Biomedical subjects
Publications and source records attributed to C R Young.
A 40-year-old woman presented a 6-week history of "fluttering" in her chest. A diagnosis of bilateral diaphragmatic myoclonus was made by fluoroscopy and electromyography of both hemidiaphragms. No central or peripheral cause was identified, but treatment with intravenous phenytoin had an immediate effect. With therapy, she has been symptom free for 12 months.
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The age of computerized gait analysis is here. There are several systems available to meet the needs of the podiatric practitioner. This author believes that the F-SCAN technology system makes a significant contribution to the practice of podiatric medicine. The system is user friendly, accurate, reproducible, and affordable. Its graphic display capabilities are colorfully attractive and easily understood. The primary focus of the F-SCAN system is that of peak pressure distribution over time. Vertical plantar pressure dispersion across the plantar surface of the foot is recorded, processed, and graphically displayed in terms of sequential gait changes. The system further allows for the manipulation of the accumulated data to present it in a more comprehensive manner. Future updates on the F-SCAN software are already close at hand and are expected to enhance the diagnostic capabilities of the system further. The four primary areas of clinical application for F-SCAN have been identified and briefly discussed. The recognition of certain biomechanical abnormalities, monitoring preorthotic and postorthotic use, evaluation of the diabetic or neuropathic foot, and presurgical and postsurgical functional examinations constitute this group. The F-SCAN system largely helps to remove some of the unavoidable guess work from essential diagnostic and therapeutic procedures. As we increase our understanding of the pathomechanics of these clinical problems, so too will we improve our management of the associated complications. Years ago, at the time when computerized gait analysis was being introduced to the podiatric profession, a frequently asked question was: What does it tell me that I don't already know or can't see by watching the patient walk?(ABSTRACT TRUNCATED AT 250 WORDS)
Monoclonal antibodies (mAbs) of predetermined specificity were prepared by immunizing with a free (i.e., not conjugated to any carrier) synthetic peptide representing region 15-22 (site 1) of sperm whale myoglobin (SpMb). The cross-reactions of Mb variants with three mAbs were studied in order to determine whether such interactions are influenced by substitutions outside the site. Finback whale Mb, which has no substitutions within region 15-22, showed lower cross-reactivity and relative binding affinity than the reference antigen, SpMb. Bottle-nose Atlantic dolphin myoglobin (BdMb) and badger myoglobin (BgMb), although they have identical substitutions within region 15-22 (Ala-15 to Gly and Val-21 to Leu), showed very different binding properties. The cross-reaction of BdMb was quite comparable to that of SpMb, while that of BgMb was much lower. Since the two proteins have identical structures in regions 15-22, the differences in their cross-reactivities are readily attributed to the effects of substitutions outside this region. Another pair of myoglobins, horse myoglobins (HsMb) and chicken myoglobin (ChMb), also have two identical substitutions (Ala-15 to Gly and Val-21 to Ile) within region 15-22, but possessed different cross-reactivity. The results indicate that the reaction of mAbs, whose specificity is precisely known and predetermined by the immunizing free peptide, can be markedly affected by substitutions outside the indicated binding region on the protein.
1. Adipose tissue from Angus and Brahman steers incubated with [1-14C]palmitate in the absence and presence of glucose exhibited a greater rate of lipid production than liver (P < 0.05). 2. Homogenates of adipose tissue used in the glycerol-3-phosphate acyltransferase assay exhibited a greater glycerolipid specific activity (nmol lipid/mg protein/30 min) when compared to liver (P < 0.05). 3. The inverse was true for liver homogenates when calculated for tissue activity (nmol lipid/g tissue/30 min). 4. Lysophosphatidate was produced in greater (P < 0.05) amounts than all other glycerolipids in the glycerol-3-phosphate acyltransferase assay. 5. The activity of phosphatidate phosphohydrolase in liver homogenates displayed greater rates than their respective adipose tissue homogenates. 6. Diacylglycerol acyltransferase activity was greater in adipose tissue homogenates compared to liver homogenates.
