PubMed Health⌕ Search

Biomedical subjects

G A Porter

Publications and source records attributed to G A Porter.

At least 19 recordsLinked to original sources
PubMed1992

Dystrophin colocalizes with beta-spectrin in distinct subsarcolemmal domains in mammalian skeletal muscle.

Duchenne's muscular dystrophy (DMD) is caused by the absence or drastic decrease of the structural protein, dystrophin, and is characterized by sarcolemmal lesions in skeletal muscle due to the stress of contraction. Dystrophin has been localized to the sarcolemma, but its organization there is not known. We report immunofluorescence studies which show that dystrophin is concentrated, along with the major muscle isoform of beta-spectrin, in three distinct domains at the sarcolemma: in elements overlying both I bands and M lines, and in occasional strands running along the longitudinal axis of the myofiber. Vinculin, which has previously been found at the sarcolemma overlying the I bands and in longitudinal strands, was present in the same three structures as spectrin and dystrophin. Controls demonstrated that the labeling was intracellular. Comparison to labeling of the lipid bilayer and of the extracellular matrix showed that the labeling for spectrin and dystrophin is associated with the intact sarcolemma and is not a result of processing artifacts. Dystrophin is not required for this lattice-like organization, as similar domains containing spectrin but not dystrophin are present in muscle from the mdx mouse and from humans with Duchenne's muscular dystrophy. We discuss the possibility that dystrophin and spectrin, along with vinculin, may function to link the contractile apparatus to the sarcolemma of normal skeletal muscle.

Amino Acid Sequence↗
PubMed1991

Lectin and immunolabeling of microvascular endothelia.

A number of recently developed localization techniques are beginning to be applied in the study of endothelial cells and their structural components. In this article we will review a number of these cytochemical approaches as well as their advantages and disadvantages and their applications. The methods will be presented for processing tissues for either L.R. White embedding or semi-thin and thin frozen sections followed by subsequent lectin and immunolabeling for fluorescence and electron microscopic examination. These techniques are easily applied in the localization of perfused exogenous proteins and of endogenous endothelial-associated proteins. The results that can be obtained from such studies are presented and discussed.

Animals↗
PubMed1991

Differential and specific labeling of epithelial and vascular endothelial cells of the rat lung by Lycopersicon esculentum and Griffonia simplicifolia I lectins.

In the rat lung, we found that the Lycopersicon esculentum (LEA) lectin specifically binds to the epithelium of bronchioles and alveoli whereas Griffonia simplicifolia I (GS-I) binds to the endothelium of alveolar capillaries. The differential binding affinity of these lectins was examined on semithin (approximately 0.5 microns) and thin (less than 0.1 (microns) frozen sections of rat lung lavaged to remove alveolar macrophages. On semithin frozen sections, LEA bound to epithelial cells lining bronchioles and the alveoli (type I, but not type II epithelial cells). On thin frozen sections, biotinylated Lycopersicon esculentum (bLEA)-streptavidin-gold conjugates were confined primarily to the luminal plasmalemma of type I cells. bGS-I-streptavidin-Texas Red was detected on the endothelial cells of alveolar capillaries and postcapillary venules but not on those of larger venules, veins or arterioles. By electron microscopy, GS-I-streptavidin-gold complexes were localized primarily to the luminal plasmalemma of thick and thin regions of the capillary endothelium. Neither lectin labeled type II alveolar cells, but both lectins labeled macrophages in the interstitia and in incompletely lavaged alveoli.

Animals↗
PubMed1990

Experimental contrast-associated nephropathy and its clinical implications.

Acute renal failure after contrast media injection has been recognized for at least 35 years but the exact mechanism responsible for the renal injury remains an enigma. The clinical characteristics of contrast-induced nephropathy (CAN) are well-known although more recently the nonoliguric presentation has occurred at an increased frequency--in 70 to 90% of cases. For nonoliguric presentation of CAN, one can expect an asymptomatic increase in serum creatinine, the mean peak occurring at 4.2 days. If oliguric, the fractional excretion of sodium will be less than 1% and resistant to either fluid challenge or loop diuretics. Preexisting renal insufficiency, with or without diabetes mellitus, increases the risk of CAN 6- to 10-fold but recovery is expected, with less than 10% of all patients requiring dialytic support. Despite the growing body of published reports, the lack of a suitable animal model to evaluate various proposed mechanisms of renal injury has compromised our ability to devise a technique for preventing CAN. A popular scheme has been proposed to describe the possible sequence by which ischemia or nephrotoxins, or both, induce acute renal failure. In particular, a vascular mechanism (i.e., ischemia), is an appealing explanation for CAN since acute changes in renal hemodynamics after contrast media injection have been confirmed by several animal experiments. Unlike other vascular beds in which contrast media induce acute vasoconstriction followed by vasodilatation, the initial effect on the renal circulation is acute vasodilatation, followed by progressive vasoconstriction, increasing renal vascular resistance and a concomitant decrease in both renal blood flow and glomerular filtration rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1990

Angiotensin converting enzyme inhibitors and the allergist.

