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Biomedical subjects

C H Miller

Publications and source records attributed to C H Miller.

At least 181 records · Page 10Linked to original sources

Corticosteroid modulation and stress-induced analgesia in rats.

Early evidence has indicated the presence and involvement of specific neural systems which can inhibit the responses to painful stimuli. More recently, further advances suggest that the opiate system may interact with other systems to modulate the analgesia produced by the opiates or various stressors. Since corticosteroids were found to be elevated under the conditions of different stress-induced analgesia (SIA), there may be interactions between the pain-inhibiting systems and the corticosteroids. Recently it was reported that acute stress or long-term adrenalectomy can result in release of beta-endorphin (beta E) and ACTH from the pituitary gland, which can be blocked by dexamethasone. In our early studies we have shown partial antagonism of the SIA by dexamethasone and complete antagonism after naloxone. In this report it was found that chronic treatment of the rats with 0.02% metyrapone in drinking water for 8 weeks resulted in minor hyperalgesia. The chronic pretreatment with metyrapone resulted in a significant potentiation of the analgesia induced via the cold swim stress model, which was reversed by 1 mg/kg (IP) naloxone. Also, hyperalgesia was noted 18 days after the bilateral adrenalectomy of the rats as measured in our laboratory by the hot plate method and as reported by Heybach and Vernikos-Danellis in 1978. These results suggest that the corticosteroid modulation (pituitary-adrenal axis) may have a role in regulating the SIA, and this may implicate the interactions of the corticosteroids with pain-inhibiting systems.

Adrenal Cortex Hormones↗

1-O-Alkyl-sn-glyceryl-3-phosphorylcholines: a novel class of neutrophil stimulants.

1-O-Alkyl-2-O-acetyl-sn-glyceryl-3-phosphorylcholine aggregates and degranulates platelets and polymorphonuclear neutrophils. Here, the bioactivities of this platelet-activating factor, its 2-O-ethyl, and its 2-lyso derivatives were examined further. Each phospholipid aggregated and degranulated rabbit platelets and neutrophils with relative potencies of about 10,000 1,000, and 1, respectively. For rabbit neutrophils, and 2-O-acetyl compound was active in nanomolar and lower concentrations; required extracellular calcium and magnesium in order to induce aggregation; and required extracellular calcium and cytochlasin B in order to induce optimal degranulation. Furthermore the 2-O-acetyl and 2-O-ethyl compounds, in concentrations about tenfold higher than those required for rabbit neutrophils, aggregated and degranulated human neutrophils. With reference to these human neutrophil responses, degranulation required, and aggregation was dramatically enhanced by, cytochalasin B. The lysoanalog was unable to induce these response in the human cells. Thus, these lipids represent a novel class of neutrophil stimulants that closely resemble certain chemotactic factors (eg, C5a and synthetic oligopeptides) in their ability to aggregate and degranulate neutrophils and in the influences which calcium, magnesium and cytochalasin B have on their bioactions. Because platelet-activating factor circulates in the blood of rabbits and, perhaps, humans during anaphylaxis and is suspected of being involved in other syndromes such as serum sickness, this lipid may have unique biologic significance: it may act to recruit platelets and neutrophils into the lesions of these and similar pathologic syndromes.

Animals↗

Selective desensitization of neutrophils: further studies with 1-O-alkyl-sn-glycero-3-phosphocholine analogues.

Human polymorphonuclear neutrophils aggregate and degranulate in response to 2 recently described platelet-activating phospholipids: 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine and 1-O-alkyl-2-O-ethyl-sn-glycero-3-phosphocholine. Here, we find that the 2 phospholipids can also desensitize neutrophils. Thus, cells incubated with either phosphocholine for 1 to 5 min in the absence of calcium and magnesium (which are required for aggregation) did not aggregate when exposed to the bivalent cations and fresh lipid stimulus. Also, cells incubated with either lipid for 5 min in the absence of cytochalasin B (which is required for degranulation) did not degranulate when exposed to cytochalasin B and fresh lipid stimulus. However, these desensitized neutrophils aggregated and degranulated fully in response to the chemotactic oligopeptide N-formyl-methionyl-leucylphenylalanine and C5a. In relation to the aggregation response, this selective desensitization was not due to lipid inactivation; it persisted after thorough cell washing; and it was not induced by a nonaggregating analogue, 1-O-alkyl-sn-glycerol-3-phosphocholine. Furthermore, cells desensitized to the formylated oligopeptide or C5a (by preincubation with either stimulus in the absence of bivalent cations) did not aggregate when challenged with the oligopeptide or C5a, respectively, but exhibited a normal or enhanced aggregation response to the 2 active phospholipids. These data support the concept that C5a, formylated oligopeptides, and phosphocholines represent 3 distinct classes of stimulants that activate and densensitize neutrophils by at least partially independent pathways. This activation and desensitization may be mediated by 3 types of cellular receptors, each of which interacts with only 1 class of stimuli.

Animals↗

Genetic analysis of von Willebrand's disease in two large pedigrees: a multivariate approach.

