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Biomedical subjects

M L Miller

Publications and source records attributed to M L Miller.

At least 145 records · Page 8Linked to original sources

Qualitative and quantitative effects on epidermal Langerhans (Ia+) and Thy-1+ dendritic cells following topical application of phorbol diesters and mezerein.

Repeated twice-weekly applications of promoting doses of 12-O-tetradecanoylphorbol-13-acetate (TPA) to the dorsal skin of female adult SENCAR mice led to a reduction in numbers per unit area of epidermal Thy-1+ dendritic cells. Although no parallel effect was observed on Ia+ Langerhans cells, a concurrent reduction of dendritic morphology of both cell types was observed. Topical administration of TPA (2 micrograms) twice weekly for 4 or 8 weeks led to reductions in Thy-1+ cell numbers of 52 and 61%, respectively, whereas a single treatment was without effect. Similar effects were observed in animals initiated with 10 nmol 7,12-dimethylbenz[a]anthracene suggesting that the response was specific to the promotion, rather than the initiation, phase of two-stage tumorigenesis. All initiated animals bore tumors after 16 promoter treatments. In comparison with the potent promoter TPA, the weak overall, but stage-specific promoters 4-O-methylTPA and mezerein showed no effects on number or morphology of either dendritic cell type. These findings are therefore consistent with an important role for quantitative and qualitative alterations in epidermal non-keratinocytes of immune function in tumor promotion.

9,10-Dimethyl-1,2-benzanthracene↗

Toluene diisocyanate-induced airway hyperreactivity in guinea pigs depleted of granulocytes.

The influence of cyclophosphamide-induced granulocyte depletion on toluene diisocyanate (TDI)-related changes in airway reactivity and pathology was assessed in guinea pigs. Twelve cyclophosphamide-treated and 12 control animals comprising each group were studied physiologically before and 2 h after a single 10-min exposure to 3 ppm of TDI. Reactivity was determined in intact unanesthetized animals by measuring specific airway conductance before and during intravenous acetylcholine infusion. After testing, tracheal tissue for light microscopic examination was obtained from three hyperreactive guinea pigs in each exposed group and compared with tissue from treated and control animals (n = 3 each) that had not been TDI exposed. Cyclophosphamide treatment caused substantial decreases in both circulating and airway granulocyte counts. However, the incidence and degree of bronchial hyperreactivity that occurred 2 h post-TDI was similar in the untreated and treated groups. Our results indicate that TDI-induced bronchial hyperreactivity 1) occurs shortly after a brief high concentration exposure and 2) appears independent of circulating or airway granulocyte counts.

Acetylcholine↗

Risk of coronary abnormalities due to Kawasaki disease in urban area with small Asian population.

The epidemiology of Kawasaki disease in the six-county Chicago metropolitan area (total population, greater than 7,100,000 inhabitants) was characterized by identifying cases, with onset occurring from 1979 to 1983, inclusively, that had been studied by echocardiography. A retrospective survey of the records from pediatric echocardiographic laboratories and pediatric cardiologists at teaching hospitals, as well as a random sample survey of nonteaching hospitals with pediatric beds in the metropolitan area, was carried out. A total of 190 cases were identified, yielding an annual mean minimum incidence of 5.95 per 100,000 children less than 5 years old. Cases occurred endemically with superimposed spring clusters in 1980 and 1983. As seen in other studies, the male-female ratio was 1.58:1, and the peak incidence occurred in children between 1 and 2 years old, with 85% of cases occurring in children under 5 years of age. The racial distribution of cases was as follows: whites, including Hispanics, 62%; blacks, 32%; Asians, 5%; and half-white/half-Asian, 1%. Asians were slightly overrepresented in that they made up only 1.7% of the study area population. The annual minimum incidence for Asian Americans was 24.4 per 100,000 children less than 5 years old; this rate was significantly greater than those for the other racial groups. Although few cases were observed in Japanese-American children, the calculated annual minimum incidence in this small group was approximately 44 per 100,000 children less than 5 years old. The highest incidence was observed in several suburban Chicago zip code areas, where annual rates as high as 84.7 per 100,000 children less than 5 years old were documented. Coronary artery abnormalities were diagnosed by echocardiography in 30 (16%) of 190 cases; the male-female ratio of patients with such abnormalities was 2.75:1. Whites and children under 1 year of age demonstrated the highest incidence of coronary artery abnormalities. White children under 1 year of age appeared to be at particularly high risk for development of coronary abnormalities, with 11 (41%) of 27 white infants manifesting such findings by echocardiography. These infants may represent a subgroup of patients who would benefit particularly from therapy with intravenous gamma globulin for prevention of coronary abnormalities and who require particularly close follow-up care.

