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Biomedical subjects

R Merrell

Publications and source records attributed to R Merrell.

18 recordsLinked to original sources

Parathyroid adenoma in a cancer center patient population.

The association of parathyroid adenoma and antecedent events or relationships was examined retrospectively in 103 patients with parathyroid adenoma drawn from a cancer institute patient population. Patients were divided into two study groups by the referral pattern-intramural or community. The major contrast between the two groups was that the intramural patients had cancer diagnoses. The factors of advanced age, female gender, and prior regional irradiation appeared to be associated with the development of parathyroid adenoma. An interrelationship of incidental cancer and parathyroid adenoma, however, was not supported. Breast and differential thyroid cancers were most frequently associated with parathyroid adenoma, but age, gender, and irradiation were bias influences.

Adenoma

Transplantation of adrenal medullary tissue to caudate nucleus using stereotactic techniques.

Stereotactic techniques were used to transplant adrenal medullary tissue to the head of the right caudate nucleus in 12 patients with Parkinson's disease. No significant lasting complications were seen. All patients had an initial improvement. 11 of the 12 patients remain improved over their preoperative condition after 6-18 months, 3 with good results and 9 with only modest improvement. At 6 months, the mean Schwab and England score had improved from 59.2 +/- 18.8 preoperatively to 75.8 +/- 15.1 (p less than or equal to 0.01) and the mean Hoehn and Yahr scale had improved from 3.42 +/- 0.90 to 2.92 +/- 0.63 (p less than or equal to 0.01).

Adrenal Medulla

Cyclosporine absorption in apancreatic dogs.

The plasma concentration time course of orally administered cyclosporine was studied in apancreatic dogs with established islet autografts and compared with that in normal control dogs. After oral administration of cyclosporine (20 mg/kg), blood samples were collected at 0, 1, 2, 3, 4, 6, 8, and 24 hours, and the plasma cyclosporine concentrations were measured by radioimmunoassay. The plasma level of cyclosporine increased promptly in both groups after dosing. Peak plasma concentrations ranged from 435 to 1,542 ng/ml and were attained at between 2 and 6 hours in the apancreatic dogs, and concentrations from 602 to 4,414 ng/ml were attained at between 1 and 6 hours in the control dogs. Even though there was substantial variation among animals, the plasma concentration curve of the apancreatic group was quite comparable with that of the control group. The Student's test for unpaired data failed to show any significant differences over the time course. Area under the concentration-time curves, maximum concentration, and times of peak concentration were calculated. These data demonstrated the capacity of apancreatic dogs with islet autografts to absorb cyclosporine when they are stable, nutritionally normal, and have full endocrine reconstitution.

Absorption

Ventral herniorrhaphy aided by pneumoperitoneum.

Twenty-four patients with large abdominal incisional hernias were alternately treated with preoperative pneumoperitoneum. The insufflation was performed on an outpatient basis each day for approximately one week prior to operation. The pneumoperitoneum-treated group was spared the necessity of developing abdominal wall flaps and presented a much easier peritoneal dissection. The operative time was 50 minutes in the 12 pneumoperitoneum-treated patients compared with an average of 150 minutes in the standard repair-treated group. There were no infections in the pneumoperitoneum-treated group compared with five (42%) in the other group. The postoperative stay of the pneumoperitoneum-treated group averaged 3.5 days compared with 12.5 days for the standard repair-treated group. Pneumoperitoneum is a valuable adjunct in the repair of large ventral hernias.

Adult

Accommodation to a reduced islet cell mass in dogs.

The quantitative insulin response to glucose stimulus can be drastically reduced by subtotal pancreatectomy. An 80% pancreatectomy was performed preserving the pancreatic duct in seven dogs. The insulin output into the portal vein and cephalic vein insulin after intravenous glucose challenge were measured. Output was recorded in 25 controls, and before and 2 wk after subtotal pancreatectomy in the seven animals. Histologic sections of the original resection were compared with the remnant of pancreas taken at the end of the study. In this model, which approaches islet cell failure in terms of glucose homeostasis, the tactics that permit enhancement of islet function can be discerned and to some degree quantitated. The pancreatic remnant does not oversecrete to approximate normal function, although glucose sensitivity is somewhat enhanced. No beta-cell hyperplasia was seen. Despite low insulin output into the portal vein, systemic insulin levels are conserved. This decrease in the plasma clearance of insulin supports glucose homeostasis. Accommodation to severe islet reduction occurs via both intrapancreatic and, more importantly, extrapancreatic mechanisms.

Animals

The independence of insulin release and ambient insulin in vitro.

The effect of insulin on its own secretion was tested in three independent experimental models using insulin concentrations that approached physiologic values. The collected secretions from glucose-stimulated islet tissue had no effect on insulin release from other islets. Perifused insulin had no effect on the release of endogenous insulin even when the assay was completely controlled for dilutional effects. Perifused insulin had no effect on the release of prelabeled insulin from glucose-stimulated islets. Similarly, proinsulin did not affect insulin release. Porcine insulin did not affect the function of porcine or canine islets. These studies strongly support the independence of glucose-stimulated insulin secretion and ambient insulin.

