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Biomedical subjects

J Berry

Publications and source records attributed to J Berry.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Determination of extent and location of coronary artery disease in patients without prior myocardial infarction by thallium-201 tomography with pharmacologic stress.

Seventy-six patients undergoing pharmacologic stress 201TI tomography and coronary angiography within 14 +/- 12 days were studied to determine how well coronary artery disease extent and location could be determined by this scintigraphic technique. No patient had prior myocardial infarction or revascularization. Scintigrams were scored visually and quantitatively. Angiographic lesions > or = 50% were considered significant. Receiver operating characteristic curves were generated for the scintigrams against the angiographic gold standard. Predictive accuracies were determined and compared with the quantitative results. Predictive accuracy was 0.49 for visual and 0.58 for computer identification of single-vessel disease, 0.52 for both visual and computer identification of multivessel disease, 0.64 for both in correctly localizing left anterior descending artery disease, 0.78 versus 0.70 for the right coronary artery and 0.72 versus 0.68 for the left circumflex artery. For the overall detection of disease, the predictive accuracies were 0.79 and 0.80. Although high diagnostic accuracy for detection of coronary artery disease by this approach has been previously documented, the assessment of extent of disease in patients without prior myocardial infarction appears limited.

Adenosine↗
PubMed1992

Systemic hypothermia in treatment of brain injury.

An extensive literature suggests that there are minimal complications of systemic hypothermia in humans at and above 30 degrees C for periods of several days. Intracranial hemorrhage has been found to complicate profound hypothermia (10-15 degrees C), and ventricular arrhythmias occur at temperatures below 30 degrees C. Our initial clinical studies were with 21 patients undergoing elective craniotomy cooled to 30-32 degrees C for 1-8 h (mean 4 h). Hypothermia was induced by surface cooling with water blankets. No complications were found. Among 11 patients with severe brain injury, cooling to levels below 32 degrees C was associated with ventricular arrhythmias in 1 patient and atrioventricular block in 1 patient. Asymptomatic hypokalemia was found routinely and treated with potassium replacement. No intracranial hemorrhage or other complications were found. With surface cooling, intravascular temperature dropped at 1.6 degrees C/h. Based on the safety of surface cooling to a core temperature of 32 degrees C for 48 h, we are conducting a randomized study of this level of hypothermia in patients with severe brain injury, cooled within 6 h of injury.

Body Temperature↗
PubMed1991

Position of the rearranged V kappa and its 5' flanking sequences determines the location of somatic mutations in the J kappa locus.

Somatic hypermutation is known to occur in the VJ kappa exon and its flanking sequences, yet little is known about the hypermutation mechanism or its exact target within the rearranged locus. Mutations may occur at the same frequency, spanning a region from the leader intron to 3' of J kappa 5, regardless of which J is chosen for VJ rearrangement. Another possibility is that mutations may be limited to the rearranged VJ kappa and its immediate flanking sequences. To distinguish between these possibilities, the JC introns of 21 alleles with V kappa rearranged to J kappa 1 were sequenced, and mutations were located. The frequency of mutations was determined for different sections of the intron and compared with the frequencies of mutations found in the JC intron of a set of VJ kappa 5 alleles. The results showed that mutations were concentrated in and around the rearranged VJ, regardless of whether J kappa 1 or J kappa 5 was used. These data imply that the hypermutational mechanism focuses on rearranged V genes.

Base Sequence↗
PubMed1991

Somatic hypermutation of the JC intron is markedly reduced in unrearranged kappa and H alleles and is unevenly distributed in rearranged alleles.

Somatic hypermutation of the Ig genes occurs in rearranged V(D)J and its flanking sequences after Ag stimulation. Even though C regions and unrearranged V segments have been found to lack mutations, it is not known whether the mutational mechanism can be active in unrearranged J segments and their flanking regions. By polymerase chain reaction and direct sequencing of the 500 bp at the 5' end of the JC intron of hybridoma DNA derived from splenic B cells, we show that the frequency of mutations in unrearranged J regions of kappa and H chain genes is 0/7849 bp (upper 95% confidence interval, less than 0.00038) and 1/3209 bp (upper 95% confidence interval, less than 0.0015), respectively. The frequency (f) for the same region of rearranged kappa and H chain genes was 29/9380 bp (95% confidence, 0.0021 less than f less than 0.0044) and 16/2750 bp (95% confidence, 0.0033 less than f less than 0.0094), respectively. The significantly higher frequency of mutations in the rearranged alleles indicates that rearrangement is needed to effect full activation of the mutational mechanism. The data also show that mutations occur predominantly in the 5'-most 250 bp of the JC kappa intron. Statistical analysis of the distribution of mutations within the 5'-most 521 bp of the JC kappa intron reveals significant deviation (p = 0.000085) from a theoretically determined uniform distribution, indicating that mutations are not evenly distributed within this region.

