Biomedical subjects

C D Smith

Publications and source records attributed to C D Smith.

At least 199 records · Page 11Linked to original sources

PubMed1992

Effect of zinc binding on the structure and stability of fibrolase, a fibrinolytic protein from snake venom.

Fibrolase is a metalloprotease with potential use as a fibrinolytic agent. Loss of the intrinsic zinc atom leads to a rapid decrease in enzymatic activity. Circular dichroism measurements indicate that there is a partial unfolding of an alpha-helical section of the protein concomitant with the loss of zinc. Removal of zinc can be affected by elevated temperatures, acidic pH values, and addition of chelating agents. At low molar concentrations, both ethylenediaminetetraacetic acid (EDTA) and dithiothreitol (DTT) were found to remove zinc efficiently. Analysis of the sequence of fibrolase identified a segment which possessed a high degree of homology with the metal binding site of other zinc proteases, such as thermolysin and the collagenases. However, the putative zinc binding site in fibrolase lacks the additional glutamate ligand found in thermolysin and subtilisin. This sequence is also predicted to adopt an alpha-helical conformation. Together, these data indicate that there is a well-defined metal binding site in fibrolase and that metal binding is the most important factor governing the stability of this protein.

Amino Acid Sequence↗

PubMed1992

Correction of ischaemic brain acidosis with SQ29,548/1-benzylimidazole.

Thromboxane A2 (TXA2) is a proaggregatory vasoconstrictor that is synthesized and released during reperfusion of ischaemic brain. We administered a TXA2 receptor antagonist, SQ29,548, and a thromboxane A synthase inhibitor, 1-benzylimidazole (1-BI), to rats subjected to 30 min of reversible forebrain ischaemia. Cerebral thromboxane B2 (TXB2), the stable metabolite of TXA2, measured after 60 min of reperfusion was 0.37 +/- 0.08 ng/mg brain protein in animals treated with SQ29,548/1-BI compared with 1.20 +/- 0.16 in ischaemic controls (p < 0.05). Cerebral pH determined by 31P magnetic resonance spectroscopy was higher in treated animals, 7.06 +/- 0.04, than in ischaemic controls, 6.5 +/- 0.01, after 20 min of reperfusion (p < or = 0.01). The significant elevation of cerebral pH in treated animals persisted at 30 (7.17 +/- 0.05 vs. 6.5 +/- 0.01; p < or = 0.01), 35 (7.17 +/- 0.05 vs. 6.44 +/- 0.04; p < or = 0.01), and 40 min of reperfusion (7.06 +/- 0.06 vs. 6.37 +/- 0.01; p < or = 0.05). We conclude that SQ29,548/1-BI reduces thromboxane levels and promotes resolution of tissue acidosis in ischaemic brain. The combination of a TXA2 receptor antagonist with a thromboxane A synthase inhibitor deserves further study as a potential treatment for acute cerebral infarction.

Acidosis↗

PubMed1992

Nissen fundoplication in children with profound neurologic disability. High risks and unmet goals.

Anti-reflux procedures have been advocated in children with profound neurologic disability referred for feeding gastrostomy when gastroesophageal reflux is present. Facilitation of care, reduction in pneumonia and vomiting, and improvement in the general health and survival of these children have been major goals of fundoplication and gastrostomy. In large pediatric series, these procedures have been reported to have low risk and negligible mortality rates. Recent reports, however, document an increased incidence of sequelae of fundoplication in children with profound neurologic disability. This paper retrospectively reviews a series of 35 nonverbal, nonambulatory pediatric patients undergoing a total of 39 fundoplications (37 Nissen, 1 Thal, and 1 Belsey) over an 11-year period. Neurologic impairment of 17 (49%) patients was acquired, 13 (37%) congenital, and 5 (14%) due to a syndrome. Perioperative complications occurred in six (17%). Three additional complications led to early postoperative death. A fourth early death was unexplained. Fourteen (40%) had recurrent pneumonia, 11 (31%) recurrent vomiting, 8 (23%) choking-gagging-retching complex, and 3 (9%) bowel obstruction requiring laparotomy. Recurrent gastroesophageal reflux was documented in seven (20%) patients. A second ARP was performed in six (17%). There were 14 (40%) late deaths. Although the major goals of anti-reflux procedure are clearly achieved in many severely impaired children with gastroesophageal reflux, the use of Nissen fundoplication to resolve the complications of swallowing disorders and improve outcome with an acceptably low risk in this complex set of patients does not appear to be established.

