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Biomedical subjects

M L Miller

Publications and source records attributed to M L Miller.

At least 109 records · Page 6Linked to original sources
PubMed1993

Dose- and time-dependent expression of transforming growth factor-beta 1 mRNA and protein in mouse epidermis and papillomas after repeated topical application of benzo[a]pyrene.

Topical weekly application of 64 micrograms of benzo[a]pyrene (BAP) for 4 wk induced transforming growth factor (TGF)-beta 1 mRNA in the epidermis of Swiss (ICR) mice, with a maximum at 6-12 h after the last treatment. The increase in TGF-beta 1 mRNA concentration was accompanied by an increase in immunohistochemically detectable intracellularly localized TGF-beta 1 protein in the suprabasal epidermis and by the appearance of extracellularly localized TGF-beta 1 in the basal layers. A dose rate of 16 micrograms/wk for 4 wk was unable to induce the same response. In contrast, after 20 weekly topical applications of 16 or 64 micrograms of BAP, an increase in TGF-beta 1 mRNA concentration and the appearance of extracellularly localized protein in the epidermis were observed. These changes in TGF-beta 1 expression were paralleled by changes in epidermal morphology. A similar group of animals treated with 4 micrograms of BAP/wk for 20 wk did not respond differently from untreated controls. Papillomas resulting from treatment with 16 or 64 micrograms of BAP/wk for 28 wk stained for intracellularly localized TGF-beta 1 predominantly in the differentiating and nondividing layers. Papillomas stained for extracellularly localized TGF-beta 1 solely in the less differentiated and dividing cells. These results suggest that tumorigenesis by BAP involves the induction of cumulative changes in epidermal TGF-beta 1 mRNA and protein concentrations as well as alterations in skin morphology associated with a tumor-promotion process.

Administration, Topical↗
PubMed1993

Formaldehyde-induced airway hyperreactivity in vivo and ex vivo in guinea pigs.

Human exposure to formaldehyde is extensive, in both the indoor and the outdoor environment. The airways are clearly an important site of action of formaldehyde. Although many previous studies have examined the effect of formaldehyde in the upper respiratory tract, it remains controversial whether this compound can affect the lower respiratory tract. To determine whether formaldehyde induces airway hyperreactivity, guinea pigs were exposed to formaldehyde or filtered air (sham control) for 2 or 8 hr. Airway smooth muscle responsiveness was evaluated in vivo and ex vivo. Specific pulmonary resistance and airway reactivity (to infused acetylcholine) increased with formaldehyde exposure. Formaldehyde exposure caused bronchoconstriction and hyperreactivity at lower concentrations when exposure duration was extended from 2 to 8 hr. Exposure to > or = 0.3 ppm formaldehyde for 8 hr was sufficient to produce a significant increase in airway reactivity, while similar effects only occurred after > 9 ppm formaldehyde for 2 hr. Formaldehyde exposure also heightens airway smooth muscle responsiveness to acetylcholine (or carbachol) ex vivo. These effects occurred with no evidence of epithelial damage or inflammation up to 4 days after formaldehyde exposure. Thus, at concentrations relevant to environmental exposure, formaldehyde, a common indoor air pollutant, alters airway smooth muscle reactivity in guinea pigs. These findings suggest that the duration of exposure is important to the induction of airway hyperreactivity and that prolonged, low-level exposures may generate abnormal physiological responses in the airways not detectable after acute exposures.

Animals↗
PubMed1993

The distribution of Sindbis virus proteins in mosquito cells as determined by immunofluorescence and immunoelectron microscopy.

Two Aedes albopictus (mosquito) subclones, C7-10 and C6/36, were examined by immunofluorescence and immunoelectron microscopy for the distribution of Sindbis virus structural and non-structural proteins. Both the viral glycoproteins, E1 and E2, and the non-structural proteins, nsP1 and nsP2, were found within vesicles and electron-dense, amorphous matrices associated with Sindbis virus infection. The labelling patterns indicated that both replication of viral RNA and production of virus particles were localized within the same structures in the infected cell. The data support previous reports that alphavirus infection is contained within specific structures in the cytoplasm and provide additional evidence that the C6/36 and C7-10 subclones may represent different tissue types in the adult insect.

Aedes↗
PubMed1992

Comparative tumor-initiating ability of 7H-dibenzo(c,g)carbazole and dibenz(a,j)acridine in mouse skin.

