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Biomedical subjects

J Berry

Publications and source records attributed to J Berry.

At least 91 records · Page 5Linked to original sources

Effects of O(2) and CO(2) Concentration on the Steady-State Fluorescence Yield of Single Guard Cell Pairs in Intact Leaf Discs of Tradescantia albiflora: Evidence for Rubisco-Mediated CO(2) Fixation and Photorespiration in Guard Cells.

A procedure for following changes in the steady-state yield of chlorophyll a fluorescence (F(s)) from single guard cell pairs in variegated leaves of Tradescantia albiflora is described. As an indicator of photosynthetic electron transport, F(s) is a very sensitive indirect measure of the balance of adenosine 5'-triphosphate (ATP) and reduced nicotinamide adenine dinucleotide phosphate (NADPH), producing reactions with the sink reactions that utilize those light-generated products. We found that F(s) under constant light is sensitive to manipulation of ambient CO(2) concentrations, as would be expected if either phosphoenolpyruvate carboxylase or ribulose-1, 5 bisphosphate carboxylase/oxygenase (Rubisco)-dependent CO(2) fixation is the sink for photosynthetic ATP and NADPH in guard cells. However, we also found that changing O(2) concentration had a strong effect on fluorescence yield, and that O(2) sensitivity was only evident when the concentration of CO(2) was low. This finding provides evidence that both O(2) and CO(2) can serve as sinks for ATP and NADPH produced by photosynthetic electron transport in guard cell chloroplasts. Identical responses were observed with mesophyll cell chloroplasts in intact leaves. This finding is difficult to reconcile with the view that guard cell chloroplasts have fundamentally different pathways of photosynthetic metabolism from other chloroplasts in C(3) plants. Indeed, Rubisco has been detected at low levels in guard cell chloroplasts, and our studies indicate that it is active in the pathways for photosynthetic carbon reduction and photorespiration in guard cells.

Journal Article↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Salvage of relapsed malignant histiocytosis by autologous bone marrow transplant.

A 21-year-old female presenting with malignant histiocytosis was initially treated with conventional aggressive chemotherapy resulting in complete remission (CR) but relapsed within 6 months of discontinuation. The patient was reinduced with two cycles of cis-platinum, cytosine arabinoside and mitoxantrone and achieved CR, at which time she received single agent high-dose melphalan followed by autologous bone marrow transplant. She remains in CR 36 months after the autograft procedure.

Abdominal Neoplasms↗

Treatment of advanced Hodgkin's disease with high dose melphalan and autologous bone marrow transplantation.

Twenty patients with Hodgkin's disease which had relapsed at least once after chemotherapy, were treated with melphalan 140-220 mg/m2 i.v. followed by reinfusion of non-cryopreserved autologous bone marrow. Four patients (20%) remain alive and disease-free 28, 45, 52, and 96 months after treatment respectively. There were no treatment-related deaths. This appears to be the only reported series of patients treated with a single agent in this situation. The results are comparable to those achieved by multi-agent regimens with autologous or allogeneic bone marrow transplantation.

Adult↗

Genetics of the phosphocholine-specific antibody response to Streptococcus pneumoniae. Germ-line but not mutated T15 antibodies are dominantly selected.

The role that somatic mutations play in the phosphocholine-specific, antibody response to Streptococcus pneumoniae was examined by studying sets of hybridomas from different individual mice. As expected most of the cell lines were from the T15 anti-phosphocholine family and were not encoded by the v1 gene of the T15 VH family and V kappa 22. A minority of antibodies were from the M603 (v1/V kappa 8) and M511 (v1/V kappa 24) families. Three additional antibodies were encoded by the v11 gene of the T15 family; two were paired with a V lambda and the other with a V kappa 1 gene. In vitro binding studies showed that T15- and M603-like antibodies had the highest affinity for S. pneumoniae. Complete sequencing of the VH and VL mRNA from 25 of the hybridomas revealed somatic mutations in 11 of the antibodies. A total of 17 independently derived T15 positive cell lines were studied in detail, six of these were mutated. These mutations were scattered throughout the V regions and the replacement to silent ratio was typical of that for framework regions. Statistical evaluation of the placement of mutations showed that there was a slight but significantly decreased frequency of mutations in complementarity determining regions. Comparisons of mutated and unmutated T15-related antibodies showed that mutations caused a decrease in binding to S. pneumoniae in every case. These results argue that the optimal specificity for this molecular form of phosphocholine is encoded in the germline and that Ag-driven events favor selection of B cells expressing these germ-line encoded antibodies.

Amino Acid Sequence↗