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Biomedical subjects

J G Adams

Publications and source records attributed to J G Adams.

At least 37 records · Page 2Linked to original sources
PubMed1995

Gender and haplotype effects upon hematological manifestations of adult sickle cell anemia.

In Africa, the beta-globin gene cluster haplotype may be associated with variation of Hb F levels in subjects with sickle cell anemia (SS). These observations have not yet been conclusively confirmed in SS out of Africa, perhaps because of small sample sizes, the predominance of haplotype heterozygotes, and diverse influences, including gender, upon Hb F levels. We studied 384 adult African-American SS patients (mean age, 31 years) and explored the relationship of gender, beta-globin gene cluster haplotype, and alpha thalassemia to hematological values and Hb F levels. Both haplotype and gender influenced Hb F concentration. In the total sample, Hb F was higher in females than in males (8.2 vs. 6.5%). In 35 males who were either homozygous for the Senegal chromosome or had the Senegal/Benin haplotype, the mean percent Hb F (8.0%) was equivalent to the Hb F level in females with Benin and Bantu haplotypes (approximately 7.5%). Both females and males homozygous for the Senegal haplotype chromosome or with the Senegal/Benin combination had a significant increase in Hb F compared to other groups. In 44 Senegal/Senegal or Senegal/Benin females the Hb F was 10.9%, or 1.0 g/dl, the highest value observed in all primary analysis groups. Preliminary analyses suggested that the presence of a Bantu chromosome blunted the gender-associated difference in Hb F, but Hb F differences between females with the Senegal/Benin haplotype (11.2%) and the Senegal/Bantu haplotype (8.8%) were not statistically significant. Hemoglobin concentrations were higher in males than in females except in subjects with at least one Senegal haplotype chromosome, where hemoglobin levels were equal. As expected, alpha thalassemia reduced the MCV, increased hemoglobin concentration, and lowered reticulocyte counts, regardless of haplotype. Hb F levels were not affected by the presence of alpha thalassemia in any group. We conclude that gender and beta-globin gene cluster haplotype interact significantly in the modulation of Hb F and anemia in adults with SS.

Adult↗
PubMed1995

Effect of pentoxifylline on tissue injury and platelet-activating factor production during ischemia-reperfusion injury.

PURPOSE: Pentoxifylline lessens the metabolic derangements associated with ischemia-reperfusion injury. This study evaluated the effects of pentoxifylline on platelet-activating factor (PAF) production and tissue injury during skeletal muscle ischemia-reperfusion injury. METHODS: The isolated canine gracilis muscle model was used. Group 1 muscles were subjected to 5 hours of ischemia and 20 hours of reperfusion (n = 10); group 2 muscles received pentoxifylline, 15 mg/kg, systemic infusion 10 minutes before reperfusion (n = 6); group 3 muscles received pentoxifylline, 25 mg/kg, systemic infusion 10 minutes before reperfusion (n = 6). PAF was measured from muscle venous effluent by the scintillation proximity assay method. Muscle injury was assessed by vital staining and planimetry. RESULTS: PAF levels in group 2 were decreased at 10, 15, and 30 minutes of reperfusion compared with group 1 but did not reach significance. PAF levels in group 3 were decreased at all times of reperfusion compared with group 1 but attained significance only at 10 minutes of reperfusion (p < 0.05). No significant differences in muscle weight were noted among the three groups. No differences in the extent of muscle necrosis was observed between group 1 (77.26% +/- 20.38%) and group 2 (60.49% +/- 23.97%) (p = 0.08); there was a significant reduction in the extent of muscle necrosis in group 3 (44.55% +/- 21.47%) compared with group 1 (p < 0.05). CONCLUSIONS: The administration of pentoxifylline at 25 mg/kg before reperfusion of ischemic skeletal muscle decreased significantly the extent of muscle necrosis and PAF levels in the venous effluents at all times of reperfusion (significantly at 10 minutes). These results suggest that pentoxifylline may decrease tissue injury of ischemia-reperfusion by inhibiting the production of PAF during critical periods of reperfusion.

Animals↗
PubMed1995

Do patients with the heparin-induced thrombocytopenia syndrome have heparin-specific antibodies?

