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Biomedical subjects

M Hirota

Publications and source records attributed to M Hirota.

At least 181 records · Page 10Linked to original sources

[Carbohydrate antigens in pleural effusion from patients with lung cancer].

Sialosylated Lewisa (S-Lea) is an active antigen determinant of CA19-9 which is well known as a tumor maker. Sialosylated Lewisx (S-Lex) is a positional isomer of S-Lea. The positive percent of S-Lex and CA19-9 in pleural effusion from the patients with primary lung cancer was 49.1% and 40.0%, respectively. However, most S-Lea positive effusions showed a positive level of S-Lex. Therefore, S-Lex is considered to be more useful as a tumor marker than CA19-9. The studies on gel chromatography of the effusion obtained from a patients showed high levels of both antigens using sephacryl S-1000 revealed that the molecular weights of S-Lex and CA19-9 were more than 2 X 10(6) and the elution profile of S-Lex coincided with that of CA19-9 fractionated effusions using the monoclonal antibodies to the antigens showed the same pattern of elution profiles of these carbohydrates. From these results, we concluded that the carriers of S-Lex and CA19-9 in pleural effusion from lung cancer might be the same molecules with a high molecular weight more than 2 X 10(6).

Adenocarcinoma↗

[Evaluation of sialylated LewisX as a tumor-associated carbohydrate antigen in the sera of patients with gastric cancer].

The clinical usefulness as a tumor-associated antigen of the new monoclonal antibody CSLEX1, which reacts with the sialylated LewisX antigen, has been evaluated serologically in 141 patients with a gastric cancer. The serum sialylated LewisX was measured by fluorescent EIA. The percent positive figure of these gastric cancer patients was 17.0% (24/141), which indicates a significant increase when compared with that of the controls. The percent-positive values, according to the clinical stage, were 9.2%, 9.1%, 15.6%, and 36.4% for stages I, II, III, and IV, respectively. The degree of liver metastasis and peritoneal dissemination of the cancer correlated with the percent-positive values of the antigen. This suggests that sialylated LewisX is useful as a tumor-associated antigen.

Adult↗

[Sialylated Lewis(x) and sialylated Lewis(a) as tumor-associated carbohydrate antigens in sera of patients with gastric cancer--usefulness of combination assay of these two antigens].

Sialylated Lewis(x) and sialylated Lewis(a) antigens, which are structural isomer each other, were serologically tested to determine the clinicopathological differences and correlation between two antigens, and were also compared with those of serum CEA in 141 patients with gastric cancer. Percent positives in sialylated Lewis(a), CEA and sialylated Lewis(x) showed 26.9%, 21.8% and 17.0% respectively. Percent positive of sialylated Lewis(x) correlated with degree of liver metastasis and peritoneal dissemination. Therefore, it is emphasized that the role of sialylated Lewis(x) is characteristics of detecting a presence of liver metastasis and/or peritoneal dissemination. On the other hand, sialylated Lewis(a) showed high percent positive in cases which had lymph nodes metastasis and mucinous or papillary adenocarcinomas. These two carbohydrate antigens indicated no correlation (r = 0.062) in the spectrum of sera. It is suggested that combination assay of sialylated Lewis(x) and sialylated Lewis(a) is useful in detecting many gastric cancer patients including CEA-negative one.

Adenocarcinoma↗

[Comparison of carbohydrate antigens--sialylated Lewisx and sialylated SSEA-1 in the sera from patients with primary lung cancer].

Serum levels of sialylated Lewisx (SLEX) and sialylated SSEA-1 (S-Xi) in 136 cases of diagnosed lung cancer (63 adenocarcinoma, 45 squamous cell carcinoma, 20 small cell carcinoma and 8 large cell carcinoma) and 111 cases of benign pulmonary disease were measured. The positive rate of these markers in the primary lung cancer group was significantly higher than those in benign pulmonary diseases. The positive rates of serum SLEX and S-Xi in all lung cancer cases were 27.2% and 27.9%, respectively. The antigen levels in the sera were higher in adenocarcinoma as compared to other histologic types, and increased as the stage advanced. It was concluded that SLEX and S-Xi are very useful markers of lung cancer for diagnosis and monitoring the clinical status.

Adenocarcinoma↗

[Two cases of tuberculous peritonitis and clinical significance of serum CA-125].

