Search PubMed⌕ Search

Biomedical subjects

J F Wilber

Publications and source records attributed to J F Wilber.

At least 127 records · Page 7Linked to original sources
PubMed1967

Estimation of the secretion rate of thyrotropin in man.

The plasma concentration of a pituitary hormone is determined by the rate of secretion, degradation, and the volume of distribution of that hormone. Using a radioimmunoassay for human thyrotropin (TSH) and human TSH-(131)I, we have estimated the rates of degradation and distribution of TSH in man and calculated the rate of secretion. Either 0.5 or 5 mug of TSH-(131)I with specific activities of 1 to 50 muc per mug was administered intravenously to 12 euthyroid subjects. Serial determinations were made of TSH-(131)I, and the half-time of disappearance (t((1/2))) was thus estimated. The average t((1/2)) in euthyroid subjects was 53.9 minutes with a volume of distribution averaging 5.8% of body weight. The mean endogenous plasma TSH concentration was 1.8 mmug per ml (2.7 muU per ml in terms of the human TSH reference standard A). The mean total TSH pool, excluding the pituitary, was 5.8 mug (8.7 mU). From these data the mean secretion rate of TSH in euthyroid man was calculated to be 110.1 mug per day (165.2 mU). Similar data were estimated for 3 mildly hypothyroid patients. The t((1/2)) were 75.1, 97.1, and 83.6 minutes, with a mean of 85.3 minutes (1.6 times normal). The mean TSH pool was 58.1 mug (10 times normal). The secretion rate was 688.7 mug per day (1,033.1 mU). In other hypothyroid patients, plasma TSH levels ranging from 6 to 230 mmug per ml (9 to 345 muU) have been found. If similar half-times and a normal distribution volume are assumed, the secretion rate of TSH in hypothyroid patients can be estimated to range from about 260 to 15,350 mug per day (390 to 23,025 mU) or from about 2 to 307 times normal. Therefore, the elevated plasma TSH levels found in hypothyroidism are a result of both slower degradation and increase in rate of secretion.

Adolescent↗
PubMedDate not supplied

The distribution of histidyl-proline diketopiperazine [cyclo(His-Pro)] in discrete rat hypothalamic nuclei.

The distribution of Histidyl-Proline Diketopiperazine [cyclo(His-Pro)], a metabolite of thyrotropin-releasing hormone (TRH), was determined by specific RIA in Palkovits micropunch pools derived from discrete hypothalamic nuclei. Highest concentrations of cyclo(His-Pro) were identified in the anterior nucleus (3.5 ng/mg protein) and the paraventricular nucleus (2.95 ng/mg protein), while lower concentrations of cyclo(His-Pro) were seen in the other 6 nuclei. In contrast, TRH concentrations were highest in the ventromedial nucleus pars medialis (3.2 ng/mg protein) and arcuate nucleus (2.7 ng/mg protein). This qualitatively different distribution of cyclo(His-Pro) from that of TRH suggests that not all of cyclo(His-Pro) is derived exclusively from TRH.

Animals↗
PubMedDate not supplied

Transmitters of the raphe-spinal complex: immunocytochemical studies.

The localization of serotonergic and various peptidergic neurons in the medullary raphe nuclei that project to the lumbosacral spinal cord have been studied using a retrograde transport method combined with immunocytochemistry. Spinally projecting neurons stained for serotonin-like, substance P-like, enkephalin-like and thyrotropin-releasing hormone-like immunoreactivity were all observed in the raphe nuclei of the medulla, as well as in the adjacent ventrolateral reticular formation. The distribution of the descending serotonergic and peptidergic neurons in the raphe nuclei as well as quantitative data on their relative numbers suggest that a large fraction of raphe-spinal neurons contain serotonin co-existing with one or more peptides in the same cell.

Animals↗
PubMedDate not supplied

Distribution and metabolism of cyclo (His-Pro): a new member of the neuropeptide family.

Cyclo (His-Pro) is a biologically active cyclic dipeptide derived from thyrotropin-releasing hormone by its limited proteolysis. We have developed a specific radioimmunoassay for this cyclic peptide and shown its presence throughout rat and monkey brains. The normal rat brain concentration of cyclo (His-Pro) ranged from 35-61 pmols/brain. The elution profiles of rat brain cyclo (His-Pro)-like immunoreactivity and synthetic radioactive cyclo (His-Pro) following gel filtration, ion-exchange chromatography, and high pressure liquid chromatography were similar. An analysis of the regional distribution of cyclo (His-Pro) and TRH in rat and monkey brains exhibited no apparent precursor-product relationship. The possible additional factors determining regional differences in the endogenous cyclo (His-Pro) concentrations are discussed. The endogenous levels of brain cyclo (His-Pro) were elevated when rats were made either hypothyroid by surgical thyroidectomy or forced to drink alcohol for six weeks. These studies demonstrate that cyclo (His-Pro) is present throughout the central nervous system in physiologically relevant concentrations which can be modulated by appropriate physiological and pharmacological manipulations. These data in conjunction with earlier reports of multiple biological activities of exogenous cyclo (His-Pro), suggest that endogenous cyclo (His-Pro) is a biologically active peptide and it may play a neurotransmitter or neuromodulator role in the central nervous system.

