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Biomedical subjects

H Allen

Publications and source records attributed to H Allen.

At least 19 recordsLinked to original sources
PubMed1992

A mutation generating a stop codon in the alpha-L-fucosidase gene of a fucosidosis patient.

Fucosidosis is an autosomal recessive, lysosomal storage disease featured by deficient activity of alpha-L-fucosidase. Lymphoid cell lines from a fucosidosis patient (JT) and a healthy individual (control) contained alpha-L-fucosidase mRNA of the same size, 2.3 Kb, as determined by Northern blot analysis. cDNA was prepared from alpha-L-fucosidase mRNA of JT and control cells and each cDNA was amplified by the polymerase chain reaction. Direct DNA sequencing of the amplified products revealed a single mutation in JT, a G1141-->T transition. This changed the codon (GAA) for Glu-375 to a stop codon (UAA). Amplification and sequencing of the area containing the G1141-->T transition in genomic DNA of JT and control cells demonstrated that the mutation was homozygous in JT. Analysis of cDNA and genomic DNA derived from lymphoid cells of mother JT revealed her to be heterozygous (G and T) at position 1141. The G1141-->T mutation is probably responsible for disease in JT.

B-Lymphocytes↗
PubMed1992

Structural requirements for the peptide-induced conformational change of free major histocompatibility complex class I heavy chains.

In an attempt to define the structural features of peptides which are important for inducing the folding of free class I heavy chains in the absence of beta 2-microglobulin, and to determine whether they are the same as those required to form stable major histocompatibility complex (MHC): peptide adducts, we have used a panel of peptides related to the Db-binding nonamer ASNENMDAM (influenza nucleoprotein residues 366-374) with altered primary structures, and a number of other peptides which have the Db-binding "motif". In this way, we have shown that in addition to the "anchor" residues which define this motif, the alpha amino and carboxyl groups at the N and C termini also play a major role in both inducing the conformational change in free heavy chain (HC) and formation of a stable Db:peptide complex. We also show that the importance of the key residues is affected by the primary sequence "context" in which they appear. In addition, we have extended our original finding that naturally processed epitopes induce a conformational change in free HC to the H2Kb HC, and show that the effect does not require the presence of the class I alpha 3 domain.

Amino Acid Sequence↗
PubMed1992

Carbon monoxide poisoning in a diver.

Carbon monoxide poisoning is a well recognized, but uncommon hazard of sport and inshore diving, which occurs either as a result of a faulty air compressor or from air contamination by the exhaust of nearby petrol engines. The incidence of carbon monoxide poisoning may be under-reported as it may mimic decompression sickness, and respond to the same treatment i.e. hyperbaric oxygen.

Adult↗
PubMed1990

Expression of epidermal-growth-factor receptor in the K562 cell line by transfection. Altered receptor biochemistry.

The epidermal-growth-factor (EGF) receptor was expressed in the human erythroleukaemic cell line K562 by transfection of the receptor cDNA. EGF-receptor biochemistry appears altered in the K562 transfectants. Autophosphorylation of the K562 receptor is not stimulated substantially by EGF. Tyrosine kinase activity of the receptor is high in the absence of EGF, whereas receptor affinity for EGF is low. K562 cells are shown to lack mRNA for transforming growth factor alpha (TGF alpha). Therefore autocrine stimulation of the K562 receptor, at least by TGF alpha, does not explain the observed receptor biochemistry. The K562 receptor is phosphorylated at a single major site in intact cells, a threonine residue that may be Thr-669. Possible mechanisms of regulation of the EGF receptor in the K562 transfectants are discussed.

DNA↗
PubMed1990

Studying the effects of the DRG-based prospective payment system on quality of care. Design, sampling, and fieldwork.

We have conducted a nationally representative before-after study of the effects of the diagnosis related groups-based prospective payment system (PPS) on quality of in-hospital care for aged Medicare patients. We used a pre-post design with multiple time points in both the pre-PPS (calendar years 1981 and 1982) and post-PPS (July 1985 through June 1986) periods. We gathered clinically detailed data from medical records of patients with one of six diseases and supplemented these data with postdischarge information from Health Care Financing Administration files. We used a stratified multistage cluster sampling design with data gathered on 16,758 patients chosen from 297 hospitals in 30 areas in five states. Our hospital participation rate was 97%; we successfully accessed 96% of the medical records we requested; and our mean item-level reliability score was 0.80. Our sample matches the nation closely on hospital urbanicity, size, teaching status, ownership, and percentages of Medicare and Medicaid patients, and patient demographics and mortality.

Cross-Sectional Studies↗
PubMed1990

Cognitive processing and its relationship to symptoms and social functioning in schizophrenia.

