A specific growth hormone-binding protein in human plasma: initial characterization.

Human (h) GH in plasma exists as a series of size isomers, which are in part explained by the presence of hGH oligomers. However, certain aspects of circulating large mol wt hGH, such as its high relative proportion compared to that in the pituitary, are poorly understood. To explore whether binding of hGH to plasma protein(s) could contribute to the phenomenon of large mol wt hGH, we incubated freshly prepared monomeric [125I]hGH or biosynthesized [3H]hGH with normal human plasma or serum at pH 7.4 for various time periods at 22 and 37 C. Plasma radioactive hGH patterns were then analyzed simultaneously with unincubated tracer hGH by Sephadex G-100 and G-200 chromatography. We found that part of the radioactivity was converted to a component with an apparent mol wt of 85,000, suggesting binding to a plasma protein(s). This phenomenon was inhibited in a dose-dependent fashion by unlabeled hGH. Saturation/Scatchard analysis indicated an association constant (Ka) of 2-3 X 10(8) M-1 and a maximum binding capacity of 20 ng hGH/ml plasma. Binding was rapid, reversible, and specific. A number of polypeptide hormones, including human placental lactogen, hPRL and rat GH, did not inhibit hGH binding. However, the 20K variant of hGH interacted weakly with the plasma binding component (Ka, 1.2 X 10(7) M-1; maximum binding capacity, 450 ng/ml). The binding component was heat labile and could be partially purified by gel permeation chromatography and affinity chromatography on a hGH-Sepharose column. Its estimated mol wt is 60,000-65,000, and it appears to bind one molecule of hGH to form a complex of 80,000-85,000 mol wt. The binding component is neither albumin nor an immunoglobulin. Under physiological conditions, a minimum of 15-18% of circulating hGH is presumably bound to this plasma component. We conclude that a specific, high affinity, low capacity binding protein for hGH with mol wt of 60,000-65,000 exists in normal and hypopituitary human plasma. hGH complexed with this protein forms part of big-big hGH. The biological significance of this binding protein remains to be investigated.

Brief screening questionnaire for determining affected state in fragile X syndrome: a consensus recommendation.

New molecular research has provided strong evidence for different forms of the fragile X mutation. These findings suggest the need to develop a more standardized and sensitive method for determining neurobehavioral effects of the fragile X gene(s), particularly for molecular studies of patients who do not have obvious mental retardation. This report describes a brief screening questionnaire designed to increase the detection of neurobehavioral dysfunction in individuals from fragile X families who are included in new molecular studies. Improved detection of the affected state in fragile X syndrome will allow more valid clinical data to be correlated with the important molecular information currently being collected.

Intragenic probe used for diagnostics in fragile X families.

The intragenic (FMR-1) probe pE5.1 was used for DNA analysis in fragile X families. With this probe fragments of altered size can be detected in female carriers, affected individuals and transmitting males. The length of the altered fragments was found to vary from one generation to another as well as between sibs. This instability of the DNA detected by pE5.1 was also seen in peripheral blood within single individuals. These phenomena are illustrated by 4 exemplary families segregating the fragile X syndrome. We demonstrate the diagnostic contribution of intragenic analysis to carrier detection as well as the identification of normal transmitting males carrying premutations. One of the families illustrates the passage of a premutation to a male through 2 generations.

Transmission of hepatitis C in a pharmacologic study.

OBJECTIVE: To describe an outbreak of hepatitis C in a clinical research study. DESIGN: Observational study. SETTING: Tertiary-care hospital. PATIENTS: Healthcare workers who volunteered to be subjects in a study of the metabolic effects of inhaled and oral corticosteroids who were unwittingly exposed to hepatitis C virus (HCV). METHODS: Epidemiological investigation and serological analyses. RESULTS: One chronic carrier of HCV was identified. Four fellow workers volunteering in the studies became infected with HCV, with 96% homology among strains. There was no evidence of spread from infected healthcare workers to patients on whom they had performed arterial punctures (2 of 214 positive, unrelated to each other and to the outbreak strain). CONCLUSION: Infection control standards in clinical research must be maintained vigorously to prevent transmission of blood-borne pathogens such as HCV.

A lifetime of events: age and gender variations in the life story.

This study adopted a structural perspective in the examination of life events in the context of an individual's life story. Ten men and ten women at each of three age groups (young, middle-aged, and older adulthood) identified, on a time line, personally significant life events from their past and anticipated future. Results indicated that women identified a greater number of life events and reported a younger age corresponding to their first event than did men; this was especially true for older women. Older participants, in general, identified fewer future events than did younger participants and reported an older age for their last event; the corresponding range of time covered from the first to the last event was also longer. Event type also varied by age and gender. Recency played a central role in the allocation of life events, although late adolescence and early adulthood were especially dense event periods for all groups. Discussion focuses on the roles of gender, age, and the life course in the ways in which events are configured in the life story.

Needlestick injury in medical students.

OBJECTIVE: To determine the incidence of needlestick injuries and the prevalence of hepatitis B vaccination among medical students, dentistry students, and hospital staff. DESIGN AND SUBJECTS: Anonymous survey of final year medical students and dentistry students enrolled at Sydney University in 1992, and nursing staff and doctors employed in the wards and emergency department of Royal Prince Alfred Hospital, Sydney. RESULTS: During their clinical training, 22% of medical students and 72% of dentistry students had received one or more contaminated, penetrating "sharps" injuries. Of hospital staff, 50% of ward nurses, 71% of ward doctors, and 50% of emergency staff had received this type of injury during the previous two years. Students were significantly more likely to be vaccinated against hepatitis B than hospital staff (P < 0.001)--98% of medical students and 95% of dentistry students had received a full course of vaccination. The rate of vaccination among hospital staff ranged from 79% in emergency staff to 85% in ward nurses. CONCLUSIONS: Clinical students sustain needlestick injuries at a rate comparable with hospital personnel and therefore face a significant risk of exposure to transmissible pathogens, including hepatitis B virus, HIV, and hepatitis C virus. The rate of hepatitis B vaccination is high among clinical hospital staff and almost universal among medical and dentistry students.