Search PubMed⌕ Search

Biomedical subjects

J W Jacobs

Publications and source records attributed to J W Jacobs.

At least 127 records · Page 7Linked to original sources
PubMed1987

Parathyroid hormonelike protein from human renal carcinoma cells. Structural and functional homology with parathyroid hormone.

A variety of solid tumors secrete proteins that are immunochemically distinct from parathyroid hormone (PTH) but activate PTH-responsive adenylate cyclase. Such PTH-like proteins have been proposed as mediators of the hypercalcemia and hypophosphatemia frequently associated with malignancies. We purified to apparent homogeneity a PTH-like protein with a molecular weight of 6,000, that is produced by human renal carcinoma cells. The amino-terminal sequence of the PTH-like protein and that of human PTH were found to display at least five identities in the first 13 positions. The purified protein bound to PTH receptors, activated adenylate cyclase in renal plasma membranes, and stimulated cAMP formation in rat osteosarcoma cells. The PTH-like protein reproduced two additional effects of PTH, stimulation of bone resorption in fetal rat limb bone cultures and inhibition of phosphate uptake in cultured opossum kidney cells. These properties are consistent with a role for PTH-like proteins as mediators of the syndrome of malignancy-associated hypercalcemia.

Carcinoma, Renal Cell↗
PubMed1987

Atrial natriuretic factor receptors.

All of the actions of atrial natriuretic factor (ANF) can be explained on the basis of ANF's interaction with specific receptors on the plasma membrane of cells in target tissues. These receptors have been identified. Binding to these receptors by ANF is time dependent and specific and occurs with high affinity. Numerous analogues of ANF have been synthesized, and in general, their affinity for ANF receptors corresponds closely to their potency in vitro and in vivo. Considerable progress has been made in physicochemically characterizing ANF receptors by photoaffinity labeling and affinity cross-linking techniques.

Animals↗
PubMed1986

Selective chemical catalysis by an antibody.

The immunoglobulin MOPC167, which binds the transition state analog p-nitrophenylphosphorylcholine with high affinity, catalyzed the hydrolysis of the corresponding carbonate 1. MOPC167 catalysis displayed saturation kinetics with catalytic constant (kcat) = 0.4 min-1 and Michaelis constant (Km) = 208 microM, showed substrate specificity, and was inhibited by p-nitrophenylphosphorylcholine. The rate of the reaction was first order in hydroxide ion concentration between pH 6.0 and 8.0. The lower limit for the rate of acceleration of hydrolysis by the antibody above the uncatalyzed reaction was 770. This study begins to define the rules for the generation of catalytic antibodies.

Antibodies↗
PubMed1986

Divorce and child custody resolution: conflicting legal and psychological paradigms.

The resolution of divorce conflict, especially the determination of child custody, is a major social policy concern of both the legal and mental health professions. The differences between the adversarial and mediation legal approaches parallel the phenomenological/psychoanalytic and the family therapy models of the mental health field. A philosophical and practical relationship exists uniting the adversarial and phenomenological/psychoanalytic traditions, while mediation is strongly aligned with family systems theory and therapy. Each paradigm offers American families alternative methods of resolving disputes. A greater synthesis of paradigms is required to give effective help to divorcing couples and their children.

Adult↗
PubMed1985

Calcitonin is a substrate for oligosaccharyltransferase in vitro.

Tumor-derived, large molecular weight forms of calcitonin, have been postulated to result from glycosylation of the hormone. To address this question we have examined the glycosylation of calcitonin in vitro and in cultured thyroidal C-cells. We show that native, undenatured calcitonin is an active substrate for oligosaccharyltransferase and that glycosylation of calcitonin by the transferase is inhibited by tunicamycin. In addition, calcitonin is an effective competitive inhibitor of the glycosylation of a known peptide substrate for oligosaccharyltransferase. Pulse-labelling of cultured medullary thyroid carcinoma cells with [3H]-mannose indicate that detectable quantities of carbohydrate-containing forms of calcitonin are produced in these cells. These data indicate that glycosylation of calcitonin is one mechanism whereby tumor cells could produce higher molecular weight forms of the hormone.

