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Biomedical subjects

M Davidson

Publications and source records attributed to M Davidson.

At least 55 records · Page 3Linked to original sources

Murine respiratory mycoplasmosis: a model to study effects of oxidants.

Previous studies have shown that exposure to nitrogen dioxide at concentrations of 5 and 10 parts per million (ppm) decreases intrapulmonary killing of Mycoplasma pulmonis, and that this decrease is related to increased lung lesions and mortality. The specific objectives of the present study were to titrate the effects of nitrogen dioxide on pulmonary clearance of M. pulmonis, determine the mechanisms by which this organism is killed within the lungs, and determine the target that the nitrogen dioxide affects. Pathogen-free C57BL/6N mice were exposed to 0, 0.5, 1, 2, or 5 ppm of nitrogen dioxide (contamination with other oxides of nitrogen compounds was 5% or less) for four hours and then immediately were exposed to aerosols of viable, radiolabeled M. pulmonis strain UAB CT. One-half of the animals in each group were killed immediately after exposure to the infectious aerosols, and the rest were killed 24 hours later. The amount of radioactivity and the number of viable M. pulmonis were determined for each group. Exposure to less than 5 ppm of nitrogen dioxide had no effect on intrapulmonary killing of M. pulmonis, although exposure to 1 ppm of nitrogen dioxide did increase mechanical removal. We were unable to develop a completely in vitro mycoplasma killing method. However, we were able to demonstrate the in vitro killing of M. pulmonis that had been allowed to associate with alveolar macrophages in vivo. Thus, mouse lungs contain unidentified factors that allow cells to kill M. pulmonis. Furthermore, we obtained evidence that suggests that prior exposure to nitrogen dioxide abrogates killing in these experiments. We also have shown that exposure to nitrogen dioxide does not increase the protein content of bronchoalveolar lavage fluid. Using immunofluorescence, more than 95% of the cells recovered by lavage were macrophages; with double-label immunofluorescence, more than 98% of the cell-associated mycoplasmas were on or in alveolar macrophages. In assessing the cytological parameters of lung lavage cells from mice exposed to nitrogen dioxide, M. pulmonis, or both, we found that both insults affected the viability of recovered macrophages. Viability immediately after exposure as measured by trypan blue exclusion or by fluorescein diacetate uptake, was 89% +/- 4% and 88% +/- 4% in the control group, respectively; 56% +/- 19% and 64% +/- 11% in the group receiving M. pulmonis alone; 23% +/- 7% and 48% +/- 9% in the group receiving nitrogen dioxide alone; and 16% +/- 6% and 25% +/- 6% in the group receiving both M. pulmonis and 10 ppm nitrogen dioxide exposures.(ABSTRACT TRUNCATED AT 400 WORDS)

Air Pollutants

DTP immunization and susceptibility to infectious diseases. Is there a relationship?

A two-part study was carried out in Alaskan Native children to evaluate the potential risk of invasive bacterial disease and the occurrence of minor illnesses after immunization with diphtheria and tetanus toxoids and whole-cell pertussis vaccine (DTP). First, a case-control comparison was performed with 186 children who had invasive Haemophilus influenzae type b or Streptococcus pneumoniae disease (cases) and 186 healthy controls matched for sex, region of residence, birth date, and number of DTP immunizations. The proportion of cases and controls immunized in the 30-day period before onset of disease for cases or reference date for controls was identical, suggesting no association with DTP immunization. In a second analysis, the occurrence of any illness, particularly infectious diseases, in 104 study subjects was compared for the period 30 days before and after 377 DTP immunizations. The rate of illness before immunization was 53%, and after immunization, 43%, again suggesting no causative effects from DTP immunization. Despite the high rates of invasive bacterial disease and nearly compete DTP immunization status in this population, no consistent relationship could be demonstrated between DTP immunization and susceptibility to infectious diseases.

Alaska

The treatment of cognitive impairment in Alzheimer's disease: beyond the cholinergic approach.