PURPOSE: Patients with the heparin-induced thrombocytopenia syndrome (HIT) have heparin-associated antibodies (HAb+), which, in the presence of heparin, are responsible for platelet activation and aggregation. This study addressed the questions: (1) are the antibodies specific for heparin; and (2) how do the antibodies cause platelet aggregation? METHODS: Plasmas from 79 patients with HIT were divided into seven plasma samples: HAb+ plasma sample 1 (24 pooled plasmas); HAb+ plasma sample 2 (50 pooled plasmas); and HAb+ plasma samples 3 through 7 (individual plasmas). Normal patient plasmas were used as controls (HAb-). RESULTS: All seven HAb+ plasma samples caused platelet aggregation (PLA) in the presence of heparin and formed a precipitation line with heparin in gel immunodiffusion plates (HAb- plasmas did neither). The HAb+ plasma samples reacted with heparin, as determined by immunoprecipitation in sodium dodecylsulfate-polyacrylamide gel, with the production of a band at 50 kd (no band with HAb- plasmas). The plasma samples 1 and 2 were passed over heparin sepharose beads three times; the unabsorbed plasmas produced 3+ PLA, the first effluent produced 2+ PLA, and the second and third effluents produced no PLA. The heparin sepharose beads stained 3+, 2+, and 1+, after the respective passages, with fluorescein-labeled goat sera containing anti-human immunoglobulin G antibody. HAb+ plasma samples were digested with pepsin to separate the F(ab')2 fragments from the Fc fragments. The F(ab')2 fragments reacted with heparin as determined by immunoprecipitation in sodium dodecylsulfate-polyacrylamide gel with the production of a band at 25 kd, but did not cause PLA in the presence of heparin. CONCLUSION: Patients with HIT have heparin-specific antibodies that react with heparin in a classic F(ab')2 reaction and require the Fc fragment for platelet aggregation.

Absorption↗
PubMed1995

A method for evaluating transmission line magnetic field mitigation strategies that incorporates biological uncertainty.

A method to determine how much reduction in public exposure to power frequency magnetic fields can be obtained for different levels of investment is presented. Which if any "effects function" best describes the relationship between field exposure and biological effect is uncertain at this time. Also, in a particular context such as construction of new transmission lines there are a variety of different technologies which might be used to reduce exposure. We describe and demonstrate a method by which exposure reduction supply curves (i.e., the cost of purchasing different amounts of exposure reduction given various mitigation options) can be estimated parametrically for different exposure conditions and effects functions, and we display illustrative results.

Cost-Benefit Analysis↗
PubMed1995

Two missense mutations in the beta-globin gene can cause severe beta thalassemia. Hemoglobin Medicine Lake (beta 32[B14]leucine-->glutamine; 98 [FG5] valine-->methionine).

We studied the molecular basis of transfusion-dependent hemolytic anemia in an infant who rapidly developed the phenotype of beta thalassemia major. DNA sequence of one beta-globin gene of the proband revealed two mutations, one for the moderately unstable hemoglobin (Hb) Köln and another for a novel codon 32 cytosine-thymidine-guanine-->cytosine-adenine-guanine transversion encoding a leucine-->glutamine mutation. A hydrophilic glutamine residue at beta 32 has an uncharged polar side chain that could potentially distort the B helix and provoke further molecular instability. This new hemoglobin was called Hb Medicine Lake. Biosynthesis studies showed a deficit of beta-globin synthesis with early loss of beta-globin chains. An abnormal unstable hemoglobin, globin chain, or tryptic globin peptide was not present, demonstrating the extreme lability of this novel globin. Hb Medicine Lake mRNA was present, but an aberrantly spliced message was not. Absence of an abnormal beta-globin gene in the mother makes it likely that a de novo mutation occurred in the proband. The molecular pathogenesis of Hb Medicine Lake illustrates a mechanism whereby the phenotype of a genetic disorder, like the mild hemolytic anemia associated with a hemoglobinopathy, can be modulated by a coincident mutation in the same gene.

Amino Acid Sequence↗
PubMed1994

Orotracheal and nasotracheal intubation in llamas.