Angiotensin converting enzyme inhibitors (ACEI) are used widely in the treatment of both hypertension and congestive heart failure. Although usually well tolerated, these medications may produce side effects that may be encountered by the allergist, including cough, angioedema, and rhinitis symptoms. The severity of ACEI-induced cough may vary, and is associated with increased bronchial hyperreactivity in some (but not all) patients as judged by methacholine sensitivity. Angiotensin converting enzyme inhibitor-induced cough may have its onset from one day to 12 months after initiation of therapy, and is not dose dependent. Angioedema caused by ACEI is usually mild and clears with discontinuation of the drug, however cases requiring intubation and tracheostomy have been reported. The mechanism of ACEI-induced cough remains unclear, but could be in part due to accumulation of substances whose degradation may also be impeded by ACEI, such as substance P, bradykinins, and/or prostaglandins. Knowledge of the side effects produced by this class of medication may help patients avoid unnecessary, costly, and often invasive diagnostic evaluations.

Angioedema↗
PubMed1990

Differential binding of the lectins Griffonia simplicifolia I and Lycopersicon esculentum to microvascular endothelium: organ-specific localization and partial glycoprotein characterization.

The lectins Griffonia simplicifolia I and Lycopersicon esculentum were used to assess the presence of endothelium-specific glycoproteins in the microvasculature of the rat myocardium, diaphragm and superficial cerebral cortex. Organs fixed by intravascular perfusion were processed to obtain semithin (0.5 micron) and thin (less than 0.1 micron) frozen sections that were reacted with biotinylated lectin followed by streptavidin conjugated to Texas Red, for semithin sections, or by streptavidin conjugated to 5-nm colloidal gold particles, for thin sections. Lycopersicon esculentum lectin exclusively labeled the endothelium of all small vessels in all three microvascular beds; it did not bind to components of either the parenchyma or the extracellular matrix. Griffonia simplicifolia I lectin exclusively labeled the endothelium of the entire microvasculature in the myocardium and diaphragm, but marked primarily pericytes in the cerebral microvasculature. It did not label any parenchymal or interstitial organ component. At the electron microscope level, the lectin Griffonia simplicifolia I labeling was associated with the plasmalemma proper and especially with plasmalemmal vesicles and their introits, and Lycopersicon esculentum lectin bound primarily to the luminal plasmalemma in the microvascular beds of the myocardium and diaphragm. In the cerebral cortex, labeling of the microvasculature was clearly different: Griffonia simplicifolia I bound primarily to pericytes and vascular smooth muscle cells whereas Lycopersicon esculentum labeled only the microvascular endothelium. Lysates prepared from the myocardium, diaphragm and cerebral cortex were processed through Griffonia simplicifolia I lectin affinity separation followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of the fraction obtained. A number of putative endothelium-specific glycoproteins was detected and found to differ qualitatively and quantitatively from organ to organ. The most prominent polypeptide, approximately 97 kDa, was present in substantial amounts in the myocardium and diaphragm, but in considerably lower concentration in the cerebral cortex. The reverse applied for a approximately 55 kDa protein. The preferential distribution of the approximately 97 kDa protein parallels differences in Griffonia simplicifolia I lectin binding by fluorescence and electron microscopy on sections of the corresponding organs. The results provide further evidence for the existence of endothelial glycoproteins specific for different microvascular beds and possibly connected with local functional differentiations.

Animals↗
PubMed1990

Nephrotoxicity of common drugs used by urologists.

Many clinically popular drugs, such as aminoglycoside antibiotics, amphotericin B, radiographic contrast media, analgesics, platinum-based cancer chemotherapy, and cyclosporine, can cause deterioration of kidney function even when the dose has been adjusted properly for renal insufficiency. The authors review the pathophysiologic mechanisms of nephrotoxicity of these drugs and prevention and treatment strategies.

Aminoglycosides↗
PubMed1989

Contrast-associated nephropathy.