Adolescent↗

PubMed1992

Plasmodium coatneyi-infected rhesus monkeys: a primate model for human cerebral malaria.

Although several animal models for human cerebral malaria have been proposed in the past, none have shown pathological findings that are similar to those seen in humans. In order to develop an animal model for human cerebral malaria, we studied the pathology of brains of Plasmodium coatneyi (primate malaria parasite)-infected rhesus monkeys. Our study demonstrated parasitized erythrocyte (PRBC) sequestration and cytoadherence of knobs on PRBC to endothelial cells in cerebral microvessels of these monkeys. This is similar to the findings seen in human cerebral malaria. Cerebral microvessels with sequestered PRBC were shown by immunohistochemistry to possess CD36, TSP and ICAM-1. These proteins were not evident in cerebral microvessels of uninfected control monkeys. Our study indicates, for the first time, that rhesus monkeys infected with P. coatneyi can be used as a primate model to study human cerebral malaria.

Animals↗

PubMed1992

A primate model for human cerebral malaria: Plasmodium coatneyi-infected rhesus monkeys.

A major factor in the pathogenesis of human cerebral malaria is blockage of cerebral microvessels by the sequestration of parasitized human red blood cells (PRBC). In vitro studies indicate that sequestration of PRBC in the microvessels is mediated by the attachment of knobs on PRBC to receptors on the endothelial cell surface such as CD36, thrombospondin (TSP), and intercellular adhesion molecule-1 (ICAM-1). However, it is difficult to test this theory in vivo because fresh human brain tissues from cerebral malarial autopsy cases are not easy to obtain. Although several animal models for human cerebral malaria have been proposed, none have shown pathologic findings that are similar to those seen in humans. In order to develop an animal model for human cerebral malaria, we studied brains of rhesus monkeys infected with the primate malaria parasite, Plasmodium coatneyi. Our study demonstrated PRBC sequestration and cytoadherence of knobs on PRBC to endothelial cells in the cerebral microvessels of these monkeys. Cerebral microvessels with sequestered PRBC were shown by immunohistochemical analysis to possess CD36, TSP, and ICAM-1. These proteins were not evident in the cerebral microvessels of uninfected control monkeys. Thus, our study indicates, for the first time, that rhesus monkeys infected with P. coatneyi can be used as a primate model to study human cerebral malaria. By using this animal model, we may be able to evaluate strategies for the development of vaccines to prevent human cerebral malaria.

Animals↗

PubMed1992

Pulmonary veno-occlusive disease and the CREST variant of scleroderma.

Pulmonary veno-occlusive disease is a rare cause of pulmonary hypertension. The authors describe a 48-year-old female with the Calcinosis-Raynaud's phenomenon-Esophageal dysmotility-Sclerodactyly-Telangiectasia (CREST) variant of scleroderma who developed acute pulmonary hypertension with pulmonary infiltrates and a normal pulmonary capillary wedge pressure. At post mortem examination typical changes of pulmonary veno-occlusive disease were found. Similarities between this and other cases in the literature suggest a possible association between the CREST variant of scleroderma and pulmonary veno-occlusive disease.

Female↗

PubMed1992

Cariostatic and ultraconservative sealed restorations: six-year results.

The objective of this clinical study was to determine the ability of an ultraconservative, sealed composite resin restoration, without a traditional cavity preparation and without the removal of the carious lesion, to arrest Class I caries. Tooth preparation was limited to placing a bevel in the enamel. These restorations were compared, over 6 years, with (1) ultraconservative, localized, sealed amalgam restorations with no extension for prevention and (2) traditional, unsealed amalgam restorations with the usual extension for prevention outline form. Caries was arrested by the ultraconservative, sealed composite resin restorations for 6 years. Complete sealant retention on the sealed amalgam restorations was somewhat lower than that on the sealed composite resin restorations; conversely, partial sealant retention was higher for the sealed amalgam group. The marginal integrity of the sealed amalgam restorations was significantly superior to that of the unsealed amalgam restorations. The sealant also protected Class I posterior composite resin restorations against wear.