We had recently experienced two cases of tuberculous peritonitis. One was suspected of ovarian cancer but finally diagnosed as tuberculosis by the exploratory laparotomy. The other was found out casually at the operation of benign ovarian tumor. Both cases accompanied with pulmonary tuberculosis. Tuberculous peritonitis should be considered in the differential diagnosis in patients with abdominal disorders. Remarkable elevation of serum CA-125 related to ovarian cancer was found in both cases. It was suggested that level of serum CA-125 might be useful for diagnosis and monitoring of the disease.

Adult↗

[Clinical evaluation of A 1 protocol in advanced neuroblastoma].

UNLABELLED: For the purpose of studying clinical evaluation of A 1 protocol for advanced neuroblastoma, chemotherapy with vincristine, cyclophosphamide, THP-adriamycin and cisplatin was performed in 8 pediatric patients with advanced neuroblastoma undergoing second look operation (4) or delayed primary operation (4). Tumor volume measured on CT, histological finding of tumor obtained at operation, blood and urinary tumor marker level were studied. RESULTS: 1) The chemotherapy is supposed to be effective for round cell type neuroblastoma. On the other hand, it is ineffective for composite type ganglioneuroblastoma. 2) More than 3 courses of A 1 protocol are necessary to yield a good effect. 3) There is no relationship between the effect of the chemotherapy and the prognosis.

Adrenal Gland Neoplasms↗

[Tuberculosis in patients undergoing hemodialysis].

The incidence of tuberculosis is very high in patients treated by hemodialysis particularly in the early stage of hemodialysis. The diagnosis of tuberculosis in dialysis patients was obscured as symptoms were nonspecific and extrapulmonary involvement was seen frequently. We investigated cell mediated immunity in dialysis patients in relation to the period of dialysis. The data indicate that dialysis patients show the following immunological impairments; 1) lymphopenia, 2) decreased B cell, 3) alteration of T cell subset, 4) decreased reaction of PPD skin test, 5) decreased T cell activity, 6) decreased IL-2 production, 7) decreased PHA induced lymphocyte blastogenesis, 8) decreased NK cell. Decreased immunologic host defence mentioned above may contribute to the high incidence of tuberculosis in the early stage as well as in the maintenance phase of dialysis.

Female↗

[Activation of neutrophil function by MDP-Lys(L 18)].

The study was carried out to confirm the effect of MDP-Lys (L 18) on the neutrophil number and function in the patients with lung cancer. The patients were enrolled only in case of leukopenia (equal or less than 3,000/mm3 after anticancer chemotherapy) and subcutaneously given 200 mcg of MDP-Lys (L 18) for 7 days. Mean leukocyte counts were found to be 3,900/mm3 and 5,500/mm3 one day and one week after MDP-Lys (L 18) treatment, respectively. The rate of "markedly effective" and "effective" was 53% (8/15). Chemiluminescence by zymosan showed a significant increase after MDP-Lys (L 18) treatment. However, no change of neutrophil function was observed in the tests of chemiluminescence by phorbol myristate acetate, superoxide (O2-) production, hydrogen peroxide (H2O2) production, chemotaxis, bacterial killing and opsonization. Transient fever was observed in 6 cases and eruption accompanied with one fever case. It was concluded that MDP-Lys (L 18) could prevent infection in cancer-bearing immunocompromised patients by increasing the neutrophil number and function.

Acetylmuramyl-Alanyl-Isoglutamine↗

A new tumor promoter from the seed oil of Jatropha curcas L., an intramolecular diester of 12-deoxy-16-hydroxyphorbol.

A new type of phorbol ester, which has a macrocyclic dicarboxylic acid diester structure, was isolated from the seed oil of Jatropha curcas L. (Euphorbiaceae). Based on the results of spectroscopic analyses of the compound and its chemical degradation products, its structure is proposed to be an intramolecular 13,16-diester of 12-deoxy-16-hydroxyphorbol, 12-deoxy-16-hydroxyphorbol-4'-[12',14'-butadienyl]-6'-[16',18',20' - nonatrienyl]-bicyclo[3.1.0]hexane-(13-O)-2'-[carboxylate]-(16-O)-3 '- [8'-butenoic-10']ate (DHPB). DHPB showed slightly weaker biological and biochemical activities than 12-O-tetradecanoylphorbol-13-acetate (TPA). DHPB induced ornithine decarboxylase in mouse skin (2.8 nmol CO2/30 min/mg protein/34 nmol application), inhibited the specific binding of [3H]-12-O-tetradecanoylphorbol-13-acetate to phorbol ester receptors (50% effective dose, 17.0 nM), and activated protein kinase C in vitro (50% effective dose, 36.0 nM). Also, a weak tumor-promoting activity of DHPB was found in a two-stage carcinogenesis experiment on mouse skin. One week after initiation of mice with 100 micrograms of 7,12-dimethyl-benz(a)anthracene, topical application, twice a week, of 2 micrograms of DHPB until week 17, followed by application of 5 microgram of DHPB until week 30 at the same rate, resulted in 46.7% incidence of tumors by week 30. The groups treated with 7,12-dimethylbenz(a)anthracene alone or DHPB alone did not produce significant numbers of tumors. These results indicate that the new phorbol ester, DHPB, is a tumor promoter with weaker activity than 12-O-tetradecanoylphorbol-13-acetate.

