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Biomedical subjects

J Marshall

Publications and source records attributed to J Marshall.

At least 361 records · Page 20Linked to original sources

The mas oncogene encodes an angiotensin receptor.

The class of receptors coupled to GTP-binding proteins share a conserved structural motif which is described as a 'seven-transmembrane segment' following the prediction that these hydrophobic segments form membrane-spanning alpha-helices. Identified examples include the mammalian opsins, alpha 1-, alpha 2-, beta 1- and beta 2-adrenergic receptors, the muscarinic receptor family, the 5-HT1C-receptor, and the substance-K receptor. In addition, two mammalian genes have been identified that code for predicted gene products with sequence similarity to these receptors, but whose ligand specificity is unknown namely, G21 and the mas oncogene. The mas oncogene shows the greatest sequence similarity to the substance-K receptor, and on this basis it was predicted that it would encode a peptide receptor with mitogenic activity which would act through the inositol lipid signalling pathways. The mas oncogene product was transiently expressed in Xenopus oocytes, and stably expressed in a transfected mammalian cell line. The results demonstrate that the mas gene product is a functional angiotensin receptor.

Angiotensins↗

Retinal pigment epithelial cells in culture produce retinal vascular mitogens.

Conditioned medium from human retinal pigment epithelial cells in culture significantly stimulated the proliferation of subcultured bovine retinal capillary endothelial cells, pericytes, and freshly isolated retinal microvessels. The vascular mitogenic activity enhanced that of retinal crude extract. No evidence emerged of an inhibitor of microvascular cellular proliferation produced by retinal pigment epithelial cells.

Animals↗

A rat brain Na+ channel alpha subunit with novel gating properties.

We have constructed a full-length rat brain Na+ channel alpha subunit cDNA that differs from the previously reported alpha subunit of Noda et al. at 6 amino acid positions. Transcription of the cDNA in vitro and injection into Xenopus oocytes resulted in the synthesis of functional Na+ channels. Although the single-channel conductance of the channels resulting from cloned cDNA was the same as that of channels resulting from injection of rat brain RNA, we observed two significant differences in the gating properties of the channels. The Na+ currents from cloned cDNA displayed much slower macroscopic inactivation compared with those from rat brain mRNA. In addition, the current-voltage relationship for currents from cloned cDNA was shifted 20-25 mV in the depolarizing direction compared with currents from rat brain RNA. Coinjection of low MW rat brain RNA restored normal inactivation of the channels indicating the presence of a component, either a structural subunit of the channel complex or a modifying enzyme, necessary for normal gating of the channel.

Amino Acid Sequence↗

Long-term healing of the central cornea after photorefractive keratectomy using an excimer laser.

Using an excimer laser at 193 nm, 3-mm diameter discs were ablated from the optical zone of monkey corneas at a variety of depths up to 130 micron. Tissue was examined by light and electron microscopy 4 and 5 weeks and 6 and 8 months postoperatively. With the exception of the deepest ablation, all corneas were clear immediately postoperatively. At 1 month, ablations of 40 micron remained clear, whereas all others showed some degree of haze. By 3 months, discs at 60 micron depth were clear, and there was less haze in others. Haze was progressively lost over 6 months, but in the deepest discs it could still be discerned on slit-lamp examination. Microscopic observation showed that reepithelialization had occurred within 24 to 48 hours. Over subsequent months, a normal morphology was maintained in this layer with the exception that basal cells were slightly more elevated particularly at the disc margins where the epithelium contained more cell layers. Stromal reorganization was accompanied by an initial phase of vacuolation and invasion by keratocytes, but by 6 months postoperatively almost all vacuolation had disappeared and keratocyte numbers had almost returned to normal. By 8 months, the morphology was near normal with the exception that Bowman's membrane was absent and there was still a degree of disorder in the immediate subepithelial stromal fibers. The basement membrane of epithelial cells was reestablished but slightly more undulant than in nonirradiated areas. This undulation was retained in the 8-month postoperative specimens and at this time a normal thickness of 60 nm was displayed.

Animals↗

Photorefractive keratectomy: a technique for laser refractive surgery.

The excimer laser offers entirely new corneal surgery procedures. In this paper, we describe conditions for one such procedure, photorefractive keratectomy, the direct reshaping of the cornea's central optical zone using tissue ablation with far ultraviolet radiation. We present equations for the required tissue ablation to achieve required refractive corrections. Conditions for beam uniformity are presented and a method of achieving better beam uniformity using beam integration by rotation is demonstrated. The healing of rabbit corneas after area ablation was observed. Five days after treatment, the surface quality of deep cuts was very irregular; the shallow cuts produced more regular results, as predicted by our calculations of beam characteristics.

Animals↗

Dietary epidemiology of cancer of the colon in western New York.

The authors interviewed 428 pathologically confirmed cases of colon cancer and controls matched on age, sex, race, and neighborhood in the New York counties containing the cities of Buffalo, Niagara Falls, and Rochester. Risk of colon cancer in both males and females, studied separately, appeared to increase with the amount of total fats and total calories ingested. In addition, we found the risk to increase with increases in the Quetelet index of relative weight (weight (kg)/height (m)2). Dietary fiber was only equivocally associated with risk. Fats and Quetelet index were associated with increased risk in a regression analysis adjusting each factor for the other, as well as for fiber, age, and socioeconomic status. The same was true for calories and Quetelet index. Future efforts to clarify a possible protective role for fiber and to disentangle the effects of fats and calories need to be undertaken. The fact that calories ingested and obesity are each associated with increased risk suggests the importance of studying calorie expenditure.

