Biomedical subjects
Publications and source records attributed to J Kuo.
Restriction of movement of the occluder of a single disc prosthetic valve is a serious and potentially fatal complication. We present a case in which the movement of the disc of a Medtronic Hall aortic valve was restricted by a loop of aortotomy closing suture inadvertently passed around the central guide of the valve.
A hepatitis B virus (HBV) immune escape variant which results from a substitution of glycine by arginine at position 145 (arginine-145) in the immunodominant neutralization epitope of the S protein was found to infect one child in a seroepidemiologic survey of 1,812 vaccinated children. The child's mother and a younger brother were also infected by the same HBV variant, despite a greater than accepted level of protective antibody (anti-HBV surface antigen) in both the index child (30 mIU/ml) and the brother (> 20,000 mIU/ml). Our findings suggest the perinatal or horizontal transmission of the arginine-145 HBV variant from mother to child, but the ability of this variant to propagate among the vaccinated children remains unknown.
Pneumolysin from Streptococcus pneumoniae was expressed in Escherichia coli as a glutathione S-transferase fusion protein and purified by affinity and hydroxylapatite chromatography. The purified recombinant pneumolysin (rPL), with a molecular mass of 53 kDa, had a specific activity of 3 x 10(5) hemolytic units per mg of protein on rabbit erythrocytes and reacted identically in immunodiffusion with the antisera against native pneumolysin. The rPL was used as a protein carrier to prepare conjugate vaccine with pneumococcal type 18C polysaccharide (PS18C). The PS18C was directly coupled to rPL by reductive animation or was indirectly coupled to rPL via a spacer molecule, adipic acid dihydrazide. The conjugates were nontoxic for mice and guinea pigs at 100 micrograms per dose. The immunogenicity and protective efficacy of both conjugates were tested in mice. A single dose of either of the vaccines elicited a rise in immunoglobulin G antibody production; after two booster injections of the vaccines, statistically significant booster responses (P < 0.001) to both rPL and PS18C were produced. The sera containing the antibodies to rPL were capable of neutralizing the hemolytic activity of rPL to rabbit erythrocytes and the cytotoxicity of rPL to bovine pulmonary endothelial cells. Immunization with the conjugate vaccines conferred statistically significant protection in mice against lethal challenge with type 18C pneumococci.
Fibrolase, the fibrinolytic enzyme from Agkistrodon contortrix contortrix snake venom, is a zinc metalloproteinase with a molecular mass of 23 kDa. We report a method to isolate two isoforms of natural fibrolase (fib1 and fib2) and three isoforms of recombinant fibrolase (r-fib1, r-fib2 and r-fib3) using CM 300 cation-exchange high-performance liquid chromatography. Utilizing mass spectrometry we characterized differences in molecular masses of the isoforms of r-fibrolase. These findings suggest that the isoforms differ by minor sequence variations at their amino-termini. Since the stability of fibrolase is exquisitely sensitive to the removal of zinc, we examined the EDTA sensitivity of the isoforms of fibrolase and r-fibrolase to determine if their different chromatographic behavior is related to differences in their zinc affinities. All of the isoforms examined appear to have similar zinc binding affinities. Thus, the IC50 (concentration of EDTA to produce 50% inhibition of enzymatic activity) for fib1 is 160 microM. For the closely related r-fib1, the IC50 is 180 microM. Similarly, r-fib3 has an IC50 of 140 microM.
The selenium in the diet of persons in arsenic-endemic areas, high levels of arsenic in the drinking water, was evaluated. The methodology used was that of 24-hr dietary recall. Daily selenium intakes of two rural towns in northern Mexico were found to be similar, approximating 72.9 and 60.6 micrograms. These values were similar to those of a previously arsenic-exposed area from California, Edison community. The Edison participants had a daily selenium intake of 61.8 micrograms. The possible negative effect of selenium to produce differences in reported geographical variation in disease could not be substantiated in this study. Other nutrient intakes, protein and energy were also found similar for communities. Differences were noted in vitamin A intake where one-third the daily requirement was experienced by Mexican participants compared to two-thirds the requirement being satisfied by those participants from Edison.
Mediastinal bleeding can be a problem after cardiac surgery, either as a result of coagulation derangements or technical problems. We evaluated 100 patients, treated with temporary chest packing for intractable bleeding, of 9,383 undergoing open heart operations during a 10-year period. Preoperatively, 60 of these patients had one or more predisposing factors for bleeding. There were four predominant sites of hemorrhage: general ooze, needle holes of the aortic and atrial suture lines, inaccessible origin, and another specific place. The chest was packed in the operating room in 84 patients and in the intensive care unit in 16. Four methods of temporary chest closure were used: the skin alone, partial sternal approximation plus skin closure, full closure, and the wound open and covered by a Steri-drape dressing. The bleeding was controlled in 65 patients who had been packed once, and in 29 patients after reexploration and multiple packings, for a total of 94 patients (94%). Sternal wound infection, generalized sepsis, and sternal dehiscence was present in 24 patients, 8 of whom died. The venue for inserting or removing the packs did not affect the incidence of infections. Our experience suggests that packing of the chest after cardiac procedures for intractable bleeding allows a reasonable patient salvage rate and complication risks.