N-heterocyclic aromatics are environmentally important carcinogenic pollutants produced by incomplete combustion of organic material. 7H-Dibenzo-(c,g)carbazole (DBC), is a potent skin and systemic carcinogen, whereas dibenz(a,j)acridine (DBA), is a carcinogen with local effects. Therefore, the overall objective of these studies was to determine the initiating ability of DBC and DBA in mouse skin using an initiation-promotion protocol. Acetone-, TPA- or BaP-treated animals were used as negative and positive controls, respectively. DBC, DBA or BaP (200 nmol) dissolved in acetone was applied once to the backs of thirty shaved Hsd:(ICR)Br female mice, followed 2 weeks later with 2 micrograms of TPA in 50 microliters of acetone applied twice a week for up to 24 weeks. Skin tumors developed in 26, 17 and 27 animals, respectively. DBC plus TPA produced a significant influx of dermal macrophages similar to that seen for BaP. Initiation with BaP, DBC or DBA moderated the effect of TPA on most other dermal parameters, particularly neutrophils. These data indicate that, DBC, with apparently different activation pathways than BaP shows similar tumor initiating ability and morphological changes as BaP.

Acetone↗
PubMed1992

Morphogenesis of Sindbis virus in three subclones of Aedes albopictus (mosquito) cells.

The morphogenesis of Sindbis virus in three Aedes albopictus subcloned cell lines was examined. Each line was distinguishable with respect to morphology, cytopathic response to infection, and progeny yield. C7-10 cells, which produced the highest titers of virus and exhibited the most severe cytopathic response, were characterized ultrastructurally by the presence of budding particles at the cell surface and at the membranes of internal vesicles. C6/36 cells, which displayed a moderate cytotoxic response, manifested similar features in response to Sindbis virus infection. Both cell types also produced a structure composed of an electron-dense matrix in which nucleocapsids were embedded. Internally matured virions were released by exocytosis from these cells. In addition to a lack of cytopathic effect, u4.4 cells also failed to exhibit obvious morphogenetic changes upon infection. Virus particles were occasionally seen within vesicles, but budding at the cell surface was not detected. The mechanism of release of internally matured virions was not apparent. These studies provide further evidence that these three subcloned mosquito cell lines represent different tissues in the larval or adult insect.

Aedes↗
PubMed1992

Immunocytometry and gene rearrangement analysis in the diagnosis of lymphoma in an idiopathic pleural effusion.

We report a patient with an idiopathic pleural effusion in whom the diagnosis of non-Hodgkin's lymphoma was established by immunocytometry of pleural fluid and confirmed by the detection of B-cell immunoglobulin gene rearrangement. Immunocytometry is a rapid, semi-automated laboratory method for phenotyping lymphoid cells by determining immunoglobulin and other cell surface antigen expression. This method defines the cell lineage (T or B cells) and the clonality (monoclonal or polyclonal) of a population of lymphocytes. The presence of a monoclonal population of lymphocytes can also be confirmed by recently developed molecular biologic techniques (e.g., Southern blotting) that provide the ability to detect rearrangements of the genes that encode either B-cell immunoglobulin proteins or T-cell antigen receptor proteins. To our knowledge, this case represents the first reported application of immunophenotypic and gene rearrangement analysis in a previously undiagnosed pleural effusion to establish the diagnosis of lymphoma. These relatively new laboratory methods may have a role in the evaluation of idiopathic lymphocytic pleural effusions.

Aged↗
PubMed1992

Treatment of systemic lupus erythematosus.

The past year continued to see both major studies and interesting case reports slowly add suggestions, if not absolute knowledge, concerning the treatment of systemic lupus erythematosus. The Lupus Nephritis Collaborative Study Group published two papers, one of which concerned the lack of efficacy of plasmapheresis in treating severe lupus nephritis. A related paper documented the utility of initial serum creatinine in predicting renal failure in patients enrolled in both arms of the plasmapheresis study. Patients in the study received high-dose oral prednisone and low-dose oral cyclophosphamide. Whether this approach is superior to pulse intravenous cyclophosphamide is yet to be determined. Two other approaches to treatment were also reported: anti-CD4, based on success in case reports, merits further study; the modified androgen, 19-nortestosterone, was unfortunately not effective. Other case reports provide additional evidence for specific treatments in certain situations, such as the use of tetracycline pleurodesis for recurrent pleural effusions. Finally, reports of new side effects for old medicines and new ones are a reminder that the treatment can be part of the problem when a lupus patient develops complications.

Bronchiolitis Obliterans↗
PubMed1991

The challenge of caring for indigent children with rheumatologic diseases.