Despite the well-founded rationale for the use of cholinomimetic and monoaminergic agents in the treatment of Alzheimer's disease, thus far, these strategies have only led to modest results. None of the drugs assessed to date have been shown to improve cognitive function to a clinically significant degree in patients with Alzheimer's disease. Some agents have produced mild improvements on specific tests, whereas others seem to slow down the progression of the disease. This article provides a brief overview of the current trends in the treatment of cognitive dysfunction in Alzheimer's disease.

Alzheimer Disease

Ethanol and synaptosomal calcium homeostasis.

The effect of ethanol on synaptosomal calcium homeostasis was studied in the rat using the fluorescent dye, fura-2, and 45Ca uptake. The mitochondrial poison, cyanide, caused a substantial rise in intracellular free Ca2+ concentration, [Ca2+]i, over that of control synaptosomes. This rise was enhanced by ethanol. Ethanol also augmented the rise in [Ca2+]i induced by ouabain, indicating that modulation of Na(+)-Ca2+ exchange is probably not the underlying mechanism. The Ca2+ channel blockers, verapamil and La3+, also failed to inhibit the rise in [Ca2+]i caused by ethanol. Preincubation of synaptosomes with caffeine, however, caused a significant decrease in the rise of [Ca2+]i due to ethanol, suggesting that ethanol exerts effects on Ca2+ homeostasis at the level of the endoplasmic reticulum.

Animals

Measurement of plasma homovanillic acid concentrations in schizophrenic patients.

1. Several lines of evidence suggest that abnormalities of central dopaminergic transmission may be involved in the expression of some schizophrenic symptoms. However, elucidation of the role of dopamine (DA) in schizophrenia has eluded investigative efforts partially because no accurate and easily repeatable measure of brain DA activity exists. 2. The development of a technique to measure homovanillic acid in plasma has offered the possibility of performing serial measurements of this major DA metabolite. 3. Assuming that plasma homovanillic acid (PHVA) concentrations is an index of brain DA activity, measurement of PHVA can play a role in elucidating the DA abnormality in schizophrenia. 4. Results to date suggest that plasma homovanillic acid concentrations are lower in chronic schizophrenic patients compared to normal controls, and that PHVA values correlate with schizophrenic symptom severity. 5. In addition, PHVA levels were shown to initially rise and subsequently decline during chronic neuroleptic administration in treatment responsive but not in treatment refractory schizophrenic patients.

Biomarkers

Increments in plasma homovanillic acid concentrations after neuroleptic discontinuation are associated with worsening of schizophrenic symptoms.

1. Thirty-two male schizophrenic patients participated in this study. 2. Plasma concentrations of the dopamine metabolite, homovanillic acid (pHVA) were assessed once on neuroleptic medication and twice a week for a maximum of six weeks after its discontinuation. 3. Psychiatric symptomatology was assessed once on neuroleptic medication and once a week for a maximum of six weeks after its discontinuation, using the brief psychiatric rating scale (BPRS). 4. pHVA and total BPRS score increased significantly after discontinuation of neuroleptic as compared to baseline. 5. The magnitude of pHVA and BPRS increments after discontinuation of neuroleptic correlated significantly. 6. Results of this study suggest that worsening of schizophrenic symptoms after discontinuation of neuroleptic treatment is associated with increased pHVA concentrations.

Adult

Intermediate filament complement of the normal and gliotic canine retina.

Intermediate filament expression of various cell types in the adult canine normal and gliotic retina was determined by an immunoperoxidase method of using monoclonal antibodies on aldehyde-fixed tissues. In the normal retina, vimentin was present in astrocytes in the nerve fibre layer, horizontal cell processes, and Müller cell fibres from the internal limiting membrane to the outer nuclear layer. Neurofilamentous axons were noted in the nerve fibre, inner plexiform layer, and outer plexiform layer, although the degree of staining intensity varied among the three molecular weight neurofilament antisera used. Glial fibrillary acidic protein (GFAP) staining was confined to the nerve fibre and ganglion cell layer; this was interpreted as representing fibrous astrocytes. Astrocyte density varied according to retinal topography with an increased number around retinal blood vessels and in the peripapillary retina. Quantitative, but not qualitative differences in staining for vimentin and the neurofilaments were noted in degenerative, gliotic retinas. In common with several other mammalian species previously studied, the canine Müller cells accumulate or express GFAP under pathological conditions involving a gliotic response.