Animals↗

Sandwich enzyme immunoassay of tumor-associated antigen sialosylated Lewisx using beta-D-galactosidase coupled to a monoclonal antibody of IgM isotype.

Enzyme conjugates with antibody of IgG type have been used extensively in immunohistochemistry, but conjugates with antibody of IgM type have not been reported. This paper describes the beta-D-galactosidase (Gal) labeling of a monoclonal IgM antibody designated CSLEX1 (for cytotoxic sialosylated Lewisx), which is directed against a tumor-associated antigen sialosylated Lewisx (S-Lex). The antibody was first acylated with a heterobifunctional agent N-(gamma-maleimidobutyryloxy)succinimide (GMBS) to introduce the maleimide groups into the molecule; excess reagent was removed by gel filtration and then the activated antibodies were crosslinked to the thiol groups of Gal. The conjugates were partially purified of free Gal by DEAE-Toyopearl column chromatography with an increasing linear concentration of NaCl. The conjugates thus prepared retained almost full enzyme activity and were demonstrated to be free of CSLEX1 by affinity chromatography using anti-galactosidase antibody bound to Sepharose 4B. The conjugates were used as a label in a sandwich enzyme immunoassay (SEIA) to detect the antigen at concentrations as low as 0.2 U/well. The SEIA was used to measure serum S-Lex levels in both healthy subjects and lung cancer patients and mean concentrations of 70 U/ml and 198.6 U/ml were detected respectively.

Animals↗

High-performance liquid chromatographic assay of serum glycated albumin.

A method for determination of serum glycated albumin by high-performance liquid chromatography is presented. The system involves anion exchange chromatography to separate albumin and consecutive boronate affinity chromatography to separate glycated and nonglycated albumin. The method is rapid (20 min), precise (coefficient of variation, 0.7-4.9%), requires only a small sample (5 microliters), and can be automated. Assay of glycated albumin by this method is not influenced by the protein concentration of the sample or the presence of glucose. The variation in glycated albumin values in consecutive samples obtained within a day from diabetic patients (coefficient of variation, 2.02 +/- 0.65%) was significantly smaller (p less than 0.001) than that of values for fructosamine (coefficient of variation, 4.33 +/- 2.0%). The values of glycated albumin in normal subjects (20.2 +/- 1.6%) were clearly less than those in diabetic patients [39.6 +/- 5.4% in 40 Type 1 (insulin-dependent) and 39.4 +/- 5.9% in 25 Type 2 (non-insulin-dependent) patients]. The serum glycated albumin level was well correlated with HbA1c in 65 diabetic patients (r = 0.60). Because the life span of albumin in the circulation is short, measurement of glycated albumin should be useful as a short-term index of glycaemic control.

Biomarkers↗

Specific radioimmunoassay of glucitol-lysine--application to lens proteins in streptozotocin-diabetic rats.

A radioimmunoassay using antibody against glucitol-lysine was developed to quantitate glycated proteins in the lens of diabetic rats. The amount of glycated protein was expressed as molar equivalents of reduced glycated hippuryl lysine (GlcRED-Hip-Lysine). Significant differences (p less than 0.01) were found in the amounts of glycated protein in the lenses of rats with streptozotocin-induced diabetes (3.92 +/- 0.59 nmol/mg protein, n = 5), those with streptozotocin-induced diabetes treated with insulin (2.94 +/- 0.36 nmol/mg protein, n = 4) and normal rats (1.23 +/- 0.22 nmol/mg protein, n = 5). There was a significant correlation between the concentration of glycated protein in the lens and the HbA1c level at the end of the 12 week experiment (r = 0.957, p less than 0.001). These results indicate that glycation of lens protein is parallel with the severity of diabetes in rats.