Contrast nephropathy can be defined as an acute impairment of renal function that follows exposure to radiocontrast materials and for which alternative explanations for renal impairment have been eliminated. Based on reported studies, the incidence of contrast associated nephropathy (CAN) varies from 0 to 22%. This wide variation can be traced to differences in study design and the criteria used to designate significant renal impairment. Irrespective of the exact incidence, 2 defined risk factors have been identified: preexisting renal disease and diabetes mellitus. Whereas preexisting renal insufficiency is the single most influential risk factor for CAN, when diabetes coexists the incidence approaches 100%. The clinical presentation of CAN is distinct, having a temporal relation between the performance of the contrast study in the high-risk patient and the onset of an increase in serum creatinine levels within the next 24 hours. Serum creatinine values greater than 50% of baseline or rising 1 mg/dl or more is diagnostic. The peak serum creatinine level occurs within 3 to 5 days of the contrast study and oliguria is associated in approximately 30% of the cases. Monitoring serum creatinine is the most useful clinical procedure in high-risk patients after angiography. At least 5 potential pathophysiologic mechanisms of CAN have been proposed: interference with renal perfusion, altered glomerular perm-selectivity, direct tubular injury, intraluminal obstruction, and immunologic mechanisms. Support for each mechanism, either singularly or in combination, can be found in published reports; however, none has achieved universal acceptance. The single most important clinical axiom regarding the prevention and management of CAN is, "Always use the least invasive diagnostic procedure available."(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1989

Risk factors for toxic nephropathies.

The best definition of risk factors for renal injury, irrespective of the aetiological agent, comes from observations in patients with acute renal failure. From such observations, two subdivisions have evolved, i.e., acute insults and host risk factors. Acute renal insults include: hypertension, sepsis, use of nephrotoxic drugs (e.g., aminoglycoside antibiotics and contrast media), haemoglobinuria or myoglobinuria, liver disease and extracellular volume depletion. Host risk factors include: advanced age, hypertension, gout and hyperuricaemia, diabetes mellitus, chronic renal failure and use of diuretics. Furthermore, the mechanism of acute renal injury can be correlated with different risk factors: for a tubular toxic agent, acting either directly on the cells or haemodynamically, a dose-dependency is characteristic; while for immunologically mediated injury, genetic predisposition is more important. The identification of risk factors for chronic toxic injury is confounded by the possibilities of multiple episodes of subclinical renal injury, the distinct possibility that a major component of the ageing process may be a loss of renal reserve, and a progressive body burden, of, e.g., cadmium, which may deplete intrinsic protective mechanisms. However, clinically relevant risk factors can alert the clinician to exercise additional caution when prescribing medications that are potentially nephrotoxic. Such factors include dehydration, pre-existing renal disease, age, co-existing diseases that cause renal ischaemia, gender, concomitantly administered drugs, and electrolyte abnormalities.

Age Factors↗
PubMed1979

Effect of milk constituents on hepatic cholesterol-genesis.

Two preparations active in reducing hepatic cholesterol biosynthesis were isolated from bovine skim milk. One of the inhibitors was in the dialysate and was identified as orotic acid (OA). The other inhibitor, present in the retentate, was not identified. Orotic acid appears to act by inhibiting cholesterol biosynthesis before the formation of mevalonate, whereas the retentate inhibitor exerts its effect beyond the formation of mevalonate in the biosynthetic pathway. Human milk also inhibited the incorporation of both labeled acetate and mevalonate into cholesterol by rat liver. Orotic acid was not detectable in human milk samples employed in this study. Administration of [6-14C]orotate to rats revealed its conversion to uracil in the liver. Subsequent work demonstrated that uracil had inhibitory activity on hepatic cholesterol biosynthesis similar to that of orotate when incubated with rat liver slices.

Acetates↗
PubMed1979

The influence of dosage regimen on experimental gentamicin nephrotoxicity: dissociation of peak serum levels from renal failure.

Peak serum levels of gentamicin were varied in rats by administering a standard nephrotoxic dosage of 40 mg/kg per day in one (QD), two, or three (TID) daily doses. The QD animals had the highest peak serum levels but showed no appreciable increase of serum creatinine concentrations over a 10-day treatment period. The TID rats had the lowest peak serum levels, but, after 10 days of drug administration, the serum creatinine concentration (2.8 +/- 0.2 mg/100 ml, mean +/- SE) was significantly higher than in control rats (0.6 +/- 0.01 mg/100 ml) (P less than 0.001). After two days of gentamicin treatment, the renal concentration of gentamicin was 269 +/- 77 micrograms/g in the QD rats and 820 +/- 29 micrograms/g in the TID rats (P less than 0.001). In this rat model, the frequency of doses was a more important factor in the development of nephrotoxicity than the peak serum concentration of gentamicin. The results suggest that dose frequency should be considered when data from different laboratories are compared.

Acute Kidney Injury↗
PubMed1979

Adrenocorticotropin-cortisol axis abnormalities in hemodialysis patients.

The ACTH-cortisol axis was studied in 15 hemodialysis patients. Basal plasma cortisol concentrations were found to be elevated and ACTH to be in the high normal range. Cortisol responded normally to exogenous ACTH, but neither cortisol nor ACTH were suppressed in response to oral dexamethasone. 11-Deoxycortisol and ACTH concentrations did not rise normally in response to either oral or iv metyrapone. We conclude that standard testing of the ACTH-cortisol axis in dialysis patients yields results suggesting Cushing's syndrome.

Adrenocorticotropic Hormone↗