Detection of Monocyte Chemotactic and Activating Factor (MCAF) and Interleukin (IL)-6 in Human Seminal Plasma and Effect of Leukospermia on These Cytokine Levels

PROBLEM : To demonstrate whether monocyte chemotactic and activating factor (MCAF) and interleukin-6 (IL-6) are present in the seminal plasma, and whether these presence is modulated by leukospermia. METHODS : Semen samples from 53 men were obtained by masturbation and examined for the presence of MCAF and IL-6 by enzyme immunoassay (EIA). Semen samples were obtained from 28 infertile men without leukospermia, 16 infertile men with leukospermia, and nine proven-fertile men. The correlation between the amount of MCAF in the seminal plasma with some spermiogram parameters and other cytokines such as IL-6 and IL-8 was statistically evaluated. RESULTS : Immunoreactive MCAF was detected in the seminal plasmas of all 53 subjects. The MCAF titer in the seminal plasma of patients with leukospermia (11.19 ± 2.75 μg/1) was significantly higher than that in the seminal plasma of the patients without leukospermia (3.24 ± 0.53 μg/1) and the fertile men (2.78 ± 0.35 μg/1) (P < 0.001). The IL-6 titer in the seminal plasma of the patients with leukospermia (21.05 ± 4.49 ng/1) was also significantly higher than that in the seminal plasma of the patients without leukospermia (8.77 ± 1.92 ng/1) and the fertile men (6.94 ± 1.27 ng/1) (P < 0.01). There was a high degree of correlation among the levels of MCAF, IL-6 and IL-8 in the seminal plasma. CONCLUSIONS : These findings demonstrated the presence of MCAF and IL-6 in the seminal plasma, and that the levels of these cytokines were elevated in the seminal plasma of the infertile patients with leukospermia.     

Long-Lasting Immune Response Induced by Recombinant Bacillus Calmette–Guérin (BCG) Secretion System

The recombinant bacillus Calmette–Guérin (rBCG) secretion system utilizing an extracellular α antigen of Mycobacterium kansasii (α-K) was characterized biochemically and immunologically. The human immunodeficiency virus type1 (HIV-1) p17 ^gag B cell epitope fused to α-K was secreted in extremely large amounts. At least three mice out of seven inoculated with rBCG generated high titres of antibody to the epitope. The long-lasting antibody production persisted more than 14 months.     

Effects of turpentine oil pretreatment on β-blocker pharmacokinetic parameters in rats

Abstract— Turpentine oil treatment (0·2 mL kg^?1, s.c.) was used to increase the plasma concentration of α₁-acid glycoprotein (0·13 mg mL^?1 in control rats) to 1·72 mg mL^?1 after 2 days, and allow assessment of its effects on the pharmacokinetics and stereoselective binding of three β-blockers. Racemates (5 mg kg^?1) were administered intravenously to control and turpentine oil-pretreated rats and the plasma concentrations were determined up to 90 min. Stereoselective analysis showed the apparent distribution volume and the area under plasma concentration-time curves (AUC) of R-(+)-propranolol to be, respectively, one-quarter and twice those of the S-(–)-enantiomer and differences in pharmacokinetic parameters between the two were magnified by turpentine oil pretreatment. Pharmacokinetic parameters of oxprenolol enantiomers were essentially similar for the controls but after turpentine oil pretreatment, a higher affinity of the R-(+)-enantiomer for plasma was observed. Acebutolol enantiomers behaved non-stereospecifically throughout. These results were consistent with predictions from the in-vitro stereospecific binding properties of these agents to purified rat α₁-acid glycoprotein.     

Long-term sequential changes of antibody to p40tax in HTLV-I carrier mothers and children

Antibody to p40^tax (anti-p40^tax) in serum specimens obtained sequentially from a human T cell lymphotropic virus type I carrier population of mothers and children were assayed. The prevalences of anti-p40^tax at the initial sampling were 88% (7/8) in children and 55% (16/29) in mothers. Two of the seven positive children lost their anti-p40^tax during the investigation period, resulting in a final prevalence of 63% (5/8) in children. However, anti-p40^tax status was constant in all the 22 mothers with multiple serum samples (15 remained positive and seven remained negative). A decline in the absorbance value of EIA for anti-p40^tax was observed in seven of the 15 anti-p40^tax positive mothers. This decline may result in the disappearance of anti-p40^tax in some of them.     

