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Biomedical subjects

H Allen

Publications and source records attributed to H Allen.

At least 37 records · Page 2Linked to original sources
PubMed1988

Mechanisms of bronchial hyperreactivity in cystic fibrosis.

We studied 14 patients with cystic fibrosis (CF) who had evidence of bronchial hyperreactivity on a standardized histamine challenge. Patients had a histamine challenge on the first day. Then they were pretreated with either 0.25 mg ipratropium bromide or 0.5 mg fenoterol hydrobromide on 2 separate days, and the histamine challenge was repeated. Baseline forced expiratory volume in 1 sec was similar on the 3 days; however, there was a small but significant (P less than 0.05) improvement after fenoterol. Mean PC20 on the control day was 1.50 mg/ml, which increased significantly after pretreatment with ipratropium (2.88 mg/ml, P less than 0.01) and fenoterol (3.64 mg/ml, P less than 0.005), indicating protection against histamine-induced bronchial hyperreactivity. The six CF patients with "coexistent asthma," as defined by recurrent episodes of wheezing responsive clinically to bronchodilator therapy, had no significant protection from ipratropium, whereas the eight "nonasthmatic" CF patients were protected by both ipratropium and fenoterol. We postulate that at least two mechanisms contribute to histamine-induced bronchial hyperreactivity in patients with CF, one related to vagally mediated reflex bronchoconstriction and another that acts independently of this mechanism.

Adolescent↗
PubMed1988

A case of congenital ectropion in Down's syndrome.

A rare case of primary congenital ectropion of all 4 eyelids in a child with Down's syndrome is reported to emphasise the problems of surgical management and to distinguish the condition from congenital eversion of the eyelids. Congenital ectropion is associated with other eyelid abnormalities and usually requires surgical measures to protect the cornea in contrast to congenital eversion which is characterised by the protrusion of oedematous conjunctiva from everted eyelids. This usually resolves spontaneously with simple supportive measures and no structural or functional eyelid abnormality remains.

Down Syndrome↗
PubMed1988

Phagocytosis of autologous lymphocytes by cervical preneoplastic and neoplastic cells.

Eighty-nine random Pap smears of the uterine cervix were examined to evaluate the phagocytic abnormal cells (PACs) of atypical, dysplastic and neoplastic tissues against infiltrated blood cells. The results revealed that none of the PACs have been identified in atypical (II) and mild dysplastic cells (IIIa). Low levels (1.2%) of PACs were initially demonstrated in patients with moderate dysplasia (IIIb) that increased 1.7-fold in subsequent severe dysplasia (IIIc) and further increased 2.8-fold in invasive carcinomas of the cervix (V). In addition, the data showed age-related responsiveness toward the development of PACs, where 82% of old patients have developed phagocytic activity in moderate dysplastic cells compared with 27% of young patients. However, the difference became less significant at the subsequent classes of the disease. These data further demonstrated that PACs are class-dependent and it may explain one mechanism by which precancerous cells escape immunosurveillance.

Adolescent↗
PubMed1988

Brain and optic system pathology in hypocholesterolemic dogs treated with a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase.

The cholesterol lowering compound lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1.1.1.34 HMG CoA reductase), was given in nine separate experiments to normocholesterolemic dogs at rates up to 180 times the maximum therapeutic dose in man (1 mg/kg/day). Mean serum total cholesterol concentrations were reduced as much as 88% below normal. Clinical evidence of neurotoxicity occurred in up to 37% of animals given 180 mg/kg/day lovastatin for 11 or more days, especially in one laboratory where the dosing regime resulted in higher concentrations of plasma drug levels. Dogs receiving 60 mg/kg/day or less never exhibited neurologic signs. The central nervous system (CNS) of affected dogs exhibited endothelial degeneration and hemorrhagic encephalopathy. Focal extravasation of horseradish peroxidase occurred frequently (6/8) in the retrolaminar optic nerve of asymptomatic or clinically affected dogs given 180 mg/kg/day lovastatin, with endothelial degeneration and discrete optic nerve degenerative lesions interpreted as ischemic. The association between the degree of hypocholesterolemia and occurrence of clinical signs was not exact. Total brain cholesterol was similar in treated and control dogs. Hypocholesterolemic dogs had proportionally lowered serum concentrations of alpha-tocopherol, but oral supplementation of this vitamin did not prevent the neurologic syndrome. Endothelial degeneration in the CNS and optic nerve may have reflected in vitro morphologic effects of HMG CoA reductase inhibitors due to extreme inhibition of nonsterol isoprene synthesis. Retinogeniculate axonal (Wallerian-like) degeneration occurred in greater than or equal to 12% of dogs given 60 mg/kg/day or more lovastatin, with central chromatolysis of occasional retinal ganglion cells. These neuroaxonal changes may have been secondary to vascular effects, but superimposed direct neurotoxic action at the high dosage levels of lovastatin could not be excluded. There was no evidence of drug induced adverse effects in the CNS of dogs given up to 30 mg/kg/day lovastatin for 2 years.