1. Two distinct fatty acid binding proteins (FABPs) were isolated and characterized from chicken duodenal mucosa. 2. Molecular weight, functional activity, immunospecificity, mRNA expression, and amino acid composition data for the 14 kDa chicken intestinal FABP was similar, yet not identical, to that of a previously isolated chicken liver FABP. 3. Bound fatty acids were shown to produce isoforms of the 14 kDa intestinal protein but not the larger molecular weight intestinal FABP.
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Natural protection from cholera is associated with local intestinal antibacterial and antitoxic antibodies, which appear to act synergistically. Although current parenteral cholera vaccines offer insufficient protection, new vaccines administered orally have more promise. Killed Vibrio cholerae, alone or given with the B subunit of cholera toxin, was evaluated in adult volunteers. Vaccinees, who received three doses of either vaccine, and unvaccinated controls ingested 10(6) V. cholerae organisms to determine the protective efficacy of the vaccines. The combination vaccine provided 64% protection, and the whole vibrio vaccine given alone provided 56% protection. In addition, illnesses in vaccines were milder than those in controls, and both vaccines gave complete protection against more severe disease. This substantial level of protection against a dose of V. cholerae that caused cholera in nearly 90% of controls suggests that these vaccines might provide at least as high a level of protection if given to the population of an endemic area. Indeed, a field efficacy trial is underway in Bangladesh, and preliminary data indicate a protective efficacy of 85% for a killed whole vibrio plus B subunit vaccine similar to that tested in volunteers and an efficacy of 58% for the killed whole vibrio vaccine alone. Thus, the studies in human volunteers were successful in predicting the substantial protection afforded by the vaccines in a cholera endemic area.
Twelve Angus X Hereford steers were assigned to either a control high-energy diet or a test diet consisting of 20% rapeseed at the expense of 20% corn. Twelve pigs were allotted to a control diet and two test diets containing either 10 or 20% canola oil (CO). Both CO and oil in the rapeseed contained 60 to 64% oleic acid. Cattle fed rapeseed exhibited little effect from the diet due to apparent indigestibility of the rapeseed. Total saturated fatty acids decreased from 40% in adipose tissue of the control pigs to 15% in the 20% CO-fed pigs. The ratio of monounsaturated to saturated fatty acids (M/S) increased from 1.19 in adipose tissue from control pigs to 3.63 with the addition of 20% CO to the diet. In muscle, the M/S ratio increased from 1.21 in control pigs to 2.46 in the 20% CO treatment group. The percentage of the saturated fatty acids in muscle decreased from 42% in the control to 23% in the 20% CO treatment. Significant increases in "oiliness" and decreases in fat firmness were observed when increasing levels of canola oil were fed. Sensory traits, cooking loss and shear-force values of pork chops were similar among treatment groups. In conclusion, monounsaturated fatty acid content can be elevated substantially in pork without adversely influencing the quality of the meat, thus producing a product perceived to be more healthful by the consumer.
During an investigation of a 1982 cholera outbreak in Truk, an area without endemic cholera, 254 post-outbreak serum specimens were collected from ill and well inhabitants of a single island. These were compared with 57 specimens collected in Truk in 1964, when heat-labile toxin-producing enterotoxigenic Escherichia coli was presumably endemic but cholera did not exist. The serum was tested for vibriocidal antibody and antitoxic antibodies to cholera toxin and heat-labile toxin and the ratio of the anti-cholera antitoxin to the anti-heat-labile antitoxin was calculated. The prevalences of elevated anti-cholera antitoxin and anti-heat-labile antitoxin levels were similar in both years: an elevated anti-cholera antitoxin was found in 30% of the 1964 and 80% of the 1982 specimens, while an elevated anti-heat-labile antitoxin was found in 40% (1964) and 84% (1982). In contrast, vibriocidal antibody titers were elevated in none of the 1964 but in 64% of the 1982 specimens, and the anti-cholera/anti-heat-labile antitoxin ratio was elevated in 4% (1964) and 42% (1982). The anti-cholera/anti-heat-labile antitoxin ratio appears to differentiate the antitoxic responses to Vibrio cholerae O1 and heat-labile toxin-producing enterotoxigenic E. coli, even in areas where both are prevalent, and should serve as a useful seroepidemiologic tool.
