Changes in expression of the lysosomal membrane glycoprotein, LAMP-1 in interdigital regions during embryonic mouse limb development, in vivo and in vitro.

Syndactyly, a failure of the digits to separate into individual units, affects about 8 to 9 per 1000 newborns and results from an aberration of the normal development of the interdigital tissues. Limb digit separation is the result of programmed cell death (apoptosis). Lysosomes play a role in the process of cell self-destruction.

In vitro model of syndactyly replicates the morphologic features observed in vivo.

Syndactyly is a common congenital hand anomaly that may occur after exposure to teratogens. We have developed an in vitro model of syndactyly to investigate the molecular mechanisms underlying this malformation of digit development. Retinoic acid, which regulates pattern formation in vertebrate limb development and is associated with teratogenic malformations, was used in the development of this syndactyly model system.

Mesenchymal commitment to digital joint formation.

Temporal and spatial commitment of in vivo and in vitro mammalian digital joint development were characterized in a murine model. Alcian blue and alizarin red staining were used to label proteoglycans of cartilage matrix and mineralized matrix in both whole mounts and histological sections. Mesenchymal differentiation toward a joint fate was identified by a lack of matrix deposition in islands of joint precursor cells between phalangeal precursors, and localized lysosomal enzyme activity was later demonstrated in these regions during formation of the joint cavity.

Human endothelial cells are defective in diabetic vascular disease.

Diabetic vascular disease is characterized pathologically by endothelial cell (EC) hyperplasia and basement membrane (BM) thickening. One key question regarding the pathogenesis of diabetic vascular disease is whether the EC or BM or both are primarily defective and responsible for these pathological changes. Previous studies, which took the approach of creating artificial diabetic conditions, have been inconclusive.

Interdigital soft tissue separation induced by retinoic acid in mouse limbs cultured in vitro.

The temporal pattern of separation of the soft tissue between mouse digits was examined in an organ culture model system. Mouse limbs of different gestational age were cultured in vitro and the pattern of separation of the digits characterized. By gestational day 12.

Endogenous epidermal growth factor regulates limb development.

Mutations associated with genes of the EGF superfamily are implicated in limb malformations. To evaluate the potential role of EGF-mediated signal transduction in the control of early mammalian limb development, we developed a simple in vitro system which is permissive for morphogenesis and cytodifferentiation in serumless, chemically defined medium. Our experimental strategy was to ascertain if the EGF precursor gene was transcribed and translated into potentially bioactive growth factor.

Cellular responses to silicone and polyurethane prosthetic surfaces.

Prosthetic devices composed of silicone or polyurethane are commonly used in surgery. These devices elicit a soft tissue reaction which may frequently be complicated by capsule formation. Histologically the capsule comprises both cellular (fibroblasts and endothelial cells (EC)) and matrix components (predominantly collagen type I).

Medial edge epithelium fate traced by cell lineage analysis during epithelial-mesenchymal transformation in vivo.

Vital cell labeling techniques were used to trace the fate of the medial edge epithelial (MEE) cells during palatal fusion in vivo. Mouse palatal tissues were labeled in utero with DiI. The fetuses continued to develop in utero and tissues of the secondary palate were examined at several later stages of palatal ontogeny.

New evidence and new hope concerning endothelial seeding of vascular grafts.

Endothelial cell (EC) seeding of prosthetic bypass grafts has been promoted as a method of improving graft patency. However, an efficient and reliable method of seeding vascular prostheses with ECs is lacking due to inefficient harvesting of ECs and poor attachment and proliferation of cells on the prosthetic surfaces. To investigate the effect of a commonly used prosthetic surface on EC attachment and proliferation, we measured the attachment and proliferation of ECs on polytetrafluoroethylene (PTFE) grafts uncoated or coated with gelatin, laminin, fibronectin, collagen type I and/or III, or RGD (arginine-glycine-aspartate)-containing peptide.

Bilateral solitary glomus tumors of the hands.

Solitary glomus tumors of the digits are uncommon, comprising only about 2% of all hand tumors. In this report, we present a case report of a patient with bilateral glomus tumors that became symptomatic 4 years apart. No inheritance pattern was apparent for this patient.

The local effects of cachectin/tumor necrosis factor on wound healing.

