonary tuberculosis was significantly greater than that of healthy controls. In contrast, PPD-induced blastogenic responses in PBMC from tuberculous patients were lower than in controls. When we divided those tuberculous patients into high and low secretor groups on the basis of the magnitude of suppressor cell induction by MN SUP, PBMC from the high secretors had lower direct blastogenic responses to PPD than those of the low secretors. The blastogenic responses of PBMC from the high secretors, but not the low secretors, were significantly lower than those of healthy subjects. MN SUP which contained high suppressor cell-inducing activity had no effect on PPD-induced blastogenesis of PBMC from a healthy donor. These data suggest that monocytes from some tuberculous patients indirectly depress lymphocyte blastogenesis through a suppressor cell-inducing factor.

Adult↗

PubMed1991

[Enzyme immunoassay for secretory immunoglobulin A on skin surface and in sweat].

Recently secretory IgA (S-IgA) was found to be secreted from the eccrine gland. By using a sandwich enzyme immunoassay, we measured the concentration of S-IgA 1) in sweat (sweat S-IgA) and 2) in the extract buffer obtained by pipetting++ on the skin (skin surface S-IgA). Skin surface hydration and skin surface lipid were measured at the sites where the samples of skin surface S-IgA were collected. (These measurements were taken immediately after the buffer was pipetted). The quantity of both sweat S-IgA and skin surface S-IgA differed according to the sites where they were collected. Sites in order of decreasing sweat S-IgA level: face, chest, forearm. Sites in order of decreasing skin surface S-IgA level: face, chest, palm, forearm, sole. (Skin surface S-IgA levels on palm and forearm were approximately equal). Although the amount of skin surface S-IgA was not related to the skin surface hydration, there was a significant correlation between skin surface S-IgA and skin surface lipid.

Adolescent↗

PubMed1991

[Studies of free theophylline in asthmatic patients].

Total and free theophylline concentrations were examined by fluorescent immunoassay using serum from 48 asthmatic patients treated with sustained-release theophylline formulation. Total and free theophylline concentrations showed a good correlation. The mean % free theophylline (free theophylline concentration X 100/total theophylline concentration) was 44.7% in children and 43.6% in adults. The % free theophylline had no relation to age of the patients or total theophylline concentration. However, the % free theophylline increased correlatively when serum pH or albumin was decreased. As changes in free theophylline concentration influence therapeutic responses and side effects, an assessment of serum pH and albumin in patients treated with theophylline is necessary.

Adolescent↗

PubMed1991

Monoclonal anti-VH141 antibodies that specifically recognize the heavy chain variable region of, and are closely related to, MOPC141 myeloma protein whose VH gene belongs to VHQ52 family.

To raise monoclonal antibodies that specifically recognize the heavy chain variable region of MOPC141 myeloma protein (VH141), which belongs to VHQ52 family, rats were immunized with Fd'-conjugated keyhole limpet haemocyanin (KLH) (Fd': Fd' fragments of MOPC141), and the spleen cells were fused with mouse myeloma cells. The resulting 900 hybridomas were screened for antibody activity against Fd'1 fragments having no constant H-chain sequences, which were prepared by cleavage of the Fd' fragments with cyanogen bromide, and two monoclonal antibodies, designated 3-2-7h and 3-5-6f, were obtained. Radioimmunoassay inhibition test showed that the two monoclonal antibodies specifically recognized the VH141, but each was directed to a different determinant on the VH141. When the functional VH gene of Abelson virus-transformed mu-producing pre-B cells, which could be strongly stained with 3-5-6f monoclonal antibody, was cloned and sequenced, the VH gene was closely relate to that of MOPC141 (88% and 94% homology at amino acid and DNA level, respectively). Taken together, the results indicated that 3-2-7h had high specificity only for the VH141, whereas 3-5-6f specifically reacted not only with the VH141 but also with the VH region closely related to that of MOPC141, and that both the monoclonal anti-VH141 antibodies were specific for a limited range of VH regions within the VHQ52 family rather than being VHQ52 family specific. These monoclonal anti-VH141 antibodies should be very useful to determine at a single cell level by immunofluorescence the usage of the VH gene(s) identical or closely related to that of MOPC141 during early B-cell development.

Amino Acid Sequence↗

PubMed1991

Preventive effect of cimetidine on chronic erosive gastritis induced by taurocholate in rats.

We studied the preventive effect of cimetidine at the microscopic level on chronic erosive gastritis induced experimentally by 6-months of administration of drinking water containing 5 mmol/l of the sodium salt of taurocholic acid (TCA) in rats. The chronic erosive gastritis was characterized by mucosal erosions, reduction of mucosal thickness and reduction in the number of parietal cells per unit area, infiltration of inflammatory cells which were mainly lymphocytes and plasmocytes, and proliferation of collagenous fibers in the gastric mucosa. A standard meal including cimetidine 0.4 and 0.8%, which was administered ad libitum with TCA, reduced the total length of erosions, normalized the mucosal thickness and the number of parietal cells, and reduced inflammatory cell infiltration in the gastric mucosa. However, cimetidine did not show any effect on the proliferation of collagenous fibers in the interstitial space of the mucosa. The doses administered were 400 mg/kg/day and 800 mg/kg/day for 6 months. Cimetidine, thus, had a preventive effect on experimental chronic erosive gastritis in rats.

Animals↗

PubMed1991

Treatment of established taurocholate-induced chronic erosive gastritis in rats with cimetidine.

