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Biomedical subjects

D Davis

Publications and source records attributed to D Davis.

At least 127 records · Page 7Linked to original sources

Lymphocytotropic strains of HIV type 1 when complexed with enhancing antibodies can infect macrophages via Fc gamma RIII, independently of CD4.

Antipeptide sera raised against the gp120/gp41 sequences of human immunodeficiency virus type 1 (HIV-1) were used to determine their capacity to enhance infection. Antisera to the five variable regions (V1 to V5) of gp120 and conserved parts of gp120 and gp41 facilitated infection of primary human macrophages with the homologous virus HIV-1 SF2mc. In contrast, heterologous virus infection with HTLV-IIIB was mediated only by antisera to the conserved regions, predominantly C4 and C5. Heterologous virus infection occurred more rapidly and was consistent between different cell donors. The neutralizing monoclonal antibody (MAb) SC258 (murine IgG2a) but not MAb 684-238 (mIgG1) against conformational epitopes of the V2 region also induced antibody-dependent infection enhancement (ADE). Therefore, preincubation with certain antibodies can cause altered tropism of the lymphocytotropic viruses mentioned above. Viral infection was completely abolished by preincubation with the F(ab)2 fragment of MAb 3G8 against the Fc gamma receptor III (CD16). A MAb (7.3F11) against the gp120-binding site of CD4 had no effect on viral infectivity. Possible mechanisms and their implications for disease progression are discussed.

Acquired Immunodeficiency Syndrome↗

Increased middle cerebral artery flow velocity during the initial phase of cardiopulmonary bypass may cause neurological dysfunction.

One hundred twenty-seven patients undergoing coronary artery bypass graft surgery were monitored by transcranial Doppler ultrasonography. Five patients had more than 50% increases in middle cerebral artery mean flow velocity during the initial phase (10-120 sec) of cardiopulmonary bypass. Four of these 5 developed neurological complications including stroke and encephalopathy. These results indicate that overperfusion of the basal cerebral arteries during cardiopulmonary bypass procedures may contribute to neurological dysfunction after the surgery.

Adult↗

Identification of the sites of N-linked glycosylation on the follicle-stimulating hormone (FSH) receptor and assessment of their role in FSH receptor function.

The FSH receptor (FSHR) contains a large extracellular domain in which exist three potential sites for N-linked glycosylation. A truncated form of the FSHR representing only the extracellular domain was created and expressed in mammalian cells. We show that this truncated receptor is glycosylated, through the carbohydrates are not as fully processed as those of the full-length receptor. This truncated receptor, which remains intracellular, binds FSH with an affinity comparable to that of the full-length FSHR. Therefore, although other regions of the FSHR may contribute to hormone binding, the extracellular domain alone can confer high affinity binding. The above results suggest that N-linked FSHR carbohydrates may, in some way, be required for FSH binding. Therefore, further experiments, done in the context of the full-length receptor, were performed to determine the actual sites of glycosylation in the FSHR as well as to elucidate their role in the functions of the FSHR. Site-directed mutagenesis was done to individually or collectively disrupt the potential sites for N-linked glycosylation. Western blot analyses of the wild type vs. mutant receptors demonstrate that, of the three potential sites for N-linked glycosylation, Asn's 174 and 276 are actually glycosylated. Binding assays demonstrate that these two N-linked FSHR carbohydrates are redundant in function since carbohydrate at either Asn174 or Asn276 allows the receptor to be expressed on the cell surface and to bind FSH with normal affinity. However, FSH binding activity is not observed with nonglycosylated mutant receptors where both sites have been collectively disrupted. Similarly, when cells expressing the wild type FSHR were treated with tunicamycin to prevent N-linked glycosylation, the resulting nonglycosylated FSHR was not able to bind FSH. In contrast, normal high affinity binding of FSH was maintained when N-linked carbohydrates were enzymatically removed from wild type receptors. Our results demonstrate that while N-linked carbohydrates on the FSH receptor are not required directly for the binding of hormone, a carbohydrate at either Asn174 or Asn276 is required for the efficient folding of the nascent receptor protein into a conformation that allows high affinity binding of hormone.

Amidohydrolases↗

Cardiac rehabilitation as secondary prevention. Agency for Health Care Policy and Research and National Heart, Lung, and Blood Institute.