Alleles↗
PubMed1991

Outcome in stage III non-Hodgkin's lymphoma in children (UKCCSG study NHL 86)--how much treatment is needed? United Kingdom Children's Cancer Study Group.

Forty-four children aged 3-13 years with Murphy stage III B cell non-Hodgkin's lymphoma were treated between May 1986 and December 1989. All have been followed up for at least 12 months. The primary site was the abdomen in 37 children, 24 of whom had involvement of other organs or nodal disease outside the abdomen. Twenty-eight received a standard dose regimen (regimen 1) and 16 had a more intensive regimen (regimen 2--MACHO). Fourteen patients (87%) who received MACHO had extensive multi-organ disease compared to 15 (53%) on regimen 1. Most of the latter had only pleural effusions. Thirty-four children are alive relapse free and considering the early relapse pattern in this disease are probably cured (actuarial event free survival = 76%). There has been one relapse (6%) after MACHO, but three toxic deaths. Six patients (21%) on the less intensive regimen have relapsed. Morbidity was high in terms of infection and need for haematological support and hospitalisation in the one third of children electively given the more intensive regimen. It is concluded that the vast majority of children with stage III disease who have disease limited to lymph nodes are curable with a moderately intensive regimen. Those with multiorgan involvement probably require more intensive treatment. It is therefore of importance to clarify prognostic factors in these patients to determine who can be cured with a less intensive regimen and who requires further dose intensification.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Patterns of mutations and selection in antibodies to the phosphocholine-specific determinant in Proteus morganii.

The contribution of somatic mutation to the generation of an antibody response was investigated by using the phosphocholine (PC) determinant in the bacterium Proteus morganii as the model Ag. The response to this determinant is restricted to a single VH/VL pair and apparently is derived from only one or two precursors per mouse. In this study we examined hybridoma antibodies from nine individual mice which produced representatives of 12 different clones. We found that all antibodies reactive with the PC Ag of P. morganii contained somatic mutations; the number ranged from 2 to 20. Two clusters of mutations were observed, one in complementarity-determining residue (CDR) 2 and the other in CDR 3 of VH. Examination of a three-dimensional model of M603, an antibody with the same V region composition as the anti-PC antibodies under study, showed that these clusters occupied an area of the binding site which presumably interacts with carrier elements of the PC epitope in P. morganii. A high incidence of recurring mutations were found in both clusters, and one of these was invariant, leading to an Asn for Asp substitution at 95. Ag binding studies with these antibodies and an additional one, which was unmutated except for the invariant substitution at 95, showed that: 1) antibodies having only the 95Asn mutation failed to bind the PC Ag of P. morganii, 2) addition of a second recurring mutation, at 52a (CDR 2), was sufficient to create strong binding to the P. morganii Ag, and 3) accumulation of mutations was directly correlated with increased binding activity for Ag. These results show that somatic mutations play a critical, if not essential, role in generating specificity for this PC Ag, and that Ag, and most likely a carrier element of the epitope, is a primary force in the continued selection and expansion of Ag-reactive B cells.

Amino Acid Sequence↗
PubMed1989

Classification of perinatal death.

Three paediatric pathologists, one perinatal paediatrician, one obstetrician, and one epidemiologist separately used information collected on 239 babies in an attempt to validate the Wigglesworth classification of perinatal deaths. This was first done using clinical data only, then using the combination of clinical and gross necropsy findings and finally using clinical, gross necropsy, histological and any other information (for example, chromosome analyses, microbiological investigations). Only 14 (6%) of deaths changed groups within the Wigglesworth classification when gross necropsy findings were considered as well as clinical findings, and altogether only 21 (9%) changed classification when complete investigations were available. There was an unacceptable amount (15%) of disagreement between the classifiers, largely the result of failure to comply with the rules laid down for classification. We set out amendments to Wigglesworth's original definitions to clarify certain ambiguities.

Autopsy↗