Poverty and lack of insurance prevent complete access to tertiary care for many children with rheumatologic diseases. Long-term solutions to provide community based support for local teams and other services are needed. Physicians need to work with colleagues in health care systems and government to make the health care system fully available to all families. Medical schools can act as catalysts in helping government agencies redefine policies to support outreach and other health care programs for the indigent. Governmental agencies must collaborate with insurance companies to change policies so as to cover all aspects of service, including those provided by arthritis health professionals. With coordinated effort, the goal of adequate services to indigent children with rheumatologic and other chronic illnesses can become reality.

Adolescent↗
PubMed1991

The expression of CD22 (Leu 14) and CD11c (LeuM5) in chronic lymphoproliferative disorders using two-color flow cytometric analysis.

The monoclonal antibodies (MoAbs) CD22 and CD11c recognize B-lymphocyte- and monocyte-associated antigens, respectively. Reports indicate that when these two MoAbs co-express, they represent a unique marker for hairy cell leukemia (HCL) although neither is specific for that disease. The authors evaluated the expression and diagnostic utility of CD22 and CD11C in specimens from 26 normal subjects, 29 patients, with various nonlymphoproliferative disorders (NLPDs), and 75 patients with different types of chronic lymphoproliferative disorders (CLDs) using two-color flow cytometric analysis of peripheral blood lymphocytes. Lymphocytes co-expressed CD22 and CD11c in less than or equal to 3% of the normal subjects and in less than or equal to 6% of the patients with NLPDs. These markers were expressed in greater than 10% of the lymphocytes of 46% (32/69) of the patients with B-cell CLDs: B-cell chronic-lymphocytic leukemia, 9/41; B-cell non-Hodgkin's lymphoma, 8/14; HCL, 11/11; B-cell lymphoproliferative disorder (NOS), 1/2; and B-cell prolymphocytic leukemia, 1/1. None (0/6) of the lymphocytes of patients with T-cell CLDs expressed greater than 10% CD22-positive (CD22+) or CD11c-positive (CD11c+) cells. The HCL cases demonstrated a unique CD22+CD11c+ fluorescence histogram pattern, distinct from other lymphoproliferative disorders, that was characterized by uniformly intense CD11c and CD22 fluorescence. Differences in the expression of the CD22+CD11C- and CD22+CD11C+ phenotypes between diagnostic groups were found, most notable was a paucity of CD22+CD11c+ cells in lymphocytes of patients with HCL. CD22 also had more variable expression than CD19 and HLA-DR in the cases of B-cell CLD. This study demonstrates that the CD22+CD11c+ phenotype is not unique to HCL but is a consistent feature of that disorder and that the immunofluorescence pattern of co-expression in HCL is diagnostically useful.

Antigens, CD↗
PubMed1991

Effect of tumor-promoting agents on density and morphometric parameters of mouse epidermal Langerhans and Thy-1+ cells.

Topical application of tumor-promoting agents to the dorsal skin of female SENCAR mice on a twice-weekly basis resulted in a reduction in density per unit area of bone marrow-derived Thy-1+ dendritic cells. Activity was observed for well-established tumor-promoting doses of promoting agents of several different chemical types, including 12-O-tetradecanoylphorbol-13-acetate (TPA, diterpene diester), anthralin (dihydroxyanthrone), and n-dodecane (n-alkane). A reduction in density of the same cells was also observed on the basis of the asialoGM1 lipid as a surface marker after TPA treatment. No parallel effect was observed for epidermal Langerhans (Ia+) cells, the second major epidermal immunofunctional cell type, except in the case of anthralin, a finding which is consistent with the reported toxicity of this agent. The stage 2 promoting agent mezerein was unique in inducing a consistent increase in Langerhans cell densities, but did not affect the density of Thy-1+ cells when applied for a prolonged period unless applied following four doses of TPA. In contrast to the SENCAR strain, the promotion-resistant Balb/c and C56BL/6 strains showed no response with respect to TPA-induced reduction of Thy-1+ cell density. In addition to effects on density, the above tumor-promoting agents induced morphological changes in both Thy-1+ and Langerhans cells. When these changes were placed on a quantitative basis by the calculation of shape and area fraction parameters, marked and significant effects were observed for the above agents, but not for the partial promoting agent mezerein nor the non-promoting phorbol diester 4-O-methyl-TPA. The effects of TPA were largely blocked by the potent anti-promoting agent fluocinolone acetonide, moreover. These findings further support an important role for quantitative and qualitative alterations in dendritic epidermal cells in tumor promotion.

