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Biomedical subjects

G Heavner

Publications and source records attributed to G Heavner.

9 recordsLinked to original sources
PubMed1996

Anergic TH1 clones specific for hepatitis B virus (HBV) core peptides are inhibitory to other HBV core-specific CD4+ T cells in vitro.

A strong and transient hepatitis B virus core (HBc)-specific CD4+ T-cell response has been shown to be associated with viral elimination in acute self-limited hepatitis B but to be absent in chronic hepatitis B. So far, little is known about immunological mechanisms involved in the regulation of the HBc-specific CD4+ T-cell response. We studied 28 patients with acute hepatitis B, and frequently a sudden decrease in the HBc-specific CD4+ T-cell response was found between 4 and 8 weeks after disease onset. Thirty-two CD4+ T-cell clones specific for amino acids 50 to 69, 81 to 105, 117 to 131, or 141 to 165 of HBc were isolated from a patient shortly before the peripheral blood mononuclear cell response to most HBc-derived peptides abruptly disappeared. TH1 clones, but not TH0 clones, could be anergized in vitro by stimulation with specific peptides even in the presence of costimulatory cells. Moreover, when anergic cells were mixed with responsive cells, the proliferation of HBc-specific TH1 or TH0 clones was inhibited antigen specifically by anergic cells. The unusual susceptibility of HBc-specific TH1 clones to anergy induction in vitro as well as their potential to inhibit other HBc-specific TH1 and TH0 clones suggests that anergy induction may be involved in the downregulation of the virus-specific immune response during acute hepatitis B in vivo.

CD4-Positive T-Lymphocytes↗
PubMed1995

Lipopolysaccharide (LPS) neutralizing peptides reveal a lipid A binding site of LPS binding protein.

Endotoxic shock follows a cascade of events initiated by release of lipopolysaccharide during infection with Gram-negative organisms. Two overlapping 15-mer peptides were identified, corresponding to residues 91-108 of human lipopolysaccharide binding protein that specifically bound the lipid A moiety of lipopolysaccharide with high affinity. The peptides inhibited binding of lipopolysaccharide to lipopolysaccharide binding protein, inhibited the chromogenic Limulus amebocyte lysate reaction, and blocked release of tumor necrosis factor alpha following lipopolysaccharide challenge both in vitro and in vivo. These results suggest lipopolysaccharide binding protein residues 91-108 form at least part of the lipopolysaccharide binding site. Moreover, derivatives of lipopolysaccharide binding protein residues 91-108 might modulate lipopolysaccharide toxicity in the clinical setting.

Acute-Phase Proteins↗
PubMed1995

Thyroid function in non-growth hormone-deficient short children during a placebo-controlled double blind trial of recombinant growth hormone therapy.

GH treatment in GH-deficient children has been reported to cause decreases in serum T4 and TSH and an increase in serum T3. We sought to determine whether GH treatment alters thyroid function in non-GH-deficient short children. Twenty children (18 boys) were followed for 12 months while receiving either GH (Humatrope, Eli Lilly; 0.074 mg/kg, sc, 3 times/week; n = 9) or placebo (n = 11). Total T4, free T4, T3, and TSH were measured every 6 months and in 12 children also at 1, 2, 3, and 9 months. A TRH test and measurement of nocturnal TSH surge were performed at baseline and after 6 months of treatment in 19 subjects. There were no significant differences at baseline in the clinical features between the placebo and GH groups. Total T4, free T4, T3, and TSH levels did not significantly differ between the placebo and GH groups at baseline and at 1, 2, 3, 6, 9, and 12 months. There were no significant differences between the two groups in TSH response to TRH or nocturnal TSH surge. Although an early transient effect of GH treatment could not be excluded, we conclude that GH treatment for 12 months does not produce sustained alterations in thyroid function in non-GH-deficient children.

Body Height↗
PubMed1993

Evaluation of growth hormone axis and responsiveness to growth stimulation of short children with osteogenesis imperfecta.

