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Biomedical subjects

C Graham

Publications and source records attributed to C Graham.

At least 19 recordsLinked to original sources
PubMed1999

Test facility for human exposure to AC and DC magnetic fields.

For more than a decade, Midwest Research Institute (MRI) has investigated the effects of exposure to 60 Hz electric and magnetic fields (EMF) on human physiology, performance, and biochemistry. This accumulated experience, new research directions, and limited resources made it important to design more comprehensive and operationally cost-effective exposure facilities. Here we describe the new, integrated laboratory exposure test facilities recently constructed at MRI and present data on relevant characteristics of the exposure systems. Concentric coil systems were developed to generate uniform magnetic fields within the three new exposure rooms, with rapid cancellation of the field to ambient levels in the rest of the laboratory. Control systems are fully automated, computer-based, and independent. These provide the operational flexibility needed to present fields of different magnitudes, frequencies, and polarization. The local geomagnetic field can be modulated and/or canceled, and both AC and DC fields can be presented in various combinations. Capabilities for conducting double-blind experiments with true active-sham exposure conditions were implemented using bifilar windings and applying current flow in the opposite direction for each wire in a pair. The new facilities provide a comprehensive capability for laboratory-based human research on the potential effects of exposure to AC and DC magnetic fields.

Automation↗
PubMed1999

Domain exchange experiments in duck delta-crystallins: functional and evolutionary implications.

Delta-crystallin, the major soluble protein component of the avian and reptilian eye lens, is homologous to the urea cycle enzyme argininosuccinate lyase (ASL). In duck lenses there are two delta crystallins, denoted delta1 and delta2. Duck delta2 is both a major structural protein of the lens and also the duck orthologue of ASL, an example of gene recruitment. Although 94% identical to delta2/ASL in the amino acid sequence, delta1 is enzymatically inactive. A series of hybrid proteins have been constructed to assess the role of each structural domain in the enzymatic mechanism. Five chimeras--221, 122, 121, 211, and 112, where the three numbers correspond to the three structural domains and the value of 1 or 2 represents the protein of origin, delta1 or delta2, respectively--were constructed and thermodynamically and kinetically analyzed. The kinetic analysis indicates that only domain 1 is crucial for restoring ASL activity to delta1 crystallin, and that amino acid substitutions in domain 2 may play a role in substrate binding. These results confirm the hypothesis that only one domain, domain 1, is responsible for the loss of catalytic activity in delta1. The thermodynamic characterization of human ASL (hASL) and duck delta1 and delta2 indicate that delta crystallins are slightly less stable than hASL, with the delta1 being the least stable. The deltaGs of unfolding are 57.25, 63.13, and 70.71 kcal mol(-1) for delta1, delta2, and hASL, respectively. This result was unexpected, and we speculate that delta crystallins have adapted to their structural role by adopting a slightly less stable conformation that might allow for enhanced protein-protein and protein-solvent interactions.

Amino Acid Sequence↗
PubMed1999

The role of psychological and biological factors in postinfective gut dysfunction.

BACKGROUND: Both psychological and physiological disturbances have been implicated in the aetiopathogenesis of irritable bowel syndrome (IBS). AIMS: To investigate how the psychological factors act, and the involvement of infective and physiological factors. METHODS: Consecutive patients hospitalised for gastroenteritis reported life events for the previous 12 months, and past illness experiences on standardised questionnaires. They also completed psychometric questionnaires for anxiety, neuroticism, somatisation, and hypochondriasis. In some patients, rectal biopsy specimens were obtained during the acute illness and at three months postinfection. RESULTS: Ninety four patients completed all questionnaires: 22 patients were diagnosed with IBS after their gastroenteritis (IBS+), and 72 patients returned to normal bowel habits (IBS-). IBS+ patients reported more life events and had higher hypochondriasis scores than IBS- patients. The predictive value of the life event and hypochondriasis measures was highly significant and independent of anxiety, neuroticism, and somatisation scores, which were also elevated in IBS+ patients. Rectal biopsy specimens from 29 patients showed a chronic inflammatory response in both IBS+ and IBS- patients. Three months later, specimens from IBS+ patients continued to show increased chronic inflammatory cell counts but those from IBS- patients had returned to normal levels. IBS+ and IBS- patients exhibited rectal hypersensitivity and hyper-reactivity and rapid colonic transit compared with normal controls, but there were no significant differences between IBS+ and IBS- patients for these physiological measurements. CONCLUSION: Psychological factors most clearly predict the development of IBS symptoms after gastroenteritis but biological mechanisms also contribute towards the expression of symptoms.

