A congenital dyserythropoietic anaemia variant presenting as hydrops fetalis.
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Anemia, Dyserythropoietic, Congenital↗
Biomedical subjects
C Carter
Publications and source records attributed to C Carter.
Monoclonal antibody definition of the DRB3 allele, HLA-Dw25.
Monoclonal antibodies are powerful tools for analyzing HLA antigen polymorphism. We have investigated the serological and biochemical nature of the DRw52-related antigen defined by the monoclonal antibody NDS10. A detailed analysis of the population distribution of NDS10 reactivity revealed that the epitope was present on a subpopulation of DRw52 positive cells. A distinct pattern of reactivity was found within DR3 individuals: all of the B18,DR3 cells were NDS10 positive, whereas the A1,B8,DR3 cells were negative. All of the DR5(w11) cells and two of three DRw12 cells reacted with NDS10. NDS10 reactivity with DRw6 was not restricted to either of the serologically defined subtypes; three of 17 DRw13 and nine of 10 DRw14 cells were NDS10 positive. NDS10 was unreactive with all of the DRw8 cells tested. Two-dimensional gel analyses revealed that the NDS10 molecule precipitated from DR3, DR5(w11) and DRw6(w14) cell lines had an identical beta chain profile. These data indicate that NDS10 recognises the Dw25 allele of the DRw52 complex.
Antibodies, Monoclonal↗
Low-level exposures to lead: the Sydney lead study.
The Sydney Lead Study is a prospective investigation of the relationship between low-level lead exposure and neurobehavioural development during the first five years of life. Of the initial cohort of 318 children, 207 remained at the end of the fourth year. Average blood lead levels at 42 and 48 months were 10.7 and 10.1 micrograms/dl, respectively, with only a minority of observations exceeding 15 micrograms/dl. The regression analyses support earlier findings from the study, in that exposure to lead resulting in the range of blood lead levels found in this cohort is not associated with mental or motor deficits in the preschool years.
Adult↗
DNA sequence of mip, a Legionella pneumophila gene associated with macrophage infectivity.
In a previous study, a 24-kilodalton (kDa) protein surface antigen of Legionella pneumophila was cloned into Escherichia coli and found to be expressed on the host cell surface. Subsequently, a site-directed mutation in this gene (designated mip) in L. pneumophila was found to impair the capacity of this bacterium to initiate intracellular infection in human macrophages. The work presented here indicates that the antigenic gene product is distinct from the 24- to 29-kDa major outer membrane protein of L. pneumophila. In addition, the antigen was identified as a highly basic protein on two-dimensional nonequilibrium polyacrylamide gels and on two-dimensional monoclonal antibody immunoblots. When the DNA fragment encoding this protein was sequenced, a long open reading frame of 699 base pairs was identified within a region to which antigen expression was previously mapped. mip mRNA isolated from both L. pneumophila and transformed E. coli had the same 5' end, as determined by primer extension analysis, indicating that the same promoter sequences are used in both species. A likely factor-independent transcriptional terminator was found 20 residues downstream of the stop codon, suggesting that mip is encoded on a monocistronic message. The inferred polypeptide began with a possible 20- to 24-residue signal sequence, and, as predicted by two-dimensional electrophoresis, had a molecular weight of 24,868 and was a potent polycation with an estimated pI of 9.8.
Amino Acid Sequence↗
Oncogenes and human breast cancer.
The role of oncogenes in breast tumorigenesis is unclear. Alterations and/or amplification of several oncogene sequences have been observed in primary human breast tumors, in breast tumor cell lines, and in mammary tumors in model systems. In principle, such alterations could be sites of primary lesions for human breast cancer, causes of tumor progression or metastasis, or simply secondary lesions of highly aberrant tumor genomes. The present study tested genetic linkage of breast cancer susceptibility to nine oncogenes in 12 extended families including 87 affected individuals. Lod scores for close linkage of each candidate sequence to breast cancer were -19.6 for HRAS, -12.3 for KRAS2, -1.0 for NRAS, -6.0 for MYC, -6.1 for MYB, -8.2 for ERBA2, -7.9 for INT2, and -5.1 for RAF1. Regions of chromosome 11p associated with tumor homozygosity and the region of 3p carrying the gene for Von Hippel-Lindau disease could also be excluded from linkage to human breast cancer. The 5-kb allele of the MOS oncogene, previously proposed to be associated with breast cancer, was absent in these families, suggesting that polymorphism at this locus is not associated with inherited susceptibility. These results strongly suggest that oncogenes are not the sites of primary alterations leading to breast cancer. On the other hand, alterations in one or more of these sequences may be associated with tumor progression.