Orotracheal or nasotracheal intubation was performed in 304 llamas and 6 alpacas during general anesthesia for surgical and diagnostic procedures. The mouth not opening wide and the presence of a prominent torus linguae make orotracheal intubation difficult, but it can be accomplished with the aid of a laryngoscope, using a technique similar to that used in small domestic ruminants. The presence of a pharyngeal diverticulum necessitates modification of nasotracheal intubation techniques to make them applicable for use in llamas and alpacas. When nasotracheal intubation, with phenylephrine lubricant-coated tubes, is not successful, oral laryngoscopy and use of a stylet in the endotracheal tube will improve chances for success. Because llamas are obligate nasal breathers, airway obstruction can develop following removal of endotracheal tubes during recovery from anesthesia. This complication can be prevented by maintaining orotracheal tubes until the animal is able to protect its airway or by using nasotracheal tubes, which allow the llama to stand before the tube has to be removed.

Animals↗
PubMed1994

A four base pair deletion 5' to the A gamma T gene is associated not only with decreased expression of the A gamma T-globin gene, but also of the G gamma-globin gene in cis.

A four base pair deletion 5' to A gamma T-globin gene at positions -222 to -225 has been reported to reduce the expression of this gene. To evaluate the prevalence and effect of this deletion, PCR-based methods were employed. The deletion had a gene frequency of 0.06 in a sample of African-American individuals with sickle cell trait, 0.18 in adult African-Americans with normal Hb AA, and 0.36 in caucasians. Seventy cord blood samples from African-American newborns with Hb AA were evaluated by both HPLC and PCR. The frequency of the A gamma T allele was 0.13. The A gamma T-globin chain was always present in a lower proportion than the A gamma I allele (70% of A gamma I), but the percentage of A gamma-globin was the same whether or not A gamma T was present. The total percentage of Hb F, however, was significantly lower in the group with the A gamma T allele (77.1% vs. 87.4%, P < 0.01). These results indicate that the four base pair deletion is not only associated with reduced expression of the A gamma T allele, but also of the G gamma allele in cis, further suggesting a possible role of this region in the modulation of the expression of the linked gamma-globin genes.

Base Sequence↗
PubMed1993

G gamma A gamma (beta+) hereditary persistence of fetal hemoglobin: the G gamma -158 C-->T mutation in cis to the -175 T-->C mutation of the A gamma-globin gene results in increased G gamma-globin synthesis.

Hereditary persistence of fetal hemoglobin (HPFH) can be generally classified into deletional and nondeletional forms. The family described in the present study has characteristics of both types of HPFH. The proband is a healthy 30-year-old black woman. Analysis of her hemoglobin revealed 40.4% HbS, 40.9% HbF (G gamma/A gamma ratio 0.53), 16.8% HbA, and 1.9% HbA2. All of her hematologic indices were normal, and the distribution of HbF in her red cells was pancellular. Family studies demonstrated that the proband has one chromosome 11 bearing the beta s-globin gene and the other bearing a G gamma A gamma (beta+) HPFH determinant in cis to the beta A-globin gene. Gene mapping studies of the region between the G gamma- and beta-globin genes were normal. However, when the A gamma and G gamma promoters were amplified by polymerase chain reaction (PCR) and sequenced, the A gamma promoter was found to have the T-->C mutation at -175, and the G gamma promoter region was found to have the C-->T mutation at -158. The -158 C-->T mutation has been associated with elevated G gamma levels and high HbF in hemolysis, although its role in causing these effects is unclear. The present study suggests that this mutation can also enhance G gamma-globin expression in cis to the -175 T-->C mutation in the absence of hemolysis. We suggest that the alteration of the A gamma gene octamer binding site by the -175 mutation, as well as the loss of a putative G gamma "silencer" caused by the -158 mutation may account for this phenotype. We propose calling these linked mutations the G gamma A gamma(beta+) HPFH.

Adult↗
PubMed1993

Selective monitoring in abdominal aortic surgery.