In-vitro Characterization of YM872, a Selective,Potent and Highly Water-soluble α-Amino-3-hydroxy-5-methylisoxazole-4-propionate Receptor Antagonist

The in-vitro pharmacological properties of (2,3-dioxo-7-(1H-imidazol-***1-yl)-6-nitro-1,2,3,4-tetrahydro-1-quinoxalinyl)-acetic acid monohydrate, YM872, a novel and highly water-soluble α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)-receptor antagonist were investigated. YM872 is highly water soluble (83 mg mL^?1 in Britton-Robinson buffer) compared with 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline (NBQX), 6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-quinoxalinedione hydrochloride (YM90K) or 6-cyano-7-nitroquinoxa-line-2,3-dione (CNQX). YM872 potently inhibits [³H]AMPA binding with a K_i (apparent equilibrium dissociation constant) value of 0.096 ± 0.0024 μM. However, YM872 had very low affinity for other ionotropic glutamate receptors, as measured by competition with [³H]kainate (high-affinity kainate binding site, concentration resulting in half the maximum inhibition (IC50) = 4.6 ± 0.14 μm), [³H]glutamate (N-methyl-D-aspartate (NMDA) receptor glutamate binding site, IC50 > 100 μM) and [³H]glycine (NMDA receptor glycine-binding site, IC50 > 100 μM). YM872 competitively antagonized kainate-induced currents in Xenopus laevis oocytes which express rat AMPA receptors, with a pA₂ value of 6.97 ± 0.01. In rat hippocampal primary cultures, YM872 blocked a 20-μM AMPA-induced increase of intracellular Ca²⁺ concentration with an IC50 value of 0.82 ± 0.031 μM, and blocked 300-μM kainate-induced neurotoxicity with an IC50 value of 1.02 μM. These results show that YM872 is a potent and highly water-soluble AMPA antagonist with great potential for treatment of neurodegenerative disorders such as stroke.     

INSULIN AND GLUCAGON SECRETION IN HEPATIC GLYCOGENOSES

ABSTRACT. Okada, S., Seino, V., Kodama, H., Yutaka, T., Inui, K., Ishida, M., Yabuuchi, H. and Seino, Y. (Department of Pediatrics, Osaka University Hospital, Fukushima-ku, Osaka and The Third Division, Department of Medicine, University of Kobe, Kobe, Japan). Insulin and glucagon secretion in hepatic glycogenoses. Acta Paediatr Scand 68: 735, 1979.—Insulin and glucagon secretion was investigated in ten patients with hepatic glycogenosis, types I and III, in order to understand the relationship between hypoglycemia and pancreatic function. In all patients, both oral glucose tolerance and intravenous arginine infusion tests revealed hypoinsulinemia. Decreased urinary C-peptide levels with standard food intake also supported hypofunction of pancreatic beta cells. On the contrary, the normal secretion pattern of glucagon in both types indicated in the arginine loading test, intact alpha cells in the pancreas. Persistent hypoinsulinism, which is apparently an adaptation to hypoglycemia, could be an important cause of nutritional dwarfism in both types of glycogenosis. The usefulness of the measurement of urinary C-peptide, which evaluates the pancreatic function and provides management for normal body growth, is discussed.     

CASE REPORT: Insulin - like growth factor II expression in hepatocellular carcinoma with alcoholic liver fibrosis accompanied by hypoglycaemia

This case of hepatocellular carcinoma (HCC) with alcoholic liver fibrosis, which was not associated with hepatitis viruses, was accompanied by hypoglycaemia. The immunoreactive insulin level was low and other hormonal examinations were almost normal. Immunohistochemical studies showed a high level of insulin-like growth factor II (IGF2) peptide in the HCC section and the size heterogeneity of serum IGF2 investigated by western blot revealed a large form at approximately 15 kDa. These results suggest that the HCC with alcoholic liver fibrosis produced IGF2 and that the hypoglycaemia was caused by tumour-associated IGF2.     

Clinical outcome of conservative therapy for stage T1, grade 3 transitional cell carcinoma of the bladder

BACKGROUND: The objective of this study was to retrospectively investigate the effectiveness of transurethral resection of bladder tumor (TURBT) and intravesical instillation therapy for stage T1, grade 3 (T1G3) transitional cell carcinoma (TCC) of the urinary bladder. METHODS: Between January 1995 and December 1997, 97 patients with T1G3 TCC of the urinary bladder were treated by TURBT and adjuvant intravesical instillation with bacillus Calmette-Guérin (BCG) or other anticancer agents. The recurrence-free survival rates were evaluated according to several clinicopathological factors. The cases that progressed to muscle invasive disease were also analysed. RESULTS: In this series, the median follow-up period was 25 months (range, 5- 41) after the initial TURBT. Intravesical recurrence was noted in 44 patients (45%), and the 1, 2, and 3 year recurrence-free survival rates were 72%, 58%, and 42%, respectively. Multivariate analyses revealed that the risk of intravesical recurrence was significantly higher for patients who did not receive BCG therapy, irrespective of age, gender, tumor size, multiplicity, pathological stage, concomitant carcinoma in situ, and lymphovascular involvement. Moreover, after a median of 10 months, disease progression occurred in seven patients (7%), of which only one patient was treated by BCG therapy after initial TURBT. CONCLUSION: These findings suggest that intravesical instillation with BCG combined with TURBT is an effective conservative treatment for T1G3 TCC of the bladder. Patients with negative prognostic factors should be treated by BCG rather than other anticancer agents after TURBT.