Breast Neoplasms↗
Biochemically detected HLA-DQ polymorphism in DR-matched donors and recipients of renal allografts.
We performed a retrospective biochemical analysis of HLA-D-region antigens of serologically DR-compatible donors and recipients of renal allografts. No incompatible D-region antigens were detected in grafts with a stable clinical course--i.e., there were no rejection episodes--whereas incompatibility for one or more D-region antigens was found in all 13 grafts with rejection. Thus, mismatched D-region antigens may provide a stimulus for early rejection in these grafts.
Cell Line↗
Living with AIDS.
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Acquired Immunodeficiency Syndrome↗
Pupil size after extracapsular cataract extraction and posterior chamber lens implantation: a prospective randomized trial of epinephrine and acetylcholine.
The effects of using epinephrine in the irrigating fluid and intracameral acetylcholine were studied by measuring changes in pupil size in the 48 hours following extracapsular cataract extraction and intraocular lens implantation in 39 eyes. Epinephrine reduced peroperative pupil constriction, but its effect was insignificant thereafter. The pupil constriction following acetylcholine was maximal at 2 hours and was still significant at 4 hours, but pupils redilated by 6 hours. Neither drug had any effect after this time. The edge of most lens implants was visible at 6 hours, after which pupils steadily constricted.
Acetylcholine↗
Sodium dependence of NMDA's effects on cyclic GMP production in immature rat cerebellar slices.
In immature rat cerebellar slices, the calcium-dependent increase in cyclic GMP levels provoked by N-methyl-D-aspartic acid (NMDA) (80 microM) displayed sodium dependence using bis-(2-hydroxyethyl)-dimethyl ammonium chloride, N-methyl-glucamine or Tris as sodium substitutes. The effects of NMDA (and also of veratrine, 100 microM) were attenuated by substitution of sodium chloride by lithium chloride. The response produced by depolarization with KCl (50 mM) was not affected by lithium substitution. As lithium is believed to permeate sodium-permeable channels but is not a substrate for sodium/calcium exchange, the data suggest that calcium entry mediated by the reverse mode of sodium/calcium exchange may play a contributory role to the calcium entry provoked by NMDA and veratrine.
Animals↗
Differential modulation of [3H]TCP binding to the NMDA receptor by L-glutamate and glycine.
At equilibrium (4 h incubation), [3H]TCP (N-(1-[2-thienyl]-cyclohexyl)-3,4-[3H]piperidine) binding to well-washed rat forebrain membranes was enhanced in a concentration-dependent and 2-APV (2-amino-5-phosphonovaleric acid)-sensitive fashion by L-glutamate (EC50 = 0.2 microM; maximal effect +280%). L-glutamate (10 microM) increased the affinity of [3H]TCP from 78 to 28 nM, but was without effect on the maximal binding capacity. The enhancing effect of L-glutamate on [3H]TCP binding was potentiated by glycine in a concentration-dependent manner (EC50 = 50 nM, maximal effect +30% in the presence of 10 microM L-glutamate; EC50 = 2 microM, maximal effect +29% in the presence of 0.1 microM L-glutamate). This effect was strychnine-insensitive. Glycine failed to enhance [3H]TCP binding in the presence of 10 microM 2-APV. The glycine effect was due to an increase in affinity (Kd = 21 nM in the presence of 10 microM glycine and 10 microM L-glutamate); glycine did not affect the maximal binding capacity. The glycine enhancement of L-glutamate-stimulated [3H]TCP binding was not antagonised by 1 microM strychnine and was mimicked by L-serine and L-alanine but not by GABA, taurine or beta-alanine. Kinetic analysis of the glycine and L-glutamate enhancement of [3H]TCP binding indicated that the L-glutamate effect was related to a decrease in the [3H]TCP dissociation rate while the glycine effect was due to an increase in the rate of [3H]TCP association in the presence of L-glutamate.