Animals

[Pancreas transplantation. II].

So far no really successful therapy has been found for diabetes mellitus, though it is a common disease and its complications, involving microangiopathy, are extremely serious. The serious limitation of all forms of insulin therapy (various types of insulin and insulin pump) is the impossibility of achieving a fast, successful response to either the variations in blood sugar levels after eating or increased glucogenogenesis caused by glycosteroids and adrenalin. The prolonged hyperglycaemic peaks which result, may well be one of the possible causes of microangiopathy. Only a system which responds to blood sugar variations by stimulating adequate insulin secretion immediately will provide correct prophylaxis for the complications of diabetes mellitus. At the moment only P-pancreatic cells have this capacity and in theory pancreas transplantation seems to be the best treatment for diabetes. However out of 105 complete pancreas transplants only 5 survived for over a year, with the aid of immunosuppressants. Equally none of the 66 allotransplants of pancreatic islands in immunosuppressed patients was successful in the long term. It is also important to bear in mind that long term immunosuppression may prove more dangerous than microangiopathy itself. For these reasons a new cell transplant system using molecular sieve membranes to create an immunological barrier is being investigated. Although it is too early to forecast long-term results, continuous progress is being made and recent discoveries about the physiology of beta pancreatic cells encourage the belief that this approach may be successful in the future.

Cell Division

Studies on cell recognition in the developing brain.

Several lines of evidence demonstrate cell-cell receptors on the surface of developing brain cells. Plasma membrane vesicles with regional and temporal binding specificities can be prepared. Active factors that block cell aggregation can be extracted from these membranes and partially purified. Quantitative studies of cell-cell adhesion demonstrate a gradient of adhesive specificity along the dorsoventral axis of the developing retina.

Animals

Embryonal cell surface recognition. Extraction of an active plasma membrane component.

Plasma membranes obtained from different neural regions of the chicken embryo have previously been shown to specifically bind to homotypic cells and prevent cell aggregation (Merrell, R., and Glaser, L. (1973) Proc. Natl. Acad. Sci. U. S. A. 70, 2794-2798). Proteins responsible for the specific inhibition of cell aggregation have been solubilized from the plasma membrane of neural retina and optic tectum by delipidation with acetone followed by extraction with lithium diiodosalicylate. The extracts show the same regional and temporal specificity as previously shown for plasma membrane recognition by the same cells (Gottlieb, D. I., Merrell, R., and Glaser, L. (1974) Proc. Natl. Acad. Sci. U. S. A. 71, 1800-1802). Two micrograms of the most purified protein fraction inhibits the aggregation of 2.5 times 10(-4) cells under standard assay conditions. This represents a 20-fold increase in specific activity compared to whole membranes.

Animals

Temporal changes in tectal cell surface specificity induced by nerve growth factor.

The change in cell surface adhesive specificity previously shown to occur between day 7 and 8 of development in the chick optic tectum ]Gottlieb et al. (1974), Proc. Nat. Acad. Sci. USA 71, 1800-1802] can be induced in rotating cultures of tectal cells by the addition of 10(-7) M mouse submaxillary gland nerve growth factor. Insulin, proinsulin, dexamethasone, and performic-acid-oxidized nerve growth factor are individually inactive in this system, but nerve growth factor in which the three tryptophan residues/subunit have been oxidized with N-bromosuccinimide is active. Thus, the specificity of this system for nerve growth factor is different than that observed with embryonic dorsal root or sympathetic ganglia, where the oxidized tryptophan derivative is inactive in stimulating neurite production. It is possible that in this system nerve growth factor serves as an analog of another specific trophic factor, presumably structurally related to nerve growth factor, may be active at much lower concentrations.

Age Factors

Temporal changes in embryonal cell surface recognition.

Plasma membranes have been prepared from optic tectum and neural retina of chick embryos. These membranes specifically inhibit the aggregation of homotypic cells. Plasma membranes prepared from each of these regions obtained from chick embryos at 7,8, and 9 days of development show specificity for homotypic cells of the same age and cross-react weakly with homotypic cells of different ages. Thus cell-surface recognition changes with age of development, and most of the cells in each region have a common cell-surface recognition specificity. Tectal cells react weakly with retinal cell membranes, but no inhibition of retinal cell aggregation by tectal cells has been noted.

Animals

Specific recognition of plasma membranes by embryonic cells.

Methods have been developed for preparation of plasma membrane fractions from embryonic neural retina and cerebellum. These membrane fractions are specifically bound by intact cells of the original tissue (homotypic binding) and not by cells from the other tissue (heterotypic binding). Aggregation of neural retina cells and cerebellar cells is prevented by addition of homotypic membranes but not by heterotypic membranes. We conclude that, under our assay conditions, these embryonic cells specifically recognize homotypic membranes, and that the specificity of recognition is the same as in the initial step in the process of cellular aggregation.

Adenosine Triphosphatases