The presence and distribution of Al and Mn in floral and seed tissues of eucalypts from Al-contaminated soils was analyzed using energy-dispersive X-ray microanalysis (EDS) in an environmental scanning electron microscope (ESEM). EDS by ESEM determined the distribution of elements between tissue types was suitable for intact samples or those with lower available moisture or intact specimens. The analytical technique was not appropriate for highly vascular samples. Other factors influencing the detection of elements by ESEM-EDS were electron scattering and the relative concentration and localization of elements within the tissues. EDS-detectable levels were significantly correlated with tissue concentrations determined by atomic absorption spectrophotometry for Mn but not for Al.
The preservation of endothelial integrity is essential for maintaining patency of vascular grafts. The internal mammary artery flow is often interrupted with the application of a soft vascular clamp to achieve a bloodless field during the anastomosis. We investigated the effect of the vascular clamp on the internal mammary artery endothelium using the scanning electron and light microscope. The endothelium was examined before and at 15 and 30 minutes after clamping in both the pedicled and the skeletonized arteries. Endothelial integrity was breached by clamping with early evidence of platelet adhesion to the damaged areas. The severity of the endothelial damage was related to the clamp time, but there was no difference in the degree of damage between the pedicled and the skeletonized arteries. We conclude that the vascular clamp causes injury to the internal mammary artery endothelium and may be implicated in early postoperative graft failure.
A 44-year-old man with aortic valve disease presented with myocardial ischaemia and ultimately infarction in the presence of suspected endocarditis. Thoracic computerised tomographic scan and coronary arteriography suggested the ischaemia was caused by external compression of the left coronary artery due to an aortic root abscess, later confirmed at surgery. Myocardial ischaemia is an infrequent accompaniment of infective endocarditis and is most commonly due to coexisting coronary disease. More rarely, emboli from vegetations may give rise to infarction. Although aortic root abscess is a well recognised complication of aortic valve endocarditis, coronary artery compression is an unusual mode of presentation and we believe this to be the first reported case of myocardial infarction resulting from external compression in this setting.
Complications following insertion of the Angelchik prosthesis are becoming increasingly recognised. We report a 35-year-old patient with both mediastinal migration and intraluminal oesophageal erosion of a prosthesis. Successful management included transthoracic removal combined with a modified onlay fundoplication over the oesophageal defect to prevent gastro-oesophageal reflux.
We describe a recently developed intracorporeal gas transfer device, its potential applications and hazards. To date, patients with potentially reversible respiratory failure have been treated with controlled oxygen therapy and positive pressure ventilation, but this treatment may itself contribute to lung parenchymal damage from barotrauma and oxygen toxicity. Total or partial extracorporeal gas exchange can be used to reduce these risks, but this treatment is complex and has significant morbidity and mortality. This gas exchange device has been designed to provide partial gas transfer with simplicity of insertion and use. The oxygenator lies in the vena cava to provide prepulmonary gas exchange. In preliminary studies with three calves we have shown that the device increases both mean mixed venous and arterial oxygen content and reduces mean arterial carbon dioxide tension.
Tn10 and IS10 transpose by a nonreplicative mechanism in which the transposon is excised from the donor molecule and integrated into a target DNA site, leaving behind a break at the original donor site. The fate of this broken donor DNA molecule is not known. We describe here two experiments that address this issue. One experiment demonstrates that a polar IS10 element gives rise to polarity-relief revertants at less than 1% the frequency of transposition of the same element in the same culture. In a second experiment, transpositions of an IS10 element from one site in the bacterial genome to another are selected and the resulting isolates examined for alterations at the donor site; none of 1088 such isolates exhibited a detectable change at the donor locus. These results are compatible with two possible fates of the transposon donor molecule: degradation ("donor suicide"), or restoration of the original information at the donor site by a recombinational repair mechanism analogous to double-strand break repair. These results argue against the possibility that the donor molecule gap is simply resealed by intramolecular rejoining.