Animals↗
Carrier detection in hemophilia A: ABO blood group, multiple measurements, and application of logistic discrimination.
In healthy 20- to 50-year-old women, the ABO blood group has a significant effect on levels of von Willebrand factor (VWF:Ag, formerly VIIIR:Ag) and on factor VIII activity (F.VIII:C). However, there is no significant effect of ABO group or subject age on the ratio log e(F.VIII:C/VWF:Ag). Multiple measurements of the "ratio" on possible carriers of hemophilia A may be combined with pedigree information using logistic discrimination to yield final risk assessment. To reduce misclassification of carriers as normal women, a lower limit, specified by the logistic model, is set on the logistic carrier probabilities. In this study, the proportion of blood group A for a population of obligate carriers was significantly higher than that expected for the general population (60% vs. 42%); for a population of control women it was lower than expected (22.5 vs. 42%). The effect for the carriers came primarily from daughters of affected fathers, as 81.3% were of blood group A. These observations indicate that a "universal" discriminant should be applied with caution.
ABO Blood-Group System↗
Factor X deficiency during treatment of relapsed acute myeloid leukaemia with amsacrine.
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Adult↗
Development, validation and application of computer-linked knowledge questionnaires in diabetes education.
Multiple choice questionnaires (MCQs) capable of being marked manually or by a newly developed optical mark reader, or by use of an inexpensive inter-active microcomputer system have been developed for the separate assessment of insulin-dependent and non-insulin-dependent patient knowledge. Forty-six insulin-related and non-insulin-related multiple choice questions covering six main areas of knowledge were constructed for inclusion into draft questionnaires. From the responses of a total of 180 completed questionnaires, piloted in 18 randomly selected clinics in 14 Regional Health Authorities in England, psychometric analysis was performed to determine reliability, discrimination coefficients, and facility indices. Seventy-three per cent of insulin-dependent diabetic patients (IDDM) and 92% of non-insulin-dependent diabetic patients (NIDDM) MCQ correct options had facility indices within the acceptable range of 30 to 90%. 82% IDDM and 93% NIDDM correct options had discrimination coefficients exceeding 0.2. Questionnaire reliability (internal consistency) using the Kudor-Richardson (KR20) formula was IDDM 0.87 and NIDDM 0.82. Evidence in support of the IDDM questionnaire's criterion validity was based on significant differences (p less than 0.05) identified between a number of knowledge area scores stratified according to HbA1 levels. Prescriptive correction for screen display and automatic hard copy feedback was designed for both incorrect and omitted question options, providing both educational (patient) and analytical (clinic) documentation. Both technical and psychometric properties of these knowledge assessment instruments should be acceptable for diabetic knowledge evaluation and instruction.
Diabetes Mellitus, Type 1↗
Boredom proneness and adolescents' personalities.
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Adolescent↗
Ifenprodil and SL 82.0715 as cerebral anti-ischemic agents. I. Evidence for efficacy in models of focal cerebral ischemia.
Recent studies have strongly implicated the excitatory neurotransmitter glutamate in the cascade of pathological mechanisms that cause neuronal loss after certain types of brain ischemia. The neurotoxic effects of glutamate are mediated, at least in global ischemia, via NMDA receptors. In the present study we have examined the effects of compounds that possess NMDA receptor antagonist properties (ifenprodil, SL 82.0715 [(+/-)-alpha-(4-chlorophenyl)-4-[(4-fluorophenyl)methyl]- 1-piperidineethanol] and 1-[1-(2-thienyl)cyclohexyl]piperidine) on the histological consequences of focal, as opposed to global, cerebral ischemia in both the rat and the cat. Ifenprodil (0.3-3 mg/kg i.v.) administered as a perfusion over 3 hr after occlusion of the feline middle cerebral artery reduced the volume of infarcted tissue (measured 4 days after occlusion) in a dose-related manner. At the highest dose a 42% reduction of infarcted volume was noted, essentially in cortical tissue. In an identical protocol, a derivative of ifenprodil, SL 82.0715, reduced the volume of infarction in a manner comparable to that described for ifenprodil. As SL 82.0715 possesses better p.o. bioavailability, this compound was also evaluated in the rat, again after middle cerebral artery occlusion. First administered 30 min after the induction of ischemia, SL 82.0715 (1 and 10 mg/kg p.o.) reduced infarction volume by 34 and 48%, respectively. The quantitative histology was performed 2 days after middle cerebral artery occlusion. The noncompetitive receptor antagonist, 1-[1-(2-thienyl)cyclohexyl]piperidine, administered (1 mg/kg i.p.) before the induction of focal ischemia, similarly and significantly decreased the final volume of infarction. As both ifenprodil and SL 82.0715 are noncompetitive antagonists of the NMDA receptor, two conclusions may be drawn from the present investigation. First, NMDA antagonism by ifenprodil and its derivative is an effective approach for tissue sparing in animal models of stroke and brain infarction. Second, these pharmacological observations provide evidence for the involvement of excitatory amino-acid induced-neurotoxicity in the evolution and consequences of focal cerebral ischemia.