Animals↗
PubMed1987

Tissue-specific expression of cell-surface Qa-2 antigen from a transfected Q7b gene of C57BL/10 mice.

We screened a cDNA library prepared from a BALB.B10 CTL clone that expresses Qa-2 antigen, and isolated four clones derived from Q7b, a Qa region gene of C57BL/10. One of these Q7b cDNAs and the Q7b chromosomal gene were subcloned into expression vectors and transfected into L cells and R1.1 thymoma cells. We found that the chromosomal Q7b gene expresses Qa-2 on the surface of R1.1 cells, but not on L cells while the Q7b cDNA expresses protein on the surface of both cell types. The levels of Qa-2 expression do not correlate with the total levels of Q7b mRNA in these transfectants. Our results suggest that the tissue-specific expression of Qa-2 may be controlled, in part, by mechanisms of alternate RNA splicing. By using hybrid gene constructs, we have mapped the tissue-specific element to the 3' part of the gene, downstream of a site near the middle of exon 4. The hybrid polypeptides differ significantly in their transmembrane and cytoplasmic regions. These portions of the protein also may play a role in the tissue-specific expression of Qa-2.

Animals↗
PubMed1987

Cell-surface expression of H-2Db requires N-linked glycans.

The question of whether beta-2 microglobulin (B2m)-independent expression of the mouse major histocompatibility complex (MHC) antigen H-2Db results from the atypical glycosylation pattern associated with this MHC antigen (i.e., three glycans instead of two) has been addressed. Cell-surface expression of transfected H-2Db in the B2m deficient cell line R1E was completely abolished by the drug tunicamycin (Tm). Introduction of a functional B2m gene by transfection did not re-establish cell-surface expression of Db in the presence of Tm. Tm had no effect, however, on the expression of a truncated Db molecule lacking the alpha 1 and alpha 2 domains which is glycosylated at amino acid position 256, suggesting that the Db molecule, unlike other class I antigens, possesses an unstable conformation in the alpha 1 and/or alpha 2 domains which requires the attachment of glycans before it is transported to the cell surface. Once attached, however, glycans may confer a stable alpha 1/alpha 2 conformation apparently peculiar to Db which allows cell-surface expression in the absence of B2m.

Antigens, Surface↗
PubMed1987

Noninvasive assessment of tissue iron stores.

Multivariate regression methods were used to create two equations for calculation of the "iron index," a predictor of bone marrow iron scores. With the use of the most efficient cut-off point, approximately 90% of 210 patients could be diagnosed correctly. Selection of a criterion that minimizes false negatives (missed iron deficiency) would increase the number of unnecessary bone marrow aspirations, but, even then, more than a third of such tests could be avoided. Rapid turnaround time would be desirable for all measurements used to calculate the iron index, although it is recognized that for most hospitalized patients the length of hospital stay is determined by severity of an underlying disease, not the presence of anemia.

Anemia↗
PubMed1986

Molecular biology of the H-2 histocompatibility complex.

The H-2 histocompatibility complex of the mouse is a multigene family, some members of which are essential for the immune response to foreign antigens. The structure and organization of these genes have been established by molecular cloning, and their regulation and function is being defined by expression of the cloned genes.