Growth deficiency is a cardinal manifestation of severe Osteogenesis Imperfecta (OI) and occurs frequently in moderate to mild OI. We have investigated the status of the hormones related to growth in 28 children with OI. Our goals were to determine whether there were any abnormalities of these hormones, whether the abnormalities correlated with types of OI, and whether OI bone could be safely stimulated to grow. The study group included 14 females and 14 males. Using the criteria developed by Sillence et al. [1979], 13 children had OI type III, 12 had OI type IV, and 3 had OI type I. Evaluation included 3 standard hGH provocative tests (AITT, L-Dopa), GRF stimulation, 24 hr q20 minute sampling of unstimulated growth hormone, and a somatomedin generation test. All patients except one had normal responses to standard provocative stimuli. Responses to GRF fell into 2 groups: one with a mean response similar to that of normal children, and one with a mean response resembling that of GH deficient children. The group with low response to GRF had a significantly lower area under the curve in the 24-hr test of unstimulated GH than did the normal response group. The OI children as a group showed a blunted IGF-1 response during the Somatomedin Generation Test, with 18/28 children having less than a two-fold stimulation. No test results correlated with OI type. Ten OI children were enrolled in a pilot growth stimulation study. Two children received protropin and 8 received clonidine for at least 6 months. Both children treated with protropin and 4/8 treated with clonidine experienced at least a doubling of their pre-treatment growth rates. Lack of growth hormone response did not correlate with type of OI or parameters from the hormonal evaluation. We speculate that there is a group of OI children who have a hypoactive growth hormone axis. Some OI bone appears to respond to GH and a treatment trial with protropin is planned for a larger number of children.

Body Height↗
PubMed1993

The growth hormone and somatomedin axis in short children with osteogenesis imperfecta.

Growth deficiency is a cardinal feature of severe osteogenesis imperfecta (OI) and a frequent feature of mild to moderate forms of this disease. We have investigated the status of hormones related to growth in 22 short prepubertal children, 13 males and 9 females, with various types of OI. Ten children had Sillence type III OI, 10 had type IV, and 2 had type I. Evaluation included GRH stimulation, three standard GH provocative tests (arginine-insulin tolerance test, L-dopa), 24-h sampling for measurement of unstimulated GH secretion and a somatomedin-C generation test. None of these children had GH deficiency by standard criteria. We found that 9 OI children had decreased responsiveness to GRH, similar to the GRH response of GH-deficient children. Overall, however, mean 24-h GH values and mean peak GH response to provocative agents of OI children were within the normal range. In the somatomedin generation test, the OI children as a group showed a blunted response, with 13 of 22 having less than a 2-fold stimulation of somatomedin-C by GH. This suggested resistance of the liver and other somatomedin-C secreting tissues to GH. The group with blunted insulin-like growth factor-I response did not correlate significantly with the group with decreased GRH response. To investigate the responsiveness of OI bone to growth stimulation, six OI children with less than average integrated GH secretion were enrolled in a pilot study in which one child received exogenous GH and six received clonidine for at least 6 months. The child treated with exogenous GH and three of six treated with clonidine experienced at least a 4.7 cm/yr increase over their pretreatment growth rates. Growth response could not be predicted from baseline studies. We conclude that abnormalities of the GH-somatomedin axis exist in some children with OI. Administration of GH or clonidine may augment growth rates in OI children; however, the effect of these agents on final stature is unknown.

Adolescent↗
PubMed1986

Tripeptide structure of bursin, a selective B-cell-differentiating hormone of the bursa of fabricius.

Differentiation of lymphoid precursor cells in a variety of species is induced by polypeptide hormones such as thymopoietin for T cells and bursin for B cells. In the present experiments, bursin isolated from the bursa of Fabricius of chicken was found to induce the phenotypic differentiation of mammalian and avian B precursor cells but not of T precursor cells in vitro. Similarly, bursin increased cyclic guanosine monophosphate in cells of the human B-cell line Daudi but not in cells of the human T-cell line CEM. These inducing properties of bursin are the reverse of the inducing properties of thymopoietin produced by the thymus and are appropriate to a physiological B-cell-inducing hormone. A tripeptide sequence (lysyl-histidyl-glycyl-amide) was determined for bursin and confirmed by synthesizing this proposed structure and demonstrating chemical identity of the natural and synthetic peptides. Similarity of biological action was indicated in induction assays by elevation of cyclic adenosine monophosphate and guanosine monophosphate in Daudi B cells but not in CEM T cells.

Animals↗
PubMed1981

Behavioral toxicity of acute and subacute exposure to triethyltin in the rat.

The behavioral effects of both acute and subacute triethyltin (TET) exposure were examined in the rat. Animals acutely exposed to TET at doses of 0, 1.5 and 3.0 mg/kg showed a dose-related decrease in motor activity when tested between 2 and 4 hr following exposure. Subacute (3 week) exposure to TET in the drinking water (5 or 10 ppm) resulted in performance decrements in the following: maze activity, open field behavior, acoustic startle response and landing foot-spread. Early signs of behavioral deficits were observed 2 weeks after 10 ppm TET. These effects were reversible within one month after termination of exposure.

Animals↗