Animals↗
Ifenprodil and SL 82.0715 as cerebral anti-ischemic agents. II. Evidence for N-methyl-D-aspartate receptor antagonist properties.
The effects of the anti-ischemic agents ifenprodil and its derivative SL 82.0715 ((+/-)-alpha-(4-chlorophenyl)-4-[(4-fluorophenyl) methyl]-1-piperidineethanol] have been analyzed in a number of models indicative of N-methyl-D-aspartate (NMDA) antagonistic potential in vitro and in vivo. Ifenprodil and SL 82.0715 potently and noncompetitively antagonize the stimulatory effects of NMDA on cyclic GMP production in immature rat cerebellar slices (IC50 values, 0.4 and 10 microM, respectively), as well as the NMDA-evoked [3H]acetylcholine release in adult rat striatal slices (IC50 values, 1.6 and 6.6 microM, respectively). Ifenprodil is 10 times more potent than (+/-)3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) but less active than the reference noncompetitive NMDA channel blockers [MK 801, ((+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclohepten-5,10-imine ], phencyclidine and 1-[1-(2-thienyl)cyclohexyl]piperidine (TCP)] in these models. Ifenprodil and SL 82.0715 partially displace (maximal displacement 40-50% at 10 microM) the NMDA receptor ligand [3H]CPP from its binding site to rat brain membranes (IC50 values, 0.1 and 0.3 microM, respectively) in a noncompetitive manner; in the micromolar range the two agents also partially displace the NMDA channel ligand [3H]TCP from its binding site to rat brain membranes, and noncompetitively antagonize the L-glutamate-induced increase in [3H]TCP binding. Ifenprodil (0.01-1 microM) partially antagonizes the depolarizing effects of NMDA on the immature rat hemisected spinal cord in vitro. In mouse cultured spinal cord neurons, ifenprodil dose-dependently antagonizes the depolarizing effects of micropressure applied NMDA. Inhibition of the effects of NMDA in this model by ifenprodil and SL 82.0715 is noncompetitive. In vivo and after systemic i.p. administration, ifenprodil and SL 82.0715 antagonize the stimulatory effects of intrastriatally dialyzed NMDA on striatal dopamine release in rats (ID50 values, 0.9 and 0.3 mg/kg, respectively), and block the harmaline-evoked increase in cerebellar cyclic GMP production in mice (ID50 values, 3 and 4 mg/kg, respectively). These results indicate that ifenprodil is a noncompetitive NMDA antagonist which has a mechanism of action distinct from either the reference competitive NMDA receptor antagonists (CPP and 2-amino-5-phosphonovalerate) or the noncompetitive NMDA channel blockers (phencyclidine, TCP and MK 801). The potent NMDA antagonistic effects of the ifenprodil class of compounds are likely to be related to the demonstrated anti-ischemic potential of these compounds.
Animals↗
Autoimmune haemolytic anaemia complicating ulcerative colitis.
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Adrenal Cortex Hormones↗
The need for victimization screening in a poor outpatient medical population.
Recent reports indicate that violence toward others is a major public health problem in the black community; however, there are few empirical studies that delineate the severity of the problem. The authors have compiled the results of a victimization screening form obtained from a poor outpatient medical population. These results are compared with a similar survey performed on a poor outpatient psychiatric population. Recommendations are made that poor medical populations should be screened for histories of victimization, because early identification of patients at risk may reduce their chances of future victimization.
Adolescent↗