Animals↗
PubMed1986

Beta 2-microglobulin is not required for cell surface expression of the murine class I histocompatibility antigen H-2Db or of a truncated H-2Db.

beta 2-Microglobulin (beta 2m) has been thought essential for transport of all major histocompatibility complex class I antigens to the cell surface. Here, we show that the mouse class I antigen H-2Db is expressed at the cell surface even when there is no beta 2m present within the cell. This was established by transfecting the H-2Db gene into the R1E cell line, which lacks beta 2m. The conformation of the Db antigen expressed by the R1E transfectant is very different from that of the native molecule. This Db antigen is not recognized by Db-allospecific and Db-restricted cytotoxic T lymphocytes or by most monoclonal antibodies to the native Db. We show further that a deletion construct of the Db gene, which consists of exon 1 linked to exons 4-8, expresses a truncated Db antigen lacking domains 1 and 2 [Db-(1 + 2)] at the cell surface after transfection into the R1E line. Previous biochemical and crystallographic data have indicated that domain 3 is associated with beta 2m; unexpectedly, Db-(1 + 2) does not associate with beta 2m when the mouse beta 2mb gene is transfected into the R1E transfectant expressing the truncated Db. This suggests that interactions with domains 1 and 2 are important for the paired association of domain 3 and beta 2m in the native Db antigen.

Animals↗
PubMed1985

Allospecific cytolytic T lymphocytes recognize conformational determinants on hybrid mouse transplantation antigens.

Alloreactive cytolytic T cell (CTL) lines and clones have been used to identify the sites of polymorphism of antigens of the major histocompatibility complex (MHC). Specific CTL were generated against wild-type H-2b products by cells from H-2b mutant mice that had one or a few amino acid changes in either the alpha 1 or alpha 2 domains of the Kb or Db class I molecules. These CTL populations, which might be expected to react with determinants expressed on single MHC domains, were examined for lytic activity on L cells expressing newly constructed hybrid class I molecules. Transformed cell lines expressing native class I molecules or hybrid class I molecules in which the alpha 1 and alpha 2 domains of H-2Kb had been substituted by those domains of H-2Db were lysed by H-2Db-specific CTL. Similarly, all H-2Kb-specific CTL recognized hybrid molecules in which the alpha 1 and alpha 2 domains of H-2Kb were inserted into the H-2Db molecule. In contrast, exchange of the alpha 1 domains of H-2Kb and H-2Db resulted in a total loss of recognition by Kb and Db-specific CTL. These results suggest that the allodeterminants recognized by H-2 mutant CTL are influenced by interactions between the alpha 1 and alpha 2 domains, findings similar to those seen using conventional alloreactive T cells (11). These results were compared to the binding of alloreactive mAbs, including 5 new mAbs specific for the Kb molecules. Finally, it was shown that primary and secondary CTL responses could be generated by direct sensitization against hybrid class I molecules, demonstrating that these molecules express neoantigenic determinants recognized by alloreactive CTL.

Animals↗
PubMed1985

Recognition of interspecies hybrid class I histocompatibility antigens by antigen-specific cytolytic T lymphocytes.