Serum immunoglobulin G antibodies to purified heat-labile enterotoxin (LT) from human (LTh) and porcine (LTp) Escherichia coli strains and cholera enterotoxin (CT) were measured by an enzyme-linked immunosorbent assay. Sera from patients with LTh E. coli infection showed a prominent response with LTh, an intermediate response with LTp, and a meager response with CT. Of 47 persons with clinical LTh-producing E. coli (herein shortened to LTh E. coli) infections, significant rises in antitoxin were detected against LTh in 36 (77%), against LTp in 30 (64%), and against CT in only 13 (28%) patients; seroconversions also occurred in 11 of 14 (79%) patients with subclinical LTh E. coli infections. In North Americans with experimental LTh E. coli infection, anti-Lth did not remain at high levels for more than 3 months. Persons with cholera manifested antitoxin responses that were similarly potent against all three toxin antigens; in fact, net optical density values were often slightly higher against LTh than against CT. The ratio of CT/LTh ELISA net optical density in convalescent sera proved to be a sensitive means to differentiate LT E. coli from cholera infection. All 11 cholera patients tested had CT/LTh ratios of greater than 0.70, whereas in only 1 of 47 LTh E. coli infections did the ratio exceed that value (it was 0.71) (P less than 0.0000000001). In single serum specimens, a net optical density of greater than or equal to 0.30 against LTh was shown to be a useful cutoff in screening sera for recent LTh E. coli or past cholera infection. The CT/LTh ratio was then used to differentiate definitively. Sera from healthy 3- to 5-year -olds and 15- to 19-year-olds in Maryland, Chile, and Bangladesh were tested against LTh and CT. The serological results fit known epidemiological observations. (i) LTh infections are rare in the United States (only 2 of 60 sera had LTh net optical density values of >/= 0.30. (ii) In contrast, evidence of recent LTh E. coli infections was very common in Chilean (69%) and Bangladeshi (57%) 3- to 5-year-olds and not uncommon in 15- to 19-year-olds (38 and 31%, respectively) in those countries. (iii) Only Bangladeshi sera showed serological evidence of cholera infections (CT/LTh ratios of > 0.70). The immunoglobulin G enzyme-linked immunosorbent assay measuring antibodies to purified LTh and CT represents a practical and effective tool for the serological study of LTh E. coli and cholera diarrheal infections.
Recent studies from this laboratory have found that synthetic peptides of proteins, as small as 6 residues, when administered in their free form (i.e. without coupling to any carrier) elicit the formation of antibodies with submolecular binding specificities to preselected protein regions. These peptides could represent either the antigenic sites of the protein or surface regions that are not immunogenic when the intact protein is the antigen. In either case the antibodies bind specifically to the intact protein, exclusively at the region used in immunization. In the present study we immunized BALb/c.ByJ and nude (BALb/c derived) strain mice with either Mb or synthetic antigenic site 5 of Mb. Radioimmune antibody binding studies showed that immunization of BALb/c.ByJ strain mice with either Mb or synthetic peptide resulted in the formation of antibodies that bound specifically to Mb, whereas nude mice did not produce such antibodies. These results indicate that the antibody response to both Mb and synthetic antigenic site is T-cell dependent.
Recent studies from this laboratory have found, contrary to a long-held belief, that synthetic peptides of a protein, as small as six residues, when immunized in their free form (i.e., without coupling to any carrier), elicit the formation of antibodies with submolecular binding specificities to preselected protein regions. These peptides could represent either the antigenic sites of the protein or surface regions that are not immunogenic when the intact protein is the antigen. In either case, the antibodies bind specifically to the intact protein, exclusively at the region used in immunization. Monoclonal antibodies with preselected specificities can also be produced by hybridoma technology from the spleens of the immunized animals. Furthermore, free synthetic peptides have been employed to generate T-cell lines and T-cell clones with specificities to preselected immunogenic locations and also to induce tolerance to such preselected locations. These fascinating breakthroughs indicate that free synthetic peptides may be used in the future as powerful tools in basic investigations and in therapeutic and diagnostic applications.
