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Biomedical subjects

R J Phillips

Publications and source records attributed to R J Phillips.

At least 55 records · Page 3Linked to original sources
PubMed1995

Suppression of meal size by intestinal nutrients is eliminated by celiac vagal deafferentation.

The arrival of nutrients in the gastrointestinal tract suppresses intake. To specify the neural pathways and receptor locations of this feedback, we examined the effects of intraduodenal infusions of 10 nutrients plus saline on short-term food intake of rats with selective deafferentations of vagal celiac branches. Three response profiles were observed: 1) isotonic saline, 5.6% glycerol, and 3% fructose did not inhibit intake of controls or selectively deafferented animals; 2) 3% glucose, 3% maltose, 3% L-phenylalanine, 12% Isocal, and 1.4% oleic acid suppressed intake of controls, but this inhibition was eliminated by vagal celiac deafferentation; and 3) 3% casein hydrolysate and 24% Isocal suppressed intake of controls and rats with selective vagotomies, although the latter exhibited significantly less suppression. In addition, elimination of celiac afferents chronically reduced meal size (i.e., first 30-min intake) without reducing daily food intake or body weight. Furthermore, D-phenylalanine infusions produced a delayed suppression of food intake in controls (possibly from intraluminal irritation); however, this reduction was eliminated with celiac deafferentation. Overall, this experiment indicates that vagal celiac afferents are critical for preabsorptive detection of some energy-yielding molecules or properties of nutrient solutions (as well as, perhaps, intraluminal inflammation), but not others, which are still detected, although only partially.

Afferent Pathways↗
PubMed1994

Antigenic expression of integrin alpha 6 beta 4 in junctional epidermolysis bullosa.

Integrin alpha 6 beta 4 is a major component of hemidesmosomes, considered to play a central role in the adhesion of basal epidermal cells to the underlying dermis. It is therefore of considerable interest in the study of the aetiology of inherited blistering disorders. We have examined the immunohistochemical characteristics of skin from 16 patients with epidermolysis bullosa using two antibodies directed against epitopes on the beta 4 subunit of alpha beta 4 integrin (G71, 3E1), one antibody directed against an epitope on the alpha 6 subunit (GoH3), GB3 an antibody for nicein, and LH7.2, an anticollagen type VII antibody. All 10 patients with junctional epidermolysis bullosa showed markedly reduced or no immunoreactivity with G71. These patients included two with GB3-positive junctional epidermolysis bullosa associated with pyloric atresia, and four with other subtypes. By contrast, five patients with dystrophic epidermolysis bullosa and one patient with epidermolysis bullosa simplex showed normal immunoreactivity with G71. In this study, G71 is shown to have a high specificity and sensitivity for the diagnosis of junctional epidermolysis bullosa. Immunoreactivity with 3E1 and GoH3 was normal in most patients, consistent with published reports showing normal immunoreactivity with other beta 4 and alpha 6 subunit antibodies. The data suggest a modification of the beta 4 subunit of integrin alpha 6 beta 4 at the dermo-epidermal junction in junctional epidermolysis bullosa.

Antibodies↗
PubMed1994

Laryngo-onycho-cutaneous syndrome: an inherited epithelial defect.

Three children with an unusual but clearly defined combination of clinical findings that appear to have been inherited in an autosomal recessive manner are described. All had developed laryngeal abnormalities, chronic skin ulceration, nail dystrophy, and conjunctival disease in infancy. In every case, dental enamel was hypoplastic and both skin and mucosal surfaces demonstrated increased susceptibility to trauma. Progression of disease occurred, to life threatening respiratory obstruction in two cases and to effective blindness and fatal respiratory obstruction in the third child. All of these children came from the Pakistani ethnic group. No medical treatment has halted progression of this disease but laser therapy has been partially successful in alleviating laryngeal manifestations. Ultrastructural and immunohistological examination of unaffected skin was undertaken in each child. No abnormality was found in the child with the mildest clinical disease. Both of the other children showed abnormal hemidesmosomes on ultrastructural examination. The most severely affected child also had abnormally weak immunoreactivity with antibodies G71 and GB3 directed against basal cell alpha 6 beta 4 integrin and the basement membrane glycoprotein nicein respectively. These abnormal findings are also seen in skin from patients with junctional epidermolysis bullosa. These three children have the laryngo-onycho-cutaneous syndrome, which may not be rare in their ethnic group. The available clinical and pathological evidence is consistent with this syndrome being caused by an inherited defect affecting the lamina lucida of the skin basement membrane zone. The laryngo-onycho-cutaneous syndrome may therefore represent a new and distinctive type of junctional epidermolysis bullosa.