Alkanes↗
PubMed1991

Benzo[a]pyrene-induced skin damage and tumor promotion in the mouse.

Epidermal cell kinetics and DNA adduct levels, and skin morphological changes were measured following weekly topical applications for 29 weeks of high (16, 32 and 64 micrograms) benzo[a]pyrene (B[a]P) doses to female ICR/Harlan mice, in order to investigate the relationship of these parameters to the timing, incidence and morphology of the elicited tumors. During the tumor latency period, [3H]thymidine labeling index, mitotic index, epidermal cell stacking, incidence of pyknotic and dark basal keratinocytes and labeled mitoses were periodically measured, as were nuclear area and DNA content. DNA adducts in skin epidermis were measured by an ELISA method over a period of 9 weeks of single weekly applications of 64, 32, 16 or 8 micrograms B[a]P. There was an initial linear increase in DNA adducts with dose in the epidermis but the increase was much less steep above 32 micrograms/week. This did not correlate with the sharp rise in tumor response above the 32 micrograms/week dose rate. Cell kinetic changes in response to the 64 micrograms/week dose reached a plateau in the first few weeks of the tumor latent period. There was little epidermal hyperplasia but an associated dose-dependent increase in [3H]thymidine labeling index, mitotic index and incidence of pyknotic and dark cells. This evidence indicated that B[a]P produced extensive cytotoxicity and cell death with regenerative proliferation under these conditions. Giant keratinocytes occurred in all dose groups. Analysis of a labeled mitosis curve indicated that B[a]P produced a G2/M block. There was a marked inflammatory response in the dermis at all B[a]P doses. Mice were observed weekly for tumor formation. Virtually all of the tumors were papillomas on initial appearance and required an average of 8 weeks to convert to carcinomas. The substantial cell killing and regenerative proliferation, and the correspondence between the dose-response patterns for epidermal damage and tumors, together with the initial appearance of tumors in the benign form, a characteristic of the action of promoting agents, provided evidence that the tissue damage associated with the high dose levels of B[a]P used in this study reflected tumor-promoting activity in this mouse epidermal tumorigenesis model. The implication of the results for mathematical models of tumor formation are discussed.

Animals↗
PubMed1991

Treatment of systemic lupus erythematosus.

Reports on a variety of therapies for systemic lupus erythematosus have been published over the past year. Most of these are single case reports or open studies. As reported last year in this journal, the potential uses of intravenous gamma globulin and plasmapheresis continue to be explored. The use of cyclophosphamide for nonrenal manifestations follows studies last year of its use for lupus nephritis. No major double-blind studies of therapy for lupus nephritis were published; however, the course of lupus patients receiving dialysis or grafts was the subject of three interesting studies. An interesting study on the ability of hydroxychloroquine to prevent disease exacerbations was also published. In summary, the reports of therapy over the past year represent variations on themes. The use of new agents will most likely be based on improvements in our understanding of the pathogenesis of systemic lupus erythematosus.

Hematologic Diseases↗
PubMed1991

Understanding the eating-disordered patient: engaging the concrete.

Anorexic patients typically present major obstacles when beginning psychotherapy, including a tendency to focus concretely on their food- and weight-related symptoms. The author seeks to clarify the meaning of this "concrete attitude" and presents a treatment approach that accepts the anorexic person's "limitations." The case of a 14-year-old anorexic girl illustrates how acceptance and understanding of the patient's concrete attitude, especially during the initial phase of treatment, can reduce the probability of a therapeutic impasse and can enhance the treatment process.

Adolescent↗
PubMed1990

Worry changes decision making: the effect of negative thoughts on cognitive processing.

The present studies demonstrate that daily worry level is predictive of cognitive processing differences and that these differences are an effect of negative thoughts. In Study 1, worriers (those who reported 50% or greater daily worry) and non-worriers performed a categorization task. The groups did not differ when the stimulus was a clear member or non-member of the category. Worriers showed a significant disruption in processing as the ambiguity of the category membership increased. Study 2 demonstrated that the disruption arose as a result of increased levels of negative thoughts. Worriers and non-worriers were assigned to two conditions, either O-worry ("Relax and let your mind wander for 15 minutes") or 15-worry ("Worry as you typically would for 15 minutes"). Non-worriers evidenced the same disruptive effects in the 15-worry condition as worriers in that condition and worriers in Study 1. Similarly, worriers in the O-worry condition showed a reduction in disruptive effects. The findings are taken as indicating that worry is accompanied by changes in cognitive processing and that these changes are similar for worriers and non-worriers.

Anxiety↗