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G V Segre

Publications and source records attributed to G V Segre.

144 records · Page 8Linked to original sources
PubMed1976

Metabolism and biological activity of parathyroid hormone in renal cortical membranes.

Recent studies from several laboratories have documented the presence of fragments of parathyroid hormone in blood or peripheral tissues or in both. Inasmuch as amino-terminal fragments are known to be biologically active, it has been suggested that fragments, rather than the intact polypeptide of 84 amino acids, might be the active molecular species in tissue fluids. Accordingly, the metabolism of native bovine parathyroid hormone, bPTH-(1-84), was studied in purified renal cortical membranes from several species and correlated with hormonal stimulation of adenylyl cyclase in these membranes in vitro. Analysis of whole incubation mixtures or membrane-bound hormone by gel electrophoresis and gel chromatography after incubation of [3H]bPTH-(1-84) or 125-I-labeled bPTH-(1-84) or unlabeled biologically active bPTH-(1-84) with purified canine renal cortical membranes revealed no evidence of proteolysis, and yet the uncleaved hormone readily stimulated adenylyl cyclase. Kinetic studies of hormone-stimulated adenylyl cyclase activity revealed no difference in rate of onset of activity between bPTH-(1-84) And the active synthetic amino-terminal tetratriacontapeptide bPTH-(1-34), and hence there was no evidence of precursor-product relationship between the native hormone and an active amino-terminal fragment. The results suggest, insofar as the activity detected in these membranes reflects the biological response of the hormone in vivo, that the native hormone is indeed biologically active at the receptor level directly without the requirement for cleavage into active fragments.

Adenylyl Cyclases↗
PubMed1976

Immunological comparisons of two synthetic human parathyroid hormone-(1-34) peptides.

The immunological properties of human parathyroid hormone-)1-34) synthesized in accord with the sequence reported by Brewer et al. and the different sequence found by Niall et al. were compared with those of highly purified native human hormone-)1-84). Analyses were performed by radioimmunoassay using 7 anti-bovine parathyroid hormone antisera and bovine parathyroid hormone-)1-34) as tracer. Whereas human parathyroid hormone-(1-34) synthesized in accord with the sequence of Niall et al. was immunologically indistinguishable from native human hormone in all 7 assay systems, striking differences were seen between human parathyroid hormone-(1-34) synthesized in accord with the sequence of Brewer et al. and the native hormone. In none of the 7 assay systems did human parathyroid hormone-(1-34) synthesized in accord with the sequence of Brewer et al. give the same displacement slopes that the reference preparation gave. The observation that immunologic probes easily discriminate between the two different human parathyroid hormone-(1-34) peptides suggests that similar immunologic approaches will be of value in exploring several important issues, particularly those relating to the sequence and conformational properties of human parathyroid hormone and its synthetic peptides and to the question of the existence of isohormonal forms.

Animals↗
PubMed1975

Prostaglandins as mediators of hypercalcemia associated with certain types of cancer.

We investigated the role of prostaglandins in the hypercalcemia associated with neoplasia. In patients with hypercalcemia and solid tumors the excretion of the major urinary metabolite of the E prostaglandins, 7 alpha-hydroxy-5, 11-diketotetranorprostane-1, 16-dioic acid (PGE-M), was significantly greater than normal, P LESS THAN 0.01 (median of 58.4 and 7.1 ng per milligram of creatinine respectively). Slightly elevated values were seen in normocalcemic patients with solid tumors (14.3 ng per milligram). The levels of the metabolite were normal in hypercalcemic patients with either hematologic neoplasia or primary hyperparathyroidism. Immunoreactive parathyroid hormone was undetectable in the plasma of all hypercalcemic patients with solid tumors. Inhibition of prostaglandin synthesis by aspirin or indomethacin reduced excretion of both the urinary metabolite and serum calcium in six hypercalcemic patients with solid tumors and elevated excretion of the metabolite. These findings support the concept that prostaglandins are mediators of the hypercalcemia caused by certain solid tumors.

Aspirin↗
PubMed1975

Peripheral metabolism of bovine parathyroid hormone in the dog.

Four dogs were infused with highly purified bovine parathyroid hormone until constant levels of immunoreactive hormone were attained in the circulation. Simultaneous samples of plasma were then obtained from the aorta, from hepatic, renal, and femoral veins, and later from a pulmonary artery and the left ventricle. Radioimmunoassay of these samples revealed mean arteriovenous differences of -23% across the liver and -19% across the kidney. No significant differences were found across the lung or lower extremity. After termination of the infusion the disappearance rate of immunoreactive hormone in external jugular-venous blood was multiexponential: the predominant initial T 1/2 was 4, 6, and 8 min, and the terminal component was 60, 54, and 99 min. respectively, in 3 dogs.

Animals↗
PubMed1974

The amino-acid sequence of the amino-terminal 37 residues of human parathyroid hormone.

The sequence of the amino-terminal 37 residues of human parathyroid hormone has been established. The hormone used in these studies was isolated in highly purified form from parathyroid adenomata and was subjected to automated degradation in a Beckman sequencer. A high-sensitivity sequencing procedure employing (35)S-labeled phenylisothiocyanate of high specific activity as the coupling agent was used. The sequence obtained differs from that of bovine parathyroid hormone in three of the first 37 positions, and from that of porcine parathyroid hormone in two positions. A single human-specific residue was found (asparagine 16). The sequence obtained differs at three positions (22, 28, and 30) from the structure for human parathyroid hormone reported recently by Brewer et al. [(1972) Proc. Nat. Acad. Sci. USA 69, 3585-3588] and synthesized by Andreatta et al. [(1973) Helv. Chim. Acta, 56, 470-473] We have carefully reviewed our data, reported here in detail, on the sequence positions in dispute. We must conclude, on the basis of all available data, that the structure that we propose is the correct structure. The objective resolution of these discrepancies in structural analysis through further chemical and immunochemical studies is important, since synthesis of human parathyroid hormone, in which there is widespread interest for physiological and clinical studies, must be based on the correct sequence of the human hormone if the peptide is to be genuinely useful.