Body Height↗

A comparative study of the cutaneous microflora of normal feet with low and high levels of odour.

A comparison of the cutaneous microflora found on normal feet with varying levels of odour has been made. High population densities of staphylococci and aerobic coryneform bacteria predispose to foot odour. There was no association between odour and the carriage on feet of any particular micro-organism, including brevibacteria. All organisms isolated were screened for exoenzyme activity. Only staphylococci produced lipase (78% of the staphylococci), whereas 97% of micrococci, 68% of aerobic coryneform bacteria, 25% of staphylococci and 94% of propionibacteria produced proteinase. The ability to degrade callous was exhibited by 47% of micrococci, 24% of aerobic coryneforms and 17% of the staphylococci. Feet with high odour had significantly higher population densities of micro-organisms with the ability to produce these exoenzymes than feet with low odour. No association was observed between foot odour and the carriage of micro-organisms capable of producing methanethiol. A hypothesis for the role of micro-organisms in the production of foot odour is proposed.

Actinomycetales↗

The variable clinical and CT findings after carotid occlusion: the role of collateral blood supply.

A retrospective review of 61 cases of angiographically confirmed occlusion of one or both carotid arteries was carried out to look at the evidence that the presence of collateral blood supply influenced the extent and type of cerebral infarction. Forty six patients had bilateral angiography from which it was possible to assess collateral filling of the internal carotid and middle cerebral arteries. As expected, patients with no CT scan evidence of infarction more frequently had transient ischaemic attacks or retinal infarcts than did those with visible cerebral infarcts. Patients with small cortical ischaemic lesions usually had appropriate neuropsychological or neurological deficits. Three patients with cortical watershed infarcts had a fluctuating deficit. Of the patients with bilateral angiograms 67% showed some filling via collaterals of the middle cerebral artery, and 43% of the internal carotid artery in the siphon. Those with collateral filling were mostly found to have normal CT scans or evidence of peripheral cortical lesions. By contrast most watershed and full territory infarcts were found in individuals whose angiograms showed no collateral filling. It is suggested that in many cases infarction occurs despite collateral flow and is due to distal embolism and that this may be relevant to the recently reported failure of the EC/IC bypass operation.

Carotid Artery Thrombosis↗

Assessment of cerebral haemodynamic reserve: correlation between PET parameters and CO2 reactivity measured by the intravenous 133 xenon injection technique.

Regional cerebral blood flow (CBF), oxygen utilisation, fractional oxygen extraction (OER) and cerebral blood volume (CBV) were measured by positron emission tomography (PET) in 21 patients with occlusive carotid artery disease. In the same patients, measurements of cerebral CO2 reactivity were performed using the intravenous xenon-133 technique. A significant correlation was found in symptomatic hemispheres between the CBF/CBV ratio and CO2 reactivity. Four patients had significant increases in OER and this was associated with a reduction in CBF/CBV ratio implying exhaustion of haemodynamic reserve. CO2 reactivity was reduced below 1.5% mm Hg in all four cases with raised OER but only in two cases with normal OER. In patients with CO2 reactivities above 1.5% mm Hg, OER was normal in all cases. It is concluded that measurements of CO2 reactivity provide a satisfactory method for assessing cerebral haemodynamic reserve.

Aged↗

Inflammatory cells and the epithelium. Mast cell/nerve interactions in the lung in vitro and in vivo.

A hypothesis is presented that mast cells in and below the epithelium of the respiratory tract show functional association with nerves to form a homeostatic regulatory unit. During inflammation, mast cells may arise in situ as well as by infiltration because epithelium contains both mast cell precursors and produces factors that support their growth in vitro. Structural studies show that mast cells associate with nerves in the lung. Using a tissue culture model, we showed that sympathetic nerves formed lasting contacts with rat basophilic leukemia (RBL) cells. Electrophysiologic studies showed that nerve contact increases RBL membrane conductance, which can be mimicked by exogenous substance P (SP). Experiments with sensitized rat tracheal mucosa in Ussing chambers showed functional evidence of interaction of mast cells with SP-containing nerves: changes in short circuit current caused by antigen were blocked by the mast cell stabilizer doxantrazole and reduced by 50% by neonatal pretreatment with capsaicin. Experiments in vivo showed that lung clearance of the aerosol probe 99mTc-DTPA was increased by antigen challenge in sensitized rats. This was blocked by neonatal capsaicin treatment, again implicating SP-containing nerves. Therefore, we conclude that the functional association of mast cells with nerves is an important mechanism in regulating the local epithelial environment.

Animals↗

Relationships between laterality of congenital upper limb reduction defects and school performance.

Eighty children (34 males, 46 females) with congenital upper limb reduction defects who attended a regional amputee clinic between 1956 and 1986 were classified as to whether they exhibited learning difficulties in school, as indicated by grade failure or by placement in learning disability classrooms. Children with right-sided defects were more likely to encounter learning difficulties than were children with left-sided defects (Chi-square = 6.8; df = 1; p less than 0.01). Children with right-limb defects also were more likely than children with left-limb defects to experience reading problems (Chi-square = 5.9; df = 1; p less than 0.05). These results suggest the need for neuropsychological and neurophysiological study of children with limb reduction defects.

Arm↗