Adolescent↗

Mechanism of mouse skin tumor promotion by n-dodecane.

Application of the alkane n-dodecane to the dorsal skin of 6-8 week old female SENCAR mice initiated with 10 nmol dimethylbenz[a]anthracene led to papilloma formation in the majority of treated animals. Compared to the potent phorbol diester 12-O-tetradecanoylphorbol-13-acetate (TPA), n-dodecane was several orders of magnitude less potent on a dose basis, and maximal papilloma response required more extended application (22 weeks for 50 mg dodecane compared to 12 weeks for 2 micrograms TPA). In two-stage promotion experiments n-dodecane appeared to act as a stage II promoting agent at appropriate doses, being comparable in activity to mezerein--an agent with well-characterized activity of this type. Dodecane, unlike mezerein, did not induce the formation of a significant number of pyknotic cells, however, suggesting that the weak promoting activity of dodecane in stage 1 was not a result of toxicity. In comparison with TPA, both mezerein and n-dodecane at promoting doses induced less sustained hyperplasia in SENCAR mouse skin, a finding also consistent with the proposal that n-dodecane is principally active in stage II of two-stage promotion models. Both agents induced ornithine decarboxylase activity in SENCAR mouse skin, the maximal induction being observed at apparently the same time after a single application.

Acetone↗

Combined genetic transformation and nutritional assay for identification of Moraxella nonliquefaciens.

A combined genetic transformation and nutritional assay is described that permits definitive identification of clinically isolated strains of Moraxella nonliquefaciens. Crude DNA preparations of strains of various Moraxella species were used to transform nutritional mutants of a stably competent strain of M. nonliquefaciens for ability to grow on a defined medium (Mn-B). DNA samples from 24 independently isolated strains of M. nonliquefaciens all resulted in massive (4+) transformation of each of two mutant assay strains. DNA samples from strains of M. bovis and M. lacunata frequently gave weak (1+) transformation of one of the mutant assay strains (Mn64) but almost always failed to transform another assay strain (Mn136). DNA samples from eight other Moraxella species failed completely to transform either of the mutant assay strains. When streaked on the defined medium used for the transformation assay (Mn-B), 23 of the 24 strains of M. nonliquefaciens grew well, but all strains of M. bovis and M. lacunata failed to grow on this medium.

Culture Media↗

Relationship between riboflavin intake and excretion in female rats after weaning of the litter.

Six groups of female rats which gave birth to offspring of 8 young (or adjusted to 8) were fed diets containing 2, 4, 6, 8, 12, or 16 mg of riboflavin per kg of dry matter. Seventeen days after birth, young were withdrawn from the mothers and these were placed in metabolic cages and excreta (urine and feces) were daily collected for 17 days. The activity coefficient of blood glutathione reductase was 1.45 in 17 days old young of group 2 whereas it was 1.12 in young of other groups. The coefficient was 1.09 in female rats at the end of the experiment. 5 and 6 days after excreta collection began urinary excretion of riboflavin reached a peak in females of groups 4 to 16. At the end of the experiment, females which were fed 8 mg of riboflavin/kg or more had an urinary excretion of the vitamin which reached a plateau at 50 micrograms/day. On the other hand fecal excretion of riboflavin markedly increased as the intake did. Data suggested that the intestinal absorption of riboflavin is limited but also that the requirement of riboflavin in lactating rats is 8 mg/kg of diet whereas it is 2 mg/kg for maintenance.

Animals↗

Toluene diisocyanate-induced airway hyperreactivity and pathology in the guinea pig.