Child, Preschool↗
PubMed1993

Cystic fibrosis presenting as kwashiorkor with florid skin rash.

Two infants with a florid erythematous rash and generalised oedema, hypoalbuminaemia, and anaemia were found to have cystic fibrosis. This rare presentation is associated with false negative sweat tests, delays in diagnosis, and a considerable mortality. It is proposed that this presentation represents a manifestation of kwashiorkor secondary to malabsorption. The recognition that these infants have kwashiorkor provides some insight into the pathogenesis and management of their illness.

Cystic Fibrosis↗
PubMed1992

Dyskeratosis congenita: delay in diagnosis and successful treatment of pancytopenia by bone marrow transplantation.

Dyskeratosis congenita is an inherited disorder characterized by nail dystrophy, skin pigmentary changes, mucosal leukoplakia, pancytopenia and an increased incidence of malignancy. Because of a widely held view that the outcome of bone marrow transplantation in dyskeratosis congenita is poor, this treatment option is sometimes not considered when pancytopenia develops. We present a child currently doing well 3 years after bone marrow transplantation, and review the literature.

Bone Marrow Transplantation↗
PubMed1992

Intraepidermal collagen type VII in dystrophic epidermolysis bullosa: report of five new cases.

The presence of intraepidermal collagen type VII has recently been used to define a subgroup of patients with mild dystrophic epidermolysis bullosa (DEB). This subgroup demonstrates virtual resolution of blistering during infancy despite often severe neonatal blistering. Using the antibody LH7.2, we have detected intraepidermal collagen type VII in five cases with DEB. These represent a much wider spectrum of clinical features and of intraepidermal and basement membrane zone (BMZ) staining patterns. Only one of our cases had features consistent with reported cases. Sequential skin biopsies from this case showed a marked change towards normal within 6 months of birth, paralleling the clinical improvement. The other four cases had sparse epidermal deposits of collagen type VII and included an affected foetus with autosomal recessive DEB. These findings suggest that the frequency of intraepidermal LH7.2 in DEB may be much higher than previously thought. The presence of abundant intraepidermal collagen type VII is of prognostic significance and can disappear over months. We recommend that biopsies of infants suspected of having EB are taken during the neonatal period.

Adolescent↗
PubMed1991

Antigen receptor-mediated phosphoinositide hydrolysis in murine T cells is not initiated via G-protein activation.

Ligation of the antigen receptors on both T and B lymphocytes induces phosphoinositide (PI) hydrolysis, Ca(2+)-mobilization and protein kinase C activation. The activation of the phosphoinositide-specific phosphodiesterase (PPI-PDE) following crosslinking of surface Ig receptors on B cells is controlled by an uncharacterized guanine nucleotide-regulatory (G) protein. Here we have used permeabilized murine T cells (both resting T cells and a conalbumin-specific CD4-positive T cell clone) to investigate a role for G protein(s) in coupling the TCR to the PPI-PDE. We found that anti-TCR McAb (or processed antigen)-induced PI hydrolysis cannot be uncoupled by permeabilizing T cells, as occurs with classical G protein-linked receptors. Furthermore, the TCR-mediated release of inositol phosphates in permeabilized T cells was not enhanced by non-hydrolyzable analogs of GTP, nor inhibited by GDP analogs. These findings therefore argue strongly against the concept that TCR-mediated PI hydrolysis is G-protein controlled.

Animals↗
PubMed1990

An open multicentre study of the efficacy and safety of a single dose of fluconazole 150 mg in the treatment of vaginal candidiasis in general practice.

The efficacy and tolerability of fluconazole given as a single oral dose of 150 mg were assessed in 1,017 patients in general practice presenting with signs and symptoms of vaginal candidiasis. At the review visit 7-14 days after treatment, about 95 per cent of patients reported being either cured or improved. High vaginal swabs taken from 43 patients out of 50 who failed following treatment revealed Candida albicans in 17 (1.8 per cent). Efficacy in patients with predisposing factors (oral contraceptives, antibiotics and recurrent vaginal candidiasis - four episodes or more in previous year) was not significantly different from that in those without these factors. Of patients who had received previous intravaginal therapy for vaginal candidiasis, 88 per cent preferred fluconazole, 10 per cent previous therapy and two per cent had no preference. Investigators assessed efficacy after fluconazole as excellent or good in 91 per cent and tolerability as excellent or good in 91 per cent of patients. Significant adverse effects were reported in less than one per cent of patients.

