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Biomedical subjects

K Kin

Publications and source records attributed to K Kin.

At least 19 recordsLinked to original sources

[Ocular penetration of UF-021, a new prostaglandin related compound, in the rabbit eye].

The ocular penetration and pigment affinity of topically applied UF-021, a newly developed prostaglandin-related compound, were investigated in rabbit eyes using 3H-labeled UF-021. Ten minutes to 24 hours after instillation of 0.12% of 3H-UF-021 solution into New Zealand white or pigmented rabbit eyes, the rabbits were sacrificed and the eyes were immediately enucleated. The extraocular muscles, conjunctiva, aqueous humor, cornea, iris, anterior and posterior sclera, ciliary body, lens, vitreous, retino-choroid complex, optic nerve were separated and blood samples were taken. The concentration of 3H-UF-021 in each sample was determined with a liquid scintillation counter. The peak concentration of UF-021 was obtained at 40 minutes and 1 hour after instillation in the iris-ciliary body and aqueous humor of albino rabbit. According to the pharmacokinetic analysis of the data, UF-021 showed good ocular penetration into the rabbit eye, and the permeability of the epithelial barrier for UF-021 was calculated to be 2.9 x 10(-3) cm/hr. The apparent elimination rate constant and the apparent absorption rate constant were also calculated to be 0.21 hr-1 and 1.28hr-1, respectively. The time course for 3H-UF-021 concentration in the eye of pigmented rabbit was almost the same as that in the eye of non-pigmented rabbit, indicating that UF-021 did not bind to pigmented tissues.

Animals

[A mechanism for reducing intraocular pressure in normal volunteers using UF-021, a prostaglandin-related compound].

The mechanism of reduction of intraocular pressure (IOP) and other ocular effects were studies after topical application of prostaglandin (PG) F2 alpha and UF-021, a new PG related compound, in eight normal volunteers. IOP, aqueous humor flow rate and outflow rate were evaluated during a period of four hours after the application. Both PGF2 alpha and UF-021 caused significant and similar IOP reduction for four hours. Neither compound produced any significant change in the aqueous humor flow rate or outflow rate, suggesting the increase of unconventional outflow rate as being the possible mechanism of IOP reduction in normal human eyes.

Adult

Tissue distribution of human alpha1-microglobulin.

Human alpha(1)-microglobulin was isolated from the urine of patients with tubular proteinuria, and its molecular weight was established by sodium dodecyl sulfate-polyacrylamide gel electrophoresis at 33,000 daltons. The carbohydrate content was 21.7%. Anti-alpha(1)-microglobulin serum was prepared and observed to react monospecifically in gel diffusion to purified alpha(1)-microglobulin, as well as to normal human serum and urine. Sera from the domestic chicken, mouse, rat, rabbit, dog, calf, cow, goat, sheep, and horse, however, did not react to anti-alpha(1)-microglobulin serum in immunodiffusion. The lymphocyte culture supernate was found to contain alpha(1)-microglobulin. Both thymus-derived(T)- and bone marrow-derived(B)-lymphocyte culture media clearly displayed a specific precipitin line against anti-alpha(1)-microglobulin serum when tested with the Ouchterlony immunodiffusion method. The tissue distribution of alpha(1)-microglobulin was studied under immunofluorescence, and a positive staining was recognized on the lymphocyte surface. Identical staining patterns were noted on both T and B lymphocytes, though B lymphocytes took a more intense stain. It would thus seem quite possible that lymphocytes are the primary source of alpha(1)-microglobulin and that this is filtered through the glomerular basement membrane and partly reabsorbed by the renal tubules. This, then, would suggest the possibility that alpha(1)-microglobulin shares some immunological role in vivo with lymphocytes and(or) is one of the membrane proteins of lymphocytes.

Alpha-Globulins

Cellular cooperation in lymphocyte activation. III. B-cell helper effect in the enhancement of T-cell response.

T and B cells were purified from human tonsil and peripheral blood by the removal of phagocytic cells, followed by filtration through a nylon fiber column (NC) and E-rosette formation. Purified T and B cells contained less than 1% of other cell types. The responses of T cells to concanavalin A (Con A) and soluble protein A were greatly enhanced in the presence of autologous B cells. Participation of B cells in T-cell enhancement was confirmed by the following observations: (a) purified B copulation, which was separated further from adherent B cells, retained its enhancing activity. (b) Another adherent cell-free B-cell preparation, which was purified from the NC-passed fraction, and (c) no T lymphoid but some B lymphoid cell lines, elicited strong T-cell enhancement. It was also found that the enhancing capacity of B cells required no metabolic activity, but rather an intact cell form and direct cell-to-cell contact with responding cells. The stimulatory determinants on B cells were resistant to trypsin and neuraminidase treatment. In this paper a hypothesis will be presented that at least two signals are prerequisite for the effective activation of T cells.

B-Lymphocytes

Human IgA1 half-molecules: clinical and immunologic features in a patient with multiple myeloma.

