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Biomedical subjects

J Shannon

Publications and source records attributed to J Shannon.

At least 19 recordsLinked to original sources

Clinical models of cardiovascular regulation after weightlessness.

After several days in microgravity, return to earth is attended by alterations in cardiovascular function. The mechanisms underlying these effects are inadequately understood. Three clinical disorders of autonomic function represent possible models of this abnormal cardiovascular function after spaceflight. They are pure autonomic failure, baroreflex failure, and orthostatic intolerance. In pure autonomic failure, virtually complete loss of sympathetic and parasympathetic function occurs along with profound and immediate orthostatic hypotension. In baroreflex failure, various degrees of debuffering of blood pressure occur. In acute and complete baroreflex failure, there is usually severe hypertension and tachycardia, while with less complete and more chronic baroreflex impairment, orthostatic abnormalities may be more apparent. In orthostatic intolerance, blood pressure fall is minor, but orthostatic symptoms are prominent and tachycardia frequently occurs. Only careful autonomic studies of human subjects in the microgravity environment will permit us to determine which of these models most closely reflects the pathophysiology brought on by a period of time in the microgravity environment.

Autonomic Nervous System

Relationship of food groups and water intake to colon cancer risk.

The association between food groupings and adenocarcinoma of the colon was investigated in a population-based case-control study of men and women ages 30-62 years. Colon cancer cases (238 men and 186 women) diagnosed from 1985 to 1989 were identified from the Seattle-Puget Sound Surveillance, Epidemiology, and End Results Registry. Controls (224 men and 190 women) were selected using a random digit telephone dialing method. Dietary information was gathered using an 80-item food frequency questionnaire. Foods were grouped and analyzed by quartile of intake, with adjustment for age and total energy intake. Among women, a reduced risk of colon cancer was associated with a high intake of fruits and vegetables [adjusted odds ratio (OR) for highest versus lowest quartile, 0.48; 95% confidence interval (CI), 0.26-0.86; P for trend, P = 0.02]. Inverse associations were also observed for the consumption of total (hot and cold) cereals (OR, 0.47; 95% CI, 0.25-0.91; P = 0.05), dairy products (OR, 0.40; 95% CI, 0.21-0.79; P = 0.05), and water (OR for > 5 glasses/day versus < or = 2 glass/day, 0.55; 95% CI, 0.31-0.99; P = 0.004). Among men, colon cancer risk was inversely associated with the intake of breads and cereals (OR, 0.43; 95% CI, 0.22-0.82; P = 0.02) and hot cereal (OR for weekly versus never eating, 0.53; 95% CI, 0.32-0.87; P = 0.01). Water consumption was marginally associated with a decreased colon cancer risk among men as well (OR for > 4 glasses/day versus < or = 1 glass/day, 0.68; 95% CI, 0.38-1.22; P = 0.16). Total meat consumption was associated with an increased risk of distal colon cancer among men (OR, 2.20; 95% CI, 1.08-4.48; P = 0.01). These results were not confounded by body mass index or other measured health behaviors. Results of this research support previous findings which associate intake of fruits, vegetables, grains, and dairy products with reduced colon cancer risk, and meat intake with an increased colon cancer risk. This study also reports a new finding of a possible inverse association of water consumption (glasses of plain water per day) with colon cancer risk.

Adenocarcinoma

Molecular cloning of a major cockroach (Blattella germanica) allergen, Bla g 2. Sequence homology to the aspartic proteases.

