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Biomedical subjects

S Kishimoto

Publications and source records attributed to S Kishimoto.

At least 397 records · Page 22Linked to original sources

The regeneration of substance P-containing nerve fibers in the process of burn wound healing in the guinea pig skin.

The regeneration of substance P (SP)-containing nerve fibers in the process of burn wound healing in the guinea pig skin has been studied by immunohistochemistry. SP-like immunoreactivity, which was specifically localized in neural elements of intact skin, was found to disappear in the burn wound including its margin on day 2 post burn. The SP-containing nerve fibers were first detected in periods later than day 2 post burn, and the regeneration seemed to occur in association with regeneration of blood vessels at the wound margins. These nerve fibers gradually increased in number and acquired maximum density on day 14 post burn. In addition, such renewed fibers showed sprouting to form a dense network, which has never been observed in intact skin, in the upper granulation tissue just beneath the regrowing epidermis. Following that peak period, the density of the fibers gradually decreased to less than that of controls. The characteristic process of regeneration of SP-containing nerve fibers, having a peak period of fiber density at least in burn wound healing, appeared similar to that of the regeneration of sympathetic catecholaminergic nerve fibers reported previously.

Animals↗

Treatment of parkinsonism with L-threo-3,4-dihydroxyphenylserine: a pharmacokinetic study.

We have examined the kinetics of oral L-threo-3,4-dihydroxyphenylserine (DOPS) alone and combined with peripheral decarboxylase inhibitors in patients with Parkinson's disease and other degenerative diseases of the brain. Combined administration of L-threo-DOPS and carbidopa or benserazide produced higher plasma concentrations of L-threo-DOPS and suppressed the increase in plasma norepinephrine. This finding indicates some advantages of combined therapy with L-threo-DOPS and decarboxylase inhibitors. Measurable quantities of DL-threo-DOPS were found in the CSF during repeated administration, but there was no consistent change in norepinephrine concentration.

Adult↗

Dissociation in the production of B cell-stimulating factors (BCGF and BCDF) and interleukin 2 by T cells from a common variable immunodeficient patient.

In the course of an analysis of lymphocyte functions of common variable immunodeficiency patients, we found one patient whose T lymphocytes released B cell differentiation factor (BCDF) and B cell growth factor (BCGF) without IL 2 production upon stimulation with Con A. The patient was a 68-yr-old woman with hypo-gamma-globulinemia (IgM: 31 mg/dl, IgG: 223 mg/dl, IgA: 23 mg/dl); she suffered from cryptococcal meningitis and pulmonary tuberculosis with a negative result of skin tests to PPD and cryptococcal antigen. The number of T cells and the ratio of T cell subsets (Leu-2a and Leu-3a) was normal. T cells showed no proliferative response to Con A and a low response to PHA (one-tenth of normal response). The addition of patient T cells to normal T cells did not inhibit the proliferation of normal T cells when stimulated by Con A. The culture supernatant of Con A-stimulated T cells contained no IL 2 activity when assayed by an IL 2-dependent T cell line. Expression of Tac antigen was not impaired by Con A stimulation and the addition of partially purified IL 2 from the supernatant of Jurkat T cell line-induced proliferation of Con A-stimulated T cells, indicating that the defect observed was not in IL 2-responding cells but in IL 2-producing cells. In contrast, the culture supernatant of the T cells stimulated by Con A or PHA contained BCDF activity as much as that of normal T cells when assayed by Cowan I-stimulated normal B cells or the B lymphoblastoid cell line SKW6-CL4. The supernatant also contained BCGF activity. These results suggest that B cell-stimulating factor (BCGF, BCDF) and IL 2 may be synthesized by different subsets of T cells or that the synthesis of those lymphokines are independently regulated in the same cells.

Adult↗

Intestinal-type alkaline phosphatase produced by human hepatoblastoma cell line HUH-6 clone 5.

Two enzyme forms of alkaline phosphatase have been partially purified from the medium spent for the culture of HUH-6 clone 5 cells, which were originally derived from hepatoblastoma tissue. The purification methods used are ammonium sulfate precipitation, ethanol precipitation, diethylaminoethyl cellulose chromatography, Affi-Gel Blue chromatography, and Sephadex G-200 gel filtration. These alkaline phosphatases have been characterized by thermostability, inhibition, and immunological and electrophoretic studies. Both are L-phenylalanine and L-tryptophan sensitive and L-homoarginine and L-leucylglycylglycine insensitive, and both react with an antiserum against intestinal alkaline phosphatase. The major enzyme form is a neuraminidase-cleavable, moderately thermostable isoenzyme which on polyacrylamide gel shows an electrophoretic mobility similar to that of liver alkaline phosphatase. The minor enzyme form is a neuraminidase-uncleavable, thermolabile isoenzyme which shows an intermediate electrophoretic mobility between liver and hepatoma alkaline phosphatases. The molecular weights of the major and minor enzymes have been estimated by gel filtration to be 170,000 and 110,000, respectively. These results support the conclusion that the two enzyme forms of HUH-6 alkaline phosphatase are intestinal in type, with the major enzyme form closely resembling hepatoma and oncoamnionic alkaline phosphatases, and the minor enzyme form resembling "intestine-like liver alkaline phosphatase." HUH-6 clone 5 cell line may be a useful in vitro model to study the regulatory mechanism for phenotypic expression of intestinal-type alkaline phosphatase isoenzymes in liver cancer cells.

