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Biomedical subjects

J Berry

Publications and source records attributed to J Berry.

At least 73 records · Page 4Linked to original sources
PubMed1994

Mutations in Ig V(D)J genes are distributed asymmetrically and independently of the position of V(D)J.

To study the distribution of somatic mutations in the DNA flanking the 5' side of rearranged Ig V genes, the 5' region of 14 to 21 mutant forms of three different V(D)J were sequenced. These were compared with a fourth V(D)J for which the flanking sequences of 10 mutant forms are known. The leader intron of these four V genes varied from 82 to 365 nucleotides in length. Analysis of the data showed that: 1) The mutation frequency is distributed asymmetrically with respect to the V(D)J exon with skewing in the 3' direction. 2) The distribution of mutations 5' of V(D)J seems to be related to the size of the leader intron. The significance of these findings for models of hypermutation is discussed.

Animals↗
PubMed1994

Conformational mimicry of a chlamydial neutralization epitope on filamentous phage.

Conformational constraints were imposed on a peptide epitope from Chlamydia trachomatis to improve its ability to elicit antibodies that cross-react with native antigen. Appropriate constraints were discovered by a strategy that required no prior knowledge of the epitope's native conformation. First, we constructed a library of 3.2 x 10(5) peptides in which the epitope's contact residues were subject to random conformational constraints, each constrained peptide being fused genetically to the surface of a filamentous phage vector. Next, we selected phage displaying the most native-like peptides in the library by affinity purification with antibodies that bind the epitope only in its native conformation. Finally, we immunized mice with the selected phage and titered the resulting antisera against both whole cells and unconstrained peptide. The ratio of anti-cell titer to anti-peptide titer, which reflects the channeling of the antibody response to the native epitope, was up to five times higher for affinity-selected phage than for unselected peptide phage. In this case, therefore, "antigenic fitness," the ability of a peptide to bind antibodies specific for native epitope, correlated with "immunogenic fitness," its ability to elicit antibodies that are effective against the native antigen on an invading pathogen. If the correlation is general, surveying thousands or millions of peptides for antigenic fitness with phage display technology may be a simple but effective pre-screen for immunogenic fitness, which is costly to assess directly.

Amino Acid Sequence↗
PubMed1994

Local intramural drug delivery using an infusion balloon following angioplasty in normal and atherosclerotic vessels.

Local intramural delivery of various pharmacologic agents following angioplasty has been proposed as a means of reducing restenosis. This study tested whether local intramural delivery of aqueous solutions using an infusion balloon could be accomplished safely in normal vessels and whether such infusion was safe following standard angioplasty in diseased vessels. Infusion of aqueous agents into normal canine arteries had no adverse effect. Infusion of several aqueous agents (< or = 4 cc at 4 atm) into diseased swine iliac arteries following balloon angioplasty did not worsen existing or create new dissections. Histologically, infusion treated vessels did not differ in either model from vessels treated with angioplasty alone. We conclude that local intramural drug infusion does not create new, or worsen existing, dissections produced during standard balloon angioplasty in diseased vessels.

Angioplasty, Balloon, Coronary↗
PubMed1994

E-SHAP: an effective treatment in selected patients with relapsed non-Hodgkin's lymphoma.

BACKGROUND: The optimal treatment of relapsed or refractory non-Hodgkin's lymphoma is unknown. The reported encouraging results of a salvage regimen, E-SHAP (etoposide 40 mg/m2/day x 4, methyl prednisolone 500 mg daily x 4, cytosine arabinoside 2 gm/m2 one dose and cisplatinum 25 mg/m2/day x 4), at the M.D. Anderson Hospital in Texas, which resulted in a 65% response rate, could not be reproduced in the United Kingdom (0% response). PATIENTS AND METHODS: Twenty-six patients with relapsed (n = 16) or refractory (n = 10) non-Hodgkin's lymphoma were treated at our Centre by a modified E-SHAP regimen (cytosine arabinoside 1 gm/m2 one dose). The treatment was intended as remission induction before BMT (n = 16), as salvage by itself (n = 5) and for palliation of symptoms (n = 5). RESULTS: The overall response rate was 72% (CR = 7 and PR = 11). A comparison of Kaplan-Meier curves showed a statistically significant improvement in median relapse-free survival in patients who had previously achieved CR (p = 0.0012), no bulky disease (P = 0.0006) and no B-symptoms (P = 0.0004). The toxicity was acceptable: 8 instances of febrile neutropenia, 2 of reversible renal impairment and 2 symptomatic electrolyte abnormalities. No fatal toxicities were encountered. The median time to treatment failure was 191 days and median overall survival was 190 days. CONCLUSIONS: E-SHAP is an active combination chemotherapy when used as a salvage regimen or for remission induction before bone marrow transplantation in selected patients with relapsed non-Hodgkin's lymphoma. Patients who previously achieved CR, with low tumour burden and no B-symptoms are the best candidates for this treatment. It has a limited palliative effect.