The study investigated whether cimetidine could heal chronic erosive gastritis induced experimentally in rats by the administration of taurocholate for 6 months. Taurocholate gastritis is associated with mucosal erosions, the infiltration of inflammatory cells, reduction of the parietal cell mass, reduction of mucosal thickness, and interstitial fibrosis, a histopathological picture similar to that of human erosive gastritis. Microscopic quantitative morphological studies were used to determine the effect of cimetidine administered freely to rats for two weeks in the form of food containing 0.4 or 0.8% of the agent after the withdrawal of taurocholate. Basal acid secretion was analysed in rats with pyloric ligation 12 hours after withdrawal of the cimetidine-containing food. Basal gastrin levels were determined after a 12-hour fast by radioimmunoassay. The total length of the mucosal erosions was significantly decreased in the cimetidine-treated rats of Group A (cimetidine: 400 mg/kg/day: median 294.6 mm) and Group B (800 mg/kg/day; 225.7 mm) when compared to Group C (control gastritis group; 626.4 mm). Both the grade of inflammatory cell infiltration and fibrosis were also significantly reduced in Groups A and B compared with Group C. The number of parietal cells per unit area (A: 101.0, B: 108.8) and the mucosal thickness of the fundic mucosa (A: 0.610, B: 0.710) and of the antral mucosa (A: 0.220, B: 0.240) were greater in Groups A and B than in Group C (85.1 and 0.52 of the fundic mucosa, 0.170 of the antral mucosa, respectively). Basal acid secretion was significantly inhibited in Groups A and B (31.8 and 26.3 mu Eq/hr/100 g body weight, respectively) when compared to Group C (69.6 mu Eq/hr/100 g body weight). Basal serum gastrin levels were significantly higher in Groups A and B (198.1 and 210.5 pg/ml, respectively) than in Group C (98.7 pg/ml). It was concluded from these results that cimetidine had a curative effect on chronic erosive gastritis induced experimentally by taurocholate. The inhibition of acid and gastrin secretion may play an important role in the mechanism of its action.

Animals↗

PubMed1990

Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth.

Neovascularization is critical for the growth of tumours and is a dominant feature in a variety of angiogenic diseases such as diabetic retinopathy, haemangiomas, arthritis and psoriasis. Recognition of the potential therapeutic benefit of controlling unabated capillary growth has led to a search for safe and effective angiogenesis inhibitors. We report here the synthesis of a family of novel inhibitors that are analogues of fumagillin, a naturally secreted antibiotic of Aspergillus fumigatus fresenius. We first isolated this fungus from a contaminated culture of capillary endothelial cells. Purified fumagillin inhibited endothelial cell proliferation in vitro and tumour-induced angiogenesis in vivo; it also inhibited tumour growth in mice, but prolonged administration was limited because it caused severe weight loss. Synthesis of fumagillin analogues yielded potent angiogenesis inhibitors ('angioinhibins') which suppress the growth of a wide variety of tumours with relatively few side-effects.

Animals↗

PubMed1990

Distribution and localization of neurokinin A-like immunoreactivity and neurokinin B-like immunoreactivity in rat peripheral tissue.

Using specific radioimmunoassays and immunocytochemistry for neurokinin A (NKA) and neurokinin B (NKB), distribution and localization of these peptides in rat peripheral tissues were studied. NKA-like immunoreactivity (NKA-LI) was present in highest levels of 15.7-23.9 pmol/g wet wt. and NKB-like immunoreactivity (NKB-LI) was in levels of 0.33-0.67 pmol/g wet wt., throughout the gastrointestinal tract involving stomach, duodenum, jejunum, ileum and colon. Immunocytochemical analysis of gastrointestinal tract revealed that NKA-LI and NKB-LI localized in ganglia of both the submucosal and myenteric plexuses as well as varicose neurons in the mucosa and the muscle layer of the small and large intestine. On the other hand, high levels of NKB-LI were observed in oesophagus (0.83 +/- 0.08 pmol/g wet wt.), adrenal (1.02 +/- 0.21), head of pancreas (0.73 +/- 0.06) and kidney (0.98 +/- 0.05). The present study shows the difference of localization of NKA-LI and NKB-LI in peripheral tissues and suggests that NKB may have some physiological role differing from that of NKA in peripheral tissues.

Animals↗

PubMed1990

Unlinked regulation of cell growth and differentiation in immature B cell lines.

We established many immunoglobulin-null immature B cell lines transformed by tsOS-59, a temperature-sensitive mutant of Abelson murine leukemia virus. In different cell lines cell growth was depressed and cell differentiation (generation of intracytoplasmic mu-positive cells from Ig- cells) was induced by the shift of culture temperature from low (35 degrees C) to high (39 degrees C). Cell lines were categorized into four groups: (i) temperature sensitive (ts) to both cell growth and differentiation, (ii) ts to cell growth but not to cell differentiation, (iii) ts to cell differentiation but not to cell growth, and (iv) ts to neither cell growth nor differentiation. These results indicated that the depression of cell growth did not necessarily induce cell differentiation, and that cell differentiation was induced regardless of whether cell growth was depressed or not. Furthermore, the results showed that the depression of cell growth and the induction of cell differentiation occurred without the reduction of tyrosine kinase activity of P120gag-abl at high, nonpermissive temperature. Our cell growth and differentiation system described here should provide us with the interesting findings of the relation between B cell growth and differentiation.

Animals↗