Abnormal IgA1 half-molecules consisting of one heavy and one light chain were found in a patient (N.N.) with typical multiple myeloma. The serum and the urine of this patient contained both 7.0S and 3.9S IgA myeloma proteins. The IgA half-molecules (3.9S) were found to have a molecular weight of 59,000 daltons and were composed of one alpha1 chain of about 40,000 daltons and one light chain of 22,000 daltons. Furthermore, enzymatic degradation suggested that the alpha chain of the N.N. half-molecules had a large deletion in its Fc portion. We suggest that its heavy and light chains were probably bound noncovalently, since the interchains connecting the heavy and light chains of these IgA half-molecules were easily dissociated with 1% SDS and 8 M urea. Cytologic studies identified at least two types of myeloma cells, and it is possible that half-molecule IgA production might result from mutation among the myeloma cells producing whole-molecule IgA.

Aged

beta2-Microglobulin production by highly purified human T and B lymphocytes in cell culture stimulated with various mitogens.

This study attempts to evaluate beta2-microglobulin production by highly purified (greater than 98%) peripheral and tonsil T and B lymphocytes cultured with various mitogens. beta2-Microglobulin was measured by the radioimmunoassay method. It was found that PHA and Con A markedly stimulated beta2-microglobulin production in cultures of T but not B lymphocytes. B lymphocytes were greatly activated, on the other hand, by Staphylococcus aureau Cowan I organisms cSpA), though the level of beta2-microglobulin production was less than that observed in PHA- and Con A-stimulated T lymphocytes. PWM only slightly increased beta2-microglobulin production of T lymphocytes, although the incorporation of [3H]-thymidine was highly enhanced. The highest level of beta2-microglobulin obtained with PHA or Con A was observed when the T/B lymphocyte ratio was between 90/10 and 80/20. These results lead to the conclusion that: (1) SpA is a specific mitogen for B lymphocytes, and its mitogenicity is independent of the presence of T lymphocytes, while PHA, Con A, and PWM are ineffective as stimulants of B lymphocytes; (2) the beta2-microglobulin producing ability of B lymphocytes is less than that of T lymphocytes, even when the lymphocytes are markedly activated; (3) the beta2-microglobulin production and DNA synthesis by T lymphocytes is markedly enhanced by the helper effect of B lymphocytes; (4) the level of beta2-microglobulin production reflects lymphocyte activation, especially in T lymphocytes stimulated with PHA or Con A.

B-Lymphocytes

Cellular cooperation in lymphocyte activation. II. Cooperative response of human peripheral T and B lymphocytes to rabbit anti-human beta 2-microglobulin.

In the present study we attempted to clarify the effects of anti-beta 2-microglobulin (a-beta 2m) on lymphocyte activation. Neither a-beta 2m IgG fraction nor F(ab')2 had a mitogenic effect on either highly purified T or B lymphocytes alone, while their mitogenic effect was observed when T and B lymphocytes were appropriately reconstituted. When T lymphocytes were reconstituted with mitomycin C (MMC) treated B lymphocytes, a negligible decrease in the response to a-beta 2m was observed compared to the response of an untreated mixture to a-beta 2m. On the other hand, when B lymphocytes were reconstituted with MMC-treated T lymphocytes, the response was markedly diminished. It was found, moreover, that the response of T lymphocytes separated by a semipermeable membrane from MMC-treated B lymphocytes was not enhanced, while a mixture of T and MMC-treated B lymphocytes in the same chamber showed a marked response. These results lead to the conclusion that the cells responding to a-beta 2m are mainly T lymphocytes whose response is strongly enhanced by B lymphocytes, and that for the mitogenic effect of a-beta 2m direct cell-to-cell interaction between T and B lymphocytes is necessary.

Animals

Synthesis and secretion of alpha 1-microglobulin by human lymphocytes.

alpha 1-Microglobulin (alpha 1-m) was purified by column chromatography from a supernatant fluid of cultured T and B lymphocytes stimulated with mitogens. This protein had a molecular weight of 33,000 as determined by sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis, migrated in the alpha 1-region on immunoelectrophoresis and proved immunologically identical to alpha 1-m which had been purified from the urine of patients with renal tubular disorders. Using indirect immunofluorescence, alpha 1-m was detected on the surface of both T and B lymphocytes, displaying the same intensity on each cell type. These findings indicate that alpha 1-m is actively produced and secreted by T and B lymphocytes.

Alpha-Globulins

Beta2-microglobulin levels of serum and ascites in malignant diseases.

Serum beta2-microglobulin levels were measured by radioimmunoassay in patients with various malignant neoplasms, ascitic patients, and also patients with definite or suspected hepatoma showing variable levels of serum alpha-fetoprotein. Elevated serum beta2-microglobulin levels greater than 2.5 mg/liter were found in various malignant neoplasms, especially in multiple myeloma (66.6%) and hepatoma (60.4%) The ascites/serum ratio of beta2-microglobulin levels in the patients with malignant ascites is significantly higher than in those with non-malignant ascites. However, ascites/serum ratios of total protein, IgG, albumin, creatinine levels were not significantly different between the two groups. Levels of serum beta2-microglobulin were correlated well with those of alpha-fetoprotein in the patients with definite or suspected hepatoma (r=0.72, P less than 0.001). From these results it was concluded that (1) high levels of serum beta2-microglobulin in these patients could be attributed to its hyperproduction by tumor cells or by the cells which had been infiltrated and activated, (2) it is useful to estimate the ascites/serum ratio of beta2-microglobulin levels in differentiating malignant from non-malignant ascites, and (3) it might suggest that a function of beta2-microglobulin is in some way related to that of alpha-fetoprotein, and the alpha-fetoprotein-synthesizing cells secrete a great deal of beta2-microglobulin, although its function remains unclear.

Adult