Limited proteolysis by venoms was analysed by the cleaved peptide band(s) in SDS-polyacrylamide gel electrophoresis. The venom from Crotalus atrox degraded interferon, interleukin-2, IgG, IgM, and a crude form of acetyl cholinesterase but had no effect on IgA. Although the venom from Androctonus australis did not exert appreciable proteolysis on any of the immunoglobulins it had potent proteolytic activities against interferon and interleukin-2. The venom from Vespula maculifrons had only a minor proteolytic effect on interferon. The proteolysis by venoms was not effectively inhibited by alpha 1-antitrypsin or a2-macroglobulin. Moreover, no appreciable proteolytic activity was detected in the venoms from Bufo arenarum, Apis mellifera and Heloderma suspectrum.
Long-term storage of recombinant human epidermal growth factor (EGF), an important promoter of cell division, results in its conversion to a new species that elutes later than native EGF on a reverse-phase column. This new species, called EGF-X, has only 20% of the biological activity of native EGF. Peptide mapping indicated that the primary structure of EGF-X differs from that of native EGF solely within the first 13 residues. N-Terminal sequencing of EGF-X revealed that about 30% of the polypeptides have been cleaved at the Asp-3/Ser-4 bond. In addition, the yields after the His residue at position 10 were extremely low, indicating that a chemical modification occurs at residue 11 that is incompatible with Edman degradation. We hypothesized that aspartic acid 11 had been converted to an isoaspartyl residue, and this was confirmed with L-isoaspartyl/D-aspartyl methyltransferase, an enzyme that methylates the side-chain carboxyl group of L-isoaspartyl residues but does not recognize normal L-aspartyl residues. EGF-X, but not EGF, was found to be a substrate of this enzyme, and proteolytic digestion of EGF-X with thermolysin localized the site of methylation to a nine-residue peptide containing position 11. We did not observe formation of the isoaspartyl derivative in EGF that had been denatured by reduction of its disulfide bonds. In addition, replacement of the aspartyl residue at position 11 with glutamic acid resulted in a fully active EGF derivative that does not form detectable amounts of EGF-X. We propose that conversion of this aspartyl residue to isoaspartate is a significant nonenzymatic degradation reaction affecting this growth factor.(ABSTRACT TRUNCATED AT 250 WORDS)
Delayed hard palate closure (after age 6-7) was widely used for palatal repair in cleft palate children from 1976 to 1982. Since 1982, the approach has been revised into early complete closure of the soft and hard palate (before age 2). The articulation skills of 60 children with cleft lip and palate (age 3-5:11) who underwent early complete palate closure were compared with 47 children of similar age with soft palate closure only. The results indicated that the early complete closure group had more children with adequate articulation skills than the delayed hard palate closure group. Detailed analysis of the articulation patterns in each group revealed that the articulation substitution patterns made by the early complete closure group followed the trends of developmental articulation patterns, i.e. unaspirated, stopping and fronting phonological features. On the contrary, the articulation substitution patterns made by the delayed hard palate closure group were more related to structural deficits, i.e. compensatory articulation. Age 3-5 is a critical period for articulation maturation. We advocate that the complete palatal closure should be achieved before age 2 in order to equip cleft palate children with an equally normal oral structures to enhance speech/language development in a normal learning process during this critical period.
We studied the response to reimmunization at 36 months of age with Haemophilus influenzae type b (Hib) polyribosylribitol phosphate (PRP) capsular polysaccharide vaccine. Children enrolled in the study had previously received PRP or PRP plus diphtheria and tetanus toxoids with pertussis vaccine at 18 months of age. A control group of children, who received a first dose at 36 months of age, was also studied. Ninety-five percent of children receiving a second dose of vaccine had a postimmunization anti-capsular antibody level of greater than or equal to 1 microgram/mL. In comparison, 70% of 36-month-old children who received their first dose of PRP had a postimmunization level greater than or equal to 1 microgram/mL (P = 0.09). The geometric mean titer at 37 months of age was 8.64 micrograms/mL in children who had received two doses of PRP vaccine, compared with 2.19 micrograms/mL in the group who received only one dose of PRP at 36 months of age (P = 0.04). We conclude that infants immunized at 17 to 19 months of age with PRP had an excellent immunologic response to reimmunization at 36 months of age.
The development of articulation before surgical closure of the hard palate was compared in 75 preschool children with cleft lip and palate and 40 preschool children born without clefts. The children were aged 2 years to 5 years 11 months. The patients had significantly poorer articulation skills than the controls at each age level. Substitutions were the most frequent error, and they did not decrease with age in the patients. Fistula size and a history of speech therapy were significant factors in the articulation error scores only in 5-year-olds. No advantage in articulation proficiency was found for those who had worn a prosthesis to occlude the hard-palate defect.
By combining somatic cell genetics, in situ hybridization and Southern hybridization, we found that the c-sis oncogene in the human myelogenous leukemia cell line ML3 is translocated from the long arm (q11----qter) of chromosome 22 to the long arm (mid-portion or q21 region) of chromosome 17. This translocation does not result in rearrangement of the c-sis oncogene.