We assessed the nature and progression of airway mucosal disease and histaminic reactivity in English short-haired guinea pigs at 2, 24, 72, 168, and 504 hours after toluene diisocyanate (TDI) exposure (4 hours of 3 ppm of TDI for 5 consecutive days). To also determine whether TDI-specific, IgE-like antibodies developed in TDI-exposed animals, passive cutaneous anaphylaxis testing was done 28 days after TDI. Bronchial reactivity was determined serially by measuring specific airway conductance as a function of increasing doses of aerosolized histamine in six exposed and three control animals studied intact and unanesthetized. The remaining 10 exposed and 10 control guinea pigs were sacrificed in groups of two at each time point to obtain airway tissue for light microscopic examination. We found that airway hyperreactivity to histamine occurred after TDI in all animals tested. It was maximal 2 hours after the 5-day exposure and remitted by 72 hours. In addition, marked airway obstruction occurred after TDI that persisted for at least 168 hours. There were dramatic signs of airway mucosal damage associated with the bronchial hyperreactivity that included substantial decreases in epithelial cilia, mucin content, and mast cells, as well as squamous metaplasia, numerous mitotic figures, and a prominent polymorphonuclear leukocytic infiltrate. Passive cutaneous anaphylaxis tests in exposed animals were negative. Our results suggest that TDI-induced bronchial hyperreactivity may be related to airway mucosal injury and inflammation.

Airway Resistance↗

Cultural perceptions of pain and pain coping among patients and dentists.

A combination of qualitative and quantitative methods were developed to describe pain and pain coping perceptions of 25 Chinese, 25 Anglo-Americans and 35 Scandinavians (54 patients and 21 dentists). Results revealed universal dimensions of pain such as time, intensity, location, quality, cause and curability. More culture-specific dimensions included the Chinese concept suantong, a multivariate concept of bone, muscle, joint, tooth and gingival pain. "Real" and "imagined" pains were mostly described by Western subjects, especially dentists; "imagined pain" being the conversion of fear or anxiety into perceived pain. These data indicate that the methods were sensitive to culture as a variable and indicate that ethnicity may play a stronger role in the perceptions of pain description than does professional socialization, but that professional socialization processes may have more influence on the perception of pain coping modes for this sample population.

Adaptation, Psychological↗

Morphology of tracheal and bronchial epithelium and type II cells of the peripheral lung of the guinea pig after inhalation of toluene diisocyanate vapors.

Toluene diisocyanate (TDI), a polymerizing agent used in production of plastics, can cause airways disease in some exposed individuals. Using guinea pigs as a model, the response of the airways and the type II cells of the peripheral lung was monitored morphologically and morphometrically after exposure to TDI vapors at 30 ppb, 260 ppb, and 3100 ppb. The two low doses of TDI caused little change in airways epithelium. There was no gross inflammatory cell infiltrate, however, surface infoldings and intracellular ciliated cysts increased in numbers. Animals exposed to 3100 ppb TDI 4 h/day for 5 days, sustained considerable damage to the epithelium, and stratified nonkeratinizing cells lined the airways until one week after exposure. Polymorphonuclear leukocytes were present in the early period after exposure. Increased numbers of eosinophils were present between one and two weeks following exposure. Mitoses in the epithelium were common during recovery. In the peripheral lung, though a modest subjective increase in the number of type II cells was seen after 3100 ppb TDI, the volume density of type II cells, and organellar components (lamellar bodies, mitochondria, cisternal bodies) did not change significantly after any exposure level of TDI.

Animals↗

The immunologic basis of lupus.

This article reviews the immunologic basis of systemic lupus erythematosus. It covers basic immunologic abnormalities, possible role of diet in autoimmune diseases, and the basis for specific abnormalities, such as renal and central nervous system disease.

Animals↗

Enhanced sensitivity to endotoxin induced by 6-sulfanilamidoindazole.