Clinical and laboratory data, including polymorphic marker traits for linkage analysis, were collected from two large multigenerational families segregating for von Willebrand disease. A new approach to the identification of gene carriers in these families, combining pedigree segregation analysis with multivariate discriminant analysis, is applied. Whereas individually the clinical symptoms and the factor VIII related activities could not distinguish between hypotheses, it was possible to find a discriminant function-showing consistency of the data with a dominant gene hypothesis, but not with a recessive gene or an environmental hypothesis. This function is estimated to lead to 3.2% and 5.5% minimum misclassification of the genotypes, respectively, in the two families. The discriminant function could be used for other families, but is should be calibrated for the specific population in which it is used. Among the markers investigated, GPT is the most likely to be linked to von Willbrand's disease, with a maximum lod score of about unity at 15% recombination.

Factor VIII↗

Uptake and release of chlorhexidine by bovine pulp and dentin specimens and their subsequent acquisition of antibacterial properties.

Bovine pulp and dentin specimens were treated with either a 0.02 or 1.00 percent solution of chlorhexidine for either 20 or 40 minutes. Culture determination of the acquisition of antibacterial properties by the treated specimens immediately and 1 week after the treatment was evaluated using the test organism Streptococcus faecalis. It was concluded that chlorhexidine is a potent antibacterial agent under the test conditions and that its use as an endodontic irrigating solution should be further evaluated.

Adsorption↗

Hemophilic arthropathy: effect of home care on treatment patterns and joint disease.

To evaluate the efficacy of home care therapy on hemophilic arthropathy, data were analyzed in 19 patients with hemophilia who had been on home therapy for more than four years. Usage of replacement material, number of bleeding episodes, and clinical and radiographic assessment of joint status were evaluated. Patients were divided into three treatment groups (prophylaxis, combination, and episodic care) for further comparison. In all treatment groups, a significant decrease in product usage occurred with age (P < 0.01). The number of bleeding episodes also decreased significantly with age (P < 0.01). The patients' joints which were clinically and radiographically normal on entry into home therapy remained free of arthropathic changes. The outcome of diseased joints varied across treatment groups, with a majority of these joints remaining stable. Younger patients evidenced new and progressive arthropathy, whereas older patients demonstrated stable arthropathy. Although no single treatment protocol appears to be indicated for all patients with hemophilpia, a treatment goal may be to treat younger patients actively in order to preserve normal joint status, stablize diseased joints, and prevent subsequent disability.

Adolescent↗

The relationship of Bacteroides melaninogenicus to symptoms associated with pulpal necrosis.

The canal contents of thirty-three cariously and traumatically exposed pulpless teeth were sampled with a special technique and cultured anaerobically for growth in prereduced thioglycollate and for Bacteroides melaninogenicus on selective blood agar plates. The presence of B. melaninogenicus was compared with the presence or absence of eight symptoms associated with pulpal necrosis and the presence or absence of growth in thioglycollate. B. melaninogenicus was found to be significantly related to pain, sinus tract formation and foul odor. Suggested relationships were found between the organism and the presence of apical sensitivity and local swelling. Growth in prereduced thioglycollate occurred more often from teeth in which B. melaninogenicus was present. With the sampling technique used, positive growth in the thioiglycollte ranged from 88 percent at the initial appointment to 72 percent at the fill appointment.

Adolescent↗

Attachment of Actinomyces naeslundii to human buccal epithelial cells.

A standardized assay was used to measure the attachment of Actinomyces naeslundii ATCC 12104 to washed human buccal epithelial cells. Treatment of the A. naeslundii cells with hyaluronidases, wheat germ lipase, protease, trypsin, heat, or sonic oscillation significantly reduced their ability to attach to epithelial cells. Treatment of the epithelial cells with the above enzymes did not influence the attachment of A. naeslundii. Extraction of A. naeslundii with NaOH also significantly reduced the ability of the bacterium to attach to human buccal epithelial cells. The neutralized and dialyzed NaOH extract contained both carbohydrate and protein substances in a ratio of about 1:1. Adding this extract back to the extracted bacterial cells partially restored their ability to attach to epithelial cells. When the NaOH extract was preincubated with epithelial cells and residual extract was removed by washing, attachment of normal A. naeslundii was partially blocked. The ability of the extracted material to block attachment was significantly reduced when treated with hyaluronidases or with wheat germ lipase. Treatment with heat, protease, or trypsin did not significantly reduce the ability of the extracted materials to block attachment. Pretreatment of the epithelial cells with hyaluronic acid or chondroitin sulfate also reduced subsequent attachment of normal A. naeslundii cells. Pretreatment of epithelial cells with dextrans, proteins, or unpure mannose did not influence subsequent attachment of A. naeslundii. Pretreatment of A. naeslundii with galactose and lactose significantly inhibited attachment to normal epithelial cells. The results suggest that the attachment of A. naeslundii to human buccal epithelial cells may involve mucopolysaccharides similar to hyaluronic acid on the surface of the bacterial cells. Other attachment mechanisms may also be operative.

Actinomyces↗