Animals↗
PubMed1985

Biosynthesis of calcitonin by human lung cancer cells.

The ectopic secretion of calcitonin (CT) by a wide variety of nonthyroidal human tumors has been studied by CT RIA, but little information is available concerning the biosynthesis of CT in these tumors. In the present study, a human lung cancer cell line (BEN), secreting high mol wt forms of CT was investigated to characterize the CT gene products synthesized. When conditioned medium from BEN cells was chromatographed through a Bio-Gel P-30 column, larger species of immunoreactive CT were detected with mol wt of approximately 8,000 and 18,000. Little, if any, CT of 3,500 mol wt was detected. To examine CT gene products produced in BEN cells, poly A+ RNA was isolated from BEN cells and subjected to cell-free translation assays and DNA/RNA hybridization assays. In the wheat germ cell-free translation assay, a single BEN cell product which migrated on sodium dodecyl sulfate-polyacrylamide gels with an apparent mol wt of 17,000 could be specifically immunoprecipitated with CT antisera. A similar sized CT-related translation product is produced in wheat germ assays programmed by mRNA prepared from human medullary thyroid carcinomas. In DNA/RNA hybridization assays, a single BEN cell mRNA species of 1,000 base pairs, identical in size to human thyroidal CT mRNA, hybridized to a radiolabeled CT cDNA probe. Hybridization of the CT cDNA probe with BEN cell mRNA was confirmed by RNA dot blot hybridization and cytoplasmic RNA blotting procedures. These results indicate that larger mol wt forms of CT secreted by BEN cells are derived from a translation product and a mRNA which are of similar, if not identical, size as CT gene products produced in human thyroidal tissues. The inability of lung tumor cells to process the CT precursor to calcitonin of 3,500 mol wt may reflect a lack of specific prohormone processing enzymes in these tumor cells or may be due to structural polymorphism in the CT precursor expressed in the lung cells.

Calcitonin↗
PubMed1985

Constitutive biosynthesis of bone Gla protein in a human osteosarcoma cell line.

A human osteosarcoma cell line derived from cells obtained from a patient with Paget's disease is shown to synthesize and secrete bone Gla protein (BGP); (osteocalcin), a noncollagenous bone matrix protein. Using a human BGP-specific RIA, we show that the human osteosarcoma cells synthesize significant amounts of BGP without any prior induction of BGP synthesis by 1,25-dihydroxyvitamin D. After specific immunoprecipitation of poly-A+ RNA in vitro translation products with antibodies to BGP, we found that BGP is synthesized as a precursor with an apparent mol wt of 13.5K, as demonstrated on 15% sodium dodecyl sulfate-polyacrylamide gels. Finally, pulse labeling of the osteosarcoma cells with [3H]proline reveals that the cells synthesize mature BGP of 12,000 mol wt as well as a higher mol wt precursor (13,500) of the protein.

Autoradiography↗
PubMed1985

Identification of a messenger ribonucleic acid fraction in human prostatic cancer cells coding for a novel osteoblast-stimulating factor.

