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Biomedical subjects

R F Smith

Publications and source records attributed to R F Smith.

At least 19 recordsLinked to original sources

Transmission-blocking antibodies recognize microfilarial chitinase in brugian lymphatic filariasis.

Brugia malayi is a parasitic nematode that causes lymphatic filariasis in humans. The monoclonal antibody MF1, which mediates clearance of peripheral microfilaremia in a gerbil infection model, recognizes two stage-specific proteins, p70 and p75, in B. malayi microfilariae. cDNA coding for the MF1 antigen was sequenced, and the predicted protein sequence shows significant similarities to chitinases from bacteria and yeast. When microfilarial extracts and purified preparations of the MF1 antigen were tested for chitinase activity, strong bands of chitin-degrading activity comigrated in SDS/PAGE with p70 and p75 and showed a reduction-dependent mobility shift characteristic of the MF1 antigen. Thus, the MF1 antigen is microfilarial chitinase, which may function to degrade chitin-containing structures in the microfilaria or in its mosquito vector during parasite development and transmission.

Amino Acid Sequence

Pattern-induced multi-sequence alignment (PIMA) algorithm employing secondary structure-dependent gap penalties for use in comparative protein modelling.

A multiple sequence alignment algorithm is described that uses a dynamic programming-based pattern construction method to align a set of homologous sequences based on their common pattern of conserved sequence elements. This pattern-induced multi-sequence alignment (PIMA) algorithm can employ secondary-structure dependent gap penalties for use in comparative modelling of new sequences when the three-dimensional structure of one or more members of the same family is known. We show that the use of secondary structure information can significantly improve the accuracy of aligning structure boundaries in a set of homologous sequences even when the structure of only one member of the family is known.

Algorithms

Deficient protein kinase C activity in turnip, a Drosophila learning mutant.

The Drosophila mutant turnip was initially isolated based on poor learning performance (Quinn, W.G., Sziber, P.P., and Booker, R. (1979) Nature 277, 212-214). Here we show that turnip is dramatically reduced in protein kinase C (PKC) activity. In addition, turnip flies are deficient in phosphorylation of a 76-kDa head membrane protein (hereafter pp76) which is a major substrate for protein kinase C in homogenates of wild-type flies. Reduced PKC activity, defective pp76 phosphorylation, and most of turnip's learning deficiency co-map genetically to a region on the X-chromosome, 18A5-18D1-2, spanned by the deletion Df(1)JA27. Apparently turnip+ is not a structural gene for PKC because Drosophila PKC genes map elsewhere in the genome. Our results suggest that turnip gene product is required for activation of PKC and that PKC plays a role in associative learning in Drosophila.

Animals

Management of infected aortoiliac aneurysms.

A 30-year retrospective review identified 13 patients treated for infected aneurysms of the abdominal aorta or iliac arteries, for an overall incidence of 0.65%. A constellation of clinical findings led to the correct preoperative diagnosis in 11 (85%) of 13 patients. Treatment methods included resection and in situ replacement grafting in seven patients, resection and extra-anatomic bypass in five patients, and resection-ligation in one patient. Four (31%) of 13 patients died within 30 days of operation, three of whom died of rupture. Overall, good results were achieved in five patients (38%), while poor results were noted in the remaining eight patients (62%). The determinants of outcome were aneurysm location or rupture, the presence of established infection, and the virulence of the infecting organism. In 10 (77%) of the 13 aneurysms, Salmonella species, Bacteroides fragilis, Staphylococcus aureus, and Pseudomonas aeruginosa accounted for all deaths, ruptures, and suprarenal aneurysm infections. These data suggest that patients with primary infections of the abdominal aorta or iliac arteries continue to present with advanced infections or aneurysm rupture that result in a high mortality.

Adult

Left flank retroperitoneal exposure: a technical aid to complex aortic reconstruction.

Over the last 5 years an extended left flank retroperitoneal approach was used in 85 of 531 (16%) aortic reconstructions deemed technically complex. Abdominal aortic aneurysm repair was performed in 70 patients (82%), bypass of aortoiliac occlusive disease was performed in 11 (13%), and aortic endarterectomy for mesenteric and/or renovascular disease was performed in 4 (5%). Indications for use of this approach included a "hostile" abdomen (43 patients), juxta/suprarenal abdominal aortic aneurysm (35), large (greater than 10 cm) abdominal aortic aneurysm (12), extreme obesity (10), associated renal and/or visceral artery stenosis requiring endarterectomy (9), inflammatory abdominal aortic aneurysm (2), and horseshoe kidney (2). Suprarenal or supraceliac aortic clamping, averaging 31 minutes, was required in 43 patients (50%). Postoperative recovery was rapid (average length of stay, 10.2 days), and morbidity was minimal despite the complex nature of these reconstructions. The perioperative mortality rate in elective operations was 1.2%. This approach facilitated proximal abdominal aortic exposure and anastomosis, especially in large, pararenal aneurysms or in situations unfavorable to a transabdominal approach. Whereas a left flank retroperitoneal approach can be used in most aortic reconstructions, it seems especially suited to those that pose significant technical challenges.

