Biomedical subjects
Publications and source records attributed to K Imai.
A case of Achilles tendon reconstruction using free vascularised fascia lata joined to a lateral thigh flap is reported. This is a simple one-stage reconstruction and a sufficiently strong tendon can be obtained.
Low molecular weight and amorphous copolyesters composed of 70 mol% L-lactic acid and 30 mol% DL-hydroxy acids such as DL-lactic acid, DL-alpha-hydroxy-n-butyric acid, DL-alpha-hydroxyisovaleric acid and DL-alpha-hydroxyisocaproic acid were synthesized by direct copolycondensation in the absence of catalysts, to evaluate their in vivo capabilities as biodegradable carriers for drug delivery systems. For this purpose, the copolyester was moulded into a small cylindrical specimen under melt-pressing technique and implanted subcutaneously in the back of male adult rats. The in vivo degradation pattern can be subdivided into three types: the formations of parabolic type (L-LA/DL-HBA copolymer), linear type (L-LA/DL-LA copolymer) and S type (L-LA/DL-HIVA and L-LA/DL-HICA copolymers). A luteinizing hormone-releasing hormone agonist, des-Gly10-(D-Leu6)-LH-RH ethylamide monoacetate (LH-RH agonist), was incorporated into the small cylinders of copolyester formulations, of which the strongest pharmacological influence was observed in a copoly(L-LA/DL-HICA) formulation system, resulting in the maintenance of effective pharmacological influence throughout an experimental period of 15 wk, at which the in vivo release rate of LH-RH agonist was held constant at approximately 45 micrograms/d.
The pathogenesis of hemorrhage induced by the i.m. injection of the hemorrhagic toxin, bilitoxin, was studied using light and electron microscopy. White mice were injected with sublethal doses of the toxin, and tissue samples were obtained at 5 and 30 min, and 1, 3 and 24 hr after the injection. There was a good correlation between amount of toxin injected and amount of hemorrhage observed. Microscopically, hemorrhage was visible in all parts of the connective tissue surrounding muscle cells just 5 min after injection and fibrin was present both intravascularly and extravascularly. At later time periods the hemorrhage was more extensive and there was more fibrin. Many vessels were plugged with platelets. At 30 min after the injection, muscle cells appeared to be damaged having either delta lesions or disrupted myofibrils. Electron microscopy revealed damaged capillaries with ruptured endothelial cells, disrupted basal lamina and intact intercellular junctions. Thus, this hemorrhagic toxin acts rapidly to disrupt the capillary endothelium without damaging the intercellular junctions, and it also appears to damage skeletal muscle cells.
An attempt was made to clarify the relationship between the synthesis of prolactin (PRL) and its secretion during the rat estrous cycle by examining the changes in PRL messenger RNA (mRNA); PRL secretion and anterior pituitary PRL content. At various stages of the estrous cycle, pituitary and serum levels of PRL and growth hormone (GH) were measured by radioimmunoassay, while their respective mRNA contents were determined by the hybridization method. The content of pituitary PRL mRNA did not increase in parallel with the increment of the serum level of the hormone. Significant increase in PRL mRNA were observed as three peaks; 1st peak at 14:00 on the proestrus (PE) day, 2nd peak at 4:00 and 3rd peak at 22:00 on the estrus (E) day. The GH levels in the pituitary and serum, or the change in PRL mRNA appeared to be unrelated to the rat estrous cycle. From the present results, we speculate that the three peaks of PRL mRNA content might be ascribable to the direct effect of estrogen on transcription, indirect activation of transcription followed by rapid and massive secretion of PRL, and mammotrope proliferation, respectively.
Nucleotide sequences of VJ (variable-joining) junctional regions of V14+ alpha-chain T-cell receptor genes show that most V alpha 14+ T cells use one alpha chain (V alpha 14J alpha 281 with a one-nucleotide N region, which is frequently used in keyhole limpet hemocyanin-specific suppressor T-cell hybridomas) in unprimed mice. Moreover, the frequency of this alpha-chain expression was greater than 1.5% of the total alpha chains found in laboratory strains, including B10 congenic mice. This is about 10(4) times higher than was expected. The V14J281 alpha-chain expression was relatively low but was significant in CD4+/CD8+ immature thymocytes and became quite high in mature single-positive T cells, implying that this alpha chain is selected during T-cell maturation. V14J281 expression increased with time after birth and reached a maximum at around 5 weeks of age. The ligand seems to be a self molecule and to be present in laboratory strains but to be absent in a wild mouse, Mus musculus molossinus, because bone marrow chimeras clearly showed that bone marrow cells derived from Mus musculus molossinus negative for this alpha chain raised V14J281-positive T cells in a C57BL/6 environment. The above results suggest that there are some selection mechanisms for this cell type other than those for conventional alpha beta T cells and also that the homogenous VJ junction of the V14J281 alpha chain plays a pivotal role in the selection of the T cell and its ligand reactivity.
