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Biomedical subjects

M Perkins

Publications and source records attributed to M Perkins.

At least 19 recordsLinked to original sources
PubMed1995

Genetic linkage for Darier disease (keratosis follicularis).

Darier disease is an autosomal dominant skin disorder characterized by abnormal keratinocyte adhesion. Recent data have provided evidence for linkage of the Darier disease locus to 12q23-24.1 in British families. We have carried out linkage analysis using the 12q markers D12S58, D12S84, D12S79, D12S86, PLA2, and D12S63 in 6 Canadian families. Pairwise linkage analysis generated positive lod scores at all 6 markers at various recombination fractions, and each family showed positive lod scores with more than one marker. The peak lod score in the multipoint analysis (Zmax) was 5.5 in the interval between markers D12S58 and D12S84. These positive lod scores in North American families of varied European ancestry confirm the location of the Darier disease gene, and suggest genetic homogeneity. The future identification and sequencing of the gene responsible for Darier disease should lead to improved understanding of the disease and of keratinocyte adhesion in general.

Adolescent↗
PubMed1992

The attenuation phenotype conferred by the M gene of the influenza A/Ann Arbor/6/60 cold-adapted virus (H2N2) on the A/Korea/82 (H3N2) reassortant virus results from a gene constellation effect.

A single gene reassortant (SGR) virus that derived its M gene from the attenuated influenza A/Ann Arbor/6/60 cold-adapted (CA) donor virus and the remaining genes from the A/Korea/82 (H3N2) wild type (WT) virus (designated A/Korea/82 CA M-SGR) was previously shown to be attenuated in mice, hamsters, ferrets, and humans. The attenuation (ATT) phenotype of this SGR virus could result directly from an altered function of the mutant M gene product of the A/Ann Arbor/6/60 CA virus, which differs from the M gene of the A/Ann Arbor/6/60 WT virus at only one amino acid or, indirectly from a gene constellation effect in which ATT results from an inefficient interaction between the products of the M gene of the A/Ann Arbor/6/60 virus and other genes of the A/Korea/82 virus. Several lines of evidence from the present study are consistent with our interpretation that the ATT phenotype of the A/Korea/82 CA M-SGR results from a gene constellation effect. First, the A/Korea/82 CA M-SGR and an A/Korea/82 SGR containing the A/Ann Arbor/6/60 WT M gene were each restricted in replication in the upper and lower respiratory tract of mice compared with the A/Korea/82 WT virus. Second, an A/Udorn/72 CA M-SGR containing the M gene from the A/Ann Arbor/6/60 CA donor virus in a background of other genes derived from the A/Udorn/72 (H3N2) WT virus was not attenuated in the respiratory tract of mice. These data suggest that the change in the amino acid sequence of the M gene product from the A/Ann Arbor/6/60 WT to CA virus is not responsible for the ATT phenotype of the A/Korea/82 CA M-SGR. In addition, evidence of the genetic instability of the A/Korea/82 CA M-SGR is presented, specifically, an extragenic mutation that results in loss of the ATT phenotype. The implications of these findings for the ATT phenotype of the live attenuated reassortant viruses derived from the A/Ann Arbor/6/60 CA donor virus are discussed.

Adaptation, Physiological↗
PubMed1992

Comparison of image analysis with flow cytometry for DNA content analysis in pigmented lesions of the skin.

The DNA ploidy of 85 melanocytic skin lesions was determined by flow cytometry (FCM) and interactive image analysis (IA) using nuclear extracts of paraffin-embedded tissue. Of the 85 lesions analyzed, 43 were malignant melanomas in different stages of evolution, 15 were dysplastic nevi, 11 were Spitz nevi, and 16 were other types of nevi. Some of the last had features of congenital nevi. Within the melanoma category, there was 42% aneuploidy by FCM versus 56% by IA. Of those melanomas aneuploid by FCM, all but one were aneuploid by IA. All dysplastic nevi, 10/11 Spitz nevi and 15/16 other nevi were diploid by both methods. One of the 16 nevi from the "other types" category was tetraploid by IA but diploid by FCM. A single Spitz nevus was tetraploid by FCM but diploid by image analysis. While our results suggest that interactive IA is potentially a more sensitive method than FCM for detecting aneuploidy in cutaneous pigmented lesions, it remains to be shown whether this will translate into better prognostic assessment of the biologic behavior of melanocytic neoplasms than provided by flow cytometric ploidy analysis.

Aneuploidy↗
PubMed1991

Pulmonary response to inhaled silica or titanium dioxide.

