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Biomedical subjects

M L Miller

Publications and source records attributed to M L Miller.

At least 163 records · Page 9Linked to original sources
PubMed1985

[Methionine supplementation in the diet of the pregnant rat. 2. Riboflavin metabolism and hepatic concentration of water, lipid and protein].

Dietary addition of methionine suppresses the liver lipidosis in gestating rat fed a diet containing 9% by weight of casein. Riboflavin metabolism is not affected by this addition neither in the dam nor in the newborn rat. Riboflavin content in liver increases in the dam along with the protein content of the diet but does not change in the newborn rat.

Animals↗
PubMed1985

Pulmonary physiology of the ferret and its potential as a model for inhalation toxicology.

Physiological measurements were made from anesthetized, tracheotomized, supine male ferrets. Six animals weighing 576 +/- 12 g, had tidal volumes (Vt) of 6.06 +/- 0.30 ml, respiratory frequencies (f) of 26.7 +/- 3.9 min(-1), dynamic lung compliance (CDYN) of 2.48 +/- 0.21 ml cmH2O(-1), pulmonary resistance (RL) of 22.56 +/- 1.61 cmH2O L(-1) sec. Pressure-volume curves from nine ferrets (including the above six) revealed almost infinitely compliant chest walls so that lung and total respiratory system curves were essentially the same. Total lung capacity (TLC) (89 +/- 5 ml) and functional residual capacity (FRC) (17.8 +/- 2.0 ml) were determined by gas freeing the lungs in vivo. The TLC of these ferrets was about the same as in 2.5 kg rabbits. Maximum expiratory flow-volume curves showed peak flows of 10.1 vital capacities (VC) sec(-1) at 75% VC and flows of 8.4 and 5.4 VC sec(-1) at 50% and 25% VC. No particular problems were encountered in making these measurements using conventional techniques available in laboratories capable of making pulmonary function measurements on rats and guinea pigs. Preliminary studies of airways reactivity showed equal increases in pulmonary resistance in response to equivalent challenges of aerosolized carbachol and histamine. Light and electron microscopic studies showed that the airways of ferrets are even more like those of humans than are the dog's. The ease with which physiological measurements can be made and the favorable aspects of the lung anatomy indicate the ferret may be more useful, as well as less expensive, than the dog for use in studies of pulmonary physiology and inhalation toxicology.

Aerosols↗
PubMed1984

Methyl trisporate E. A sex pheromone in Phycomyces blakesleeanus.

Combined mating type cultures of Phycomyces blakesleeanus accumulate 41 mg of trisporic acids/l of medium, of which 30% is trisporic acid E. The methyl ester of trisporic acid E exhibits the same zygophore -inducing activity in bioassays with P. blakesleeanus and Mucor mucedo as does the pheromone methyl trisporate C. The structure of methyl trisporate E is 1,5-dimethyl-2-hydroxyl-4-oxo-6-(2'-hydroxyl-6'- methylocta -5',7'-d ien-8'-yl) -5-cyclohexene-1-carboxylic acid methyl ester.

Animals↗
PubMed1984

Heterogeneity of oral tolerance defects in autoimmune mice.

Three strains of mice, BXSB, MRL-lpr/lpr, and NZB, which spontaneously develop autoimmune syndromes, all fail to become tolerant to challenge with bovine gamma-globulin (BGG) in adjuvant by prior intraperitoneal (ip) injection of BGG in tolerogenic form. In the present study, these three strains were examined for the ability of a single enteric dose of BGG or ovalbumin (OVA) to tolerize to subsequent challenge with the corresponding antigen in adjuvant. In contrast to lack of ip tolerance to BGG, BXSB mice were tolerant to gastrointestinal (GI) BGG as well as to GI OVA, suggesting that ip and GI forms of tolerance to BGG operate through distinct mechanisms in these mice. MRL-lpr/lpr mice had normal tolerance to GI OVA but not GI BGG. The presence of enteric tolerance to one antigen but not another suggests that the responsible cellular defects vary from one antigen to another. NZB mice lacked tolerance to both GI BGG and GI OVA. Splenectomy of NZB mice allowed normal tolerance to enteric BGG; spleen cells administered to splenectomized NZB mice interfered with BGG tolerance. Congenic NZB.xid mice were tolerant only to OVA. These results suggest that in NZB mice Lyb 5+ cells interfere with tolerance to enteric OVA and Lyb 5- spleen cells interfere with tolerance to enteric BGG.

Animals↗
PubMed1984

Immunoregulatory Leu-7+ and T8+ lymphocytes in B-cell follicular lymphomas.

