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Biomedical subjects

L L Smith

Publications and source records attributed to L L Smith.

At least 181 records · Page 10Linked to original sources
PubMed1985

Ataxia-telangiectasia or Louis-Bar syndrome.

Ataxia-telangiectasia (A-T) is a clinical syndrome that commonly shows oculocutaneous telangiectasia, progressive cerebellar ataxia, recurrent sinopulmonary infections, increased incidence of malignancy, x-ray hypersensitivity, and autosomal recessive inheritance. Profound dysfunction of both humoral and cell-mediated immune systems is demonstrated by low IgA levels, an immature thymus, a poor response to antigenic challenges, and recurrent infections. The high risk of malignancy may be related to poor immune surveillance. Two cases (sisters) are reported demonstrating the typical features of the disease along with the results of a trial of the immunopotentiating drug, levamisole, in one of them. The features of A-T are reviewed and include the more recent findings of elevated serum carcinofetal proteins and chromosomal aberrations.

Adolescent↗
PubMed1985

Fibromuscular dysplasia of the internal carotid artery treated by operative transluminal balloon angioplasty.

Operative treatment of critical stenoses of the internal carotid artery secondary to fibromuscular dysplasia has been performed for nearly 2 decades using graduated metal dilators. While percutaneous transluminal balloon angioplasty of the internal carotid via the femoral artery has several advantages over the operative metal dilator method, cerebral embolization is a matter for concern. The authors have performed operative transluminal balloon angioplasty in such cases, permitting backbleeding with removal of any thrombi or debris. This technique combines the advantages of dilatation by a Grüntzig balloon with post-dilatation carotid backbleeding. Five patients have been successfully treated thus far using this technique.

Aged↗
PubMed1985

Sequential internal mammary artery grafts. Expanded utilization of an ideal conduit.

The internal mammary artery, when used as a conduit for coronary artery bypass, offers a better long-term patency rate and survival rate than the saphenous vein; however, its utility has been limited. Among other factors, the availability of only two internal mammary arteries for anastomosis has been a major limitation. In an attempt to overcome this limitation, we constructed sequential internal mammary artery grafts in 87 patients. In 49 patients (Group I), only one internal mammary artery was used for sequential anastomosis. In another 31 patients (Group II), one internal mammary artery was used for sequential anastomosis and the other was used for single end-to-side anastomosis. Both internal mammary arteries were used in seven patients (Group III) for the construction of sequential anastomoses. Postoperatively, 64 patients were evaluated by exercise stress tests. None of these patients had a positive stress test although seven patients (11%) had electrocardiographic changes that were considered equivocal. Coronary angiography was performed in 35 of the 87 patients, with 92 vein grafts and 90 internal mammary artery anastomotic sites evaluated within 1 year of operation. A total of 83 vein grafts and 84 internal mammary artery anastomotic sites evaluated within 1 year of operation. A total of 83 vein grafts and 84 internal mammary artery anastomoses were found to be patent. Thus the patency rate for vein grafts was 90% and for internal mammary artery grafts, 93%. During the follow-up period (8 to 52 months), three patients died and one was lost to follow-up. Among the remaining patients, 79 had complete relief from symptoms, three had minimal symptoms, and one patient obtained no relief from symptoms. Based on these results, we have concluded that the extended use of internal mammary artery, constructing sequential anastomoses, is technically feasible and provides adequate perfusion to the area of myocardium supplied by such grafts.

Adult↗
PubMed1984

A search for mutagens in human aortal lipid extracts.

In view of hypotheses suggesting mutagenesis is implicated in atherosclerosis, a total of 18 lipid extracts of human aortal tissues was examined by the standard Ames mutagenicity bioassay using Salmonella typhimurium or by a liquid modification thereof. One lipid extract of intimal-medial tissue contained detectable mutagenic activity against test strain TA98 in the liquid medium bioassay and against TA1538 in the standard plate assay following metabolic activation. Six other samples appeared to have weak activity against strains TA98, TA1538, or TA100. The other aortal samples were nonmutagenic.

Aorta↗
PubMed1984

On reaction of sterol hydroperoxides with superoxide.

Reduction of sterol hydroperoxides 3 beta-hydroxy-5 alpha-cholest-6-ene-5-hydroperoxide and cholesterol 7 alpha-hydroperoxide by KO2 (or other strong base in air) solubilized by crown ether in dimethylsulfoxide gave only corresponding alcohols, but in the presence of cholesterol (or other sterols) gave 3 beta-hydroxycholest-5-en-7-one together with the corresponding alcohols. Both hydroperoxides likewise gave the corresponding alcohol and ketone products with KO2 in benzene and in oxidations by ceric ammonium nitrate in a biphasic system. The 7-ketone product is recognized as deriving from termination reactions of sterol peroxyl and/or oxyl radicals.

Chemical Phenomena↗
PubMed1983

Structural requirements of compounds to inhibit pulmonary diamine accumulation.