Adolescent↗

PubMed1992

The protein kinase inhibitor, staurosporine, does not inhibit phosphoinositide kinases.

The effects of the protein kinase inhibitor staurosporine on phosphatidylinositol (PI) kinase and phosphatidylinositol 4-phosphate (PIP) kinase activities in brain membranes, and the synthesis of polyphosphoinositides in cultured NIH 3T3 fibroblasts were examined. Staurosporine, at concentrations up to 1 microM did not significantly modulate either PI kinase or PIP kinase activity in brain membranes. DNA synthesis was dose-dependently inhibited by sub-nanomolar concentrations of staurosporine; however, cells treated with up to 1 microM staurosporine contained levels of PIP and phosphatidylinositol 4,5-bisphosphate (PIP2) similar to those observed in untreated cells. Therefore, phosphoinositide kinases do not appear to be either directly or indirectly affected by staurosporine.

1-Phosphatidylinositol 4-Kinase↗

PubMed1992

Cyclic interdigestive pancreatic exocrine secretion: is it mediated by neural or hormonal mechanisms?

Cyclic interdigestive exocrine pancreatic secretion and duodenal motility are closely linked. However, the mechanisms controlling this association are not well understood. The aim of this study was to determine whether a neural or hormonal mechanism controls the temporal association of interdigestive secretion and duodenal motility. In five dogs, the pancreas was autotransplanted to the pelvis with anastomosis of the pancreatic duct orifice to the bladder. Electrodes were positioned to monitor motility patterns of the in situ duodenum. After 10 days, dogs were studied on four occasions during fasting. Pancreatic output of amylase activity continued to cycle, but the periodicity of enzyme peaks (mean +/- SE) was different from the period of the duodenal migrating motor complex (MMC) (60 +/- 3 vs. 125 +/- 7 minutes; P less than 0.05). When grouped according to phase of duodenal MMC, amylase output per 10 minutes during phase I was significantly less than the outputs during phase II or III (135 +/- 52, 214 +/- 78, and 228 +/- 73 x 10(3) U; P less than 0.05). However, there was no temporal relationship of the cyclic output of amylase to duodenal phase III. No differences were found when amylase output was analyzed for the 30 minutes before phase III compared with the 30 minutes after phase III (687 +/- 253 vs. 378 +/- 110 x 10(3) U; P greater than 0.05). Plasma motilin concentrations varied with duodenal MMC, but no relationship existed between plasma motilin or plasma pancreatic polypeptide and peaks in amylase output. This study suggests that the close temporal coordination of interdigestive pancreatic exocrine secretion and duodenal motility is controlled primarily by a neural mechanism.

Amylases↗

PubMed1992

Sealed restorations: 5-year results.

This clinical study determined the feasibility of a sealed resin composite restoration to arrest dental caries using a minimal tooth preparation: a bevel in enamel only without removal of the carious lesion. These ultra-conservative sealed composite restorations placed over caries (CompS/C) were compared with ultra-conservative sealed amalgam restorations (AGS) that had no "extension for prevention". The CompS/C restorations were also compared with the traditional (unsealed) amalgam restorations (AGU) with the "extension for prevention" outline form. Caries progress, as determined by standardized radiographs, revealed that after 5 years caries remained arrested under the CompS/C restorations; the marginal integrity was similar for the CompS/C and the AGS groups, and exhibited highly significant superiority to the AGU restorations (Chi square, P less than = 0.00004). Complete sealant retention over the amalgam restorations (AGS group) was less than over the composite restorations (CompS/C), and conversely, partial sealant retention was higher for the AGS group. Sealants also appeared to protect the posterior composite restorations against wear.

Adolescent↗

PubMed1992

Liver transplantation: living-related donations.