Prostatic cancer is frequently associated with new bone formation although the tumor-derived factors responsible for changes in bone cell function have not been identified. We have examined the synthesis of osteoblast-stimulating factors in a cultured human prostatic cancer cell line (PC-3) and show that conditioned medium from PC-3 cells stimulate mitogenesis and alkaline phosphatase in cells with the osteoblast phenotype (cultured rat osteosarcoma cells) and collagen synthesis in fetal rat calvaria. In order to characterize tumor-derived gene products which stimulate cells of the osteoblast phenotype messenger RNA (mRNA) was isolated from PC-3 cells and microinjected into Xenopus laevis oocytes. mRNA-directed translation products which were secreted into the oocyte medium were collected and assayed for a number of osteoblast stimulating properties. Translation products from PC-3 mRNA-injected oocytes stimulated division of cultured osteosarcoma cells by 8-fold and increased DNA synthesis as measured by incorporation of [3H]thymidine into these cells. In addition, tumor-derived translation products stimulated the production of alkaline phosphatase activity, a marker enzyme for bone formation, in cultured osteosarcoma cells. Oocytes injected either with water or with mRNA from a tumor not associated with bone formation were devoid of these activities. Total mRNA from the human prostatic cancer cells was then denatured and fractionated by size by agarose gel electrophoresis. When individual fractions of mRNA were eluted from the gel, translated in Xenopus oocytes, and the secreted translation products were tested for alkaline phosphatase-stimulating activity on osteoblast-like cells, the majority of the activity could be recovered in a mRNA fraction which was approximately 1800 bases in length. These results indicate that the PC-3 prostatic cancer cell line synthesizes a mRNA of approximately 1800 bases which codes for a heretofore unrecognized osteoblast-stimulating factor.

Alkaline Phosphatase↗
PubMed1984

Amino acid sequence of bovine heart coupling factor 6.

The amino acid sequence of bovine heart mitochondrial coupling factor 6 (F6) has been determined by automated Edman degradation of the whole protein and derived peptides. Preparations based on heat precipitation and ethanol extraction showed allotypic variation at three positions while material further purified by HPLC yielded only one sequence that also differed by a Phe-Thr replacement at residue 62. The mature protein contains 76 amino acids with a calculated molecular weight of 9006 and a pI of approximately equal to 5, in good agreement with experimentally measured values. The charged amino acids are mainly clustered at the termini and in one section in the middle; these three polar segments are separated by two segments relatively rich in nonpolar residues. Chou-Fasman analysis suggests three stretches of alpha-helix coinciding (or within) the high-charge-density sequences with a single beta-turn at the first polar-nonpolar junction. Comparison of the F6 sequence with those of other proteins did not reveal any homologous structures.

Adenosine Triphosphatases↗
PubMed1984

Implantation of a strip of fascia in the venous wall.

In 12 adult rabbits, according to the pull through technique a strip of muscular fascia was implanted in the wall of the femoral vein. Of 11 of these animals, sacrificed at intervals varying from 0 days to 3 months after the operation, the area of implantation was removed and histologically studied. Two cases showed wound infection and one case, moreover, venous thrombosis. Among the other 9 cases, in 2 specimens the end of the strip was found to lie within the venous wall, while in the remaining 7 specimens the strip protruded into the venous lumen. In the latter cases, the strip proved to be firmly attached to the venous wall within 4 days; within the same time the protruding part of the strip became completely covered by venous endothelial cells. Loose connective and fatty tissue adherent to the strip only disappeared, when the end of the strip freely floated in the streaming blood.

Animals↗
PubMed1983

Absence of parathyroid hormone messenger RNA in nonparathyroid tumors associated with hypercalcemia.

We used a sensitive and specific hybridization assay that detects evidence of parathyroid hormone synthesis in tumors to investigate whether this hormone mediates the hypercalcemia of malignant disease. The assay uses radiolabeled, cloned parathyroid hormone DNA to hybridize selectively with parathyroid hormone messenger RNA. We assayed 13 human and 3 animal tumors of diverse cell origins that are frequently associated with the hypercalcemia of cancer. Five of the human tumors were obtained from patients known to be hypercalcemic at the time of tumor excision, two were from normocalcemic patients, and six were from patients with breast cancer whose serum calcium levels were unknown. Messenger RNA was prepared from cultured cell lines or tumors; active RNA fractions were hybridized with either human or bovine cloned parathyroid hormone DNA that had been labeled to a high specific activity with [32P]nucleotide. We were unable to detect parathyroid hormone RNA transcripts in any of the tumors. Our results indicate that parathyroid hormone rarely, if ever, causes hypercalcemia in malignant disease.