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Expression of mRNAs of carcinoembryonic antigen (CEA) and nonspecific cross-reacting antigen (NCA) genes in colorectal carcinomas and adenomas was investigated by in situ hybridization (ISH) with specific biotinylated probes. Hybridization was clearly detected throughout the cytoplasm of 7 out of 15 adenomas and 13 out of 15 carcinomas with the CEA cDNA probe, and in 6 out of 15 adenomas and 10 out of 15 carcinomas with the NCA cDNA probe. The intensity of signal appeared to be stronger in carcinomas than that in adenomas, and the CEA and NCA mRNAs were expressed together in most of the positive tissue specimens. On the other hand, noninvaded tissues adjacent to the carcinoma did not show any signal except for 4 cases faintly stained with the NCA probe. This finding was partly confirmed by Northern blot analysis which indicated that the specific bands for the CEA and NCA mRNAs were more intense in RNAs from carcinoma tissues than in those from adjacent noninvaded tissues. These data suggest that the ISH technique with biotinylated probes could be of use for analyzing expression and localization of CEA and related genes on tissue sections.
Monoclonal antibody (MAb) MUSE11 detects an adenocarcinoma-associated antigen and is useful for the serodiagnosis of pancreas cancer. We established a sandwich enzyme immunoassay using MAb MUSE11 and MAb DF3 against a breast cancer-associated mucin core protein as a catcher and a tracer, respectively. With this assay system, the binding of the tracer MAb DF3 to an antigen in the human kidney tissue lysate was clearly inhibited by MAb MUSE11. In addition, MAb MUSE11 showed a significant binding activity to the synthetic peptide corresponding to the tandem repeat of a human epithelial mucin core protein. These data suggest that MAb MUSE11 could detect the polypeptide core of a mucin, and may be of use for studying mucin as a gene product.
The Gunma Urological Oncology Study Group has performed a multivariate statistical analysis of prognostic factors based on 353 patients with prostate cancer diagnosed between 1974 and 1984. This paper discusses the prognostic significance of erythrocyte sedimentation rate (ESR) in these patients with prostate cancer. Based on three ranges (less than 20, greater than 20- less than 50, greater than 50 mm/h) of ESR, a significant difference of survival rates among the patients was found by means of univariate analysis. ESR apparently includes components which represent anemia or infection. Hemoglobin, frequently used as a prognostic factor, was compared with ESR by means of multivariate analysis, and ESR was found to be a more useful prognostic factor than hemoglobin. Moreover ESR showed the highest partial coefficient value among the items studied (clinical stage, pathological differentiation, age, acid phosphatase, gait disturbance). It seems that ESR includes not only anemia and infection components but also provides a clue to the degree of bone metastasis or the degree of prostate cancer progression.
Monoclonal antibody (MoAb) KT38 raised against a human T leukaemic cell line TALL-1, reacted with another T leukaemic cell line Jurkat, but not with any other cell lines tested. The co-modulation of CD3 and KT38 antigen was observed with stimulations of either MoAb T3 or KT38 on both TALL-1 and Jurkat. Upon radioimmunoprecipitation and SDS-PAGE analysis, MoAb KT38 precipitated the heterodimer of 40-60 kD from Jurkat and TALL-1 under reducing conditions. Thus, MoAb KT38 is considered to be an anti-T idiotype (Ti) antibody to TALL-1 and Jurkat cells. MoAb KT38 was also shown to react with a minor population of peripheral blood lymphocytes (PBL) and with very few cells (0.5-2.0%) in the paracortical area of the lymph node. When PBL were stimulated in a KT38-coated culture flask for 5 days, the percentage of KT38-positive PBL was markedly increased. The CD3 antigen on these cultured PBL in the flask was modulated by the stimulation with MoAb KT38. Thus, it is suggested that a common idiotope exists on the T cell receptor of Jurkat, TALL-1 and a small percentage (1.9-6.1%) of PBL.