This Quick Reference Guide for Clinicians highlights the conclusions and recommendations from Cardiac Rehabilitation, Clinical Practice Guideline No. 17, which was formulated by a panel representing the major health care disciplines involved in cardiac rehabilitation. The conclusions and recommendations were derived from an extensive and critical review of the scientific literature pertaining to cardiac rehabilitation, as well as from the expert opinion of the panel. This guide addresses the role of cardiac rehabilitation and the potential benefits to be derived in the comprehensive care of the 13.5 million patients with heart disease in the United States, as well as the 4.7 million patients with heart failure and the several thousand patients undergoing heart transplantation. This Quick Reference Guide for Clinicians highlights the major effects of multifactorial cardiac rehabilitation services: medical evaluation; prescribed exercise; cardiac risk factor modification; and education, counseling, and behavioral interventions. The outcomes of and recommendations for cardiac rehabilitation services are categorized as to their effects on exercise tolerance, strength training, exercise habits, symptoms, smoking, lipids, body weight, blood pressure, psychological well-being, social adjustment and functioning, return to work, morbidity and safety issues, mortality and safety issues, and pathophysiologic measures. Patients with heart failure and after cardiac transplantation, as well as elderly patients, are specifically addressed. Alternate approaches to the delivery of cardiac rehabilitation services are presented.

Aged↗

Rapid monitoring of changes in water diffusion coefficients during reversible ischemia in cat and rat brain.

Changes in the diffusion constant of water during reversible brain ischemia and cardiac arrest were monitored with a 10-s time resolution. Results (five cats, three rats) indicate that these changes are reversible and that the bulk of the changes are not caused by temperature or motion related to brain pulsations and blood flow. The rapid time course of the changes corresponds to the known time course for changes in energy state, signal transduction, and ionic homeostasis.

Animals↗

Melatonin-like immunoreactivity in the presence of different chemicals as determined by the radioimmunoassay.

To determine the nature of the molecule(s) that is responsible for the melatonin-like immunoreactivity (MLI), we measured the effect of pretreatment of plasma samples with detergents, reducing agent, and proteinase K. Nonidet P-40 Triton X-100, and ethylacetate extraction had no effect, while sodium deoxycholate, sodium dodecyl sulfate, beta-mercaptoethanol, ether extraction, proteinase K, and temperature increased the MLI. Since the radioimmunoassay (RIA) was sensitive to proteinase K, ionic detergents, and a reducing compound, we hypothesize that a proteinaceous molecule might be responsible for this MLI. We compared our column procedure for RIA of plasma melatonin (1) with procedures involving extraction with either ethylacetate or ether. In our hands preextraction of samples with organic solvents caused a loss of immunoreactivity. We also found that passing samples through the column is more efficient in eliminating interference in the melatonin assay than extracting samples either with ethylacetate or ether.

Chromatography↗

Effects of illness attribution and depression on the quality of life among persons with serious mental illness.

Attributing one's problems to a mental illness is associated with reduced subjective quality of life (QOL) among persons with schizophrenia, controlling for a broad range of socio-demographic, social, clinical, and psychosocial variables. Persons who attributed their problems to a 'physical, medical, or biological' problem in contrast to a 'mental illness' reported more positive social relations and higher overall quality of life. Much of the negative effect of mental illness attributions is explained by perceived stigma, lower self-esteem, and a higher level of depressive symptomatology. Depressive symptoms have an independent negative effect on QOL net of all other variables. These findings have important implications for the appropriate rehabilitation of persons with mental illness and require further scrutiny with prospective data.

Adult↗

Neuromotor precursors of schizophrenia.

Previous research suggests that in addition to being a characteristic of schizophrenia, neuromotor dysfunction also predates the onset of the syndrome. The research reported here was intended to examine further the neuromotor development of children with preschizophrenia traits. This study is part of a larger "archival-observational" project that uses childhood home movies to explore the developmental precursors of schizophrenia. Group comparisons revealed a higher rate of neuromotor abnormalities in the preschizophrenia children when compared to their healthy siblings, preaffective disorder subjects, the healthy siblings of patients with affective disorder, and subjects from families with no mental illness. The preschizophrenia subjects also showed poorer motor skills when compared to their healthy siblings and preaffective disorder subjects. When diagnostic group comparisons were made within age spans, the group differences were significant only in the first 2 years of life. Post hoc analyses also revealed that the preschizophrenia subjects' neuromotor abnormalities occurred primarily on the left side of the body. The abnormalities included choreoathetoid movements and posturing of the upper limbs, similar to the motor signs described in earlier reports on diagnosed schizophrenia patients. The findings are discussed in light of their implications for the developmental origins of schizophrenia. Limitations of the study, including problems with sample representativeness and the reliance on observational data, are also discussed.

