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Biomedical subjects

N Rich

Publications and source records attributed to N Rich.

27 records · Page 2Linked to original sources

Differential involvement of calcium channels and protein kinase-C activity in GnRH-induced phospholipase-C, -A2 and -D activation in a gonadotrope cell line (alpha T3-1).

The mode of action of GnRH on pituitary gonadotropes involves metabolism of phospholipids, protein kinase-C (PKC) and voltage sensitive Ca2+ channels (VSCC) activation. We have studied the differential role of PKC and VSCC on the coupling of the GnRH receptor with phospholipases-C (PLC), -A2 (PLA2) and -D (PLD) activities in a gonadotrope cell line (alpha T3-1), by measuring the production of inositol phosphates (IPs), arachidonic acid (AA) and phosphatidylethanol (PEt) respectively. We demonstrated that in these cells GnRH stimulated through a specific receptor, IPs formation, a rapid and sustained diacylglycerol generation, consequently AA release and a delayed PEt production in a dose-dependent manner. In contrast to GnRH-induced PLC activity, the PLA2 and PLD stimulation by the neuropeptide involved Ca2+ mobilization via VSCC activation. BAY-K8644 a VSCC agonist significantly potentiated, while the VSCC antagonist nitrendipine markedly inhibited GnRH-induced AA release and PEt production. TPA, a phorbol ester which induced a rapid and important redistribution of PKC, although unable to elicit PLC or PLA2 stimulation, specifically provoked PLD activation in a PKC-dependent but Ca(2+)-independent manner. The PKC stimulation by TPA significantly inhibited the GnRH-stimulated IPs and AA formation, while it potentiated the GnRH-evoked PEt production. This negative feed-back of PKC on GnRH-Induced PLC and PLA2 activities was reversed when PKC was either down regulated after long TPA treatments or inhibited by the PKC inhibitors, staurosporine or GF109203X. The GnRH-induced PEt formation was markedly diminished in PKC depleted cells or after PKC inhibition. Under such conditions, both agonist and antagonist of VSCC became less effective in modulating the remaining GnRH-evoked PEt formation. These results suggest that PKC, in coordination with Ca2+, plays a key role in regulating the cross-talk between the multiple phospholipases implicated in the GnRH signal transduction.

Animals↗

Subcutaneous tissue oxygen pressure: a reliable index of peripheral perfusion in humans after injury.

The usual initial life-threatening effect of injury is hypovolemic shock. In the hierarchical physiologic response to hypovolemia, perfusion of peripheral tissues is sacrificed early and restored late. But the usual hemodynamic and metabolic measurements of blood pressure, urine output, and base deficit are not reliable indices of peripheral perfusion. Although the Clark electrode can quantitate tissue oxygen pressure and thereby serve as an index of perfusion, its use is compromised by several technical deficiencies. Recently, an optical method (optode) using fluorescent technology has been developed for measurement of oxygen tension in subcutaneous tissue (P sgO2). Our studies compared this device with the Clark electrode in the laboratory and tested its value in both animal and clinical studies of hypovolemic shock. The results of these several studies demonstrated that: (1) the new oximeter tracked a rapid fall or rapid rise of oxygen tension between room air (150 mm Hg) and 0 mm Hg ( a glucose oxidase/catalase solution) as well as the Clark electrode without encountering its technical problems; (2) with an acute hemorrhage to 20% of base line, the PsgO2 was found to decline rapidly in parallel with the decline of mean arterial pressure (MAP). Although the MAP rapidly returned to normal after immediate complete return of all shed blood, the PsgO2 did not reach normal levels for at least 2 hours, suggesting persistent peripheral vasoconstriction. (3) Studies in progress suggest that between 35 and 78% of trauma patients (n = 18) adequately resuscitated for hypovolemia b customary criteria have a decreased level of PsgO2 for as long as 60 hours after resuscitation for injury. If care is taken to prevent other causes of catecholamine induced vasoconstriction such as pain, fear, cold, and arterial hypoxia, these several results suggest that a certain number of injured patients are inadequately resuscitated despite the return to normal of conventional hemodynamic measurements. The serial analysis of PsgO2 may assist in managing patients and promote better understanding of the responses to injury.

Animals↗

Maffucci's syndrome (hemangiomatosis osteolytica): a report of four cases.

Maffucci's syndrome is a congenital nonfamilial syndrome combining dyschondroplasia, (enchondromatosis) and hemangiomatosis. It is a rare disease; only 200 cases have been reported throughout the world in the past 140 years. Over the past 20 years, four patients have been admitted with signs and symptoms consistent with Maffucci's syndrome. Three were children ages 3, 7, and 9 years. The fourth was 23 years old. Two were male and two female. All had hemangiomas at birth, and all had skeletal deformities and enchondromas. All complained of pain and heaviness of the involved extremity. Three patients had the arterial inflow evaluated with arteriograms, and one had magnetic resonance imaging. Two also had venograms. Two patients had excision of their hemangiomas, and one had sclerotherapy and compression therapy. All had bone biopsies performed. None of the enchondromas or the soft tissue lesions had undergone sarcomatous transformation.

Adult↗

Epifluorescence microscopic observation of monolayers of dipalmitoylphosphatidylcholine: dependence of domain size on compression rates.

A fluorescence microscopic technique was used to observe phase transitions in monolayers of DPPC. The sizes of the domain structures observed were found to be dependent on the rate of compression of the monolayer. The distribution of domain sizes for different rates of compression were unimodal, but the scatter in the sizes was greater during slow compressions.

1,2-Dipalmitoylphosphatidylcholine↗

Bone as a secondary missile: an experimental study in the fragmenting of bone by high-velocity missiles.

Destruction to soft tissues by bone fragments has been described in the literature. Civilian and military injuries have been reported in which bone fragments have acted as secondary missiles. This experimental study demonstrates, in detail, the formation of the temporary cavity within bone and the forward motion of these bone spicules. The knowledge of the ballistics will assist in the treatment of wounds caused by high-velocity missiles.

Animals↗

Computer assisted microdensitometric analysis of footprinting autoradiographic DATA.

A system comprised of a linear scanning microdensitometer interfaced to a personal computer has been developed to facilitate analysis of ligand-DNA footprinting autoradiograms. The system, which can be used to record density and sequence information from autoradiographic films, enables the user to relate the area under an autoradiographic band to the concentration of radiolabeled molecules present in the electrophoresis gel. This report describes the computer program which performs the calculations and discusses the ability of the system to accurately determine oligonucleotide concentration, as a function of band separation, photographic response, and the computational algorithm used to calculate band areas.

Autoradiography↗

Ischemia of the upper extremity due to noncardiac emboli.

Nine cases of microemboli of arterial origin to the upper extremity are reported. The source of emboli in five of these cases was in the subclavian artery compressed by osseous anomalies in the thoracic outlet. Three aneurysms, one in a subclavian vein graft and two traumatic false aneurysms in the hand, were also noted to be the sources of distal emboli. One unproved case of emboli from an atherosclerotic plaque of the subclavian artery is also reported. Chronicity of symptoms and delay in operation are often noted and lead to difficulties in surgical management. The compressing osseous structures causing the vascular lesion in the thoracic outlet syndrome must be resected, along with removal of the source of emboli. Cervicodorsal sympathectomy is often needed in cases of extensive thrombosis and/or long-standing ischemia. Embolectomy is usually a futile procedure when the main arterial trunk contains old, organized thrombus. Differential diagnostic problems between collagen vascular disease, vasculitis, vasospastic disease, and microembolic disease in cases of unilateral Raynaud's phenomenon are pointed out.

Adult↗