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Molecules bearing the carbohydrate antigen 19-9 (CA19-9) epitope were prepared from serum and ascites of a patient with colon cancer or from the SW 1116 cell culture supernatant. Their plasma clearance mechanism was investigated in rats. The clearance curves of the molecules from three different sources showed a biphasic decrease. The coexistence of epitopes of CA19-9 and desialylated CA19-9 (Lea) in the same molecule was demonstrated by double-determinant enzyme immunoassays. CA19-9-bearing molecules with a low expression of Lea epitope, which were derived from the serum of a patient with colon cancer, showed mainly a slow disappearance, while the molecules with a high expression of Lea epitope from SW 1116 cells showed mainly a rapid disappearance. Thus, the clearance rate of the CA19-9-bearing molecules might be determined by their degrees of sialylation. This observation will be helpful for understanding the in vivo metabolism of CA19-9-bearing molecules.
The effects of prazosin HCl treatment on several variables were determined in 16 patients suffering from micturition disturbances associated with benign prostatic hypertrophy. After administration of the drug in doses of 1-2 mg/day, subjective symptoms improved in 11 patients (68.8%). Urine retention rate, maximum urine flow rate, and average urine flow rate exhibited statistically significant improvement, but voided urine volume did not. Urethral pressures declined significantly in the bladder neck and prostatic urethra but not in the pressure at the external sphincter. The results suggest prazosin HCl may be effective in small doses in symptomatic treatment of benign prostatic hypertrophy.
The effect of several porphyrins on Fe2(+)-ascorbic acid-stimulated lipid peroxidation was examined in rat liver homogenates. Not only protoporphyrin IX (PP) but also mesoporphyrin IX and hematoporphyrin inhibited the lipid peroxidation. Some porphyrins, in which 6- and 7-carboxyethyl groups were esterified with a methyl group, such as protoporphyrin IX dimethyl ester and mesoporphyrin IX dimethyl ester, had no antioxidative effect. Hemin and zinc protoporphyrin IX, which are metal-chelated porphyrins, inhibited the lipid peroxidation while cobalt protoporphyrin IX and tin protoporphyrin IX showed no antioxidative effect. Thus, some of the porphyrins used in the present study showed an antioxidative effect as did PP, but the others did not show such an effect.
For several years we have screened natural products having aldose reductase (AR) inhibitory activity. 3,3',4-Tri-O-methylellagic acid 4'-sulfate potassium salt (2) was isolated from a Mexican herb "Sinfito" (Potentilla candicans) as a potent AR inhibitory active constituent. 2 was more potent (IC50 = 8.0 x 10(-8)M) than ellagic acid, which is one of the natural inhibitors of AR. So we examined the synthesis of ellagic acid derivatives and found that the sulfate group is one of the important function.
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Vitellogenin synthesis during a decrease in egg production caused by depriving food and water was investigated in Single Comb White Leghorn hens. They were transferred from long days of 14L: 10D to short days of 10L: 14D 5 days before food and water deprivation. Then food was deprived for 5 days and water for 2 days. The body weight was markedly decreased by the treatment and reached its minimum after 5 days. The egg production rate which was 85% before the treatment was nil after 4 days. On day 3 the circulating vitellogenin concentrations, measured by a newly established RIA system, was markedly decreased by deprivation of food and water to 22% of the pretreatment level. The concentrations remained less than 10% during cessation of egg laying. Serum luteinizing hormone (LH) and progesterone concentrations decreased gradually, but estradiol 17 beta (E2) decreased abruptly. This acute decrease closely coincided with the decrease in egg production and the weight of the oviduct and ovary. These concentrations were gradually increased after day 16 and returned to the normal level after 46 days. Circulating thyroxine (T4) and triiodothyronine (T3) concentrations gradually increased from the beginning of the change in the day length and peaked on day 7 or 9, whereas reverse (r)T3 rapidly increased. The concentrations again decreased at the beginning of molting which occurred later due to the deprivation of food and water. Thus, these results demonstrated for the first time that the decrease in egg production induced by deprivation of food and water closely related to the decrease in vitellogenin synthesis as well as gonadal and pituitary functions. Further, recovery of egg production was coupled with the increase in the ovary and oviduct weight, and circulating LH, E2, progesterone, and vitellogenin.
A new alpha chain variant, alpha 110(G17)Ala----Thr, was detected because of subunit dissociation during the determination of the Hb A1c by automated cation exchange high performance liquid chromatography. The abnormal hemoglobin overlapped the cathodic edge of the band of Hb A in isoelectrofocusing. It was slightly unstable in the isopropanol test and had a slightly increased oxygen affinity. The abnormal alpha chain eluted slightly faster than the normal alpha chain in reversed phase high performance liquid chromatography. The amino acid substitution was determined by purification of S-alkylated alpha T-12,13 tryptic peptide, chymotryptic digestion, and sequencing of an octapeptide alpha 110-117. The abnormal alpha chain comprised about 14% of the total alpha chain. A biosynthetic study did not suggest selective loss of the abnormal chain in reticulocytes.