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Biomedical subjects

J M Davidson

Publications and source records attributed to J M Davidson.

At least 181 records · Page 10Linked to original sources

Isolation of a collagen-binding fragment from fibronectin and cold-insoluble globulin.

Limited proteolytic cleavage of fibronectin and plasma cold-insoluble globulin with cathepsin D produced two major fragments. The smaller, Mr = 72,000 fragment bound to collagen and contained most of the cysteine in the molecule. This region contains intrachain disulfide bonds which maintain a conformation that is necessary for interaction with collagen. Cleavage of the intact protein and the 72,000-dalton fragment with plasmin localized the collagen-binding region in cold-insoluble globulin to a sequence of about 42,000 daltons. This region is located approximately two-thirds of the linear distance from the NH2 terminus of each chain in the dimeric molecule.

Amino Acids↗

NH2-terminal sequence of the chick proalpha1(I) chain synthesized in the reticulocyte lysate system. Evidence for a transient hydrophobic leader sequence.

Translation of chick procollagen mRNA in a reticulocyte lysate system yields a larger proalpha1(I) chain than is observed in vivo. The NH2-terminal sequence of this putative precursor, determined by automated radiosequencing, is Met-Phe-Ser-Phe-Val-X-Ser-Arg-Leu-Leu-Leu-Leu-Ile-Ala-Ala-X-X-Leu-Leu. This sequence closely resembles the transient hydrophobic leader (signal) sequences observed on most secreted proteins. When synthesized in the presence of microsomal membranes from dog pancreas, which contain signal peptidase activity, proalpha chains with the electrophoretic mobility of underhydroxylated procollagen polypeptides synthesized in vivo are produced. Estimates of the molecular weight of the NH2-terminal extension of the precursor suggest that the leader sequence may be longer than those commonly found in precursors of secreted proteins.

Amino Acid Sequence↗

Priming action of estrogen: minimum duration of exposure for feedback and behavioral effects.

The minimum duration of the centrally-mediated "priming" effects of estrogen on "positive feedback" release of LH and sexual receptivity (lordosis) was studied. Spayed rats were given Silastic implants of estradiol followed 3 days later by an s.c. injection of progesterone and testing. 30-min implantation of preincubated estradiol capsules sufficed for behavioral responses, but did not stimulate the LH surge. When the capsules were not preincubated, however, LH surges did occur, presumably because of the greater release of estrogen. It is concluded that the minimum duration of the estrogen priming effects is considerably less than the period of natural preovulatory surge of estrogen at proestrus.

Animals↗

Effects of androgen on sexual behavior in hypogonadal men.

Despite the widespread use of androgen in the treatment of hypogonadal men, its efficacy in restoring sexual behavior to hypogonadal patients has not been established in appropriately controlled behavioral studies. Accordingly, testosterone enanthate or vehicle was injected once every 4 weeks im in a double blind experiment. The subjects were six adult males, aged 32-65 yr, two with gonadal failure and four with secondary hypogonadism. Two doses of testosterone (100 and 400 mg) were administered for approximately 5 months, with the treatments varied at random within and among subjects. Details of sexual activity and experience were followed by the use of daily logs. Frequencies of erections, including nocturnal erections and coitus, showed significant dose-related responses to androgen treatment which closely followed the fluctuations in the circulating testosterone level. As indicated by the Profile of Mood States test, behavioral responses did not appear to be mediated by changes in mood. We concluded that the stimulatory effects of testosterone on sexual activity are rapid, reliable, and not due to a placebo effect. To maintain plasma testosterone and adequate sexual function within normal levels, even high doses of testosterone enanthate should be given no less frequency than once every 3 weeks.

Adult↗

Organization of extracellular proteins on the connective tissue cell surface: relevance to cell-matrix interactions in vitro and in vivo.

A model has been developed that proposes a cell surface-associated protein meshwork, composed in part of fibronectin and collagen, for a connective tissue cell attached to a substratum. In support of this model are the observations that collagen and fibronectin interact and that these proteins are similarly distributed on the fibroblast cell surface. We suggest that this external meshwork interacts directly or indirectly with the internal cytoskeleton and with the extracellular matrix and thereby mediates several cellular properties, including adhesion, shape, and motility. Loss of cell surface fibronectin as a result of viral transformation, or due to treatment of normal cells with tunicamycin, an inhibitor of protein glycosylation, may contribute to the reduced adhesion and altered morphology observed in these circumstances. We therefore predict that the changes in these properties observed with virally transformed cells, mitotic cells, and cells treated with proteolytic enzymes are related to alterations in the external protein meshwork.

Animals↗

Adrenocortical activity during meditation.

We studied acute plasma cortisol and testosterone concentration changes during the practice known as "transcendental meditation" (TM) and during control rest. Three groups of normal, young adult volunteers were studied: a group of controls, these same controls restudied as practitioners after 3 to 4 months of TM practice, and a group of long-term, regular TM practitioners (3 to 5 years of practice). No change was found in controls during rest. Cortisol declined, but not significantly, in restudied controls, while cortisol decreased significantly in long-term practitioners during meditation and remained somewhat low afterward. No change in testerone concentration was noted during either rest or TM. Apparently, the practice of TM becomes associated with psychophysiologic response(s) which acutely inhibit pituitary-adrenal activity.

Adrenal Cortex↗

A computer system for clinical microbiology.