Inhalation of allergens produced by the German cockroach (Blattella germanica) elicits IgE antibody formation and the development of asthma in genetically predisposed individuals. We compared the allergenic importance of two cockroach (CR) allergens, Bla g 1 and Bla g 2, and determined the complete amino acid sequence of the major 36-kDa allergen, Bla g2. A survey of 106 sera from CR allergic patients showed the prevalence of IgE antibodies to Bla g 1 and Bla g 2 to be 30.2% and 57.6%, respectively. Immediate skin tests on 7 selected patients gave positive reactions using 10(-3) micrograms/ml either allergen, whereas controls showed no response to 10 micrograms/ml. Natural Bla g 2 was purified and the sequence of the NH2 terminus and tryptic peptides, comprising 36% of the molecule, was determined. The cDNA for Bla g 2 was cloned from a B. germanica expression library and encoded a 24-amino acid signal peptide and a 328-amino acid mature protein, which showed the highest degree of identity to mosquito (Aedes aegypti) lysosomal aspartic protease (30.8%), with similar identity to pepsin, cathepsins D and E, renin, and chymosin. Bla g 2 mRNA and protein were detected in B. germanica, but not in Periplaneta americana, the other principal domiciliary CR species in the U.S. High concentrations of Bla g 2 were found in CR digestive organs (esophagus, gut, and proventriculus). The results show that Bla g 2 is a major species-specific allergen of B. germanica and suggest that the allergen functions as a digestive enzyme in the cockroach.

Allergens

Cocaine abuse in methadone maintenance patients is associated with low serum methadone concentrations.

Cocaine abuse in methadone maintenance patients has emerged as a significant clinical problem. To determine if raising the daily methadone dosage is an effective way to eliminate cocaine abuse, 74 methadone maintenance patients maintained at daily dosages between 30 and 80 mg and who chronically abused cocaine were studied by a standard protocol. A total of 21 (28.4%) subjects ceased cocaine abuse when their methadone dosage was progressively raised to a maximal daily dose of 160 mg. Cocaine abuse appeared to accelerate elimination of methadone, since inadequate methadone serum concentrations (below 100 ng/ml) were found in 48 of 67 (71.6%) subjects tested 24 hours after a 100 mg oral methadone dose. Although cocaine abuse in methadone maintenance patients may respond to raising the daily methadone dosage, alternative treatments for cocaine abuse in methadone maintenance patients must be identified since cocaine abuse may lower serum methadone concentrations.

Adult

Role of infused CD8+ cells in the induction of peripheral tolerance.

The CD8 molecule when present on a cell recognized by a mature T cell has been shown to have an inhibitory effect on the development of an in vitro immune response by that T cell. To test whether CD8 has a role in the induction of peripheral tolerance in vivo, we have studied tolerance induction in B6 female mice carrying a transgenic TCR specific to male H-Y Ag. Previous studies have shown that male Ag reactive cells are inactivated in these mice after the i.v. injection of viable male lymphoid cells. Here, B6 female transgenic mice were injected with B6 male lymph node cells from CD4 or CD8 gene knockout mice, and the fate of male Ag-specific T cells was followed in vivo. Our results indicate that injection of male CD4 knockout (express CD8) lymphoid cells but not CD8 knockout (do not express CD8) lymphoid cells induced a significant reduction of male H-Y Ag reactive cells in the periphery, suggesting that CD8 plays an important role in the induction of peripheral tolerance of class I-restricted T cells. These results imply that peripheral tolerance can be induced not just by absence of signals required for activation but by the presence of additional signals.

Animals

Gamma delta T cells differentiate into a functional but nonproliferative state during a normal immune response.

To obtain a homogeneous population of gamma delta T cells to investigate their role in an immune response, we have made a scid mouse doubly transgenic for rearranged gamma and delta genes. The receptor (KN6) encoded by these genes is specific for the major histocompatibility complex class I protein encoded by the T22b gene. This mouse contains high levels of transgenic gamma delta T cells in the spleen and thymus and no other T lymphocytes. Immunization of these KN6-scid (H-2d, TLd) mice with 10(7) C57BL/6J (abbreviated B6) (H-2b, TLb) spleen cells resulted in proliferation and activation of the gamma delta T cells in spleen and clearing of the allogeneic B6 lymphocytes. Subsequently, the majority of activated cells died by apoptosis and the remaining cells were anergic with regard to proliferation. The anergic cells did not respond to restimulation by B6 spleen cells in vitro or in vivo, and addition of exogenous interleukin 2 failed to restore the response to B6 cells. Cytotoxicity, a property of KN6+ cells during a primary stimulation, was no longer detectable in the proliferatively anergic cells. However, B6 spleen cells injected into mice primed 12 days previously were cleared with a much greater efficiency than on primary challenge and in an antigen-specific manner. We conclude that after exposure to antigen, gamma delta T cells rapidly proliferate into blasts; the majority of the blasts rapidly die, with the nonproliferating cells remaining in a highly active state for several weeks and able to initiate elimination of lymphoid cells bearing the TLb epitope.