Monitoring via a pulmonary artery catheter has been advocated for all patients undergoing abdominal aortic surgery. This study was performed to identify a subgroup of patients who could be safely monitored with a central venous catheter. One hundred twenty-eight consecutive patients undergoing elective infrarenal abdominal aortic surgery were prospectively evaluated for risk of developing perioperative myocardial dysfunction based on criteria determined by the history and physical examination, chest radiography, and electrocardiography. Forty-five patients were identified as having no clinical evidence of coronary artery disease. These patients were then monitored perioperatively using a central venous catheter. All patients monitored via a central venous catheter underwent surgery for abdominal aortic aneurysmal disease (66.7%) or aortoiliac disease (33.3%) without intraoperative complications. There were 15 postoperative complications in 12 (26.7%) patients, comprised mainly of pulmonary (7) and gastrointestinal (3) complications. The cardiac-related morbidity was 4.4 per cent and consisted of congestive heart failure (1) and renal failure (1). No perioperative myocardial infarctions were detected. One (2.2%) postoperative death secondary to aspiration pneumonia occurred. The results of this data suggest that there exists a subgroup of patients undergoing elective infrarenal abdominal aortic surgery that can be monitored safely via a central venous catheter in the perioperative period.

Adult↗
PubMed1992

Dominant thalassemia-like phenotypes associated with mutations in exon 3 of the beta-globin gene.

Mutations producing beta-thalassemia reach individual gene frequencies greater than .01 in malarial-endemic regions because beta-thalassemia trait individuals have increased genetic fitness over that of normal individuals. Exon 3 of the beta-globin gene has been relatively spared as a site of common beta-thalassemia mutations. Frameshifts caused by the loss of a single nucleotide and nonsense mutations produce beta-thalassemia trait when they occur in exons 1 and 2. In contrast, they usually produce chronic hemolytic anemia when present in exon 3. Certain missense mutations in exon 3 produce unstable globins and thalassemia intermedia with hemolysis in heterozygotes. Here we report two new mutations in exon 3 of the beta-globin gene. One is a single nucleotide deletion in codon 109 in a 78-year-old Lithuanian with chronic hemolytic anemia and features of thalassemia. It leads to an abnormal globin (beta Manhattan) that is elongated to 156 amino acids. The second is a CAG-CGG missense mutation at codon 127 that causes a Gln----Pro substitution (beta Houston) and a thalassemia intermedia with hemolysis in three generations of a British-American family. Although the clinical phenotypes of these two patients differed little, differences in globin-synthetic ratios were significant, presumably reflecting differences in the ability of each abnormal beta-globin to form alpha beta dimers. The paucity of high-frequency exon 3 mutations and their worldwide distribution is likely attributable to their phenotypic severity and loss of increased genetic fitness vis-a-vis malaria.

Aged↗
PubMed1992

Usefulness of preoperative laboratory assessment of patients undergoing elective herniorrhaphy.

Preoperative laboratory utilization was evaluated in a retrospective review of 169 adults undergoing elective inguinal herniorrhaphy at a county/university hospital and at a private/community hospital. Tests monitored included a complete blood cell count, urinalysis, serum electrolytes, chest roentgenography, and electrocardiography. Abnormal results and results that altered the patients' treatment were sought. Two groups of patients were evaluated. Group 1 (n = 105) had no disease except for the inguinal hernia; group 2 (n = 64) had evidence of another disease process. Preoperative evaluation of patients in group 1 was similar at the county/university hospital and at the private/community hospital except for increased electrolyte screening at the county/university hospital among patients younger than age 40 years. No differences between hospitals were present among patients in group 2. Abnormal results not predicted by medical history or physical examination were found in 1% of patients in group 1 and 1.4% of patients in group 2. Only four patients (2%) had their treatment altered by these findings. Preoperative laboratory evaluation of these patients revealed that an abnormal test result not predicted by history and physical examination is rare. Routine preoperative laboratory testing is of little value in this patient population.

Adult↗
PubMed1992

Ethical conflicts in the prehospital setting.