Lymphocyte subpopulations were profiled in lymph nodes and tonsils showing follicular hyperplasia and in follicular lymphomas with monoclonal antibodies on frozen tissue sections. Immunoregulatory lymphocyte subsets identified with T8 and Leu-7 monoclonal antibodies were quantified within the follicular centers (FC) of the nonneoplastic tissue and neoplastic follicles of the lymphomas with an optical grid defining a unit surface area (USA) of 0.04 mm2. T8+ cells were essentially confined to the interfollicular areas, with a few cells occupying the FC of the nonneoplastic specimens (mean, two and five cells/USA for tonsils and benign lymph nodes, respectively). Although lymphomas exhibited a similar pattern of distribution of T8+ cells, 17 T8+ cells/USA were observed in the follicular small cleaved cell (FSCL) group and eight T8+ cells/USA within the follicular mixed small cleaved and large cell (FML) group. Leu-7+ cells were almost entirely confined to the FC of the nonneoplastic tissues and increased (mean, 17 and 19 cells/USA for tonsils and benign lymph nodes, respectively) compared with the T8+ population. Variable distributions of Leu-7+ cells were found in the FSCL group, with a mean of 16 cells/USA. Very few Leu-7+ cells were present in the FML group. Natural killer cells and/or cytotoxic/suppressor T lymphocytes may play an immunoregulatory role in modulating the growth of follicular lymphomas.

Antibodies, Monoclonal↗
PubMed1984

Inherited predisposition to iridocyclitis with juvenile rheumatoid arthritis: selectivity among HLA-DR5 haplotypes.

HLA-DR5 is associated with a chronic iridocyclitis and juvenile rheumatoid arthritis with onset in early childhood. Previously published data provided indirect evidence for selective linkage between two HLA-B alleles and HLA-DR5. To test this observation further, 38 families, the probands of which have chronic iridocyclitis and juvenile rheumatoid arthritis, were HLA typed so that haplotypes associated with disease could be established. HLA-DR5 was linked to HLA-Bw44 or to HLA-Bw35 and to HLA-Cw4 in the majority of haplotypes obtained in the probands. Both HLA-Bw44, -DR5 and HLA-Bw35, -Cw4, -DR5 occurred more commonly in the proband haplotypes than in the control haplotypes. The frequency of the haplotype HLA-Bw44, -DR5 was 0.133 compared with 0.007 (X2 = 27.04, P less than 10(-6] and for HLA-Bw35, -Cw4, -DR5, it was 0.093 compared with 0.11 (X2 = 13.83, P = 0.0002). The relative risks were 20.77 and 9.23, respectively, versus 3.52 for HLA-DR5 alone. HLA-Bw44 occurred much more commonly in proband HLA-DR5 haplotypes (0.455) compared with control HLA-DR5 haplotypes (0.067) (X2 = 8.26, P less than 0.01). Not all HLA-DR5-bearing haplotypes predisposed equally to chronic iridocyclitis and early-onset pauciarticular juvenile rheumatoid arthritis.

Arthritis, Juvenile↗
PubMed1984

NIH conference. Systemic lupus erythematosus: insights from animal models.

Systemic lupus erythematosus is a multisystem, antibody-mediated, autoimmune disorder that occurs spontaneously in humans and mice. Genetic factors appear to play an important predisposing role in the disorder: The presence of certain genes may produce a generalized immune abnormality, whereas others may lead to specific autoantibodies. Environmental triggers increase autoantibody production and augment the expression of illness. Bacterial and viral illnesses can provide stimulation by activating macrophages and T cells that, in turn, stimulate B cells. In the absence of normal control mechanisms, the stimulatory process is not suppressed, and excessive stem cell proliferation results in abnormal B-cell proliferation. A trigger for the disease is the signaling of the proliferating B cells to differentiate into antibody-forming cells. Most autoantibody-producing B cells can be eliminated from mice with lupus erythematosus by virtue of the presence of the gene, xid. In addition, administration of an analog of arachidonic acid is an effective treatment for murine lupus erythematosus.

Animals↗
PubMed1984

Capital reform.

Explore the source record for details and available documents.

Hospital Planning↗
PubMed1984

Genetic studies in NZB mice. VI. Association of autoimmune traits in recombinant inbred lines.

Because recombinant inbred lines, which are homozygous at most loci, can have any combination of parental genes, the numbers and the association of genes responsible for traits can be suggested by examining phenotypic distribution in these lines. Such studies, reported herein, uncovered two major families of nonlinked genetic loci whose interactions underlie autoimmune abnormalities in NZB mice. One family of genes leads to antibodies to murine leukemia virus, ssDNA, and erythrocytes, as well as to defective tolerance to bovine gamma-globulin. The other group of genes leads to polyclonal B cell activation, stem cell abnormalities, endogenous murine leukemia virus expression, and NTA. These studies help explain previously observed dissociations between the traits associated with these two groups of genes. Such genetic analyses provide the basis for future molecular biologic studies of the genes and gene products that underlie autoimmune disease.