The diamine, putrescine, is accumulated into slices of rat lung by a temperature and energy dependent process similar to that responsible for the uptake of cadaverine, the polyamines spermidine and spermine, and the herbicide paraquat. Structure-activity studies using monoamines and diaminoalkanes, amino acids and guanidino compounds, have shown that in order to inhibit the pulmonary accumulation of putrescine, chemicals should possess at least one but preferably two nitrogen-containing cationic groups. In the series of alpha, w-diaminoalkanes studied, the inhibitory potential increased with increasing chain length, reaching a plateau at 1,7-diaminoheptane. These observations together with the fact that putrescine is a good substrate for the uptake system (Km 15 microM, Vmax 704 nmoles/g wet wt/hr) suggest that effective inhibitors require at least four methylene groups between their cationic centres and that diamines with more methylene groups may fold to give this separation. With both the monoamines and the alpha, w-diaminoalkanes, changes in the free energies of interaction suggest that the observed increases in inhibitory potential with increasing chain length are due to increased hydrophobic bonding, which is a consequence of the addition of methylene groups to the alkyl chain. Furthermore, the ability of compounds to inhibit putrescine uptake appears to be related to their propensity to bind with the appropriate site for putrescine. Steric hindrance of this ionic interaction by the quaternisation of the cationic centres of the inhibitors with methyl groups, results in a total loss of measurable inhibitory activity. Also, the introduction of anionic carboxyl groups into inhibitors result in a loss of inhibitory potential, probably due to ionic repulsion. The antileukaemic drug, methylglyoxal-bis-guanylhydrazone (MeGAG), and its congeners, were some of the most potent inhibitors of putrescine uptake studied. Our findings suggest similarities between the uptake system for putrescine into the lung with other uptake systems described for MeGAG and certain polyamines.

Amines↗
PubMed1983

The accumulation of putrescine and paraquat into lung slices taken from BHT treated mice.

Putrescine and paraquat have been shown to accumulate in slices of mouse lung by a process which obeys saturation kinetics. The Vmax for the process was similar for both compounds (1.18 and 1.29 mumol/g wet wt/h) although the apparent Km for putrescine was 15 microM compared with 209 microM for paraquat. Mice were given a range of doses of BHT (i.p.) and the sequence and nature of the changes in morphology of the lung determined by light and electron microscopy. Lung slices were prepared from mice given BHT, and their ability to accumulate both paraquat and putrescine was determined. Within 4 days of dosing with 200 mg BHT/kg, there was marked cellular proliferation in the lung with an increase in the number of type II epithelial cells. Seven days after dosing the lungs had generally returned to their normal morphology with only occasional areas in some lungs showing evidence of damage. Between 1 day and 7 days after dosing, slices of mouse lung showed a reduced ability to accumulate paraquat or putrescine. This did not return to control values until 14 days. The greatest reduction in the accumulation of either compound was seen 4 days after dosing when the proliferation of the type II epithelial cells was most marked. Mice given 150 mg BHT/kg showed similar but less extensive morphological change and the ability of lung cells from these mice to accumulate paraquat or putrescine was not as severely reduced compared with mice given 200 mg BHT/kg. With doses of 100 mg BHT/kg the accumulation of paraquat and putrescine was only slightly reduced and there was a correspondingly minimal affect on lung morphology. The lungs of mice given 50 mg BHT/kg were unaffected as was their ability to accumulate either compound. The results from this study, when taken in the context of previously reported data, support the conclusion that paraquat is accumulated into the lung by a process responsible for the uptake of putrescine. In the rat, paraquat and putrescine are known to accumulate in alveolar type II cells and therefore it appears that the regenerating alveolar type II epithelial cell is functionally unable to accumulate these compounds and may be considered physiologically similar to type II epithelial cells in immature animals.

Animals↗
PubMed1982

The accumulation of diamines and polyamines into rat lung slices.

The diamine cadaverine, and the polyamines spermidine and spermine have been shown to accumulate into rat lung slices by an uptake process which obeyed saturation kinetics. The apparent Km values for the accumulation process of cadaverine, spermidine and spermine were 19, 11 and 15 microM respectively with Vmax values of 937, 768 and 617 nmoles/g wet weight/hr respectively. The accumulation was KCN sensitive, indicative of an energy dependent process, although spermine did show some non-specific binding to lung tissue. Cadaverine, spermidine and spermine were not accumulated by slices of liver, kidney, heart and spleen to concentrations much greater than that in the medium. They were accumulated, however, by a KCN sensitive process into brain slices although the accumulation was much less than that which occurred in lung slices. The diamine, putrescine, exhibited a concentration-dependent inhibition of the ability of lung slices to accumulate cadaverine and the polyamines. These data have led us to conclude that the transport process in the lung, which has recently been shown to accumulate the diamine putrescine, is also capable of accumulating cadaverine, spermidine and spermine. Thus, by analogy with putrescine, there exists in specific lung cells a membrane receptor(s) which is selective in its acceptance and transport of diamines and polyamines.

Animals↗
PubMed1982

The formation of mixed disulphides in rat lung following paraquat administration. Correlation with changes in intermediary metabolism.