The pulmonary response to mineral dust inhalation was investigated by characterizing markers of lung injury and inflammation, macrophage activation, dust clearance, and histopathology. Rats were exposed (6 hr/day x 5 days) to air or 50 mg/m3 crystalline silica (SiO2) or titanium dioxide (TiO2). At 7, 14, 28, and 63 days after exposure, bronchoalveolar lavage fluid (BALF) was analyzed for lactate dehydrogenase (LDH), total protein, and N-acetylglucosaminidase, as well as cell number, type, and viability. Alveolar macrophages (AM) obtained in BALF were cultured with or without LPS and release of interleukin-1 (IL-1) and fibronectin was determined. Histopathology was conducted at 28 and 63 days. The exposure protocol resulted in 1.8-1.9 mg of mineral dust being deposited in the pulmonary region. Clearance of SiO2 was significantly less than TiO2. SiO2 increased BALF neutrophils (Days 14, 28, and 63), total protein (Days 28 and 63), and LDH and lymphocytes (Day 63). SiO2 increased AM-derived fibronectin release (Day 63) and LPS-induced IL-1 release (all time points), but not spontaneous release of IL-1. TiO2 did not change BALF biochemical or cellular parameters or AM secretory activity. Histopathology revealed minimal interstitial inflammation with SiO2 and no significant response in control or TiO2 rats. These results demonstrate the pulmonary response to inhaled SiO2 can be differentiated from the relatively innocuous TiO2 by changes in BALF markers of injury and inflammation further supporting the use of BALF analysis to make relative assessments of pulmonary toxicity. The stimulation of macrophage fibronectin release by the fibrogenic dust SiO2 and not TiO2 is consistent with a role for this glycoprotein in lung injury and repair. Last, the early and persistent effect of SiO2 on LPS-induced AM IL-1 release indicates this response may represent a sensitive early marker of dust-induced changes in the AM population.

Administration, Inhalation↗
PubMed1991

Asperger's syndrome: who is being abused?

Six case histories of children referred and admitted to a psychiatric inpatient unit at a tertiary referral centre because of concerns about poor functioning and possible emotional abuse are presented. On initial assessment the children appeared to be well functioning and the impression was confirmed that their emotional needs were not being met by their parents. After detailed inpatient appraisal the diagnosis of Asperger's syndrome was made in all six cases, exemplified mainly by a formal concrete way of thinking and an inability to identify and understand human emotions and relationships. The impact of the diagnosis on the parents and their consequent relationships with their child and their willingness to work with professionals is discussed.

Affective Symptoms↗
PubMed1988

Stage-dependent processing and localization of a Plasmodium falciparum protein of 130,000 molecular weight.

A Plasmodium falciparum protein of 130,000 molecular weight (m.w.) has been identified, cloned in Escherichia coli, and completely sequenced (Kochan et al. 1986). The protein appeared to bind to soluble glycophorin, a host erythrocyte surface protein. In the present study, extracts of parasites from different intraerythrocytic stages were immunoblotted with antibodies, raised against a 30,000 m.w. fusion protein corresponding to the 3' end of the 130,000 m.w. protein. It was demonstrated that the protein is synthesized at the trophozoite stage, accumulates at the schizont stage, and is processed at the merozoite stage to a triplet of three polypeptides. The processed proteins are present in the culture supernatant at the time of merozoite burst from the red cell. Immunofluorescent staining of the parasite at different intracellular stages indicates that the protein is localized on the parasite at the trophozoite stage. At late trophozoite stage, it appears to be transported to the erythrocyte cytoplasm, where it is present in small vesicles or inclusions. In mature schizonts the protein accumulates around the plasma membrane of the erythrocyte. At the segmenter stage, just prior to merozoite release, it appears also to surround the intracellular merozoite, as well as the erythrocyte plasma membrane. The soluble 130,000 m.w. protein binds to erythrocytes but binds significantly greater to erythrocyte membranes, suggesting it binds to an internal domain of glycophorin rather than the domain exposed on the surface. The 130,000 m.w. protein is present in 11 different geographic isolates of P. falciparum from diverse geographic origins. Its molecular weight is similar in all isolates.

Animals↗
PubMed1987

Gliogenesis in the embryonic avian optic tectum: neuronal-glial interactions influence astroglial phenotype maturation.

We have analyzed the development of neuroglial cells in the chick optic tectum under 3 sets of developmental conditions to assess the role of heterotypic cell-cell interactions in gliogenesis. Immunochemical and biochemical methods were employed to measure and localize the expression of the glial markers glutamine synthetase, glial fibrillary acidic protein, S-100 protein, carbonic anhydrase-C and myelin basic protein as functions of development in situ and in aggregation and monolayer cultures of dissociated embryonic tissue. The results showed that certain astroglial cells can be recognized as early as day 9 of development in situ. Oligodendroglial development manifests several days later and the full range of glial subtypes are not evident until nearly the time of hatching. Culture of 7-day embryonic tectum cells either in aggregates or in monolayer cultures failed to yield definitive oligodendroglia. Fibrous astroglia, as defined by glutamine synthetase and glial fibrillary acidic protein, developed well in both culturing systems. However, as previously noted in the embryonic neural retina system, glutamine synthetase expression was marked dependent on neuronal-glial associations.

Animals↗
PubMed1986

A tandemly repeated sequence determines the binding domain for an erythrocyte receptor binding protein of P. falciparum.

Erythrocyte invasion by the malarial merozoite is a receptor-mediated process, an obligatory step in the development of the parasite. The Plasmodium falciparum protein GBP-130, which binds to the erythrocyte receptor glycophorin, is shown here to encode the binding site in a domain composed of a tandemly repeated 50 amino acid sequence. The amino acid sequence of GBP-130, deduced from the cloned and sequenced gene, reveals that the protein contains 11 highly conserved 50 amino acid repeats and a charged N-terminal region of 225 amino acids. Binding studies on recombinant proteins expressing different numbers of repeats suggest that a correlation exists between glycophorin binding and repeat number. Thus, a repeat domain, a common feature of plasmodial antigens, has been shown to have a function independent of the immune system. This conclusion is further supported by the ability of antibodies directed against the repeat sequence to inhibit the in vitro invasion of erythrocytes by merozoites.

Amino Acid Sequence↗
PubMed1985

Isolation of the gene for a glycophorin-binding protein implicated in erythrocyte invasion by a malaria parasite.

Plasmodium falciparum, the most lethal of the malarial parasites that infect humans, undergoes three cycles of development in its vertebrate host and elicits stage-specific immune responses. This stage specificity of the immune response has made it difficult to isolate antigens that would be useful in developing a vaccine against malaria. A complementary DNA clone for a glycophorin-binding protein of Plasmodium falciparum merozoites has been isolated and characterized. The protein interacts with glycophorin, the erythrocyte receptor, during invasion of the host cell by the parasite. Antigenic determinants of this protein expressed in Escherichia coli have been used to produce antibodies to a glycophorin-binding protein. The antibodies show schizont-specific immunofluorescence and react with the merozoite protein. The primary sequence of these determinants reveals a 150-nucleotide tandem-repeating sequence coding for a 50-amino-acid repeat. The characterization of the Plasmodium falciparum glycophorin-binding protein represents one approach toward designing serologic agents to block the parasite's development in the vertebrate host.

Animals↗
PubMed1983

Electron spin resonances of a living system (Drosophila) on normal and carcinogenic diets.

This investigation was a study of the free radical concentration of a living system, Drosophila melanogaster, by electron spin resonance spectroscopy. The paramagnetic content of the organism was measured as a function of age, mutant strain, and diet (normal vs. carcinogenic). In all cases, 4 to 6 days after ecdysis the free radical concentration decreased to approximately 70% of its value as measured shortly after ecdysis. The different mutant strains exhibited distinctly different free radical concentrations in accord with visual observations of the degree of pigmentation. Drosophila raised on a carcinogenic diet always showed a lower concentration of free radicals than the control groups on a normal diet.

Animals↗
PubMed1983

Acute mountain sickness, antacids, and ventilation during rapid, active ascent of Mount Rainier.

A double-blind randomized study of 45 climbers on Mt. Rainier was conducted to test the effectiveness of antacids in preventing acute mountain sickness. All 45 climbed to 3353 m, and 31 continued to the summit. Ten climbers listed acute mountain sickness as the reason for not attaining the summit. Of symptoms monitored throughout the climb, neither headache, nausea, dizziness, pounding heart, nor shortness of breath differed in severity between antacid-treated and placebo-treated groups. In both groups vital capacity decreased significantly with ascent (p less than 0.05), while peak flow (p less than 0.005) and minute ventilation (p less than 0.001) increased significantly. The 7 climbers with the most severe AMS symptom scores above 4000 m had significantly lower peak flow at sea level prior to ascent compared with the other 25 climbers who completed sea level tests (p less than 0.005). The results of this study fail to document efficacy for antacid use for the prevention of acute mountain sickness.

Adult↗