The LRLT procedure appears to be a promising alternative and adjunct to conventional liver transplantation. The advantages to this technique are a donor for each recipient, an improved quality of graft, and a reduction in pretransplant mortality in children. The procedure is not without risks, but the overall benefits seem to outweigh these risks, and only future experience will tell otherwise. Will there continue to be a need for such a procedure? We believe there will be, because the number of candidates needing transplantation will continue to grow and the demand for cadaveric organs will never be met. However, the procedure is extremely labor and resource intensive, and it is our belief that only a handful of large major medical centers will be able to adopt a live-donor program.

Adult↗

PubMed1991

Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease.

The relationship between Alzheimer disease (AD) and aging is not currently known. In this study, postmortem frontal- and occipital-pole brain samples were obtained from 16 subjects with AD, 8 age-matched controls, and 5 young controls. These samples were analyzed both for protein oxidation products (carbonyl) and the activities of two enzymes vulnerable to mixed-function oxidation, glutamine synthetase and creatine kinase. Glutamine synthetase is more sensitive to mixed-function oxidation than creatine kinase. Carbonyl content rises exponentially with age, at double the rate in the frontal pole compared with the occipital pole. Compared with young controls, both aged groups (AD and age-matched controls) have increased carbonyl content and decreased glutamine synthetase and creatine kinase activities, which are more marked in the frontal than occipital pole in all instances. We conclude that protein oxidation products accumulate in the brain and that oxidation-vulnerable enzyme activities decrease with aging in the same regional pattern (frontal more affected than occipital). However, only glutamine synthetase activity distinguishes AD from age-matched controls: Because glutamine synthetase activity is differentially reduced in the frontal pole in AD, we suggest that AD may represent a specific brain vulnerability to age-related oxidation.

Adult↗

PubMed1991

Balloon tracheoplasty in children: results of a 15-year experience.

Strictures of the trachea traditionally have been dilated by antegrade bouginage. This method not only dilates but imparts a shearing force to the wall of the trachea. The resultant trauma may contribute to further scarring and aggravation of the stricture. We report a 15-year experience with 37 patients and 158 tracheal dilatations using balloon catheters that impart only radially directed forces and can be precisely placed and gradually inflated. Various adjunctive techniques have been performed, including: (1) electrocautery of granulation tissue; (2) parenteral and local use of steroids; and (3) intraluminal stenting after dilation. Recent experience indicates that this combination of methods is important in improving patient outcome. The principal indications for balloon tracheoplasty include acquired tracheal stenosis from various causes, and congenital subglottic stenosis. Almost all patients received some immediate benefit from balloon tracheoplasty. Fifty-four percent of the patients achieved long-term improvement (with a minimum follow-up of 2 months). Additionally, 10 of 20 children who had been unable to previously tolerate removal of an indwelling tracheostomy tube proceeded to extubation. We have had poor success in treating bronchial and glottic stenosis. Endoscopically directed hydrostatic balloon tracheoplasty is a safe and effective method for the treatment of tracheal stenosis of varying causes. Multiple dilatations are required that gradually improve the character of the tracheal lumen. In selected cases, the procedure may delay or avoid the need for an open tracheoplasty.

Adolescent↗

PubMed1991

Stability of the thrombolytic protein fibrolase: effect of temperature and pH on activity and conformation.

The effect of temperature and pH on the activity and conformation of the thrombolytic protein fibrolase was examined. Fibrolase maintained proteolytic activity over 10 days at room temperature (approximately 22 degrees C). At 37 degrees C, greater than 50% of the proteolytic activity was lost within 2 days and no activity remained after 10 days. Circular dichroism (CD) spectra at elevated temperatures showed that alpha-helical structure was lost in a cooperative transition (Tm of 50 degrees C at pH 8). Structural changes were detected by NMR prior to unfolding which were not observable by CD, and the Tm determined by NMR was 46 degrees C at pD 8. The effect of pH on the proteolytic activity and structure of fibrolase was examined over the pH range from 1 to 10. Activity was maintained at neutral to alkaline pH values from pH 6.5 to pH 10.0 but decreased substantially in acidic media. While CD spectra indicated little variation in secondary structure over the pH range 5 to 9, significant differences were noted at pH 2 to 3. The melting temperature of fibrolase decreased to 43 degrees C at pH 5. Protein concentrations determined over the pH range of 1 to 10 showed an apparent solubility minimum at pH 5.0, which did not correspond to the isoelectric point of 6.5. Explanations for these observations are proposed.