Alcoholism↗
PubMedDate not supplied

Evidence for the presence of immunoreactive histidyl-proline diketopiperazine [cyclo (His-Pro)] in the adult human brain.

The current study was undertaken to evaluate the presence of cyclo (His-Pro) in adult human brain tissues obtained at autopsy. We found evidence for immunoreactive cyclo (His-Pro), which diluted in parallel to the radioimmunoassay standard curve and which had mobility on HPLC that was similar to synthetic cyclo (His-Pro), in several regions of the adult human brain. Whereas the levels of cyclo (His-Pro) in the pituitary stalk-median eminence were high (2.2 ng/mg protein), the concentrations in the whole hypothalamus were much lower (0.105 ng/mg protein). Among the extrahypothalamic brain regions examined, the levels of cyclo (His-Pro) were highest in the cerebellar hemisphere (0.168 ng/mg protein) and olfactory bulbs (0.180 ng/mg protein) and were lowest in the hippocampus (0.080 ng/mg protein) and occipital cortex (0.079 ng/mg protein). Thus, immunoreactive cyclo (His-Pro) has widespread distribution in the adult human brain and the potential exists for this cyclic diepeptide to play a role in human brain function.

Adolescent↗
PubMedDate not supplied

Distribution and characterization of cyclo (His-Pro)-like immunoreactivity in anuran (frog) skins.

The distribution of cyclo (His-Pro)-like immunoreactivity in frog skins from seven frog species was examined. The chromatographic elution profile of cyclo (His-Pro)-like immunoreactivity in amphibian skins measured by radioimmunoassay corresponded precisely to that of [3H-Pro]-cyclo (His-Pro) after DEAE-Cellulose, Sephadex G-25 and high-pressure liquid chromatography. The concentrations of cyclo (His-Pro) in frog skins were much higher than the concentrations of TRH previously observed in skin and the concentrations of cyclo (His-Pro) in both brain and gastrointestinal tract.

Animals↗
PubMedDate not supplied

Persistence of immunoreactive TRH and GnRH in long-term primary anterior pituitary cultures.

Intact anterior pituitary tissue and primary anterior pituitary cultures were stained with 1:30,000 anti-TRH and 1:10,000 anti-GnRH using the peroxidase antiperoxidase immunocytochemical technique. Stains applied to serial ultrathin sections of intact pituitaries showed that TRH immunoreactivity could be localized in secretory granules of thyrotropes, gonadotropes and corticotropes whereas GnRH immunoreactivity was found only in gonadotropes and corticotropes. Long-term primary pituitary cultures were studied to remove the anterior pituitary cells from hypothalamic influences. In these cell populations both TRH and GnRH immunoreactivity persisted. In addition, quantification of the stained cells at the light microscopic level demonstrated that the volume fraction of TRH and GnRH immunoreactive cells remained constant up to 3 weeks of culture. Studies of serial ultrathin sections through cells from these cultures showed TRH or GnRH localized in secretory granules of cells that contained LH and ACTH, but not TSH. Both liquid and solid phase immunoabsorption specificity controls were used to validate the immunocytochemical stains. These studies suggest that the pituitary TRH and GnRH immunoreactivities may not be completely of hypothalamic origin, but may also be endogenous to a subpopulation of unique multihormonal pituitary cells.

Animals↗
PubMedDate not supplied

Identification and characterization of cyclo(His-Pro)-like immunoreactivity in amniotic fluid.

Amniotic fluid (AF) from 25 term pregnancies was analyzed for cyclo(His-Pro)-like immunoreactivity (CHP-LI). CHP-LI was detected in all AF samples and was indistinguishable from synthetic CHP by immunoidentity, by gel chromatography on Sephadex G-25, and by high pressure liquid chromatography. The mean concentration of CHP-LI in AF was 13,622 +/- 1288 pg/ml (+/- SE) and concentrations were not altered by maternal labor. Plasma concentrations of CHP-LI were similar in 4 pregnant and 4 control subjects [2260 +/- 432 pg/ml vs. 2162 +/- 419 pg/ml (+/- SE), respectively]. We conclude that 1) CHP-LI is readily detected in AF from term pregnancies and is indistinguishable from synthetic CHP, and 2) concentrations of CHP-LI in human AF are significantly higher than concentrations of maternal plasma CHP-LI, suggesting CHP AF originates by mechanisms other than diffusion from maternal plasma.

Amniotic Fluid↗