Alkaline Phosphatase↗

A polypeptide containing 55 amino acid residues coded by the pre-S region of hepatitis B virus deoxyribonucleic acid bears the receptor for polymerized human as well as chimpanzee albumins.

The receptor for polymerized human and chimpanzee albumins has been identified on a hepatitis B surface antigen polypeptide of approximately 31,000 daltons. The polypeptide, designated P31, is composed of the major polypeptide of hepatitis B surface antigen (P22) and an additional, as yet unidentified, amino acid sequence. We split P31 with cyanogen bromide and obtained a polypeptide of approximately 8000 daltons (P8) that contained carbohydrate. P8 could bind to polymerized human and chimpanzee albumins, but not to polymerized albumins from animals without susceptibility to hepatitis B virus. The amino acid composition of P8 closely resembled that of 55 amino-acid sequence coded by the pre-S region in the deoxyribonucleic acid of hepatitis B virus. Using monoclonal antibody against P8, a solid-phase sandwich radioimmunoassay was developed for the specific determination of hepatitis B surface antigen bearing the receptor for polymerized albumin in the serum of patients with hepatitis B virus infection.

Amino Acid Sequence↗

Effects of tamoxifen on estrogen-induced enhancement or inhibition of tumor growth in mouse Leydig cell tumor lines.

In order to avoid the complex dual effects of estrogen and antiestrogen, the attempt was made to establish the tumor lines in which estrogens show either stimulatory or inhibitory property in terms of the tumor growth. The administration of estrogen to host mice bearing one of the mouse Leydig cell tumor lines, called T 124958-R, resulted in marked enhancement of the tumor growth even at pharmacological levels of estrogen. On the other hand, estrogenization of host mice almost completely inhibited the growth of the other tumor line (T 22137) without detectable stimulatory effects. The physiocochemical properties of the cytosol estrogen receptor in both sublines were found to be similar in relation to the affinity toward ligands, steroid specificity, sedimentation profile, and the dissociation rate kinetics. Using these tumor lines, the action mechanism of tamoxifen on the tumor growth was examined. Daily administration of this compound (30 micrograms/mouse) led to enhanced tumor growth in T 124958-R, while the growth of T 22137 was inhibited by the same procedure. In the combination experiments, tamoxifen was found to be unable to antagonize estrogen-induced enhancement or inhibition of the growth in these tumors. In addition, both tumors contained similar levels of the antiestrogen binding sites. These results suggest that tamoxifen modulated the tumor growth through its estrogenic potency.

Animals↗

Beneficial effect of taurine on congestive heart failure induced by chronic aortic regurgitation in rabbits.

Taurine (2-aminoethanesulfonic acid) is known to have a cardiotonic action. The present study was designed to see whether oral treatment with taurine could improve the status of congestive heart failure induced by aortic regurgitation. Nine rabbits were treated daily with taurine (100 mg/kg) after producing aortic regurgitation. Cumulative mortality at 8 weeks in the non-treated group was 52% compared with 11% in the taurine-treated group (p less than 0.05). Cardiac function (max dP/dt) was significantly decreased in rabbits with aortic regurgitation, whereas in taurine-treated rabbits, cardiac function was maintained the same as control. The present data suggest that taurine prevented the rapid progress of heart failure, and consequently prolonged the life expectancy.

Animals↗

Polyclonal activation of xid B cells by auto-Ia-reactive T cell clones.

The mechanism of T cell-dependent activation of xid B cells into Ig-producing cells was studied by employing H-2-restricted, antigen-specific T cell clones. Helper factors (B cell stimulatory factors, BSF) released from KLH-specific T cell lines could induce polyclonal Ig production in B cells from (CBA/N X BALB/c)F1 (NBF1) female mice but not from CBA/N or NBF1 male mice. Direct addition of helper T cell lines induced Ig production in xid B cells from CBA/N or NBF1 male mice. A T cell clone, MK6, which was derived from NBF1 male mice and specific against Iad determinant, could activate NBF1 male but not CBA/N B cells. Another clone, CK4, derived from CBA/N mice and having specificity against KLH plus I-Ak determinant could activate both CBA/N and NBF1 male B cells into IgM- and IgG-producing cells in the absence of KLH, and monoclonal anti-I-Ak antibody specifically blocked such activation. These results suggest that xid B cells are able to be activated by the signal provided by the recognition of Ia molecules on B cells by auto-Ia-reactive T cells. Xid B cells from CBA/N mice that had been co-cultured with a T cell line specific against I-Ak determinant for 24 hr became reactive to BSF and capable of differentiating into Ig-producing cells in the presence of BSF. The results showed that even xid B cells could be responsive to BSF if they were in a certain activation stage.

Animals↗

Enzyme immunoassay of human plasma fibronectin in malignant, collagen and liver diseases.

A competitive enzyme immunoassay for the measurement of human plasma fibronectin (PFN) was developed, using polystyrene beads as a solid phase and glucose oxidase as a marker enzyme. This method gave a reproducible standard curve in the range of 0.5-50 micrograms/ml. The mean PFN level in normal persons was 345 micrograms/ml (standard deviation 68.4 micrograms/ml, n = 30). The PFN levels in patients with malignant, collagen and liver diseases were also measured. The mean PFN level in patients with collagen disease was significantly higher than that in normal persons, whereas the mean PFN levels in patients with malignant and liver diseases were not significantly different.

Adult↗