Circular Dichroism↗

PubMed1991

Rhabdomyolysis and renal failure following a wolf attack: case report.

Trauma-induced rhabdomyolysis and myoglobinuric renal failure are well recognized. The mechanism of trauma in reported cases has been burns, crush injuries, or compression syndromes. We report a case of myoglobinuric renal failure in a 5-year-old boy who suffered primarily lacerations and penetrating wounds from a wolf attack. We are unaware of any other reports of nonvenomous bites or penetrating trauma causing rhabdomyolysis and myoglobinuric renal failure. Early suspicion, diagnosis, and treatment of this condition result in an excellent prognosis. Pathogenesis, treatment, and a review of the literature are presented.

Acute Kidney Injury↗

PubMed1991

Ultraconservative sealed restorations: three-year results.

The overall objective of this clinical study was to determine the feasibility of using a sealed composite restoration to arrest caries without the removal of the carious lesion and without the traditional cavity preparation. The minimal tooth preparation (a bevel in enamel) usually did not require any anesthetic injection and conserved tooth structure. These ultraconservative sealed composite restorations placed over caries (CompS/C) have been compared with ultraconservative sealed amalgam restorations (AGS) and with the traditional outline form (unsealed) amalgam restorations (AGU). This clinical study has shown that: (1) caries can be arrested by the CompS/C restoration for a period of three years; (2) the marginal integrity of the AGS restorations showed a definite trend toward improvement as compared to the AGU restorations; and (3) complete sealant retention over posterior restorations was similar in both the CompS/C and the AGS groups during the first two years; however, at Year 3 complete sealant retention was 16 percent higher in the CompS/C than in the AGS group.

Adolescent↗

PubMed1991

Intestinal and renal Na+/glucose cotransporters share common structures.

Polyclonal antibodies were raised to peptides selected from three different regions of the cloned rabbit intestinal Na+/glucose cotransporter. Western blot analysis was used to identify the fully mature protein in intestinal and renal brush borders. Two of the antibodies specifically identified a approximately 70-kDa protein band in rabbit intestinal brush borders but did not specifically immunoreact with membranes that do not have Na(+)-dependent glucose transport activity. The immunoreactive proteins had an apparent isoelectric point between pH 4.7 and 6.8. The antibodies also specifically recognized a similar-sized protein in human and seven other mammalian intestinal brush borders. Similar protein bands were identified in four mammalian renal brush-border membranes, indicating shared epitopes between intestinal and renal cotransport proteins. In some species, e.g., lamb and pig, the epitope for one antibody was missing in both intestinal and renal brush borders, suggesting that this epitope is not essential for function. These results suggest that 1) the cloned intestinal Na+/glucose cotransporter is that identified in earlier biochemical studies, 2) there is close structural similarity between intestinal and renal cotransporters, and 3) the structure of these proteins has been conserved during evolution.

Animals↗

PubMed1991

Clinical features and magnetic resonance imaging in congenital and childhood stroke.

Fifty-three (5%) of 1064 consecutively imaged children showed an arterial vascular pattern on magnetic resonance images, accounting for 12% of all abnormal studies. Signal abnormalities on T2-weighted scans persisted years after the clinical stroke occurrence. Ipsilateral atrophy of the pons or midbrain was found in 25% of subjects and was strongly associated with congenital lesions. Most infarctions occurred before or during the neonatal period; only 31% were acquired later. We did not find the paucity of posterior circulation lesions or the marked excess of left middle cerebral artery lesions seen in other series. Cardiac disease and venous infarction had an unexpectedly low occurrence. All of the children with arterial border zone infarction had been resuscitated in the neonatal period, while 37% of the children with a single artery infarction had no clinical history of acute illness.

Adolescent↗