Administration, Oral↗
PubMed1989

Analysis of signaling via surface immunoglobulin receptors on B cells from CBA/N mice.

CBA/N mice, which carry the xid immunodeficiency, lack a mature subpopulation of B cells. The residual B cells in these mice do not make antibodies to type-2 T-independent antigens, nor do they synthesize DNA in response to mitogenic forms of anti-Ig antibodies. It is therefore an attractive hypothesis that the surface immunoglobulin receptors (sIgR) on xid B cells signal abnormally following cross-linking. We show here that anti-Ig antibodies do cause inositol phospholipid hydrolysis and Ca2+ mobilization in xid B cells. However, the response of these cells are only 40%-50% of those of normal B cells. Studies with permeabilized cells demonstrated that the hyporesponsiveness is not due to ineffective coupling of sIgR to their associated G-protein. Rather it is apparently due to a quantitative and/or qualitative deficiency in the polyphosphoinositide-specific phosphodiesterase which mediates sIgR-induced inositol phospholipid hydrolysis. These observations may provide a biochemical explanation for the immunological abnormalities resulting from the xid mutation.

Animals↗
PubMed1989

The molecular basis of granuloma formation in schistosomiasis. IV. T cell-derived suppressor-inducer and suppressor-effector factor reactivities are regulated by a TCR beta chain analog.

In Schistosomiasis mansoni, granulomatous modulation is mediated by antigenically and genetically restricted T suppressor-inducer and suppressor-effector cells and the soluble factors which they produce. The T suppressor-inducer factor (TsiF) is produced by an L3T4+, 14-30+ T cell. TsiF does not suppress directly, but induces the production of T-cell-derived suppressor-effector factor (TseF). TseF directly suppresses granuloma formation in vitro and in vivo. This study describes the molecular properties of TsiF. The factor is a nonimmunoglobulin heterodimer which can be separated into two component chains by dithiothreitol (DTT) reduction. The alpha chain imparts antigenic specificity and bears both the AgR and the epitope recognized by mAb 14-30 which characterizes T cells and factors of the Tsi phenotype. The beta chain imparts genetic restriction and bears both the I-J phenotypic marker and a T-cell receptor for Ag (TCR) V beta 8 determinant. These two chains can complement each other in vitro to reconstitute functional activity. The beta chain also determines the functional activity of T cell-derived suppressor factor (TsF). A beta chain, derived from TsiF, can complement the alpha chain derived from TsiF or TseF to reconstitute TsiF, but not TseF functional activity. Conversely the beta chain of TseF can reconstitute only TseF activity. These findings suggest that TsiF bears structural homologies to the TCR borne by Tsi cells and that the beta chain mediates the mode of functional interactions between TsFs and their target cells.

Animals↗
PubMed1989

Randomised study of prophylactic parenteral sulbactam/ampicillin and cephazolin in biliary surgery: significant benefit in jaundiced patients.

Two hundred consecutive patients undergoing biliary-tract surgery were entered into a randomized trial of prophylactic single dose cephazolin or sulbactam/ampicillin. There was no overall difference in the infection rates between the two antibiotic groups, but in the group of patients with jaundice there was an excess of wound infections in the cephazolin group compared to the sulbactam/ampicillin group (35% vs. 14%). We conclude that sulbactam/ampicillin is a satisfactory prophylactic agent for use in biliary-tract surgical sepsis, and that it may be superior to cephazolin in jaundiced patients.

Ampicillin↗
PubMed1988

Verapamil and bendrofluazide in the treatment of hypertension: a controlled study of effectiveness alone and in combination.

The effects of verapamil and bendrofluazide used singly and in combination were examined in patients with primary hypertension in a patient blind, partly observer blind placebo controlled study of parallel group design; there were ten subjects in each arm of the trial. Verapamil 160 mg twice daily caused supine mean arterial pressure to fall by 21 mmHg; this reduction was significantly greater (p less than 0.05) than that induced by bendrofluazide 5 mg daily which caused a fall of only 10 mmHg. The addition of verapamil 160 mg twice daily to bendrofluazide 5 mg daily caused a further fall in pressure of 18 mmHg (p less than 0.005), but the reduction in pressure when bendrofluazide was added to verapamil was only 1 mmHg and not significant. Bendrofluazide therapy caused a fall in plasma potassium concentration and an increase in plasma urate concentration; urinary calcium excretion was reduced. Verapamil caused no detectable biochemical alterations in plasma or urine.

Adult↗
PubMed1988

Venous air embolism during a craniofacial procedure.