Animals↗

Renal lesions in Cockayne syndrome.

Two siblings with typical features of the Cockayne syndrome were studied at autopsy. Many glomeruli revealed a paucity of capillary loops and had thickened capillary walls. Some glomeruli with advanced lesions showed collapse of the glomerular tufts or complete hyalinization. Atrophy of tubules and interstitial fibrosis were also observed. There were no significant arteriosclerotic changes in the vessels. Ultrastructural studies demonstrated thickened glomerular basement membranes with bends and folds. These histopathological findings are different to those previously reported with the exception of the 1966 report by Ohno and Hirooka.

Basement Membrane↗

Primary hypothyroidism in an adult patient with protein-calorie malnutrition: a study of its mechanism and the effect of amino acid deficiency.

A man with diabetes mellitus, chronic hepatitis, chronic pancreatitis, and blind loop syndrome but without any previous thyroid disease developed three episodes of transient primary hypothyroidism associated with protein-calorie malnutrition (PCM). Clinical examinations suggested that this primary hypothyroidism was not caused by chronic thyroiditis, iodine deficiency, or iodine excess. Since the three times association of primary hypothyroidism with PCM suggested the possibility that the primary hypothyroidism was caused by PCM, we have tried to clarify its mechanism. For this purpose we have investigated the change of thyroid functions during protein-calorie repletion and the effect of amino acid deficiency. Total parenteral nutrition with full supplementation of amino acids resulted in a rapid increase in serum thyroxine (T4), triiodothyronine (T3), free T4, and reverse T3, and subsequently, a rapid decrease in TSH in several days after the nutrition was begun. When amino acid solution was changed to that depleted of phenylalanine and tyrosine after the restoration of thyroid functions, serum T4 and T3 showed a gradual decrease, but serum free T4 and TSH remained within normal range. However, resupplementation of phenylalanine and tyrosine after 8 weeks of depletion gave a rapid increase in serum T4, T3, free T4, and reverse T3. These results suggested that the primary hypothyroidism was caused by an impaired T4 production and that the deficiency of amino acids in PCM partly contributed to the impairment of T4 production.

Aged↗

Effect of glucagon-like peptide-1 on insulin secretion.

The insulinotropic actions of two forms of glucagon-like peptide 1 (GLP-1) containing 31 and 37 amino acid residues on perfused rat pancreas were compared with that of gastric inhibitory polypeptide (GIP), hitherto the most potent intestinal insulinotropic polypeptide known. The smaller form, C-terminally amidated GLP-1-(7-36), strongly enhanced insulin secretion stimulated by 11.1 mM D-glucose at a concentration as low as 0.1 nM. Comparable effects of GIP and GLP-1-(1-37) on insulin secretion were observed at concentrations of 1.0 nM and 10.0 nM, respectively. At the doses tested, neither GLP-1s nor GIP had any effect on insulin secretion induced by 3.3 mM D-glucose. At a concentration of 1.0 nM, GLP-1-(7-36 amide) also enhanced insulin secretion induced by 5 mM L-arginine whereas at concentrations of up to 10.0 nM, GLP-1-(1-37) did not. The results show that the smaller form of GLP-1 is more strongly insulinotropic than GIP. These findings suggest that the smaller GLP-1 may have a physiologically more important role as a modulator of insulin release.

Animals↗

Comparison of half-disappearance times, distribution volumes and metabolic clearance rates of exogenous glucagon-like peptide 1 and glucagon in rats.

The pharmacokinetics of glucagon-like peptide-1 (GLP-1) in vivo after bolus and continuous i.v. administrations of the peptide were compared with those of glucagon in rats. The half-disappearance time (t1/2) distribution volume (Vd) and metabolic clearance rate (MCR) of GLP-1 given as a bolus injection and by constant infusion, were, respectively, as follows: t1/2 (min), 47.7 +/- 14.5 and 39.5 +/- 15.5 (mean +/- S.D.); Vd (ml), 903.8 +/- 62.4 and 516.3 +/- 92.1 and MCR (ml kg-1 min-1), 27.4 +/- 10.8 and 18.6 +/- 8.6. These values differed significantly from the respective values for glucagon (t1/2, 3.3 +/- 0.6 and 5.8 +/- 1.0; Vd, 206.5 +/- 25.9 and 240.0 +/- 76.1; and MCR, 83.1 +/- 8.2 and 46.7 +/- 13.3). These findings demonstrate that GLP-1 is degraded more slowly than glucagon in vivo.

Animals↗