Animals

Clinical and prognostic significance of serum magnesium concentration in patients with severe chronic congestive heart failure: the PROMISE Study.

OBJECTIVES: The aim of this study was to determine the prognostic significance of alterations in serum magnesium in patients with moderate to severe congestive heart failure. BACKGROUND: Reductions in serum magnesium have been postulated to play a role in promoting arrhythmias and to have an adverse impact on survival in congestive heart failure, although support for this postulate is lacking. METHODS: Serum magnesium levels were measured in 1,068 patients enrolled in a survival study of class III or IV heart failure at the time of double-blind randomization to milrinone, a phosphodiesterase inhibitor, or placebo. All patients received conventional therapy with digoxin, diuretic drugs and a converting enzyme inhibitor throughout the trial. The median follow-up period was 6.1 months (range 1 day to 20 months). RESULTS: Patients with high serum magnesium (defined as > or = 1.9 mEq/liter, n = 242) were less likely to survive than were patients with a normal magnesium level (n = 627) (p < 0.05, risk ratio = 1.41). Patients with a low magnesium level (defined as < or = 1.5 mEq/liter, n = 199) had no difference in survival compared with the group with a normal magnesium level (p = NS, risk ratio = 0.89). At baseline, the patients in the high magnesium group were older and had more severe functional and renal impairment. An analysis after adjustment for these variables demonstrated no difference in survival comparing the low, normal and high magnesium groups. Although the three groups had no difference in frequency of ventricular tachycardia, length of longest run or frequency of ventricular premature beats on baseline Holter monitoring, the group with hypomagnesemia had more frequent ventricular couplets. CONCLUSIONS: Serum magnesium does not appear to be an independent risk factor for either sudden death or death due to all causes in patients with moderate to severe heart failure. Hypomagnesemia is associated with an increase in the frequency of certain forms of ventricular ectopic activity, but this is not associated with an increase in clinical events. The higher mortality rate among the patients with hypermagnesemia is attributable to older age, more advanced heart failure and renal insufficiency.

Aged

Purification and microsequencing of the intra-acrosomal protein SP-10. Evidence that SP-10 heterogeneity results from endoproteolytic processes.

The human sperm antigen SP-10 has been shown to be a testis-specific, intra-acrosomal protein that is associated with the membranes and matrix of the acrosomal vesicle. Sperm extracts, analyzed on Western blots with a monoclonal antibody to SP-10, have shown heterogeneity of SP-10 peptides ranging from 17.5-34 kDa. Although the entire SP-10 amino acid sequence of 265 amino acids (28.3 kDa) has been deduced from sequencing SP-10 cDNAs, the nature of multiple SP-10 peptide bands is incompletely understood. In this study, we developed a three-step purification method for SP-10 peptides using monoclonal antibody affinity chromatography, reverse-phase HPLC, and preparative gel electrophoresis. Eight SP-10 peptides separated by this protocol and sequenced using Edman degradation showed amino termini that corresponded to regions on the deduced SP-10 amino acid sequence. Peptides with progressively lower apparent mass aligned further toward the carboxy terminus. On the basis of putative cleavage sites on the SP-10 sequence, endoproteases that act at five different peptide bonds are predicted to cleave SP-10: these hydrolyze following arginine (a trypsin-like protease, possibly acrosin), and following serine, proline, glycine, and glutamic acid (previously undescribed intra-acrosomal protease specificities). The present studies 1) provide a purification method for SP-10 peptides; 2) confirm that the SP-10 cDNAs previously sequenced encode authentic SP-10; and 3) yield indirect evidence that endoproteases act to contribute to SP-10 heterogeneity.