Abdomen

An evaluation of an InPouch TV culture method for diagnosing Trichomonas vaginalis infection.

A new culture method for Trichomonas vaginalis, the InPouch TV test, was evaluated for its sensitivity and specificity in supporting growth of trichomonads. Five clinical isolates remained viable for periods from 41 to 131 days. A strain from the ATTC 30001 remained viable for 91 days. As few as four trichomonads/ml of culture medium could be viewed microscopically within 24 h. Doubling time for growth of trichomonad varied between 5 to 8 h. In a clinical study of 102 wet-mount negative specimens, 15 culture positive patients were observed with the InPouch TV test compared with 12 of the same patients with Hollander's fluid medium.

Animals

Characterization of Andante, a new Drosophila clock mutant, and its interactions with other clock mutants.

A new clock mutant, named Andante, has been identified on the X chromosome of Drosophila melanogaster. Andante lengthens the period of the circadian eclosion and locomotor activity rhythms by 1.5-2.0 hours. The phase response curves for the eclosion and activity rhythms, indicating light-induced phase shifts, show a similar degree of lengthening. Andante also lengthens the periods of other clock mutants, including Clock, and alleles of the period locus. Analysis of locomotor activity rhythms reveals that Andante is semi-dominant, and Andante rhythms are highly temperature compensated. The sine oculis mutation, which eliminates the outer visual system, has no effect on the period of Andante. Deficiency mapping indicates that Andante is located in the 1OE1-2 to 1OF1 region of the X chromosome, close to the miniature-dusky locus. Whereas Andante flies have a dusky wing phenotype, dusky flies do not have an Andante clock phenotype.

Activity Cycles

The utility of cardiac evaluation in the hemodynamically stable patient with suspected myocardial contusion.

Myocardial contusion following isolated blunt thoracic trauma (BTT) remains a diagnostic and therapeutic dilemma. To identify the presence of cardiac abnormality following BTT, 123 hemodynamically stable patients were prospectively evaluated with serial electrocardiograms (ECG) and cardiac enzymes (total CPK and CPK-MB). Gated cardiac radionuclide angiography (MUGA) scans were performed within 48 hours following admission. Patients included in the study sustained significant thoracic trauma identified by physical findings or mechanism of injury. Sixty-three patients (51%) were identified with either abnormal ECG, or abnormal total CPK, CPK-MB, MUGA scan, or combination of the above. Thirty-seven patients (58.7%) manifested an ECG abnormality defined as ST-segment or T-wave abnormality. Twenty-two patients (34.9%) had total CPK value greater than or equal to 50 International Units (I.U.) or CPK-MB fractions greater than or equal to five per cent. MUGA scan was abnormal (right ventricular ejection fraction less than 40 per cent and/or wall motion abnormality) in 12 patients (19%). Eight patients with MUGA scan abnormality had normal ECG and/or normal total CPK, CPK-MB values. Evaluation of all patients up to six months revealed no mortality, malignant arrhythmias, or cardiac failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Effect of preslaughter experience on behaviour, plasma cortisol and muscle pH in farmed red deer.

Three groups of farmed red deer were shot in the field, three groups were slaughtered on the farm and three groups were transported to commercial slaughterhouses. The behaviour of the animals was observed and peripheral plasma cortisol concentrations were measured immediately after slaughter and neck muscle pH was measured 24 hours after slaughter. The deer could be handled and herded without agitation when only one unhindered direction was open to them and nothing in the environment caused alarm. Shallow angled loading ramps were preferable. Deer shot in the field and deer penned without handling had low average plasma cortisol concentrations (less than 7 ng/ml) and a muscle pH less than 5.74 whereas deer which had been herded on the farm, or transported to a slaughterhouse, had high cortisol concentrations (greater than 20 ng/ml) and a muscle pH above 5.74. However, only four of 66 male deer transported to a slaughterhouse had a muscle pH above 6.0, the pH associated with dark cutting meat in red deer.