The Department of Clinical Microbiology at St Thomas' Hospital has been producing bacteriological reports on a computer for more than three years and is now producing some 2300 reports per week. The system is operated entirely by laboratory staff without special training, and involves the use of optical mark reader (OMR) forms as worksheets, automatic validation and release of most reports, the use of local terminals, and scrutiny of reports by pathologists using a visual display unit. The OMR worksheet records not only the final result but also most of the tests and observations made on the samples; it is the only working document used by technicians. One specialist clinic submits its laboratory requests on an OMR form, which is subsequently used to record the results. The reports are printed and also filed in the computer to produce analyses for hospital, laboratory, and clinical management.

Computers↗

Effects of lesions in various structures of the suprachiasmatic-preoptic region on LH regulation and sexual behavior in female rats.

Lesions of the suprachiasmatic nuclei (SCN) completely eliminated phasic LH release in ovariectomized rats as measured by the positive feedback response to estradiol benzoate (EB)/progesterone or the response to mating. Basal LH levels and the negative feedback response to EB were not affected. Lesions of the medial preoptic area (MPOA) or bed nucleus-dorsal MPOA also inhibited phasic LH release in ovariectomized rats as measured by positive feedback. However, the inhibition was not complete if there was no damage to the SCN, and the degree of inhibition was correlated with the size ofthe lesion. Basal LH levels and negative feedback were not significant affected. It is suggested that both the SCN and MPOA are involved in phasic LH release, the former in its role as a neural regulator of circadian rhythms and the latter as part of a diffuse system possibly including estrogen-sensitive and/or LH-RH neurons. Sexual behavior (lordosis) in hormone-primed, ovariectomized rats was not significantly affected by lesions of any structure in the suprachiasmatic-preoptic region.

Animals↗

Neuroendocrine mechanisms mediating the suppression of circulating testosterone levels associated with chronic stress in male rats.

Neuroendocrine mechanisms involved in the reduction of testosterone (T) levels induced by the chronic surgical stress of s.c. gauze implantation were investigated in male rats. The reduction resulted from a decline in T secretion and not an increase in clearance of the hormone from the circulation. In most cases, the decrement was accompanied by a reduction in LH levels, indicating that decreased LH stimulation is the primary factor mediating the drop in T levels. The suppressive effect of surgical stress on LH and T levels was apparently not mediated by the pituitary-adrenal system.

Adrenal Glands↗

Hormonal response to stress in the squirrel monkey (Saimiri sciureus).

The pituitary-adrenal and gonadal responses following stress were evaluated in the squirrel monkey. Plasma levels of cortisol (CS), ACTH and testosterone (T) were determined during a 4-h period following the combined stress of capture and ether anesthesia. The results indicated that the squirrel monkey manifests higher basal levels of steroids than typically found in other mammals. The endocrine response following stress was biphasic, involving an initial elevation and subsequent decline in hormone levels. Males manifested significantly higher plasma levels of CS and T and lower plasma levels of ACTH than did females.

Adrenal Glands↗

Intermediates in the conversion of procollagen to collagen. Evidence for stepwise limited proteolysis of the COOH-terminal peptide extensions.

Intermediates in the conversion of procollagen to collagen were isolated from radioactively labeled chick cranial bones by ion-exchange chromatography. Cleavage of these proteins with vertebrate collagenase revealed that each of the several forms of these intermediates lacked NH2-terminal but retained COOH-terminal extensions. The chain composition of each intermediate was resolved by two-dimensional slab gel electrophoresis. The intermediates differed from each other in having sustained cleavages in zero, one or two pcalpha chains. The relative proportions of intermediates with different intact pcalpha chains, observed in conversion of procollagen, have enabled us to construct a detailed model of the stepwise limited proteolysis of procollagen.

Amino Acids↗

Effects of testosterone implants and hypothalamic lesions on luteinizing hormone regulation in the castrated male rat.

The effects of intrahypothalamic and subcutaneous implants of testosterone (T) and those of hypothalamic lesions on resting levels of circulating LH and pituitary responsiveness to exogenous LHRH were studied in castrated male rats to elucidate hypothalamic and pituitary regulation of LH secretion. Two hundred mug implants of testosterone propionate (TP) in the median eminence region suppressed plasma LH titers before evidence of direct inhibition of pituitary function (as indicated by testing with LHRH) was found. Such implants release appreciable amounts of T into the peripheral circulation in the immediate post-operative period, and SC Silastic (constant release) capsules containing T have similar effects. The findings suggest that, regardless of the site of implant, the initial negative feedback inhibition of LH by T is not dependent on direct action at the pituitary levels but rather appears to be a hypothalamic effect. In the days following exposure to hypothalamic or peripheral implantation of T, however, a progressively developing decline in the response to exogenous LHRH was observed. In order to determine whether this effect results from suppression of endogenous LHRH release, the median eminence-arcuate region was destroyed to remove the source of LHRH. In these animals, the suppression of plasma LH was evident on the first day after the lesion, but pituitary responsiveness to LHRH was unaffected until after one week. When Sialastic capsules were implanted SC into lesioned animals, a more rapid (less than 1 week) inhibition of pituitary responsivity ensued. Suprachiasmatic lesions did not affect basal LH secretion or pituitary responses to LHRH. The data provide evidence for a dual feedback action of T on LH in castrated male rats: an initial inhibitory effect presumably due to hypothalamic inhibition (commencing at around 6h after hypothalamic of SC implantation of T), and a subsequent suppression of pituitary responisveness (after one day) presumably due to direct action of T on the pituitary. In addition to these phenomena, findings in rats bearing median eminence-arcurate lesions suggest that the removal of endogenous LHRH by itself leads to an eventual decline in pituitary responsiveness (greater than one week postoperatively).

Animals↗