Adolescent↗

Age and skill differences in adaptive competence.

Previous research has documented qualitative changes in certain cognitive abilities during the older adult years, such as in short-term memory, perceptual and motor skills, and attentional capacities. Other work has suggested that a number of significant age-related changes, across a variety of cognitive abilities, are based on social experiences, such as occupational or recreational activities. The current study is based on earlier research by Perlmutter and her colleagues (1990) and examines age and skill-related differences among adults engaged in a social-recreational activity. BINGO players, ranging in age from nineteen to seventy-four, and having from less than two months to over twenty years of playing experience, were given a variety of psychometric, cognitive, and experimental measures. The participants were also observed as they played real BINGO games. No age-related differences were found on the psychometric or memory measures, suggesting that BINGO playing experience may have positive benefits for many older adults. Skilled players at all age levels were found to be more efficient in their game-playing actions. The oldest and most experienced players did not differ from the younger, equally experienced, players on the cognitive and skill-based tasks. These findings demonstrate the need to investigate adaptive competence in those situations in which social-environmental factors play a role in enhancing older adults' cognitive skills.

Adaptation, Psychological↗

Comparison of related perceptual tests.

117 female and 76 male undergraduates were administered the ETS Hidden Figures, ETS Gestalt Completion, Harshman Figures, and the SEK Test. Results were interpreted as indicating that the two types of perceptual tests (flexibility and speed) were not factorially independent as the SEK Test correlations did not load upon the same factor as that for the ETS Hidden Figures Test. Men scored higher on the Hidden Figures and Harshman Figures but on the Gestalt completion task left-handed men and right-handed women scored higher.

Adult↗

Kinetics and free energy gaps of electron-transfer reactions in Rhodobacter sphaeroides reaction centers.

The rates of the light-driven, electron-transfer reactions in the photosynthetic reaction center (RC) of Rhodobacter sphaeroides are examined in mutant strains in which tyrosine (M)210 is replaced by phenylalanine, isoleucine, or tryptophan. The spectra of the absorbance changes between 700 and 975 nm, following excitation by 0.6-ps pulses at 605 nm, are analyzed globally by singular value decomposition. The spectra measured at room temperature are interpreted in terms of a model in which the excited bacteriochlorophyll dimer (P*) transfers an electron to a bacteriopheophytin (HL) with time constants of 3.5 +/- 0.3, 10.5 +/- 1.0, 16 +/- 2, and 41 +/- 4 ps in wild-type RCs and the Phe, Ile, and Trp mutants, respectively, and an electron then moves from HL- to a quinone (QA) with a time constant of 0.16 ns in wild-type RCs, 0.24 ns in the Phe mutant, and 0.20 ns in the Ile and Trp mutants. The first step speeds up with decreasing temperature in wild-type RCs, remains virtually unchanged in the Phe mutant, and slows down in the Ile and Trp mutants. At 80 K, the signals in the 850-975-nm region include an apparent shift of the stimulated emission or absorption spectrum of P*, with a time constant of 5 ps in the Ile mutant and 13 pcs in the Trp mutant. Most of the electron transfer to HL occurs with time constants of 55 and 155 ps in the Ile and Trp mutants, respectively, and probably occurs from the relaxed form of P*. Electron transfer from the initial state cannot be ruled out, however. Relaxations of P* are not resolved in wild-type RCs or the Phe mutant. The midpoint potential (Em) of the P/P+ redox couple is measured by an electrochemical technique; the Em values are 500 +/- 5, 530 +/- 6, 533 +/- 3, and 552 +/- 10 mV for the wild-type and the Phe, Ile, and Trp mutant RCs, respectively. These values are corroborated by chemical titrations. The free energy change (delta G degrees) associated with formation of the P+HL-radical pair from P* also is determined by measuring the amplitude of fluorescence on the nanosecond time scale after blocking electron transfer from HL- to QA. The free energy of P+HL- is elevated by an amount comparable to that calculated from the increase in the Em of P in the Ile mutant and by about 16 meV more than this in the Phe and Trp mutants.(ABSTRACT TRUNCATED AT 400 WORDS)

Electron Transport↗

Disruption of potential sites for N-linked glycosylation does not impair hormone binding to the lutropin/choriogonadotropin receptor if Asn-173 is left intact.