Previous experimental studies have suggested that tumor necrosis factor (TNF) may have either a beneficial or a detrimental role in wound healing. Control and doxorubicin-treated (6 mg/kg, intravenously) rats underwent paired dorsal 5-cm linear wounds and had either vehicle or recombinant (r)TNF (0.5, 5, or 50 micrograms) applied locally to the wound.

Increased calcium levels alter cellular and molecular events in wound healing.

Surgical morbidity is dictated directly by wound healing. We have studied the effects of elevated calcium levels using cultured keratinocytes in vitro on two of the rate-limiting steps of wound healing, chemotaxis (directed migration) and adhesion. We found that the increased calcium (10 mmol/L) significantly inhibited both keratinocyte chemotaxis and adhesion (p less than 0.

Cholinergic stimulation of pancreatic polypeptide release by a meal, bombesin, neurotensin, tetragastrin, cholecystokinin, and cerulein.

It has been demonstrated that pancreatic polypeptide (PP) release can be markedly impaired by vagotomy or anticholinergic drugs. The current studies examine the role of cholinomimetic stimulation on PP release in dogs. Eight conscious animals underwent a series of tests: (1) a test meal (10 g/kg Alpo); (2) tetragastrin infusion (4 micrograms/kg/hr); (3) bombesin infusion (1.

Bombesin and insulin-stimulated pancreatic polypeptide release as a discriminator of vagal integrity.

Intact vagi after ulcer operations are often implicated in the cause of recurrent ulcer. The stimulation of gastric acid by insulin hypoglycemia is dangerous and the measurement of acid secretion after gastrectomy unreliable. This study was undertaken to assess and compare PP release by bombesin or insulin as an indicator of vagal integrity.

Opiate modulation of pancreatic polypeptide release by a meal in the dog.

It has been reported that morphine abolished the plasma pancreatic polypeptide (PP) response to a meal in man, but the mechanism of this action is unclear. This study was designed to investigate the effect of low doses of the endogenous opiate peptide. Met-enkephalin and naloxone on basal- and meal-stimulated PP release in order to examine the role of opioid modulation in the release of this hormone.

The early diagnosis of gastrinoma.

Despite the increasing awareness of gastrinoma and its lethal peptic ulcer sequelae, the diagnosis is often initially missed or made as a terminal event. The authors screened all patients with peptic ulcer symptoms serious enough to warrant hospital admission or those associated with diarrhea, nephrolithiasis, hypercalcemia, or pituitary abnormality. In a one-year period (1979-1980) nine (of 14 suspected) new gastrinoma patients were identified using a sensitive and specific gastrin radioimmunoassay in combination with provocative tests including IV secretin, calcium, and food.

Effect of methionine-enkephalin and naloxone on bombesin-stimulated gastric acid secretion, gastrin, and pancreatic polypeptide release in the dog.

In four dogs with chronic gastric fistulae, bombesin infusion was used to stimulate the release of gastrin and pancreatic polypeptide (PP) as well as rates of gastric acid secretion. Neither methionine-enkephalin (met-enkephalin) nor naloxone alone or the combination of these agents altered bombesin-stimulated gastrin release. met-enkephalin alone (but not naloxone) significantly inhibited the gastric secretory response to bombesin, but this inhibitory effect was not influenced by the simultaneous infusion of naloxone; the data suggested that the effect of met-enkephalin was indirect, and perhaps modulated by another inhibitory mechanism.

Evidence for an intestinal mechanism of pancreatic polypeptide release.

The purpose of this study was to define the existence of an intestinal phase of pancreatic polypeptide (PP) release and to assess whether it was mediated by a cholinergic-sensitive mechanism. Four conscious dogs with 20-cm upper intestinal Thiry-Vella loops and chronic gastric fistulas were used. The Thiry-Vella (T-V) loops were perfused with 10% liver extract or 0.

The effect of somatostatin and 16,16-dimethyl-prostaglandin E2 on bombesin-stimulated canine gastric acid, plasma gastrin and pancreatic polypeptide secretion.

We studied the effect of the intravenous infusion of 16,16-dimethylprostaglandin E2 methyl ester (di-M-PGE2) and somatostatin on bombesin-stimulated gastric acid secretion, plasma gastrin and plasma pancreatic polypeptide in four chronic gastric fistula dogs. Bombesin-stimulated gastric acid secretion was significantly inhibited by somatostatin and virtually abolished by di-M-PGE2. Both agents caused significant, but indistinguishable inhibition of gastrin release (P less than 0.