Acrosome

Epidemiology of pelvic inflammatory disease at University Medical Center, Jacksonville.

Patients hospitalized with acute pelvic inflammatory disease at University Medical Center of Jacksonville had a mean age of 26.8 years. Contraception use was minimal and mean gravidity was two. Hospitalized patients had a high incidence of peritonitis and tubo-ovarian abscess. N. gonorrhoeae was cultured in 50%. Mean temperature on admission was 100.5 degrees and mean white blood cell count 15,400. Mean hospitalization was 5.5 days. Two of nine patients tested for HIV were positive (22% of those tested, 2% of all patients reviewed).

Abscess

Quantitative urine testing. A new tool for diagnosing and treating cocaine use.

The new quantitative urine tests for cocaine are an easy and inexpensive method of diagnosing and monitoring use of this drug and thus are practical for the primary care physician's office. They may help differentiate between occasional and addicted users, thus establishing the severity of the problem for the patient and family, employer, or school officials. Although the tests cannot be used for legal applications, they have great clinical value. The receptivity of patients and third parties to urine testing has been gratifying. Physicians are encouraged to consider use of these tests in office assessment.

Adolescent

Rat pulmonary surfactant protein A is expressed as two differently sized mRNA species which arise from differential polyadenylation of one transcript.

In rat, the surfactant-associated glycoprotein A, SP-A, is encoded by two mRNA species of 0.9 and 1.6 kb. Each transcript is polyadenylated and is found in approximately the same ratio in total cellular RNA isolated from either alveolar type II cells or from whole lung. The two mRNA species have identical coding regions and differ only in the length of the 3' untranslated sequences. Restriction analysis and partial sequence analysis of rat genomic clones indicate that each mRNA species arises from one gene, with the difference in size most easily accounted for by differential polyadenylation. During fetal development, the accumulation of mRNA encoding SP-A is detectable by day 18 but increases many-fold on day 19. However, there are no apparent alterations in the prevalence of either mRNA species during fetal development or in the early postnatal period.

Amino Acid Sequence

Thoracic outlet syndrome: a comprehensive evaluation.

Using various modalities, 480 patients were evaluated for thoracic outlet compression syndrome. Of this group, 300 patients were eventually diagnosed as having thoracic outlet syndrome after extensive evaluation. Ninety of these patients underwent a total of 103 operative procedures for thoracic outlet decompression. Nerve conduction velocities and directional Doppler studies were the most useful adjuncts in making the diagnosis. Surgical therapy after proper selection yielded an 80.6 per cent long-term "good" operative result and an additional 6.9 per cent long-term "fair" operative result in follow-up to 12 years.

Adult

Intraoperative autologous transfusion during major aortic reconstructive procedures.

To evaluate the benefits and disadvantages of autologous intraoperative transfusion during major aortic reconstructive procedures, we retrospectively studied 50 patients who had major aortic revascularization procedures without the use of autologous transfusion devices (group 1) and prospectively evaluated a second 50-patient cohort having similar procedures, but with the use of the autologous transfusion device for salvaging and reinfusing lost blood. Both groups were assessed for preoperative risk factors and postoperative complications. We found a somewhat lower morbidity in the autotransfusion group and more complete replacement of blood loss. Autologous transfusion accounted for approximately 75% of all transfused blood in group 2, tremendously reducing blood bank requirements. In addition to reduction of immediate postoperative morbidity, further risks associated with homologous transfusion such as hemolysis, posttransfusion hepatitis, transfusion-related acute lung injury, anaphylaxis, and transfusion-transmitted acquired immunodeficiency syndrome (AIDS) were markedly reduced or eliminated.

Aged