Adult↗
PubMed1983

Treatment of divorcing fathers: social and psychotherapeutic considerations.

The author summarizes the psychotherapeutic issues most frequently encountered in his crisis treatment of 16 divorcing fathers for whom divorce was fundamentally a child-centered crisis. Fear and guilt over separation from children and wife, outrage and disappointment with the legal system, anxiety about the social and sexual readjustment to single life, and the need to develop strategies for continued child contact were most prevalent. The author's suggestions for the management of these issues include the therapist's familiarization with divorce as it affects and is influenced by intrapsychic, interpersonal, familial, and legal systems.

Adjustment Disorders↗
PubMed1983

Characterization and localization of calcitonin messenger ribonucleic acid in rat thyroid.

DNA/RNA hybridization assays have been used to examine calcitonin (CT) RNA production in normal rat thyroids. A cloned CT cDNA which codes for the entire rat CT precursor was radiolabeled to a high specific activity and used in hybridization assays to explore 1) the sizes and relative quantities of CT RNA extractable from thyroids obtained from rats of differing ages; 2) the effect of calcium on the in vitro production of CT RNA in rat thyroid tissue slices; and 3) the localization, by hybridization histochemistry, of C cells in rat thyroid that contain CT RNA. The relative concentrations of CT RNA, per microgram of total thyroid RNA, increased remarkably with age, with 14-month-old rats having approximately 14-fold elevated concentrations of thyroidal CT RNA compared to 19-day-old rat fetuses. Of interest was the finding that a second larger species of CT RNA is only evident in thyroids obtained from 14-month-old animals. The effect of calcium on the in vitro production of CT RNA in rat thyroid tissues was studied over 3- and 6-h periods. Although previous investigations have shown that calcium causes an immediate and linear increase in CT secretion from the thyroid gland, no net increase vs. controls in the amount of CT RNA extractable from calcium-stimulated thyroid slices was observed. Finally, hybridization histochemistry, a technique that identifies in fixed tissue sections those areas that contain a specific mRNA population, was used to localize C cells in the thyroid containing CT RNA. Specific areas of rat thyroid hybridized with the CT cDNA probe and autoradiography revealed these areas to be parafollicular cells located only in the central portion of the thyroid lobes, mRNA quantities detected by hybridization histochemistry showed little variation over the central area of the thyroid, indicating the C cells in this region of the thyroid are accumulating CT RNA at approximately the same rate.

Animals↗
PubMed1982

Somatostatin-28 encoded in a cloned cDNA obtained from a rat medullary thyroid carcinoma.

We have constructed and cloned in bacteria complementary DNAs derived from a transplantable rat medullary thyroid carcinoma. Using a hybridization probe encoding an anglerfish islet pre-prosomatostatin, a precursor of the tetradecapeptide somatostatin, we have identified and isolated a clone containing a 400-base pair complementary DNA encoding most of the rat carcinoma pre-prosomatostatin. The amino acid sequence of the tetradecapeptide somatostatin and of the amino-terminally extended form, somatostatin-28 was deduced from the nucleotide sequence of the complementary DNA. Somatostatin-28 was found at the COOH terminus of a polypeptide of at least 80 amino acids indicating that somatostatin-28 arises by cleavage from a large precursor. The sequences of somatostatin-28 and somatostatin-14 are strictly conserved between the rat and other mammals. Such conservation of these sequences indicates strong selective pressures during evolution to maintain the sequence and suggests that somatostatin-28 may serve some essential biologic functions apart from, or in addition to, the important regulatory actions of somatostatin-14. Additionally, we found a high degree of homology in the amino acid sequences of the NH2-terminal extension peptides in the anglerfish islet and the rat carcinoma pre-prosomatostatins pointing further to a possible biologic function of these extension peptides.

Amino Acid Sequence↗