Adolescent↗
PubMed1999

Relationship between allergic contact dermatitis and electrophilicity.

To evaluate the role of electrophilicity in the induction of allergic contact dermatitis (ACD) in humans, we compared the structure-activity relationship (SAR) model of ACD with those of electrophilic and nonelectrophilic subsets of chemicals in the ACD database. For these analyses, electrophilicity was defined as the potential of a chemical to induce mutations in Salmonella. It was found that electrophilicity accounted for approximately 30-40% of ACD-inducing ability, and the remainder was associated with nonelectrophilic structures. The identification of these moieties opens the possibility for studying their role in ACD.

Algorithms↗
PubMed1998

Investigation of vesicular rashes for HSV and VZV by PCR.

Vesicular fluid from rashes of 132 patients was tested by a multiplex PCR shown to be specific for herpes simplex virus (HSV) type 1 and 2, and varicella zoster virus (VZV) genomic DNA. The results were compared with those obtained by examination by electron microscopy and virus isolation by cell culture. The PCR did not differentiate between HSV 1 and 2. By PCR, 64 HSV infections and 53 VZV infections were identified, with presumed 100% sensitivity and specificity. Fifteen specimens tested negative by PCR, electron microscopy, and virus isolation for herpes viruses. The sensitivities of virus isolation and electron microscopy for detection of herpes simplex virus were 56% and 80%. For varicella zoster virus, the sensitivities of virus isolation and electron microscopy were 47% and 60%. These data illustrate the advantage of rapid PCR diagnosis of herpes simplex virus and varicella zoster virus in vesicle fluids.

Adolescent↗
PubMed1998

Changes in pulmonary mechanics after lung volume reduction surgery.

Lung volume reduction surgery (LVRS) is a promising new treatment for emphysema and leads to increased flow rates. We investigated the mechanisms by which flow rates could increase and the correlates of lessened dyspnea in patients undergoing LVRS before and 3 months after LVRS in patients with severe emphysema. The following were done: routine pulmonary function testing, measurements of elastic recoil (Pel), tidal breathing patterns, inspiratory work of breathing (Winsp), construction of static recoil-maximum flow curves, and measurement of baseline and transitional dyspnea index (TDI). There were increases in forced vital capacity (FVC: 2.24 +/- 0.71 to 2.92 +/- 0.63 liters; p < 0.05), forced expired volume in 1 (FEV1: 0.64 +/- .16 to 1.03 +/- 0.28 liters; p < 0.01), and decreases in all divisions of lung volume, e.g. total lung capacity (TLC: 6.86 +/- 1.41 to 5.96 +/- 1.49 liters; p < 0.01). Maximum Pel increased (11.7 +/- 3.7 to 19.8 +/- 7.8 cmH2O; p < 0.02) as did the coefficient of retraction (CR = Pel/TLC: 1.8 +/- 0.7 to 3.6 +/- 3.6 +/- 2.2 cmH2O/liter). However, the individual responses in other parameters were markedly different among patients. There was no consistent trend in changes in the slope or position of the static recoil-maximum flow curve or Winsp. The only positive correlate of improved dyspnea (TDI = 3.22 +/- 2.22; p < 0.01) was improvement in CR, FEV1 being a weak negative correlate and change in lung volume not being a correlate at all. We conclude that there is a heterogeneous response of the airways to LVRS. Increased elastic recoil was the primary determinant of improved flow rates after LVRS and is the only positive correlate for improvement in dyspnea.

Aged↗
PubMed1998

Cloning and tissue expression of the mouse ortholog of AIM1, a betagamma-crystallin superfamily member.

We report the isolation of the murine ortholog of AIM1, a human gene whose expression is associated with the reversal of tumorigenicity in an experimental model of melanoma. Mouse and human AIM1 are more than 90% identical in amino acid sequence in the betagamma-crystallin repeats and the C-terminal domain, and more than 75% identical in the extended N-terminal domain. Consistent with the isolated cDNA representing the authentic AIM1 ortholog, linkage analysis localized mouse Aim1 to proximal mouse Chromosome (Chr) 10 in a conserved linkage group with genes localized to human Chr band 6q21. Searches of EST databases identified a second AIM1-like gene in both mouse and human, suggesting the existence of a gene family. Northern analysis demonstrates Aim1 is expressed most abundantly in adult skin, lung, heart, liver, and kidney and is temporally regulated during embryogenesis. Aim1 is expressed highly in the shaft region of the hair follicles and the presumptive ectoderm, but not at detectable levels in melanocytes or melanocyte precursor cells.