Abattoirs

Intraoperative autotransfusion in vascular surgery.

To determine the impact of intraoperative autotransfusion on vascular surgical care, data related to 304 major vascular surgical operations performed over a 42-month period were retrospectively analyzed. Procedures included abdominal aortic aneurysmectomy (N = 152), aortobilateral femoral bypass (N = 60), thoracoabdominal aortic aneurysmectomy (N = 20), and other vascular procedures (N = 68). Fifty percent of the transfusion requirement was met by autotransfusion for the average patient. The per patient average volumes (liters) autotransfused were as follows: elective abdominal aortic aneurysmectomy, 0.87 L and nonelective, 1.45 L; elective aortobilateral femoral bypass, 0.63 L; elective thoracoabdominal aortic aneurysmectomy, 2.47 L, and nonelective, 2.15 L; and elective other, 0.53 L and nonelective, 1.30 L. Results of immediate postoperative and hospital discharge hemoglobin, hematocrit, and coagulation studies (prothrombin time, partial thromboplastin time, and platelets) did not differ from results of preoperative studies in any group. Neither mortality nor morbidity was related to intraoperative autotransfusion. These data suggest that intraoperative autotransfusion is a safe blood replacement method during major vascular surgical operations.

Adult

Automatic generation of primary sequence patterns from sets of related protein sequences.

We have developed a computer algorithm that can extract the pattern of conserved primary sequence elements common to all members of a homologous protein family. The method involves clustering the pairwise similarity scores among a set of related sequences to generate a binary dendrogram (tree). The tree is then reduced in a stepwise manner by progressively replacing the node connecting the two most similar termini by one common pattern until only a single common "root" pattern remains. A pattern is generated at a node by (i) performing a local optimal alignment on the sequence/pattern pair connected by the node with the use of an extended dynamic programming algorithm and then (ii) constructing a single common pattern from this alignment with a nested hierarchy of amino acid classes to identify the minimal inclusive amino acid class covering each paired set of elements in the alignment. Gaps within an alignment are created and/or extended using a "pay once" gap penalty rule, and gapped positions are converted into gap characters that function as 0 or 1 amino acid of any type during subsequent alignment. This method has been used to generate a library of covering patterns for homologous families in the National Biomedical Research Foundation/Protein Identification Resource protein sequence data base. We show that a covering pattern can be more diagnostic for sequence family membership than any of the individual sequences used to construct the pattern.

Amino Acid Sequence

The impact of volume on outcome in seriously injured trauma patients: two years' experience of the Chicago Trauma System.

The American College of Surgeons has stated that in considering the development of trauma systems it is important to ensure an appropriate volume of seriously injured patients be seen by each trauma center in order to achieve acceptable mortality rates. Clinical data supporting this recommendation are lacking. An analysis was performed on 1,643 seriously injured trauma patients to determine the relationship between volume and mortality rates. Three separate statistical methods were used: Pearson correlation coefficients, mortality odds ratios, and direct pairwise mortality comparisons. In addition, Tobit analysis was introduced as a method to analyze the relationship between volume and mortality. Mortality rates were adjusted for the confounding variable of serious head injury. Pearson correlation coefficients for volume vs. adjusted mortality was -0.65. Mortality odds ratios comparing the low-volume (less than 140 pts) trauma centers vs. the high-volume (greater than 200 pts) trauma centers was 1.3 for adjusted mortality rates (95% CI = 1.01-1.66; p = 0.04). Categorical analysis showed significantly different mortality rates in the centers before and after adjusting for patient mix. Tobit analysis showed the relationship between volume and mortality to be significant, accounting for 30-40% of the observed variation in mortality rates. In addition, Tobit analysis allowed construction of a model to predict mortality rates, given specific volumes of patients. Our data suggest that an inverse relationship exists between volume and mortality, and support the necessity of configuring trauma systems in a manner that will ensure designated trauma centers will see a high volume of seriously injured patients.

Adult

Ureteral complications and aortoiliac reconstruction.