Adenoma↗
PubMed1972

Parathyroid Hormone in Human Plasma: IMMUNOCHEMICAL CHARACTERIZATION AND BIOLOGICAL IMPLICATIONS.

Antigenic recognition of four anti-bovine parathyroid hormone antisera was characterized by their reactivity with bovine hormonal fragments (1-34, 1-13, 14-34, 19-34, 53-84) and human hormone extracted from parathyroid adenomas. All antisera were found to have antibody populations which recognized more than one antigenic determinant and all antisera differed in their specificity and reactivity for the fragments of bovine hormone. By modification of two antisera, GP-1 and GP-133, by preincubation with excess concentrations of 1-34 or 53-84 fragments, antigenic recognition was restricted to defined regions of the hormonal sequence.When assays using these modified antisera were applied to the study of hormones extracted from glands, greater immunochemical similarities were seen between bovine and human parathyroid hormone using assays that were specific for the measurement of amino-terminal portions of the hormones than of the carboxy-terminal portions.When assays using these antisera were applied to the study of endogenous parathyroid hormone in human plasma, the immunoreactive hormone in the general circulation was shown to substantially lack an amino-terminal portion of the sequence of the intact hormone, including an antigenic determinant requiring all or some of the 14-19 region. This deletion accounts, at least in part, for the immunochemical heterogeneity of plasma parathyroid hormone in man. Radioimmunoassay of fractions of peripheral plasma subjected to gel filtration confirms that the dominant form of the immunoreactive hormone in the general circulation of man is a hormonal fragment that is totally devoid of amino-terminal reactivity. Because of this deletion, it can be concluded that most of the immunoreactive parathyroid hormone in the general circulation of man must be biologically inactive.

Journal Article↗
PubMed1968

Optimal antibiotic therapy in cholera.

Intravenous replacement of the diarrhoeal fluid and electrolyte losses to restore a physiological state of hydration is well established as the basis for successful management of cholera patients. The use of oral tetracycline as an adjunct in reducing the volume and duration of diarrhoea, as well as eradicating the vibrio from the gastrointestinal tract, has been proven beneficial. An optimal dose schedule has not been established previously, and clinical or bacteriological relapses have been generally reported. Chloramphenicol and sulfaguanidine have also been mentioned as adjuncts. The present report shows that 3 g or 4 g of tetracycline in one of 3 dose schedules were predictably efficacious. Chloramphenicol, while of benefit, was not as effective and sulfaguanidine was of little benefit compared with the tetracycline regimens.

Adolescent↗
PubMedDate not supplied

Properties of amino-terminal parathyroid hormone-related peptides modified at positions 11-13.

Biological properties of amino-terminal PTHrP analogues modified in the region 11-13 were examined using ROS 17/2.8 cells. [Leu11,D-Trp12,Arg13,Tyr36]PTHrP(1-36)amide had a 17-fold lower binding affinity for the receptor (apparent Kd: 5 x 10(-8) M) than [Tyr36]PTHrP(1-36)amide or [Arg11,13,Tyr36]PTHrP(1-36)amide (apparent Kd for both: 2 x 10(-9) M). Moreover, it is only a weak partial agonist despite completely inhibiting radioligand binding. [Leu11,D-Trp12,Arg13,Tyr36,Cys38]PTHrP(7-3 8) and PTHrP(7-34)amide had similar receptor affinities (apparent Kds: 5 x 10(-8) M and 8 x 10(-8) M), while that of [Nle8,18,Tyr34]bPTH(7-34)amide was more than 10-fold lower (apparent Kd: 2 x 10(-6) M). These changes in biological properties suggest that high affinity receptor binding requires both amino- and carboxyl-terminal domains of the PTHrP(1-36) sequence and/or intramolecular interactions which are impaired by the D-Trp substitution for Gly12.

Amino Acid Sequence↗
PubMedDate not supplied

In situ localization of PTH/PTHrP receptor mRNA in the bone of fetal and young rats.

We characterized cells that express parathyroid hormone/parathyroid hormone related peptide (PTH/PTHrP) receptor mRNA in bones of fetal and postnatal rats by in situ hybridization. During endochondral development of fetal bones, PTH/PTHrP receptor transcripts were highly expressed both in maturing chondrocytes and in osteoblasts in the periosteum and ossification center, but not in fully hypertrophic chondrocytes. Similar to the localization in the fetal bones, PTH/PTHrP receptor mRNA expression was highly localized to maturing chondrocytes in the articular cartilage and growth plate, and to osteoblasts in the femur of young rats. In both young and fetal rats, transcripts for Type X collagen were localized to hypertrophic chondrocytes, mostly between chondrocytes and bone cells both of which express PTH/PTHrP receptor mRNA. Transcripts for PTH/PTHrP receptors and alkaline phosphatase co-localized in the bone of young rats, but they did not co-localize in fetal bones at the early stages of endochondral ossification. These results show that PTH/PTHrP receptor mRNA is expressed in a cell-type and stage-specific manner during skeletal development.

Animals↗