We have investigated the hypothesis that the formation of mixed disulphides between protein sulphydryl and glutathione may be responsible for controlling the activity of the pentose phosphate pathway and fatty acid synthesis in rat lung. Using lung slices, taken form rats 2 h after dosing with a range of concentrations (5-80 mg/kg) of the pulmonary toxin paraquat, the pentose phosphate pathway was found to be stimulated in direct proportion to a reduction in fatty acid synthesis. These effects were also linearly related to an increase in mixed (total) disulphide levels in the lung. This was quantitatively similar to an increase in mixed (glutathione) disulphides, although non-protein sulphydryl and oxidised glutathione levels remained normal. Thus, an early biochemical event in the mechanism of the paraquat toxicity in the lung involves an increased formation of mixed (glutathione) disulphides and simultaneous regulation of pentose phosphate pathway activity and fatty acid synthesis. These data support the concept that the formation of mixed disulphides of protein and glutathione is a mechanism for maintaining NADPH levels despite the 'redox' stress caused by the cyclical and NADPH dependent reduction and reoxidation of paraquat.

Animals↗
PubMed1982

The changing pattern of hemolytic streptococcal gangrene.

We reviewed nine cases in which either limg-threatening or life-threatening complications developed due to streptococcal infection. Our findings indicate important changes in the pattern of this fulminating illness since its original description in 1924. A higher mortality reflects increased longevity with a greater frequency of impaired host resistance and degenerative diseases involving vital organs. Initial symptoms and signs often mimic acute thrombophlebitis, acute arthritis, deep soft-tissue trauma, or acute vascular occlusion. The emergence of multiple organ failure and serious coagulation disorders are a challenge to current therapy. A diagnostic algorithm was developed to aid in the early diagnosis and management of this life-threatening infection.

Adult↗
PubMed1982

Rate of endothelialization in venous thrombi: an experimental study.

Little is known about the rate of endothelialization of venous thrombi. This study was performed to determine the time required for complete endothelialization of the head of standardized thrombi in medium-sized veins (4 to 5 mm) in dogs. This information was sought to help determine the optimal duration of anticoagulation therapy in patients with acute venous thrombi. While endothelial growth was observed as early as three days, endothelialization of the head of the thrombus was not complete until 14 days in seven of eight venous thrombi. These experimental findings suggest that therapeutic anticoagulation should be continued for at least ten to 14 days if maximum benefit is to be achieved.

Animals↗
PubMed1982

Young Scientists Award lecture 1981: The identification of an accumulation system for diamines and polyamines into the lung and its relevance to paraquat toxicity.

The energy dependent accumulation of the herbicide paraquat into the lung is known to be a major factor responsible for the selective toxicity of paraquat to this organ. The studies reported in this paper were designed to examine the hypothesis that the transport process responsible for the accumulation of paraquat is present to accumulate endogenous substrates from the plasma. Paraquat is accumulated into the lung by a process which is different from that responsible for the uptake of the monoamine, 5-hydroxytryptamine (5HT). Furthermore, 5HT is known to be accumulated into the endothelial cells of the lung whereas paraquat was accumulated, at least in part, by the alveolar type I and type II epithelial cells. In the search for compounds which would reduce the uptake of paraquat into the lung a series of diamines were found to be the most effective inhibitors. In particular the diamine, putrescine, effectively inhibited the uptake of paraquat into the lung and was itself accumulated by a process which obeyed saturation kinetics. The apparent Km for the process was 7 microM with a Vmax of 330 mumoles/g wet weight lung/h. This apparent Km is an order of magnitude lower than that for the uptake of paraquat. The uptake of putrescine was inhibited when paraquat was present in the incubation medium or when the metabolic inhibitors rotenone, or iodoacetate together with KCN were added. Putrescine was not accumulated by slices of liver, kidney, heart or spleen. It was taken up into brain slices by a KCN sensitive process although the accumulation was much less than that which occurred in lung slices. Thus, in these respects the uptake of putrescine is similar to that which has been described for paraquat. The uptake of putrescine into lung slices with damaged type I and type II alveolar epithelial cells was reduced as was the uptake of paraquat. The reduction was similar for both compounds suggesting they were both taken up into the same cellular compartment. The studies described in this paper suggest that (i) the process in the lung which accumulates paraquat is that which is normally responsible for the uptake of putrescine in particular and endogenous diamines and polyamines in general and (ii) this uptake process is located in the alveolar type I and type II epithelial cells.

Animals↗
PubMed1982

Further investigations of mutagenic cholesterol preparations.

The previously demonstrated mutagenicity of naturally air-aged (autoxidized) USP cholesterol in test strains of Salmonella typhimurium has been confirmed. In contrast, autoxidized brassicasterol, 7-dehydrocholesterol, ergosterol, lanosterol, sitosterol, and stigmasterol were non-mutagenic in the same assay, and 38 individual cholesterol derivatives, including many cholesterol autoxidation products, were also non-mutagenic. The mutagenic species from mutagenic cholesterol preparations were shown to be neutral steroids that are very much more polar than the cholesterol autoxidation products so far identified. High-performance liquid chromatography resolved mutagenic cholesterol preparations into several mutagenic and non-mutagenic fractions. The chemical nature of the mutagens is suggested as involving oxidation of the sterol B-ring and of the side-chain.

Cholesterol↗