This study analyses the relationship between contextual processing ability and symptom and social status in schizophrenia. The results showed that current symptom status is related to occupational status, and contextual processing is related to current symptom status and employment history. Current symptom severity in chronic schizophrenics may indicate an increased frequency and/or duration of symptom episodes in the past, and therefore an increase in the periods in which contextual processing was disturbed, which would therefore account for the observed decrease in work achievements.

Adult↗
PubMed1989

Specific molecular interaction between the insulin receptor and a D product of MHC class I.

The density of MHC class I was determined on a murine thymoma cell line (R1), an H-2 negative variant (R1E), and R1E-derived cell lines in which H-2 expression was restored by transfection of various MHC class I genes (Db, Kb, and truncated Db) and/or a beta-2-microglobulin gene (beta 2-m; B2). Appreciable MHC class I expression was found on R1 cells and on the variants in which MHC class I expression was restored by transfection of Db/beta 2-m or Kb/beta 2-m genes. Only approximately 20% difference was observed between the number of Db molecules and Kb molecules on the R1E/B2/Db and on R1E/B2/Kb, respectively. However, specific insulin binding was significantly different between these lines. By using a computer assisted curve fitting program, the insulin binding data for R1 and R1E/B2/Db cell lines best fitted a two-site model (K approximately 6 x 10(-9) M for high-affinity sites and a 2 to 3 x 10(-7) M for low-affinity sites), whereas all other lines only expressed one type of insulin binding site. These sites were unrelated to IGF-I and IGF-II receptors. Cross-linking of 125I-labeled insulin demonstrated specific binding of the ligand to a Mr approximately 130,000 dalton band in all lines. In the R1E/B2/Db cells, insulin also cross-linked to cell membrane molecules with Mr approximately 48,000 and approximately 60,000 Da, which were identified by immunoprecipitation to be the H chain of MHC class I and the heavy chain of MHC class I plus beta 2-m, respectively. It is concluded that the insulin receptors in the cell membrane interact specifically with D-products of MHC class I and that class I molecules of MHC may have a crucial role in insulin receptor expression. This may reflect a more general nonimmunologic role of MHC class I.

Animals↗
PubMed1989

Role of beta 2-microglobulin in the intracellular transport and surface expression of murine class I histocompatibility molecules.

We have examined the requirement for beta 2-microglobulin (beta 2m) in the intracellular transport of murine class I histocompatibility molecules to the cell surface. R1E cells that are defective in the synthesis of beta 2m were transfected with either the class I H-2Kb or H-2Db genes alone, or together with the beta 2m gene. Kb or Db heavy chains synthesized in the presence of beta 2m were transported rapidly through the cell and expressed efficiently at the cell surface. In the absence of beta 2m, no "free" Kb heavy chains were detectable at the cell surface and their intracellular transport was blocked at an early stage. In contrast, a significant quantity of "free" Db heavy chains could be detected at the cell surface as we have reported previously. However, we have shown here that defects in intracellular transport were apparent in that the majority (approximately 70%) of newly synthesized Db heavy chains accumulated intracellularly and were degraded. Therefore, although Kb and Db heavy chains differ in their abilities to be expressed at the cell surface in the absence of beta 2m they both require association with beta 2m for efficient intracellular transport. In addition, R1E cells transfected with a deletion construct of the Kb gene expressed a truncated molecule lacking the alpha 3 extracellular domain (Kb-3) at the cell surface, but, like free Db, most newly synthesized Kb-3 molecules accumulated intracellularly. The free Kb, Kb-3, and Db heavy chains were not recognized by most mAb specific for Kb and Db, respectively. Therefore, even the transported forms of free Db and Kb-3 were not native in conformation, which is surprising given the current view that correct folding is essential for intracellular transport. Interestingly, the free Db and Kb-3 heavy chains that reached the cell surface differed in their detergent binding properties from those retained within the cell. This suggests that the transported heavy chains may have folded differently thus allowing their export to the cell surface.

Animals↗
PubMed1989

Birth-interval dynamics in rural Bangladesh and maternal weight.

This article reports on the results of a study conducted in rural Bangladesh on the influence of maternal weight on the components of birth intervals, including gestation and intrauterine mortality, the duration of postpartum amenorrhea, and the duration of waiting time to conception (the menstrual interval). When biological factors (including maternal age, parity, and supplementation practices) and behavioral variables, including religion, education, and occupation, were controlled, maternal weight was found to be related to the risk of intrauterine mortality and to the probability of resuming menses in the postpartum period. The implications of these findings for policies and programs in developing countries are discussed.

Amenorrhea↗
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↗