Two reciprocal interspecies hybrid class I histocompatibility genes have been constructed between genomic clones of human HLA-A2 and murine H-2Kb. The proteins encoded by these genes have been designated A21+2/Kb, where the polymorphic domains, alpha 1 and alpha 2, of HLA-A2 are linked to the carboxyl-terminal domains (alpha 3, transmembrane, and intracytoplasmic domains) of H-2Kb, and Kb1+2/A2, where the alpha 1 and alpha 2 domains of the H-2Kb antigen are linked to the carboxyl-terminal domains of HLA-A2. These genes have been transfected and expressed in recipient mouse L cells and human RD (rhabdomyosarcoma) cells. Both hybrid antigens were found to be serologically intact when tested with a panel of antigen-specific monoclonal antibodies. The monoclonal antibody W6/32, which recognizes a monomorphic determinant on all HLA-A, -B, and -C antigens, recognizes the alpha 1 and/or the alpha 2 domain, rather than the more conserved alpha 3 domain. Human cytolytic T lymphocytes (CTL) specific for the HLA-A2 antigen recognized the A2 and A21+2/Kb proteins only when expressed in human cells and not when expressed in mouse cells, even when surface antigen levels were 10-fold greater on the mouse cells than on the human cells. In contrast, a long-term, murine anti-H-2b CTL line not only lysed mouse L-cell lines that expressed the parental Kb and hybrid Kb1+2/A2 antigens but also lysed the Kb and Kb1+2/A2 human cell RD transformants as well. In both cases, the level of CTL recognition and lysis of the transformants that expressed the native antigen Kb was greater than of those transformants that expressed the hybrid antigen Kb1+2/A2. These data suggest that the carboxyl-terminal domains play some role in CTL allorecognition. The lack of human CTL recognition of HLA molecules expressed in mouse L cells, however, cannot be explained by the presence of a xenogeneic carboxyl terminus. Since murine CTL can recognize their target antigen when expressed on the surface of human cells, the possibility remains either that a ligand necessary for other molecular interactions of human CTL may be absent on mouse target cells or that murine and human CTL differ in affinity of binding to target antigens in the absence of accessory-molecule interactions.

Animals↗
PubMed1984

Behavioral studies with mice exposed to DC and 60-Hz magnetic fields.

Behavioral measures were evaluated in adult CD-1 and LAF-1 mice continuously exposed for 72 h to a 1.5-Tesla (1 T = 10(4) Gauss) homogeneous DC magnetic field, and in LAF-1 mice continuously exposed for 72 h to a sinusoidal 60-Hz, 1.65-mT (rms) homogeneous AC field. Three types of behavioral tests were employed: (1) Memory of an electroshock-motivated passive avoidance task was assessed in animals that had been trained immediately prior to the field exposure. The strength of memory was varied either by altering the strength of the electric footshock during training, or by administering a cerebral protein synthesis inhibitor, anisomycin, at the time of training. (2) General locomotor activity was measured using a quadrant-crossing test immediately after termination of the magnetic field exposure. (3) Sensitivity of the experimental subjects to the seizure-inducing neuropharmacological agent, pentylenetrazole , was assessed immediately after the field exposure on the basis of three criteria: (a) the percentage of subjects exhibiting a generalized seizure, (b) the mean time to seizure, and (c) the mean seizure level. The results of these studies revealed no behavioral alterations in exposed mice relative to controls in any of the experimental tests with the 1.5-T DC field or the 60-Hz, 1.65-mT (rms) AC field.

Animals↗
PubMed1984

Development of differences in response latencies to right and left visual fields.

Robust lateralization developed in right-handed adults who were asked to judge letter pairs as "same" or "different" during 4608 trials. By the end of the first two blocks (768 trials) "same" responses were favored when presented in the RVF (transmitted directly to the left hemisphere) and "different" responses were favored when presented in the LVF (transmitted direction to the right hemisphere). This gradually reversed over sessions with "same" responses becoming faster for letters presented in the LVF, and "different" responses becoming faster for stimuli presented in the RVF. The laterality acquired under these conditions was cumulative and reproducible, appeared in all 16 subjects, and was preserved between sessions a week apart. The data suggest that laterality is a flexible and reversible characteristic of the human brain even when stimulus and task remain constant.

Discrimination Learning↗
PubMed1984

The safety of contrast echocardiography: report of the Committee on Contrast Echocardiography for the American Society of Echocardiography.

The results of a survey of 363 physicians performing echocardiography were evaluated to assess the relative safety of contrast echocardiography. Fifteen physicians reported a variety of transient side effects, including neurologic and respiratory symptoms. Although contrast echocardiography appeared to carry some risk for side effects, that risk was low (0.062%) and no residual side effects or complications were observed. In view of the significant benefits reported for contrast echocardiography, it appears to remain a valuable technique that is safer than currently available alternative diagnostic modalities. However, during contrast echocardiography, precautions should be taken to prevent the injection of visible amounts of air, especially in patients with a right to left shunt or arterial catheters.

Contrast Media↗