A 33-year experience with 58 ureteral complications in 50 of 3580 patients undergoing aortoiliac reconstruction was analyzed. Ureteral obstruction was treated before or in conjunction with aneurysm repair in six patients with aneurysmal disease. The remaining 44 patients had 46 ureteral complications after aortic reconstruction; complications included hydronephrosis (42), ureteral leak (3), and ureteral necrosis (1). A high incidence of associated graft complications was noted. Graft thrombosis developed in one of the six patients undergoing prior or simultaneous ureteral procedures, and graft infection developed in another. Thirty-six graft complications developed in 24 (55%) of the 44 patients with postoperative ureteral complications. The complications included 19 anastomotic aneurysms, eight graft limb thromboses, six graft infections, and three aortoenteric fistulas. Twenty-nine of the 44 patients with postoperative ureteral complications underwent ureteral or graft operations or both. These included five patients having ureteral operations alone, seven with a ureteral procedure and subsequent graft operation, eight requiring simultaneous ureteral and graft procedures, and nine undergoing a graft operation with ureteral observation. Six of these 29 patients (21%) died after operation, all from graft complications including aortoenteric fistulas (three), ruptured anastomotic aneurysms (two), and graft infection (one). Graft complications affected 55% of 44 patients with postoperative ureteral complications, compared to 12% of 3536 patients without ureteral complications (p less than 0.0001). Patients with postoperative ureteral complications were 4.4 times as likely to have graft complications compared to those without ureteral complications (p less than 0.0001). These data suggest that such urologic complications may be markers for recognition of or harbingers for graft complications.

Adult

Renal insufficiency in community patients with mild asymptomatic microhematuria.

Primary-care physicians often must decide when patients with asymptomatic microhematuria warrant further testing for renal parenchymal disease. Because previous data had shown a greater frequency of elevated serum creatinine concentration in a population with asymptomatic microhematuria than in control subjects without hematuria, we reviewed the records of 125 patients with isolated asymptomatic microhematuria and elevated serum creatinine (AM/EC) and 83 comparison patients with no hematuria and elevated serum creatinine (NH/EC) from a previous population-based study to determine the relationship between renal parenchymal disease and isolated asymptomatic microhematuria. Serum creatinine was often elevated transiently because of volume depletion or shock, or elevations occurred in relationship to a terminal illness. Thus, only 63 AM/EC patients and 45 NH/EC control subjects had primary renal parenchymal disease or systemic disorders that caused an elevated serum creatinine. The patients selected from the asymptomatic microhematuria population because of elevated serum creatinine most often had low-grade hematuria and were typically 75 years of age or older. No disease was consistently found more frequently in the AM/EC patients than in the NH/EC group. Intervention at the time of the detection of hematuria might have altered the prognosis in 8% and probably would not have altered the prognosis in 78%. Therefore, exhaustive diagnostic testing to detect renal parenchymal diseases cannot be advised in asymptomatic elderly patients with low-grade (grade 1) microhematuria unless more specific indications are present.

Adult

Identification of new protein kinase-related genes in three herpesviruses, herpes simplex virus, varicella-zoster virus, and Epstein-Barr virus.

By using amino acid sequence patterns (motifs) diagnostic of conserved regions within the catalytic domains of protein kinases, homologous open reading frames of three herpesviruses were identified as protein kinase-related genes. The three sequences, herpes simplex virus gene UL13, varicella-zoster virus gene 47, and Epstein-Barr virus gene BGLF4, resemble serine/threonine kinases rather than tyrosine kinases.

Amino Acid Sequence

Toxicology screening in urban trauma patients: drug prevalence and its relationship to trauma severity and management.

Although toxicology screening is often used when treating trauma patients, its utility and significance remain controversial. Data from 623 toxicology screens performed in urban trauma center patients with mental status alterations are reported. The study patients were predominantly black and male, with a mean age of 32 (+/- 22) years. Overall, 86% of screens were positive. Substances of abuse, including ethanol, were noted in 525 (84%) of urine toxicology screens. Ethanol, cannabinoids, and cocaine were the drugs most commonly found in urine, with positivity noted in 53%, 37%, and 34% of screens. Serum analysis was 44% positive, with ethanol noted in 41% of patients. In blacks, the odds ratio of illicit drug use before trauma ranged from 1.9 to 4.2 (p less than 0.005), and in those aged 17 to 40 years, the odds ratio for illicit urine drugs ranged from 4.7 to 16.8 (p less than 0.001). In patients older than 40 years, the odds of a positive serum ethanol level were 1.7 times greater than in younger patients, and a level above 300 mg% was 3.8 times more likely in this age group (p less than 0.001). When serum ethanol was detected, the odds ratio of a head injury was 1.4 relative to patients without serum ethanol (p less than 0.06), and the odds ratio for abdominal injury was 1.6 for patients with serum ethanol (p less than 0.03). The odds of a TS less than 12 were 1.8 (p less than 0.05), and the odds of a GCS less than 12 were 3.3 (p less than 0.001) with ethanol levels greater than 100 mg%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent