Biomedical subjects
C Allen
Publications and source records attributed to C Allen.
Routine prenatal determination of chorionicity in multiple gestation: a plea to the obstetrician.
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Testing the role of p53 in the expression of genetic instability and apoptosis in ataxia-telangiectasia.
We have obtained initial evidence supporting a new model for the human disease ataxia-telangiectasia (A-T), in which the A-T and p53 genes play crucial roles in a signal transduction network that activates multiple cellular functions in response to DNA damage. Three of the model's predictions were tested. (1) Disrupting cell cycle checkpoints should increase spontaneous rates in normal cells. In order to interfere with the G1/S checkpoint, we transfected a normal cell line with vectors expressing either a dominant-negative p53ala143 mutant or a human papilloma virus E6 gene. These transformants showed 10-80-fold elevations in spontaneous recombination rates when compared with their parent. (2) A-T cells should be sensitive to DNA damage-induced apoptosis. Widespread apoptosis was detectable in four A-T fibroblast lines, but not two control lines, beginning 24 h after exposure to X-rays or streptonigrin, but not UV. Streptonigrin also induced widespread apoptosis in A-T lymphoblasts but not in control lymphoblasts. (3) Disruption of p53 function in A-T cells should increase their mutagen resistance by interfering with apoptosis. Stable transfection of either the p53143ala or the HPV18 E6 construct was associated with acquisition of streptonigrin and radiation resistance, while transfection with the p53143ala construct did not affect the streptonigrin sensitivity of a control cell line.
Inclusive photon production from pp-bar collisions at sqrt s =1.8 TeV.
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Study of source size in pp-bar collisions at sqrt s =1.8 TeV using pion interferometry.
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Mass-identified particle production in proton-antiproton collisions at sqrt s =300, 540, 1000, and 1800 GeV.
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Mutant cell line demonstrating a block in insulin and insulin-like growth factor type 1 (IGF-1) induced mitogenesis.
Recently, we have isolated a Chinese hamster cell variant (IV-A1-j) resistant to an insulin-diphtheria-A chain toxic conjugate (Leckett and Germinario: Cytotechnology [in press]. This cell line exhibited a decreased level of insulin binding, but normal growth in serum-containing medium when compared to the parental cell line (V-79). In this paper we further demonstrate that while IV-A1-j cells are capable of growing in serum-containing medium, they are insensitive to the mitogenic actions of either insulin or IGF-1. In contrast, epidermal growth factor (EGF) and/or alpha-thrombin (THR) generate a mitogenic effect in IV-A1-j cells comparable to that observed in the parental V-79 cells. The combination of EGF and/or THR with either insulin or IGF-1 results in an increase in V-79 cell growth above EGF and/or THR alone. On the other hand, insulin or IGF-1 in the presence of other mitogens did not stimulate further growth in IV-A1-j cells. While insulin binding was lower in IV-A1-j cells, internalization of 125I-insulin was not different in the two cell types. Additionally, insulin-stimulated glycogen synthesis and protein synthesis were not different in the two cell types. These observations are consistent with insulin and IGF-1 sharing a mitogenic signalling pathway in Chinese hamster fibroblasts and that this pathway is distinct from other growth factor signalling pathways. The fact that this pathway is defective in the IV-A1-j cell line indicates the potential usefulness of these cells in identifying a key step(s) in the insulin (IGF-1) mitogenic pathway.
Restraint stress differentially affects the pathogenesis of an experimental influenza viral infection in three inbred strains of mice.
Genetic variation in the response to stress may play a critical role in susceptibility to inflammatory diseases and development of the immune response. Experimental influenza viral infection was used to study the effects of restraint stress (RST) on pathogenesis and development of the immune response. Three inbred strains of mice (C57BL/6, DBA/2, and C3H/HeN) were infected with influenza A/PR8 and subjected to repetitive cycles of RST during development of the immune response. RST diminished cellular immune and inflammatory responses in all three strains; yet only the DBA/2 strain demonstrated RST-associated reduction in influenza viral-induced mortality.
Apocrine metaplasia: a new type of müllerian metaplasia.
Apocrine differentiation was an incidental finding in an ovarian cyst. This is considered to be a further example of Müllerian metaplasia that has not been described before and which, theoretically, could occur in any organ of Müllerian derivation (ovary, uterus, cervix or fallopian tube). It is suggested that sites of such metaplasia could in turn be the origin of primary apocrine carcinoma in any of the above locations.
Hyperon production from proton-antiproton collisions at sqrt s =1.8 TeV.
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Paraneoplastic pemphigus: a report of three cases including one long-term survivor.
BACKGROUND: Paraneoplastic pemphigus is a newly described autoimmune disease characterized by painful mucosal ulcerations and polymorphous skin lesions in association with an underlying neoplasm. All reported patients with an associated malignant neoplasm have had a poor prognosis. OBJECTIVE: We present three new cases of paraneoplastic pemphigus associated with a malignant neoplasm and further characterize this disease. METHODS: We used clinical criteria, histologic and immunopathologic examinations, and immunophenotyping to characterize this disease. In addition, we performed immunoprecipitation studies with extracts of radiolabeled human keratinocytes to characterize the antigens to which patient serum binds. RESULTS: All three patients had clinical, histologic, and immunopathologic findings that were strongly suggestive of paraneoplastic pemphigus. Their sera immunoprecipitated a complex of four polypeptides from human keratinocyte extracts with molecular weights of 250, 230, 210, and 190 kd, confirming the diagnosis of paraneoplastic pemphigus. The 250, 230, and 210 kd antigens comigrated with desmoplakin I, the 230 kd bullous pemphigoid antigen, and desmoplakin II, respectively. Lymphocyte immunophenotyping revealed large populations of monoclonal CD19+, CD5+ B cells in two cases. Although two of the patients died, one patient is alive and well 2 years after the diagnosis of paraneoplastic pemphigus. CONCLUSION: We report three cases of paraneoplastic pemphigus. One patient is alive and well 2 years after diagnosis, which suggests that a subgroup of patients may have a more benign course.
Responses to physician bonding editorial.
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Tyrosine phosphorylation of a membrane protein from Pseudomonas solanacearum.
We have investigated a tyrosine kinase activity from Pseudomonas solanacearum, an economically important plant pathogen. In vitro incubation of membrane fractions with [gamma-32P]ATP and subsequent sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed an 85-kDa phosphoprotein. Phosphorylation of this protein on tyrosine residues was demonstrated by phosphoamino acid analysis of base hydrolysis products and by immunoanalysis of Western blots (immunoblots) with antiphosphotyrosine monoclonal antibody. In vitro incubation of membranes with ATP was not required for recognition by the antibody, indicating that the 85-kDa protein is phosphorylated in vivo. These results demonstrate that membranes from P. solanacearum exhibit a tyrosine kinase activity toward an endogenous membrane protein. This bacterium provides an opportunity to study the structure and function of a prokaryotic tyrosine kinase.
Combined high grade sarcoma and serous ovarian neoplasm.
A case of an ovarian serous epithelial neoplasm of borderline type admixed with sarcomatous elements is reported. This combination seems to be extremely rare with only four cases previously reported. It may represent a type of collision tumour or the development of a sarcoma in a growth with borderline differentiation.
Glycemic control and peripheral nerve conduction in children and young adults after 5-6 mo of IDDM. Wisconsin Diabetes Registry.
OBJECTIVE: A cohort of people (n = 86) was examined in the first few months after insulin-dependent diabetes mellitus (IDDM) diagnosis to evaluate the effect of hyperglycemia on nerve conduction velocities and latencies. RESEARCH DESIGN AND METHODS: Unselected cases with IDDM, who were 6-29 yr of age, were identified at diagnosis from a large, geographically defined area of southern Wisconsin. Peripheral nerve conduction was measured on a sample from this cohort. RESULTS: Peroneal nerve conduction velocity was significantly inversely related to glycosylated hemoglobin (P less than 0.05, age and height adjusted). All other nerve conduction velocities and latencies (median motor, median sensory, and sural) showed the same tendency, but the associations were not statistically significant. Twenty-four-hour urine C-peptide and duration of diabetes (3-11 mo) were not consistently related to nerve conduction parameters after controlling for age and height. CONCLUSIONS: These findings suggest that as early as 5-6 mo after diabetes diagnosis, and at a time frequently characterized by partial remission of IDDM, hyperglycemia has a role in the acute slowing of nerve conduction velocity. Other factors such as residual endogenous insulin production do not appear to influence these early changes.
Glycemic control in early IDDM. The Wisconsin Diabetes Registry.
OBJECTIVE: A cohort (n = 277) was followed from diabetes diagnosis to evaluate longitudinal glycemic control, urinary C-peptide levels, and certain features of diabetes self-management. RESEARCH DESIGN AND METHODS: Unselected cases with IDDM, who were less than 30 yr of age, were identified at diagnosis from a 28-county area in Wisconsin. Subjects were asked to submit blood every 4 mo for GHb testing, to report aspects of diabetes self-management every 6 mo, and to collect a 24-h urine specimen 4 mo after diagnosis. RESULTS: In the 1st yr of diabetes, the rate of increase (0.23%/mo) in GHb was significant for the cohort (P less than 0.001) and for almost all age and sex subgroups. In the 2nd yr, there was no significant rate of increase for the cohort as a whole (P greater than 0.10). Adolescent males (10-19 yr of age) had a mean GHb level for year 2 higher than males of other age-groups and higher than female adolescents (P less than 0.001). Adolescent males had a significant rate of increase in GHb for year 2 (P = 0.02), unlike all other age and sex subgroups. Adolescents had higher initial 24-h urine C-peptide levels than children less than 10 yr of age (P less than 0.01). During the 2nd yr of diabetes, the percentage of adolescent males reporting three or more insulin injections/day was lower than any other subgroup. CONCLUSIONS: These data-suggest that glycemic control stabilizes during the 2nd yr of IDDM, except in adolescent males, and that this may be due partly to aspects of self-management.
Arachnid envenomations.
Humans have interacted with arachnids since their prehistoric trip from the Garden of Eden. Modern travel has placed both patient and physician in contact with creatures and diseases far outside the scope of our day-to-day medical practice. The understanding of life cycles and toxicity of these fascinating spiders and scorpions better prepares the emergency physician to provide more comprehensive medical care and perform as a knowledgeable patient advocate.
Clinical features of Behçet's disease. Report of four cases.
Behçet's disease is a multisystem inflammatory disorder of unknown etiology. The unifying histologic reaction pattern is a leukocytoclastic vasculitis that affects predominantly the skin, oral mucosa, and eyes. Many other sites of involvement have been reported but are inconsistently found in individual patients. Early recognition and treatment of Behçet's disease may help prevent devastating permanent sequelae such as blindness. Because oral involvement is often the first manifestation of this disorder, dental practitioners are in a unique position to help these patients. We report four cases of Behçet's disease in North American patients. Diagnostic criteria and treatment options are reviewed.