The rat lutropin/choriogonadotropin receptor (rLHR) is a G protein-coupled receptor, the large extracellular domain of which binds human choriogonadotropin (hCG) with high affinity. Within the extracellular domain are six potential sites for N-linked glycosylation. Although several studies have attempted to determine if N-linked carbohydrates are necessary for hormone binding, the results have been in apparent disagreement. In this study we have used site-directed mutagenesis to singly and collectively alter the consensus sequences for N-linked glycosylation in the rLHR. In particular, we examined the binding activity in both intact cells as well as detergent-solubilized extracts so that the effects on trafficking to the plasma membrane could be determined. In addition, we independently examined the effects of substituting a particular Asn versus Thr or Ser residue within a given glycosylation consensus sequence. Our data suggest that substitution of Asn-173 with Gln results in both a decreased ability of the receptor to be expressed on the plasma membrane as well as a vastly decreased binding affinity of the receptor for hCG. However, if the consensus sequence for N-linked glycosylation at Asn-173 is altered by substitution of Thr-175 with Ala (instead of Asn-173 to Gln), the resulting receptor binds hCG with high affinity although it is still impaired in its ability to be expressed at the plasma membrane. Furthermore, if all consensus sequences for N-linked glycosylation are mutated collectively while maintaining Asn-173 (by substituting Thr-175 with Ala instead of Asn-173 to Gln), the resulting deglycosylated receptor, although not expressed on the plasma membrane, binds hCG with high affinity.(ABSTRACT TRUNCATED AT 250 WORDS)

Asparagine↗

Significant improvement of stiff-person syndrome after paraspinal injection of botulinum toxin A.

Following several months of low back pain, a 36-year-old man developed progressive stiffness of the abdominal, low back, and thigh muscles. On examination, these muscles demonstrated marked hypertonia consistent with the clinical diagnosis of stiff-person syndrome. The patient demonstrated increased lumbar lordosis and had focal hyperhidrosis at different sites. Electromyography showed continuous activity of the paraspinal and thigh muscles, and serum and cerebrospinal fluid antibodies to glutamic acid decarboxylase (GAD) were markedly elevated. Diazepam and Lioresal offered partial pain relief. Paraspinal muscle administration of botulinum toxin A reduced the tone of paraspinal and thigh muscles significantly and resulted in marked improvement of ambulation and cessation of pain.

Adult↗

Factors that influence radioimmunoassay of human plasma melatonin: a modified column procedure to eliminate interference.

We describe here the effect of various agents and conditions that can influence the assay of plasma melatonin and report a modified column method which minimizes these interferences. Melatonin was measured by a sensitive radioimmunoassay which can detect melatonin from 5 to 500 pg/ml; the assay was linear about 0-60 pg/ml range. The hemolysis of samples increases the apparent level of melatonin in plasma. When the hemolyzed samples were passed through the SEP-cartridge and washed with methanol, the normal basal level was restored. Elution from the column was highest at 100% methanol and proportionate with the "spiked" value of melatonin. The addition of hemoglobin standard and serum albumin decreases the assayed value of melatonin while the addition of red blood cells and heparin increases the level. EDTA, oxalate, and citrate do not influence the basal level of melatonin. Samples that have been affected by these various agents and conditions can be normalized by passing samples through the column. Up to three cycles of freezing and quick thawing of plasma had no effect on the assay of melatonin; however, beyond three cycles levels were reduced. Long-term storage (up to 4 years) has no influence on the assay.

Animals↗

Heart transplantation for tumor.

Unresectable cardiac tumors, although unusual, are often rapidly fatal. A 31-year-old woman presented with a large tumor arising from the left ventricle and causing symptoms of a constrictive cardiomyopathy. After evaluation with echocardiography, angiography, and computed tomography, an exploration was carried out to confirm the extent of disease. Orthotopic heart transplantation was subsequently performed when a donor organ became available. She is now alive and disease-free 12 months after transplantation.

Adult↗