New approaches for biological monitoring of radiation workers.

Methods for measuring somatic mutation and chromosome aberration in humans are currently advancing and provide important new opportunities for biologic dosimetry of nuclear workers. Methods to test somatic mutation in four human genes (hprt, hla-a, glycophorin A, and beta globin) are reviewed briefly and evaluated for their applicability to biological radiation dosimetry of nuclear workers. Two somatic mutation tests can be currently recommended: an HPRT method applied to recently exposed workers and the glycophorin A method applied to workers exposed over their working lifetime.

Impaired vasodilation of forearm resistance vessels in hypercholesterolemic humans.

The effect of hypercholesterolemia on vascular function was studied in humans. To eliminate the potential confounding effects of atherosclerosis, vascular reactivity was measured in the forearm resistance vessels of 11 normal subjects (serum LDL cholesterol = 111 +/- 7 mg/dl) and 13 patients with hypercholesterolemia (serum LDL cholesterol = 211 +/- 19 mg/dl, P less than 0.05).

Characterization of the binding of human tissue-type plasminogen activator to platelets.

Cell surface binding sites for the constituent proteins of the fibrinolytic system may play a role in the localization and regulation of fibrinolysis. In the present study, specific binding of recombinant human tissue-type plasminogen activator (rt-PA) to human blood platelets was identified and characterized. 125I-labeled rt-PA was found to bind specifically, saturably, and reversibly to the surface of gel-filtered platelets, reaching equilibrium within 5 min at 22 degrees C.

N-acetylcysteine potentiates platelet inhibition by endothelium-derived relaxing factor.

Recent evidence suggests that endothelium-derived relaxing factor exhibits properties of nitric oxide. Like nitric oxide, it inhibits platelet function and mediates its effects by elevating intracellular cyclic GMP. In this study we have investigated the role of reduced thiol in the mechanism of action of endothelium-derived relaxing factor on platelets.

Double mitral valve orifice and primary pulmonary hypertension.

We describe the combination of double mitral valve orifice of the complete bridge variety, or type 1, and primary pulmonary hypertension, a previously unreported association. The complete diagnosis was established by two-dimensional Doppler echocardiography and the hemodynamics corroborated by cardiac catheterization.

Potential DNA methods for measuring the human heritable mutation rate.

Potential methods are reviewed for estimating human heritable mutation rates by comparing the DNA of parents of offspring. In the 4 years since the Alta Workshop on this subject, information has accumulated on several of the six methods detailed in that meeting. Some of the methods now appear to be infeasible, and all continue to be too inefficient for practical implementation.

An S6 kinase activated during liver regeneration is related to the insulin-stimulated S6 kinase in H4 hepatoma cells.

Protein kinase activity toward the 40 S ribosomal protein S6 is activated 6-fold in regenerating rat liver following 70% hepatectomy. The kinase is maximally activated within 2 h after surgery, remains active up to 36 h after surgery, and declines rapidly thereafter. The post-hepatectomy S6 kinase activity exhibits structural and functional similarity to an insulin-stimulated S6 kinase in H4 hepatoma cells.

Dysphagia after total laryngectomy.

Quantitative analysis of swallowing after total laryngectomy has been compared with the data obtained in normal subjects. Lack of negative pressure production in the PE segment has been related to the dysphagia and prolonged bolus transit times. High pressures in the oropharynx may be a cause of fistulas.

Manofluorographic analysis of swallowing.

A quantitative evaluation of the pharyngeal swallow is described using a new method--manofluorography. Eleven parameters have been established, and the clinical significance of the most important ones has been highlighted. The propulsive tongue action and hypopharyngeal suction pump have been designated as the major bolus driving forces.

Human mononuclear cells which produce interferon-alpha during NK(HSV-FS) assays are HLA-DR positive cells distinct from cytolytic natural killer effectors.

Human mononuclear cells were previously shown to produce interferon-alpha (IFN) during 14 hr assays using herpes simplex virus type-1 infected fibroblasts [NK(HSV-FS)]. In this study, we have compared the effectors responsible for mediating NK(HSV-FS) cytolytic activity to those which produce IFN-alpha. Both activities were found to reside in non-adherent fractions, negative for non-specific esterase-staining cells.

Manofluorography of deglutition after total laryngopharyngectomy.

Manofluorography is a new technique for the evaluation of swallowing that provides simultaneous display of manometry and videofluoroscopy on one video screen. Data are presented from a study of deglutition in 10 patients who had prior total laryngopharyngectomy with replacement by either jejunal graft or gastric pull-up. Factors that enhance bolus passage are the presence of a widely patent graft and an intact swallowing reflex.

Role of platelets in cholesteryl ester formation by U-937 cells.

The conversion of tissue macrophages into cholesteryl ester-rich foam cells is a crucial early event in atherogenesis. We studied the platelet as a potential source of cholesterol for esterification by macrophages because (a) platelets are rich in free cholesterol, (b) they adhere to macrophages early in atherogenesis, and (c) vascular injury can induce foam cell formation in the absence of hyperlipoproteinemia. We found that washed, activated human platelets from normocholesterolemic donors stimulated cholesteryl ester formation by the human monocyte-derived cell, U-937.

Biomarkers in the detection of human heritable and germinal mutagenesis.

An important potential use of biomarkers in human toxicology is the detection of induced mutational events in offspring and germ cells of exposed individuals. The importance, of course, is in risk estimation and the identification and prevention of exposure conditions that are harmful to the human genome. The challenge is to discover methods of sufficient power to find the rare, random, mutational events and to discriminate such events from other sources of molecular variation.

Function in the pharyngoesophageal segment.

Examination of the pharyngoesophageal (PE) segment is usually limited to manometry or barium swallow. Manofluorography is a technique which allows simultaneous analysis of both manometry and videofluoroscopy of deglutition on a single video screen. Using manofluorography, the physician can see the cause of the manometric pressure waves.

Manofluorography of deglutition after supraglottic laryngectomy.

Manofluorography (mano: manometry, fluoro: videofluoroscopy, graphy: picture) provides a simultaneous display of manometry and fluoroscopy on one video screen. This study uses manofluorography to analyze the swallowing patterns of nine patients who had undergone supraglottic laryngectomy. The results show that during swallowing the pharyngeal mechanism for preventing aspiration depends upon three processes: (1) tight lingual-laryngeal contact, (2) coordination of the swallowing reflex, and (3) tongue base and pharyngeal constrictor clearing of the hypopharynx and laryngeal inlet.

Examination of swallowing after total laryngectomy using manofluorography.

Investigation of postlaryngectomy dysphagia is usually limited to the standard barium swallow. Manofluorography (mano, manometry; fluoro, videofluoroscopy; graphy, picture) is a new technique that permits analysis of simultaneous manometry and videofluoroscopy of deglutition. Manofluorography provides more detailed analysis of the swallowing dynamics during the pharyngeal stage of deglutition than either barium studies or manometry used alone.