6-Sulfanilamidoindazole (6-SAI) is a sulfonamide that induces inflammation in the ankles and hind paws of older rats and sensitizes the animals to the lethal actions of endotoxin. Sensitization is associated with reductions in plasma glucose concentration but not changes in phagocytic function of the RES or increases in lysosomal or hepatic enzymes. Death in 6-SAI-pretreated but not control rats was associated with fibrin deposition in the glomerular capillaries (generalized Shwartzman reaction) and inflamed paws. Endotoxin shock in both 6-SAI-pretreated and control rats was associated with increases in activities of lysosomal and hepatic enzymes and hypoglycemia. Methylprednisolone but not desoxycorticosterone pretreatment protected 6-SAI-fed rats against endotoxin lethality and the generalized Shwartzman reaction and maintained the plasma glucose concentration but did not prevent loss of lysosomal integrity. Simultaneous administrations of small doses of phenylbutazone with 6-SAI suppressed inflammation but did not protect against endotoxin lethality or the generalized Shwartzman reaction.

Acid Phosphatase↗

HLA gene frequencies in children and adults with systemic onset juvenile rheumatoid arthritis.

The HLA genetic region was studied in 51 patients with systemic onset juvenile rheumatoid arthritis: 35 with childhood onset and 16 with adult onset (adult Still's disease). HLA genotypes were established by including family members, 261 of whom were also typed in the study. The most marked difference between patients and controls involved the HLA-DR4 gene, which occurred with a frequency of 0.348 in the childhood onset patients and 0.170 in the controls (chi 2 = 8.97, P = 0.0028, adjusted P = 0.017). In contrast, the adult onset patients showed a marginal increase in HLA-DR7, but were similar to controls with respect to HLA-DR4. HLA-Bw35 was increased in children with systemic onset disease, in accordance with earlier findings. The results suggest that patients with systemic onset juvenile rheumatoid arthritis have complex HLA associations which are different in childhood onset and adult onset disease.

Adolescent↗

Effect of the BXSB Y chromosome accelerating gene on autoantibody production.

The Y chromosome of the BXSB mouse is able to accelerate and adversely alter the autoimmune disease of inbred BXSB mice and in male F1 hybrids. In order to further study the effects of the BXSB Y chromosome, we developed three inbred congenic strains, each bearing the BXSB Y: CBA/J.BXSB-Y, NZW.BXSB-Y, and NZB.BXSB-Y. The BXSB Y did not induce anti-DNA or anti-red blood cell (RBC) autoantibodies in either CBA/J or NZW congenic strains. Thus, it is an accelerating rather than an inducing factor. NZB.BXSB-Y congenic mice had accelerated anti-RBC but not anti-DNA. Studies of recombinant inbred by BXSB F1 mice indicated that the BXSB Y did not act to promote the activity of the NZB gene underlying anti-DNA. These and studies of (BXSB X NZB.BXSB-Y) F1 mice suggested that BXSB autosomal genes are required for the full anti-DNA accelerating activity of the BXSB Y. These mice provide a basis for future molecular genetic studies of the BXSB Y.

Animals↗

Effect of exposure to 500 ppm sulfur dioxide on the lungs of the ferret.

Male ferrets (Mustela putorius furo) were exposed 3 h/day, 3 days/week for 12 weeks to 500 ppm SO2. Determinations were made of airway responsiveness by producing histamine dose-effect curves. Lung tissues were fixed and studied by light and electron microscopy. Epithelial cells of the trachea and bronchus were most affected. Lesions observed included changes in ciliated cells, edema and cell infiltration. The most responsive animals to histamine were 2 from the exposed group. Nasal discharge and dried mucus were observed after 3 days of exposure. Coughing was first noted after 2 weeks. Results favor further pursuit of the use of the ferret as a model for human airways disease.

Animals↗

Complementation with HLA-A and HLA-D locus alleles in ankylosing spondylitis with peripheral arthritis.

Fifty-nine patients with HLA-B27 positive ankylosing spondylitis were HLA genotyped to look for immunogenetic differences between patients with associated peripheral arthritis and those with disease limited to the axial skeleton. An association was found between the peripheral arthropathy and 2 antigens, HLA-A11 and HLA-DR7 at the p less than 0.05 level. Complementation between these 2 alleles and HLA-B27 occurred in both the cis and trans positions. Four patients with peripheral arthritis had a rare HLA-B27 haplotype (HLA-B27, HLA-DR7) which was not found in the group with axial disease alone.

Adolescent↗