Amino Acid Sequence↗
PubMed1998

Immunologic cross-reactivity between respiratory chemical sensitizers: reactive dyes and cyanuric chloride.

BACKGROUND: CyCl is a low molecular weight reactive chemical used as an intermediate in the production of plastics, herbicides, pharmaceuticals, and fiber-reactive dyes. It is a potent inducer of specific IgE antibody. The CyCl functionality is a structural component of monochlorotriazine and dichlorotriazine dyes. OBJECTIVE: We have investigated the immunologic cross-reactivity between cyanuric chloride (CyCl) and reactive dyes and it was hypothesized that this moiety might be a dye epitope and that it might stimulate an allergic antibody response in dye-exposed workers. METHODS: To test this hypothesis, we have used sera with IgE antibodies to CyCl and also sera from dye-exposed workers who have IgE antibodies to Procion Orange MX2R, an azo dye containing the dichlorotriazine group. As a control group we have used dye-exposed workers with IgE antibody to Remazol Black B, a diazo dye containing the vinyl sulfone-reactive group. RESULTS: Using RAST and RAST inhibitions, we identified negligible cross-reactivity between CyCl and dichlorotriazine dye. CONCLUSION: The results of this study imply that the allergenic moiety on the dye residue resides in the chromophore rather than in the common structural component of CyCl and dichlorotriazine dyes.

Antibody Specificity↗
PubMed1998

Dementia and ethnicity.

Ethnic differences in rates of dementia nationally, within multiethnic communities, and internationally have important repercussions. The question "Do ethnic differences exist in rates of dementia?" is a crucial one that has implications for service delivery and also offers opportunities for future research on possible etiological factors. Epidemiological surveys suggest that ethnic and geographical differences do occur in rates of dementia, but cross-cultural surveys are fraught with problems. The need for further methodologically sound, cross-cultural comparative studies is paramount to confirm or disclaim the ethnic differences observed to date.

Africa↗
PubMed1998

Cutaneous vascular infarcts secondary to spontaneous platelet aggregation.

We report a 23-year-old woman presenting with multiple cutaneous infarcts who was found to have spontaneous platelet aggregation (SPA). Her skin lesions showed a good response to aspirin therapy and platelet aggregation returned to normal. Subsequently, she was found to have and was treated for pulmonary tuberculosis. The SPA may have been related to this via the formation of immune complexes. Isolated cutaneous infarcts have not previously been described in association with SPA. The role of spontaneous and increased platelet aggregation in skin disorders is discussed.

Adult↗
PubMed1998

Prediction of nocturnal plasma melatonin from morning urinary measures.

A growing literature indicates that blood levels of the hormone melatonin may have important implications for human health and well-being. Melatonin is synthesized and released into the general circulation at night, however, and it is seldom feasible to draw blood samples at night in epidemiological studies. There is some evidence that levels of urinary melatonin and of 6-sulfatoxymelatonin (aMT6s), the major metabolite of melatonin, accurately reflect nocturnal plasma melatonin. If this is the case, urinary assays could be powerful tools for epidemiological studies. A laboratory-based study was performed to examine the relationships between nocturnal plasma melatonin, morning urinary melatonin, and morning urinary aMT6s levels in 78 men. The relationship between total nocturnal plasma melatonin and both urinary aMT6s corrected for creatinine and urinary melatonin is significant. Combining the two urinary measures accounts for 72% of the variance in total plasma melatonin. Peak nocturnal plasma melatonin also was significantly related to urinary melatonin and to aMT6s. The urinary measures show good sensitivity and specificity in identifying individual differences in nocturnal plasma melatonin levels. These results support the inclusion of morning urine samples to assess the contribution of the hormone melatonin in occupational or residential studies involving healthy, young men.

Adolescent↗
PubMed1998

Nocturnal exposure to intermittent 60 Hz magnetic fields alters human cardiac rhythm.

