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Biomedical subjects

J L Borges

Publications and source records attributed to J L Borges.

At least 37 records · Page 2Linked to original sources

Biological activity of a growth hormone-releasing factor secreted by a human tumor.

A substance released by a pancreatic islet cell tumor induced signs and symptoms of acromegaly in a young woman. The culture medium in which the tumor was placed after resection was added to rat anterior pituitary cells and incubated in vitro. Both newly synthesized and total rat growth hormone (GH) release as well as cellular cyclic AMP accumulation were stimulated in a dose-dependent manner by the tumor medium. Coincubation with somatostatin blocked these effects. The increase of cyclic AMP preceded the enhanced GH release, indicating that cyclic AMP may be a second messenger for the tumor factor(s). Neither prolactin nor luteinizing hormone secretion was affected by the tumor medium. When measured by a perfused cell column apparatus, there was a rapid and dramatic release of GH by the dispersed rat pituitary cells during a 2.5-, 10-, and 40-min pulse of tumor medium; both the onset and termination of the GH response reached maximal or control values, respectively, within 5 min. Pretreatment of the tumor medium with pepsin markedly attenuated the tumor medium activity, indicating the peptide nature of the factor(s). Finally, ultrastructural analysis indicated that the somatotrophs were degranulated by the tumor medium, whereas there was no similar effect apparent on the mammotrophs. Whether this tumor polypeptide is identical to native hypothalamic GH-releasing hormone remains to be proved.

Adult↗

Ca+2 dependence of gonadotropin-releasing hormone-stimulated luteinizing hormone secretion: in vitro studies using continuously perifused dispersed rat anterior pituitary cells.

A continuously perifused dispersed rat anterior pituitary cell system was used to determine the importance of calcium (Ca+2) on the release of LH by GnRH. In response to continuous exposure to 10 nM GnRH, LH was released in a biphasic fashion; arbitrarily, phase I was defined as being the LH released during the initial 40 min and phase II as the subsequent release. Withdrawal of Ca+2 from the perifusion medium during phases I or II of LH release led to a rapid inhibition of the LH secretion. Cells were exposed to GnRH for 2.5 min, washed with medium for 30 min, and then reexposed to GnRH for 30 min. This sequence was repeated 1 h later under identical conditions in the presence of a Ca+2 blocking agent; D600 (20 or 100 microM). D600 inhibited both the 2.5- and the 30-min GnRH-stimulated LH release. The results were expressed as the ratio obtained by dividing the total LH released during the second GnRH exposure (either 2.5 or 30 min) by the total LH released during the respective initial GnRH exposure of same duration. For the cells perifused with 20 microM D600 the ratios +/- SE (D600 vs. control) were 0.48 +/- 0.06 vs. 1.28 +/- 0.13 (P = 0.0001) and 0.29 +/- 0.05 vs. 1.01 +/- 0.08 (P less than or equal to 0.0001) for the 2.5- and 30-min exposures, respectively. For the cells perifused with 100 microM D600 the ratios +/- SE (D600 vs. control) were 0.18 +/- 0.05 vs. 1.28 +/- 0.13 (P less than or equal to 0.00001) and 0.12 +/- 0.03 vs. 1.01 +/- 0.08 (P = 0.002) for the 2.5- and 30-min exposures, respectively, revealing an even more profound inhibitory effect of D600 on GnRH stimulated LH secretion. Our data both confirm previous reports that Ca+2 is involved in LH release and demonstrate that Ca+2 is an essential requirement during both phases of GnRH-stimulated LH release in perifused dispersed rat anterior pituitary cells.

Animals↗

Human pancreatic growth hormone-releasing factor-40 (hpGRF-40) allows stimulation of GH release by TRH.

The effects of synthetic hpGRF-40 on GH release from continuously perifused male rat anterior pituitary cells were studied. Pulses (2.5 min) of hpGRF-40 stimulated GH release in a log-linear dose response relationship: concentrations of 0.03, 0.1, 0.3, 1, 3, 10, 30 and 100 nM given in a random order elicited a GH response above baseline of 1.2 +/- 0.3, 2.4 +/- 0.4, 2.8 +/- 0.2, 4.3 +/- 0.2, 6.2 +/- 0.7, 7.0 +/- 1.0, 8.7 +/- 1.7, and 10.8 +/- 0.8 micrograms/10(7) cells (mean +/- SEM; n = 3; r = 0.93), respectively. During a 5-h hpGRF-40 infusion, GH stimulation peaked within 5 min and waned to near baseline by the end of the fifth h. The integrated GH responses to 0.03, 0.1 and 0.3 nM hpGRF-40 were 37.6 +/- 7.4, 52.9 +/- 8.5, and 66.15 +/- 8.2 micrograms/10(7) (mean +/- SEM; n = 3; r = 0.72), respectively. The interaction of TRH and hpGRF-40 in the control of GH secretion was studied to investigate the mechanism of the "paradoxical" TRH stimulation of GH release associated with GH excess states in humans. Dispersed cells were perifused with either 100 nM TRH for 0.5 h, 5 nM hpGRF-40 for 4 h, or 5 nM hpGRF-40 for 4 h, to which a 0.5 h pulse of TRH was added at 2 h. GH levels did not change significantly in the presence of TRH alone. When TRH was added to the ongoing hpGRF-40 perifusion, GH release increased from 1.4 +/- 0.06 to 4.0 +/- 1.0 micrograms/min.10(7) cells (n = 4; P = 0.03). Thus, dispersed pituitary cells are highly sensitive to very low concentrations of hpGRF-40 administered as both an acute pulse and as a tonic infusion. When the cells are exposed to a maximal concentration of hpGRF-40 (i.e. 5 nM), TRH becomes a secretagogue at the pituitary level, thus suggesting the site and mechanism of the "paradoxical" GH response to TRH observed in some acromegalics.