Animals

Manometric variations following spiral myotomy for long-gap esophageal atresia.

We have previously demonstrated that a spiral myotomy and delayed definitive procedure is a viable alternative for esophageal reconstruction in long-gap esophageal atresia. In this study we sought to determine whether this procedure leads to esophageal motility disturbances and to compare the manometric findings with controls as well as with those seen in children with esophageal atresia and primary anastomosis. Six beagles had esophageal transection and a spiral myotomy, one had esophageal transection without a myotomy, and two served as normal controls. Following esophageal reconstruction, esophageal manometry was studied in all dogs using a standard pull-through technique. We found that the three control dogs all had similar manometric findings with normal peristalsis. In contrast, the dogs with a spiral myotomy all had propagation of waves in the myotomized segment but termination of waves at the anastomotic site. There was delayed velocity through the myotomized segment and retrograde peristalsis distally. Finally, upper esophageal sphincter pressure was elevated, while lower esophageal sphincter pressure was similar to that in the normal dogs. These findings are similar to those described in children with primary anastomosis and suggest that (a) spinal myotomy is a good alternative to other esophageal replacement options in patients with long-gap esophageal atresia and that (b) the motility dysfunction observed in children with esophageal atresia following primary anastomosis may be secondary to the disruption of the vagus nerve and that may be part of the congenital abnormality or secondary to surgical trauma.

Animals

Monoclonal antibodies to proteins from cocksfoot grass (Dactylis glomerata) pollen: isolation and N-terminal sequence of a major allergen.

Monoclonal antibodies (Mabs) raised to an aqueous extract of cocksfoot grass (Dactylis glomerata) pollen have been characterised. Mab 1B9 was demonstrated by SDS-PAGE and Western blotting to recognise a major allergen of an approximate molecular weight of 28 kD in this extract, termed DG3, and a component with a molecular weight of between 35 and 40 kD in an extract of Secale cereale (cultivated rye) pollen. The 28 kD component of cocksfoot grass pollen isolated by affinity chromatography using Mab 1B9 was recognised by IgE antibodies in 80% (8 of 10) atopic sera, but only weakly by 25% (1 of 4) non-atopic sera tested. N-terminal sequencing of DG3 purified by affinity chromatography, 2 D electrophoresis and electroblotting to polyvinylidenedifluoride revealed significant homology with a group-V allergen (Phl p V) from timothy grass (Phleum pratense).

Amino Acid Sequence

Eye tracking impairment in clinically identified patients with schizotypal personality disorder.

Eye tracking accuracy, which has been found to be impaired in schizophrenic patients and their relatives, was assessed in 26 patients with schizotypal personality disorder, 17 control subjects with other non-schizophrenia-related personality disorders, 29 normal control subjects, and 44 schizophrenic patients. Both schizotypal and schizophrenic patients, but not control subjects with other personality disorders, demonstrated significantly more impaired tracking than the normal control subjects. These results suggest that patients with clinically defined schizotypal personality disorder may be biologically related to schizophrenic patients as part of a spectrum of schizophrenia-related disorders.

Adult

Cyclic-AMP production by polymorphonuclear leukocytes in psychiatric disorders.

The cyclic adenosine monophosphate (cAMP) responses to histamine, prostaglandin-E1, and isoproterenol in polymorphonuclear leukocytes from drug-free normal controls and patients with schizophrenia or major depressive disorder were compared. These three groups of subjects did not differ in their cAMP responses to receptor activation. Exacerbated and remitted patients with either schizophrenia or major depressive disorder did not differ in their cAMP responses. The data indicate that in polymorphonuclear leukocytes, the cAMP responses to activation of histamine H2, prostaglandin-E1, or beta-adrenergic receptors are neither state-independent nor state-dependent markers for schizophrenia or major depressive disorder.