Thus, we have briefly touched upon several sources of potential postsurgical complications. When these various conditions arise, they most often interfere with the overall healing process or total recovery period. In addition to causing aggravation and concern to the surgeon, they frequently complicate the operative impressions of the patient. The basic prevention techniques discussed should provide a substantial decrease in postsurgical complications. In summary, proper medical history and physical examination, vascular evaluation, biomechanical, radiographic, and laboratory studies are important. To employ good surgical preparation and sterile technique is also an important preventive measure. Plan your site of incision to maximize the approach to the bone correction while minimizing trauma to the underlying soft tissue structures. Always be prepared with adequate and back up instrumentation, including new surgical blades, burs, or Brophies. Use the instrumentation that best accomplishes the work proposed or contemplated. Good tissue handling and dissection along with adequate flushing of the wound site with sterile saline solutions are necessary. The well-informed patient can also reduce or prevent postoperative complications by the fact that they have been educated and informed about the pre-, intra-, and postoperative course of events. In conclusion, we have presented the most common postsurgical complications, their possible etiology, prevention, and management. Hopefully, these subjects will stimulate the practitioner to be more aware of such complications and therefore recognize and treat these less than desirable events appropriately.
Texas Star-SR, an A- B+ mutant derived by nitrosoguanidine treatment from Vibrio cholerae El Tor Ogawa strain 3083, was fed to 68 volunteers as an oral vaccine in doses of 10(5) to 5 X 10(10) organisms with NaHCO3. Sixteen (24%) vaccinees experienced some loose stools (unrelated to vaccine dose), but in only one did the total stool volume exceed 1.0 liter. The vaccine strain was cultured from duodenal fluid of 35 of 46 (76%) persons who ingested doses of 10(8) organisms or greater. No A+ B+ toxinogenic revertants were found among 456 clinical isolates tested. Sixty-three vaccinees (93%) manifested seroconversions of vibriocidal antibody, whereas only 20 (29%) had significant rises in serum antitoxin titers. Paired intestinal fluids from 41 volunteers showed significant rises of secretory immunoglobulin A against lipopolysaccharide (29%), Ogawa outer membrane preparation (29%), and toxin (12%) antigens. In challenge studies with pathogenic V. cholerae El Tor Ogawa and El Tor Inaba, the attack rate in vaccinees (7 of 25) was significantly lower than in controls (18 of 25) (vaccine efficacy, 61%); furthermore, the diarrheal stool volume in vaccinees was significantly less than that in controls (P less than 0.01). Texas Star-SR served as a prototype to investigate the concept of immunoprophylaxis by means of attenuated strains as oral vaccines. These observations provide an invaluable background for planning future studies with newly developed attenuated strains prepared by recombinant DNA techniques.
Previous studies from this laboratory have resulted in the determination of the antigenic structure of sperm-whale myoglobin (Mb). In the present work, we have investigated the fine specificity requirements for T-cell recognition of one of the Mb antigenic sites (antigenic site 5). The antigenic site (peptide 145-153) and seven progressively longer peptides, increasing in length stepwise by two residues at a time, up to 22 residues in length (peptide 132-153), were synthesized. In addition, four truncated peptides were synthesized with intentional deletions at Tyr-151 and Ala-144. The T-cell recognition of these purified synthetic peptides was examined here in detail in three strains of mice (BALB/cByJ, B10.D2/n and SJL/J). Mb-primed mice afforded T-cells which proliferated to smaller peptides (two or four residues longer than the site; i.e. peptides 145-153 and 143-153) and more so to the longer peptides 135-153 and 132-153 and to Mb. No response was obtained to the truncated peptides, thus underscoring the fine specificity T-cells. No response was obtained also to intermediate-sized peptides. The latter result, due to an unfavourable mode of folding, suggested a conformational dependency in T-lymphocyte recognition.