Animals↗

Intranasal administration of human pancreatic tumor GH-releasing factor-40 stimulates GH release in normal men.

Human pancreatic tumor GH releasing factor-40 (hpGRF-40) selectively stimulates GH secretion in normal men and in some adult patients with GH deficiency. As the latter finding suggests that some children with GH deficiency may benefit from therapy with hpGRF-40 or an analogue, we investigated the effect of hpGRF-40 administered intranasally on GH release. Six normal men were given hpGRF-40 (30 ug/kg; test day) or an equivalent volume of vehicle alone (control day) at 0900 h. Immunoreactive GH was measured in serum obtained at intervals between 0800-1200 h. Mean (+/- SEM) integrated serum levels of GH (ng/ml/h) prior to and following administration of vehicle were not different (1.27 +/- 0.57 vs 0.87 +/- 0.28; p = 0.54). However, following hpGRF-40 administration, GH levels increased significantly (0.53 +/- 0.03 vs 2.88 +/- 0.75; p = 0.022). Peak levels of serum GH were detected within 30 min following hpGRF-40. Except for mild burning of the nasal mucosa reported by one subject, no side effects were noted. We conclude that, if hpGRF-40 or an analogue is shown to be useful in the treatment of some children with GH deficiency, the intranasal route of administration may be utilized and will be more acceptable for chronic therapy than intravenous, intramuscular, or subcutaneous injection.

Administration, Intranasal↗

Acanthosis nigricans, hirsutism, insulin resistance and insulin receptor defect.

A 24-year-old negress with the triad of acanthosis nigricans, hirsutism associated with polycystic ovaries and insulin resistance is reported. Metabolic studies were done 3 years after a bilateral ovarian wedge resection. Partial remission of the hirsutism and return of menstrual cycles occurred after surgery. Extreme resistance to endogenous and exogenous insulin was observed. Three studies of insulin receptors on circulating red blood cells (RBC) showed abnormal inhibition-competition curves, characterized by increased percentage insulin binding at higher unlabelled insulin levels. Scatchard plots suggested an apparent increase in the number of low affinity receptors. Despite the changes in receptor-insulin interaction, the defect does not seem to explain the insulin resistance since binding of insulin to a target tissue (RBC) appeared to be quantitatively normal at physiological insulin levels, suggesting a simultaneous post receptor defect.

Acanthosis Nigricans↗

Modified Woodward procedure for Sprengel deformity of the shoulder: long-term results.

Sprengel deformity of the shoulder is characterized by elevation and medial rotation of the inferior pole of the scapula. Surgical treatment is recommended in significantly involved patients to improve cosmetic appearance and function of the involved shoulder. We report long-term results of a Woodward procedure modified by excision of the prominent superomedial border of the scapula for correction of this deformity in 15 patients. Preoperatively, the total abduction of the shoulder averaged 115 degrees, and on follow-up the abduction had improved to an average of 150 degrees. In all patients except one, there was marked improvement in appearance as assessed on Cavendish scale. All patients except two had achieved skeletal maturity at the last follow-up. Eighty-six percent of patients expressed satisfaction with operative results. Our data support the concept that correction achieved by a modified Woodward procedure is not altered by growth and is maintained beyond skeletal maturity.

Adolescent↗

A radiolucent spine frame: a modification of the Relton-Hall spine frame.

A radiolucent spine frame for obtaining intraoperative spine radiographs while performing surgery for scoliosis has been designed at the Alfred I. duPont Institute and is described here. This frame, constructed of strong radiolucent plastic compounds, is easy to use and maintain.

Child↗

Köhler's bone disease of the tarsal navicular.

Fourteen patients with Köhler's bone disease of the tarsal navicular in 16 feet were reviewed at an average follow-up of 31 years 6 months after diagnosis. The type and length of treatment did not affect the final outcome; however, short-leg cast immobilization did decrease the duration of symptoms. Two feet were symptomatic at the time of follow-up: one foot had a talocalcaneal coalition with degenerative changes, and the other foot had a large accessory navicular. Both of these feet were rated as having a fair result. The remaining 12 feet were classified as having a good result. Patients with Köhler's bone disease can be expected to have a normal foot at adulthood. Should the patient become symptomatic, other causes of foot pain should be investigated.

Child↗

[Totally implantable vascular reservoir for chemotherapy: initial experience].

The authors present their experience with the totally implanted vascular reservoirs for chemotherapy. Thirty-one reservoirs were implanted in 29 patients. Complications were observed in 19.3% of the cases imposing the removal of 12.9% of them. No reservoir have been lately removed because of infection or obstruction. Based on their results, the authors conclude that the totally implanted reservoir is extremely helpful for patients submitted to chemotherapy for long periods.

Adolescent↗

[Cerebral toxoplasmosis in a kidney transplant patient. A clinical case and review of the literature].

Infection caused by Toxoplasma gondii is a frequent event in Portugal. When this occurs in immunocompetent individuals it is rarely a matter of concern; the contrary occurs with immunosuppressed patients or in pregnancy. Transplant patients are treated with immunosuppressive drugs which mainly disturb their mechanisms of cellular immunity, and that opens the way to infections by opportunistic intracellular microorganisms. We recently treated a renal transplant patient who suffered from cerebral toxoplasmosis, and this provided an opportunity for a review of the other 20 patients reported in medical literature to date.

Adult↗