Adult

Invasive pneumococcal disease in an Alaska native population, 1980 through 1986.

From 1980 through 1986, one hundred fourteen Alaska Native patients from the Yukon-Kuskokwim Delta had community-acquired invasive pneumococcal disease confirmed by isolates of Streptococcus pneumoniae from normally sterile body sites. The annual bacteremia rates per 100,000 persons were 105 cases for all ages, 1195 cases for infants under 2 years of age, and 130 cases for adults over 59 years of age. These were six to 34 times higher than rates reported for other US populations. The most common underlying conditions in infants diagnosed before 24 months of age were previously diagnosed anemia and pneumonia, while alcoholism and anemia were most common in adults. The case-fatality rate for infants under 2 years of age was 3.2%, and the case-fatality rate for adults over 59 years of age was 30%. Serotyping of more than half the isolates identified 96% of these isolates to be present in the currently available pneumococcal polysaccharide vaccine. The pneumococcal disease rates reported herein are likely to be underestimates since most diseases that occur in this region are treated at the village level without laboratory confirmation.

Adolescent

Effects of fornix transection and cingulate cortical ablation on spatial memory in rhesus monkeys.

This study, together with a parallel study in rats (Markowska et al. 1988), attempted to relate the effects of hippocampal-system damage on similar tasks in both rats and monkeys. Not only were monkeys given a task (Experiment 1) which was of the sort usually used with rats, but in the companion study rats were given tasks (Experiment 2) like those usually used with monkeys. Experiment 1 examined the performance of rhesus monkeys with hippocampal-system damage on a spatial working memory task. Monkeys were trained preoperatively on delayed nonmatching-to-sample in a T-maze, placed into groups matched for their preoperative learning scores, and then received one of three treatments: 1) transection of the fornix; 2) ablation of the cingulate cortex; or 3) a sham operation. Monkeys with fornix transection were severely and significantly impaired, but monkeys with cingulate cortical ablations were not significantly impaired, relative to the controls. The results demonstrate that monkeys with fornix transection are severely impaired on a spatial working memory task requiring locomotion and, taken together with earlier work, suggest that the effect of fornix transection in both rodents and nonhuman primates is at least qualitatively similar (see Markowska et al. 1988). Experiment 2 assessed the role of the fornix and cingulate cortex in three conditional tasks in which the monkeys were provided with various spatial cues to indicate which one of two objects was rewarded. Both experimental groups were unimpaired, relative to the control group, on all three tasks, indicating that fornix transection does not produce a general impairment in place learning.

Animals

The role of alpha-macroglobulin in experimental intestinal ischemia.

Intestinal ischemia can lead to mucosal damage and presumably increased intestinal permeability. alpha-Macroglobulin (alpha-MG) is a plasma protein responsible for the inhibition and clearance of systemic proteases, including those derived from the intestinal lumen. In this study, we sought to determine the relationship between intestinal ischemia and alpha-MG in dogs using a nonsurgical model of ischemia. In addition, we sought to detect plasma alpha-MG complexes after ischemic injury. We found that alpha-MG levels were significantly reduced 24 h after induction of occlusion compared with those values obtained immediately after vascular occlusion. The onset of the decline in alpha-MG coincided with the onset of full-thickness intestinal damage, alpha-MG levels in the control animals were unchanged. However, alpha-MG complexes were not elevated in the experimental dogs after ischemia. We suggest that the decline in alpha-MG levels reflects a response to excessive protease uptake across a damaged intestine, leading to increase formation of alpha-MG-protease complexes, which are then rapidly cleared. The absence of detectable systemic complexes suggests that in ischemia, clearance is effective in removing the complexes from the bloodstream, alpha-MG appears to play an important role in protecting against proteolytic damage in prolonged intestinal ischemia.

Animals