The possibility of venous air embolism exists whenever the craniofacial operative field is above the level of the heart. Craniotomy with the high-torque craniotome is hypothesized to have produced venous air embolism in the patient described in this report. The diagnosis of venous air embolism is determined by transesophageal Doppler probe, transesophageal echocardiogram or external echocardiogram, and end-tidal N2 and CO2 determinations. Treatment includes control of the air entry sites, aspiration of air from the right atrium via a catheter placed prior to operation, and discontinuing nitrous oxide. If these measures are unsuccessful, the operative field should be transposed below heart level and the procedure terminated. In the event of significant hemodynamic compromise, closed cardiac massage should be tried; if that fails, open cardiac massage and direct aspiration are necessary. The true incidence of venous air embolism in craniofacial operations may be much higher than previously suspected. We therefore recommend placement of appropriate monitoring equipment to detect intracardiac air in those major craniofacial procedures in which there is a potential for intravascular air ingress.

Craniosynostoses↗
PubMed1984

The dilator response to K+ is reduced in the forearm resistance vessels of men with primary hypertension.

The dilator response to local infusion of K+ has been assessed in the forearm resistance vessels of 17 men with primary hypertension and 11 controls, by using a standard plethysmographic method. The response to infusion of K+ at 0.1 mmol/min was smaller in the patients with hypertension than in the normal controls (P less than 0.03). The results are consistent with the view that the activity of the sodium pump is depressed in the resistance vessels of patients with hypertension, but they yield no evidence as to whether or not this abnormality contributes to the elevation of the peripheral resistance.

Adult↗
PubMed1984

Effect of small increments in plasma calcium concentration on the responsiveness of forearm resistance vessels to verapamil in normal subjects.

The effect of a small increase in local plasma calcium concentration on the responsiveness of the forearm resistance vessels to verapamil has been examined in normal subjects, by using a plethysmographic method with infusion of calcium and other agents into the brachial artery. Infusion of calcium at a rate which increased the concentration in forearm venous blood by about 0.5 mmol/l caused basal blood flow to fall by 19% and the dilator response to verapamil to fall by 35% (n = 8; P less than 0.02). When, after 46 min, the infusion of calcium was discontinued, the dilator response to verapamil increased to reach a level 53% higher than the initial control (n = 8; P less than 0.02). Infusion of calcium had no effect on the dilator response to sodium nitroprusside. Infusion of noradrenaline at a rate which caused a greater reduction in basal flow than that induced by calcium had no effect on the response to verapamil. It is concluded that the dilator response to verapamil, which is thought to reflect activity of the potential operated system for calcium entry, is selectively depressed by a small elevation of plasma calcium concentration, but subsequently becomes elevated. These findings point to an important role for calcium in the regulation of membrane function in the resistance vessels and support the view that altered calcium handling may contribute to the development of primary hypertension.

Adult↗
PubMed1984

Small increments in plasma calcium concentration reduce the responsiveness of forearm resistance vessels to verapamil in men with primary hypertension.

The effect on the forearm resistance vessels of small increases in the local plasma concentration of calcium and magnesium has been examined in 20 men with primary hypertension. Studies were carried out by a standard plethysmographic method with infusion of drugs into the brachial artery. Infusion of calcium at 10 mumol/min into the forearm caused basal blood flow to fall by 9% (n = 17;0.1 greater than P greater than 0.05) and the dilator response to verapamil to fall by 28% (P less than 0.005). Infusion of magnesium at the same rate caused basal blood flow to rise by 22% (n = 12; P less than 0.05), but the dilator response to verapamil was not significantly changed. The response of the resistance vessels to verapamil is known to be enhanced in patients with hypertension, and the results show that this response is attenuated by a small increase in the local calcium concentration. The findings are consistent with the view that altered handling of calcium by the cell membrane contributes to the functional abnormality of the hypertensive resistance vessel.

Adult↗
PubMed1983

Homologous genes for X-linked chondrodysplasia punctata in man and mouse.

X-linked dominant chondrodysplasia punctata is a human gene defect characterized by punctate foci of epiphyseal calcification, cataracts, ichthyosis, and systematized atrophoderma. In a comparative study, the murine X-linked mutant 'bare patches' was found to display strikingly similar skeletal, ocular, and cutaneous anomalies. The human as well as the murine phenotypes occur exclusively in the female sex, apparently because the underlying mutations are lethal for male embryos. In both traits, the cutaneous lesions are arranged in a linear and blotchy pattern reflecting lyonization. The observed similarities constitute strong evidence that the two genes are homologous. The proposed homology is a further example of the evolutionary conservatism of the X-chromosome in mammals.

Animals↗