The CARD15 2936insC mutation and TLR4 896 A>G polymorphism in African Americans and risk of preterm premature rupture of membranes (PPROM)

Infection is believed to be a leading cause of preterm premature rupture of membranes (PPROM). The bacterial cell wall component, lipopolysaccharide (LPS), is thought to initiate tissue responses leading to PPROM in the setting of Gram negative infection. LPS is recognized by the innate immune system, including the proteins encoded by the CARD15 and TLR4 genes. A recently described mutation (2936insC) in CARD15 and a polymorphism in TLR4 896 A>G impair responses to LPS. The objective of this study was to determine if African Americans, who have a higher incidence of PPROM than Caucasians, have different frequencies of the mutant CARD15 allele and the TLR4 hyporesponsive variant, and if risk of PPROM is influenced by fetal carriage of these alleles. The allele frequencies for the CARD15 mutation and the TLR4 896G variant in African Americans were similar to those reported for Caucasians. There was no association between the TLR4 alleles examined and PPROM. However, the CARD15 mutation was only detected in controls and not in PPROM cases. We conclude that the CARD15 mutation and hyporesponsive TLR4 allele do not contribute to ethnic variation in the incidence of PPROM.     

IgG-KAPPA-PRODUCING PRIMARY PLASMACYTOMA OF THE THYROID GLAND WITH PREOPERATIVE SERUM M PROTEIN

A case of primary plasmacytoma of the thyroid gland which occurred in a 63-year-old woman is reported. Histologic and ultramicroscopic examination revealed that the excised thyroid tumor was plasmacytoma superimposed on lymphocytic thyroiditis. Immunohistological study showed that the tumor cells produced intracytoplasmic immunoglobulin (IgG-kappa). Electropho-retic and immunoelectrophoretic studies disclosed the presence of monoclonal immunoglobulin (IgG-kappa) in samples of the patient's serum which had been obtained preoperatively. After completion of irradiation therapy to the neck following tumor removal, the serum monoclonal immunoglobulin disappeared. The patient is currently alive and well without any evidence of the tumor three years after surgery.     

Experimental induction of uterine cancer in rats by N-ethyl-N'-nitro-N-nitrosoguanidine dissolved in polyethylene glycol

In the present experiment we attempted to experimentally induce uterine cancer in rats by injecting into the uterine cavity N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) dissolved in polyethylene glycol (PEG). Fifty-nine female F-344 rats, 7-8 weeks old, were divided into three groups and each received in the left uterine cavity with laparotomy a single dose of ENNG dissolved in PEG according to the following schedule: Group 1 received 75 mg ENNG/kg body wt.; Group 2 had 20 mg ENNG/kg body wt.: and Group 3 was given only PEG. In Group 1 it was observed that adenocarcinoma and sarcoma were present in the uterine corpus while squamous cell carcinoma occurred in the uterine cervix. In Group 2, although tumors such as adenocarcinoma, adenoma and sarcoma were observed in the uterine corpus, no tumor was present in the uterine cervix. No tumor growth whatsoever was observed in Group 3. From the above results it is apparent that the present method is an efficient means for experimentally inducing uterine cancer and that the site of tumor generation varies according to the concentration of ENNG administered.     

Glucose uptake by individual skeletal muscles during running using whole-body positron emission tomography

The purpose of this study was to examine, by positron emission tomography (PET), the distribution of [¹⁸F]fluoro-deoxy-glucose ([¹⁸F]FDG) uptake by human muscles during 35?min of running. Thirteen healthy male subjects were studied, seven of whom participated in the exercise study. Running intensity was kept constant such that the subjects' heart rates were maintained at between 140 and 150?beats per minute. [¹⁸F]FDG [62.9 (14.8)?MBq, mean (SD)] was injected after 15?min of running. PET imaging was started immediately after the running ended. The ratio of [¹⁸F]FDG uptake by muscles in runners to that in control subjects (r-c ratio) varied from three to six for the muscles of the foot and leg below the knee joint. The r-c ratio of the medial head of the gastrocnemius (MG) was higher than that of its lateral head (LG). The r-c ratio of the rectus femoris (RF) was lower than that of the other three muscles of the quadriceps femoris (QF). The r-c ratio of inactive muscles located above the waist was approximately 0.7. These results suggest that, during the moderate running of this study: (1) glucose uptake by muscles of the foot and leg below the knee joint clearly increases, (2) the r-c ratio differs significantly among the skeletal muscles, which act synergistically, and (3) glucose uptake by inactive skeletal muscles decreases.     

Immunopharmacological study of CCA (Lobenzarit disodium), an anti-arthritis agent--I. Abrogation of IL 1 secretion by LPS-stimulated human monocytes and induction of gamma-interferon production with CCA

In vitro effects of CCA, an anti-arthritis agent, were studied upon autologous mixed lymphocyte reaction (AMLR), lymphocyte mitogenesis, IL 1 and IL 2 production, immunoglobulin production and gamma-interferon (IFN) production. CCA at 50 micrograms/ml, which was not toxic to cells, blocked AMLR, IL 1 production and immunoglobulin production (IgM and IgG) significantly, while CCA at the same dose did not affect IL 2 production and lymphocyte mitogenic responses to Staphylococcus aureus Cowan I(SAC) and pokeweed mitogen(PWM). CCA at both 20 ng/ml and 20 micrograms/ml induced human gamma/IFN. Addition of IL 1 and/or IL 2 reversed inhibitory effect of CCA on AMLR. These data suggest that CCA exerts its actions by mainly affecting T cells and monocytes and can be used as an immunomodulator.     

Double antibody enzyme immunoassay for the quantitation of adenosine 3', 5' -cyclic monophosphate (cyclic AMP) and guanosine 3', 5'-cyclic monophosphate (cyclic GMP) in tissue and plasma

A sensitive double antibody enzyme immunoassay for the quantitation of cyclic AMP and cyclic GMP is presented. Specific antisera to each nucleotide were raised in rabbits by immunization with succinyl cyclic nucleotide-human serum albumin conjugates. For competitive reaction, antibodies were incubated with a mixture of succinyl cyclic nucleotide labelled with beta-D-galactosidase and unlabelled succinylated standard or sample cyclic nucleotides. The antibody-bound enzyme-hapten was separated from free hapten by anti-rabbit IgG immobilized to a polystyrene ball. Activity of the enzyme on the solid phase was fluorometrically determined. The assay system made it possible to ascertain values as low as 5 fmole of cyclic AMP or cyclic GMP. Cyclic nucleotides in plasma could be accurately determined by this method without requiring a deproteinizing reagent as the first step of assay.     

Modulation of neuronal histamine in control of food intake

Neuronal histamine affects physiological functions of the hypothalamus. To investigate involvement of histamine receptors in feeding, histamine antagonists were infused into the rat third cerebroventricle. All H1- but no H2-antagonists tested, induced transient feeding during the early light when concentration of hypothalamic histamine was highest. No periprandial drinking was observed. Ambulation concomitantly increased during feeding. The effect on feeding was attenuated when brain histamine was normally low during the early dark or was decreased by alpha-fluoromethylhistidine (alpha-FMH). Bilateral microinjection indicated that the ventromedial hypothalamus, but not the lateral hypothalamus or the paraventricular nucleus, was a main locus for the induction of feeding by an H1-antagonist. The effect was completely abolished when brain histamine was decreased by pretreatment with alpha-FMH. Hypothalamic neuronal histamine suppresses food intake, at least in part, through H1-receptors in the VMH, and diurnal fluctuations of food intake may mirror neuronal histamine level.