Adolescent↗
PubMed1994

Antibody recognition of a neutralization epitope on the major outer membrane protein of Chlamydia trachomatis.

Two BALB/c mice were immunized with serovar C Chlamydia trachomatis elementary bodies, and 63 hybridomas producing monoclonal antibodies to C. trachomatis were recovered. Eight hybridomas which were specific for an identical peptide epitope (AGLQND) in serovar C major outer membrane protein variable domain I were identified. Detailed immunochemical study of the antigen-antibody interaction and genetic characterization of the antibody variable-region gene sequences showed that distinct B-cell clonal lineages were elicited by the epitope sequence. Since each antibody had a distinct pattern of fine specificity for recognition of the epitope and displayed different degrees of cross-reactivity with a related serovar (serovar A), we conclude that B-cell recognition of an immunodominant neutralization epitope can be pleiotropic. Differences in B-cell recognition of a neutralization epitope may delay the emergence by mutation of antigenic-drift variants of the C. trachomatis major outer membrane protein.

Amino Acid Sequence↗
PubMed1993

Influence of membrane Ig receptor density and affinity on B cell signaling by antigen. Implications for affinity maturation.

We have initiated a series of experiments to explore the effect of changes in density of the surface Ig receptor (mIg) on Ag:mIg interactions. We transfected into the surface Ig-negative B cell line M12.4 H and L chain constructs known to effect a 10-fold change in antibody binding affinity for the naturally occurring hapten phosphocholine (PC). Two sets of stable transfectants were generated and those expressing levels of mIg comparable to the range normally seen on splenic B cells were studied. One set expressed an unmutated VH and an unmutated VL. The second set expressed the same pair of V regions except for a single somatic change in CDR3 of VH; this substitution increases the affinity of antibody for PC from 3 x 10(4) M-1 to 3 x 10(5) M-1. Ag:mIg interactions were assessed in the transfected cell lines by measuring calcium mobilization induced by stimulation with soluble PC Ag. As expected, the mutation that increased affinity for PC increased the sensitivity of transfectants to PC Ag. Relatively small changes in receptor number had a dramatic effect in the quantity and quality of a calcium response. Significantly, we found that Ag-specific signaling could occur with only a few thousand receptors per cell. Signaling differences were most noticeable with PC protein Ag (T-dependent form) compared with PC polysaccharide Ag (T-independent form). These results suggest that the down-regulation of mIg that follows B cell activation may have evolved to assist in the selection of B cell clones with higher affinity for Ag. Furthermore, the results also provide an explanation for why selection of higher affinity clones can occur with protein Ag but only poorly so with polymeric Ag.

Animals↗
PubMed1993

Neuropsychological deficits in abstinent cocaine abusers: preliminary findings after two weeks of abstinence.

Sixteen subjects hospitalized for treatment of cocaine dependence were administered a battery of neuropsychological tests within 72 h of last cocaine use and again approximately 2 weeks later. Twenty-one non-cocaine using control subjects, matched for age, gender, ethnicity and education, also received neuropsychological testing. Abstinence from mood altering substances during the 2-week study period was verified for both groups on three occasions using quantitative urine analysis. The results suggest that recent cocaine use is associated with impairment in memory, visuospatial abilities, and concentration during the acute phase of withdrawal, independent of withdrawal-related depression. Furthermore, many of these deficits appear to persist at least 2 weeks beyond cessation of cocaine use.

Adult↗
PubMed1993

Hamartoma of the tongue.

A female infant nine months of age presented with a bilobed swelling at the base of her tongue. Histological examination showed it to be a hamartoma of the tongue. Lingual hamartomas are rare. There are fifteen case reports of lingual hamartoma in the world literature. Our case is presented and the previous case reports are reviewed.