Heart rate variability (HRV) results from the action of neuronal and cardiovascular reflexes, including those involved in the control of temperature, blood pressure and respiration. Quantitative spectral analyses of alterations in HRV using the digital Fourier transform technique provide useful in vivo indicators of beat-to-beat variations in sympathetic and parasympathetic nerve activity. Recently, decreases in HRV have been shown to have clinical value in the prediction of cardiovascular morbidity and mortality. While previous studies have shown that exposure to power-frequency electric and magnetic fields alters mean heart rate, the studies reported here are the first to examine effects of exposure on HRV. This report describes three double-blind studies involving a total of 77 human volunteers. In the first two studies, nocturnal exposure to an intermittent, circularly polarized magnetic field at 200 mG significantly reduced HRV in the spectral band associated with temperature and blood pressure control mechanisms (P = 0.035 and P = 0.02), and increased variability in the spectral band associated with respiration (P = 0.06 and P = 0.008). In the third study the field was presented continuously rather than intermittently, and no significant effects on HRV were found. The changes seen as a function of intermittent magnetic field exposure are similar, but not identical, to those reported as predictive of cardiovascular morbidity and mortality. Furthermore, the changes resemble those reported during stage II sleep. Further research will be required to determine whether exposure to magnetic fields alters stage II sleep and to define further the anatomical structures where field-related interactions between magnetic fields and human physiology should be sought.

Adolescent↗
PubMed1997

Alternative splicing of Pax6 in bovine eye and evolutionary conservation of intron sequences.

Pax-6 is essential for eye development and for tissue-specific gene expression within the eye. Splicing of an alternative exon (5a) leads to variant DNA binding specificity in Pax6. Here we show that in the mature bovine eye the relative abundance of the alternative Pax6-5a mRNA varies markedly, particularly between the lens and iris. Additional alternative splicing products were identified which may lead to "domain swapping" or truncation of Pax6 proteins. Comparison of amphibian (Xenopus) and mammalian (bovine) Pax-6 genes revealed highly conserved intronic sequences flanking exon 5a, including potential lariat sites which may have a role in the mechanism of alternative splicing.

Alternative Splicing↗
PubMed1997

Efficacy of laser-assisted uvulopalatoplasty.

BACKGROUND AND OBJECTIVE: Laser-assisted uvulopalatoplasty (LAUP) is being used increasingly as a surgical treatment for snoring and obstructive sleep apnea (OSA). There is limited evidence for the success of LAUP in eliminating OSA. This study assesses the efficacy of LAUP in eliminating snoring and OSA and addresses which patients may be the best candidates for LAUP treatment. STUDY DESIGN/MATERIALS AND METHODS: From January 1994 to January 1996, 297 patients were evaluated for snoring, with 190 (64%) exhibiting some degree of OSA documented by a PSG: 41/ 190 (22%) mild OSA; 33/190 (17%) moderate OSA; 85/190 (45%) severe OSA; 31/190 (16%) severity unknown. Ninety patients (90/ 297) have undergone LAUP treatment: 58/90 (64%) with OSA and 32/90 (36%) with snoring only. RESULTS: Our results indicate a significant reduction of snoring in patients without OSA, but diminishing success in patients with increasing degrees of OSA. Additionally, LAUP was not efficacious in treating OSA: pre-op respiratory disturbance index (RDI) of 10.8 vs. post-op RDI of 19.5 for mild OSA (P = 0.14); pre-op RDI of 22.9 vs. post-op RDI of 25.4 for moderate OSA (P = 0.43); pre-op RDI of 56.8 vs. post-op RDI of 46.3 (P < 0.05), which is statistically but not clinically significant (i.e., RDI remained in the severe range). CONCLUSION: We conclude that LAUP is an effective treatment for nonapneic snoring, but does not provide sufficient resolution of OSA, and based on our results, LAUP should be considered as an adjunctive therapy rather than a sole treatment for OSA in most cases.

Adult↗
PubMed1997

Structure-activity model of chemicals that cause human respiratory sensitization.

We report a structure-activity model of chemicals with the potential to cause respiratory allergy developed through the CASE/MultiCASE systems. Chemicals documented to elicit a decrease in FEV1 of > or = 20% within 24 h of inhalation provocation challenge were used to form a learning set. Additional requirements for inclusion in the learning set were that chemicals had at least two contiguous nonhydrogen atoms and were nonmetallic. Forty chemicals met these criteria. The model identified several "structural alerts" including the isocyanate functionality (N = C = O), primary and secondary amines, substituted aromatic moieties, and distance descriptors. An external data-withholding exercise used to validate the model yielded a sensitivity of 0.95 and a specificity of 0.95. This model is applicable to initial prediction of the sensitizing ability of untested chemicals and may provide mechanistic insight into the process(es) of respiratory sensitization.

Administration, Inhalation↗