STUDY OBJECTIVE: To assess the range of ethical conflicts that confront prehospital care providers. DESIGN: Convenience sample, from October 1989 to January 1990. SETTING: An urban advanced life support emergency medical service that transports approximately 3,000 patients per month. METHODS: Six hundred seven paramedic responses were analyzed by a single observer. An ethical conflict was identified when the paramedic faced a dilemma about what "ought to be done" and the paramedic's values conflicted or potentially conflicted with the patient's. Cases with potential ethical consequence were brought to experts in medical ethics and epidemiology for further analysis and classification. RESULTS: Ethical conflicts arose in 14.4% of paramedic responses (88 of 607 cases). Twenty-seven percent of the conflicts involved issues of informed consent, such as refusal of treatment or transport, conflicts of hospital destination, treatment of minors, and consent for research. Difficulties regarding the duty of the paramedics, usually under threatening circumstances, accounted for 19% of the dilemmas encountered. Requests for limitation of resuscitation accounted for 14%. Other circumstances that presented ethical conflicts involved questions of patient competence (17%), resource allocation (10%), confidentiality (8%), truth telling (3%), and training (1%). CONCLUSION: The data demonstrate a range of ethical conflicts in the prehospital setting and point to areas in which policy needs to be developed. The data also can be used in a prehospital ethics curriculum for paramedics and physicians. Because case sampling was not strictly random, absolute conclusions should not be drawn regarding the frequency of the dilemmas.

Beneficence↗
PubMed1992

Beta-thalassemia intermedia with exceptionally high hemoglobin A2: relationship to mutations in the beta-gene promoter.

Small deletions of the 5' portion of the beta-globin gene that remove the promoters but stop 3' to the delta-globin gene are recognized as the sole cause of beta-thalassemia with exceptionally high hemoglobin A2 (HbA2) levels. Two patients with beta-thalassemia intermedia and exceptionally high levels of HbA2 (10.4 and 12.0%) were examined. One patient was a combined heterozygote for the -88 C----T and a novel -87 C----A mutation, while the other was homozygous for the -29 A----G beta(+)-thalassemia mutation. The remainder of the beta genes were normal. There was no evidence for deletions involving the 5' portion of the beta gene or the region between the beta and delta genes. Gene mapping studies excluded the possibility of a beta delta-anti-Lepore hemoglobin gene with beta promoters and delta coding sequences. There were no mutations in the promoters of the G gamma or A gamma-globin genes that have been associated with the hereditary persistence of HbF phenotype. The delta-globin gene promoters were normal from codon 17 to position -145 relative to the mRNA capping site. There appears to be considerable heterogeneity of HbA2 and HbF levels in patients who are homozygous or mixed heterozygotes for mutations in the TATA box and other promoter elements of the beta-globin gene. The capacity for proteolysis within the erythrocyte may vary among individuals. The authors hypothesize that in the exceptionally high HbA2 beta-thalassemia intermedia phenotype, proteolysis of superfluous alpha-globin chains is less efficient than in patients with customary levels of HbA2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Mutation and killing of Escherichia coli expressing a cloned Bacillus subtilis gene whose product alters DNA conformation.

Expression of the Bacillus subtilis gene coding for SspC, a small, acid-soluble protein, caused both killing and mutation in a number of Escherichia coli B and K-12 strains. SspC was previously shown to bind E. coli DNA in vivo, and in vitro this protein binds DNA and converts it into an A-like conformation. Analysis of revertants of nonsense mutations showed that SspC caused single-base changes, and a greater proportion of these were at A-T base pairs. Mutation in the recA gene abolished the induction of mutations upon synthesis of SspC, but the killing was only slightly greater than in RecA+ cells. Mutations in the umuC and umuD genes eliminated most of the mutagenic effect of SspC but not the killing, while the lexA mutation increased mutagenesis but did not appreciably affect the killing. Since there was neither killing nor mutation of E. coli after synthesis of a mutant SspC which does not bind DNA, it appears likely that the binding of wild-type SspC to DNA, with the attendant conformational change, was responsible for the killing and mutation. A strain containing the B. subtilis gene that is constitutive for the RecA protein at 42 degrees C showed a lower frequency of mutation when that temperature was used to induce the RecA protein than when the temperature was 30 degrees C, where the RecA level is low, suggesting that at the elevated temperature the high RecA level could be inhibiting binding of the B. subtilis protein to DNA.

Bacillus subtilis↗