Female↗
PubMed1993

A phase II study of moderate hypothermia in severe brain injury.

Forty-six patients with severe nonpenetrating brain injury [Glasgow Coma Scale (GCS) 4-7] were randomized to standard management at 37 degrees C (n = 22) and to standard management with systemic hypothermia to 32 to 33 degrees C (n = 24). The two groups were balanced in terms of age (Wilcoxon's rank sum test, p > 0.95), randomizing GCS (chi-square test, p = 0.54), and primary diagnosis. Cooling was begun within 6 h of injury by use of cooling blankets. Metocurine and morphine were given hourly during induction and maintenance of hypothermia. Rewarming was at a rate of 1 degree C per 4 h beginning 48 h after intravascular temperature had reached 33 degrees C. Muscle relaxants and sedation were continued until core temperature reached 35 degrees C. There were no cardiac or coagulopathy-related complications. Seizure incidence was lower in the hypothermia group (Fisher's exact text, p = 0.019). Sepsis was seen more commonly in the hypothermia group, but difference was not statistically significant (chi-square test). Mean Glasgow Outcome Scale (GOS) score at 3 months after injury showed an absolute increase of 16% (i.e., 36.4-52.2%) in the number of patients in the Good Recovery/Moderate Disability (GR/MD) category as compared with Severe Disability/Vegetative/Dead (SD/V/D) (chi-square test, p > 0.287). Based on evidence of improved neurologic outcome with minimal toxicity, we believe that phase III testing of moderate systemic hypothermia in patients with severe head injury is warranted.

Adolescent↗
PubMed1992

Antigen binding and idiotype analysis of antibodies obtained after electroporation of heavy and light chain genes encoding phosphocholine-specific antibodies: a model for T15-idiotype dominance.

Antibodies bearing the T15 idiotype dominate the murine primary immune response to phosphocholine (PC). Analysis of antigen binding of antibodies derived from V1:DFL16.1:JH1 (VH1) germline and N region-derived variant heavy (H) chains and kappa 22, kappa 24, and kappa 8 light (L) chains demonstrates that the T15H:kappa 22L (T15) antibody binds PC at least 20-40 times better than other antibodies derived from alternate germline forms of the VH1 H chain and kappa 22, kappa 24, or kappa 8 L chains. To achieve affinities in the same range as the T15 antibody, kappa 24 and kappa 8 L chain-containing antibodies must have H chains derived from variant N region or somatically mutated VH1 genes. Single amino acid differences at the VD junction of the various germline and N region variant VH1 H chains dictate the L chain that can associate with the H chain to produce a PC-specific antibody. Several H:L combinations give rise to T15 or M167 idiotype-positive antibodies that lack specificity for PC, and single amino acid substitutions or insertions at the VH1:D junction result in the loss of T15 or M167 idiotopes. Based on these observations, our data support a molecular model involving both preferential gene rearrangement and antigen-driven B cell selection to explain T15 idiotype dominance in the immune response to PC. In the absence of N region diversification, large numbers of neonatal B cells bearing the T15H:kappa 22L surface immunoglobulin M (sIgM) receptors would be selected and expanded by autologous or environmental PC antigen into the long-lived peripheral B cell pool.

Amino Acid Sequence↗
PubMed1992

Relative changes in salivary Na+ and K+ concentrations relating to stress induction.

Three independent studies are reported in which periods of "relaxation" (A) and presumed stressors (B) were given to female students in an ABA design. The "stressors" were: (1) obligatory time-wasting activity; (2) a mental "IQ" test; and (3) delivering a speech. Saliva was collected immediately after "relaxation" and "stress" periods. "Stress" and "arousal" state were retrospectively assessed in experiments (1) and (2) by subject self-rating and in experiment 1 also by trained observers for the periods A and B. The molar [K+/Na+] ratio was determined for each saliva sample. The prediction that [K+/Na+] would increase with stress induction was supported by statistically significant results with stressors 1 and 2 (p less than 0.01), but speech delivery (3) resulted in a significant rise of [K+/Na+] after the stressor period. Correlations between [K+/Na+] and "stress" and "arousal" ratings also substantiated the prediction.

Adolescent↗