Animals↗
PubMed1984

Implementing self-scheduling.

Self-scheduling is one method that nurse administrators can use to increase their staff nurses, feelings of autonomy and job satisfaction. In this article the author describes the benefits of self-scheduling and presents a model for implementing this system.

Humans↗
PubMed1983

Contribution of mesenchymal cell death and mitotic alteration to asymmetric limb malformations induced by MNNG.

N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induces fetal asymmetric limb malformations with exposure of pregnant mice to 50 mg/kg on day 11 of gestation. Hindlimbs were more frequently malformed than forelimbs, and a fourfold greater incidence of postaxial ectrodactyly was found in left forelimbs than in right forelimbs, and a two fold excess in left hindlimbs compared to right hindlimbs. The level of cell death and mitotic index were measured in forelimbs and hindlimbs from treated and control embryos at 1, 4, 18, 24, 48, and 72 hr after exposure to ascertain if these parameters could be correlated with the differential teratogenic susceptibility of the limbs. An increase in necrotic index was first detected in treated limbs at 4 hr, increased at 18 hr, peaked at 24 hr, and began declining at 48 hr to reach the control baseline at 72 hr. At 24 hr, the correlation between the level of cell death and susceptibility of malformation was the strongest, with the left hindlimb having a necrotic index of 58%, the right hindlimb 47%, the left forelimb 30% and the right forelimb 12%. In both forelimbs and hindlimbs, MNNG treatment initially depressed mitotic activity followed by an elevation at 48 hr relative to controls. The magnitude of the depression, extent of the elevation, and overall pattern of mitotic activity could not be uniformly related to limb defects. These results indicate that the amount of cell death in limb buds at 24 hr after MNNG exposure may predict target organ susceptibility. Depressions in mitotic activity and alterations in the pattern of mitosis were also observed which were not as clearly correlated with the incidence of malformations as was the amount of cell death.

Animals↗
PubMed1983

Natural and antibody-dependent cellular cytotoxicity in children with systemic lupus erythematosus and juvenile dermatomyositis.

Thirteen children with systemic lupus erythematosus (SLE) and 5 with juvenile dermatomyositis (JDM) were studied for natural cytotoxicity (NK) and antibody-dependent cellular cytotoxicity (ADCC). In vitro prednisolone at pharmacological levels failed to alter NK or ADCC in adult controls, nor did it alter ADCC in any children studied. ADCC was normal, but NK was decreased in SLE (p less than .005) and JDM (p less than .05) compared to controls. Since NK but not ADCC is decreased in these patients, different lymphocyte populations may mediate these 2 cytotoxic functions.

Adolescent↗
PubMed1982

Studies of DNA damage and cell death in embryonic limb buds induced by teratogenic exposure to cyclophosphamide.

Many teratologic investigations have shown that certain types of chemical insults to the embryo (those altering replication, transcription, and translation) can cause excessive cell death in tissues destined to become malformed. Chemical carcinogens also induce cell death in target tissues, but the critical event is believed to be heritable alteration in the DNA of surviving cells. In the present study, an attempt was made to study the interaction between cell death and DNA damage in the initiation of birth defects. The pattern of DNA damage induced by cyclophosphamide was examined at time intervals before, during, and after the necrotic episode in mouse embryo limb buds. The alkaline elution assay was used to measure alkali-labile sites in single-strand DNA due to its adaptability to small tissue samples. An ip dose of 20 mg/kg of cyclophosphamide induced forelimb malformations in 85% of surviving mouse fetuses and 30% embryolethality when administered at 9 am on Day 11. As early as 5 hr after exposure, a slight excess of necrosis was observed in treated limbs by light microscopy, while at 24 hr, massive necrosis was evident. By 48 and 72 hr, excess necrosis was not observed in treated limbs. When alkaline elution analysis was conducted at prenecrotic (1-, and 5-hr), necrotic (24-hr), and postnecrotic (48-, and 72-hr) intervals, a trend toward increasing DNA damage in treated limbs with time was observed. The greatest differences in elution values occurred during the postnecrotic period. Although mean retention values were not significantly different, significantly increased variance was obtained in retention values of treated limbs at all time intervals other than 1 hr. This may reflect the actual in vivo situation where relatively few cells within a heterogeneous population of cells carry sublethal DNA damage into the postnecrotic period. These results suggest that not all limb bud cells affected by teratogenic exposure to cyclophosphamide die, but that some persist to the postnecrotic period carrying heritable alterations in their DNA.

Abnormalities, Drug-Induced↗