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J M Adams

Publications and source records attributed to J M Adams.

At least 217 records · Page 12Linked to original sources

Transcripts of the immunoglobulin C mu gene vary in structure and splicing during lymphoid development.

Two classes of transcripts of the mouse immunoglobulin mu constant region (C mu) gene can be distinguished. Whereas B cells contain mu mRNAs of 2.4 and 2.7 kilobases (kb), many T lymphoma, Abelson pre-B lymphoma, and myeloid tumor cell lines contain polyadenylylated RNA species bearing C mu sequences (C mu RNAs) of 1.9, 2.1, 2.3, and 3.0 kb. Production of C mu RNAs, unlike mu mRNAs, does not require recombination with the joining region (JH) locus. To define the structure of C mu RNAs, RNA from representative cell lines was fractionated by gel electrophoresis, transferred to diazobenzyloxymethyl paper, and tested for hybridization with 23 DNA fragments that collectively span a chromosomal mu gene, cloned from a plasmacytoma. All the C mu RNAs bear sequences derived from each of the four C mu domains, but none contain the intervening sequences separating domains; thus each represents a spliced RNA species. The 1.9-kb C mu RNA contains the 3' sequence characteristic of secreted mu chain, whereas the longer species bear that of membrane-bound mu chin. Hence C mu RNAs and mu mRNAs are equivalent throughout the C mu and 3' terminal regions. They differ markedly, however, in their 5' regions, because the 3.0-and 2.3-kb C mu RNAs bear sequences from within the conventional JH-C mu intervening sequence. Because these sequences are several kb from C mu, this region must contain at least one hitherto unsuspected splice site. C mu RNAs may not express immunological diversity, because no evidence was found that they bear variable regions. T and pre-B lymphoid and myeloid cells contain equivalent C mu RNA species, which coexist with mu mRNAs in some pre-B and B lymphoid lines. C mu RNA expression appears to reflect an activated state of the C mu gene common to cells at early stages of T, B, and myeloid development.

Animals↗

Expression of the immunoglobulin C mu gene in mouse T and B lymphoid and myeloid cell lines.

We have used cloned nucleotide sequences as probes to search for immunoglobulin RNA in T and B lymphoid and nonlymphoid tumor cell lines. Polyadenylated RNA from the cells was fractionated electrophoretically by size and fixed to diazobenzyloxymethyl-paper, and then immunoglobulin RNA species were revealed by hybridization with 32P-labeled cloned sequences for mu heavy chain and kappa light chain. kappa mRNA was detected only in B lymphoid lines known to synthesize kappa chains. No mu RNA was detectable in erythroleukemia, mastocytoma, or sarcoma cells. RNA bearing mu constant region (C mu) sequences, however, was detected in four of nine T lymphoma and four of five myeloid tumor cell lines tested, as well as in B lymphoma and "pre-B" Abelson lymphoma cells. In contrast to the single mu RNA species of 2.6 kilobases (kb) in a plasmacytoma, individual T lymphoma and myeloid lines yielded up to three discrete mu RNA species of apparent size 1.9, 2.2, and 3.0 kb, each different from the two mu RNA species in a B lymphoma line (2.4 and 2.7 kb) or the single species in "pre-B" lymphoma cells (2.9 kb). Both chromosomal complements of the C mu gene in STRij-4 T cells were found to be rearranged from their embryonic (germ line) context. The results suggest that the C mu gene functions not only in T cells, wherein the ability to recognize antigen is long established, but also in myeloid cells.

Animals↗

Somatic rearrangements forming active immunoglobulin mu genes in B and T lymphoid cell lines.

We have cloned an active gene for an immunoglobulin mu heavy (H) chain, bearing the variable (VH), joining (JH), and constant (C mu) sequences expressed in the IgM-secreting mouse plasmacytoma HPC-76. The mu gene was formed by somatic recombination between a VH gene and one of several JH genes, which are located about 7.7 kilobase pairs from the C mu gene in embryo DNA. The JH-C mu intervening sequence has suffered a deletion of about 2.7 kilobase pairs in HPC-76. Because the delection encompasses sequences required to switch an expressed VH-JH gene from C mu to another CH gene, it may represent a mechanism for "freezing" a lymphocyte clone at the stage of IgM expression. For the second (inactive) C mu allele in HPC-76, the entire joining and switch regions have been deleted; functional inactivation of one allele may thus represent one mechanism by which a lymphocyte clone restricts expression to a single allele (allelic exclusion). Probes generated from the cloned mu gene allowed examination of the JH locus in B, Abelson "pre-B," and T lymphoma cell lines and a myeloid line, all of which cotain RNA species bearing C mu sequences. The B and pre-B lines exhibited recombination within both alleles of the JH locus, suggesting that both alleles may be expressed in some cells. The absence of the JH gene 5' to the recombination sites favors a deletion mechanism for VH-JH joining. Recombination within the JH locus was also detected in two out of four T lymphoma lines, but not in the myeloid line. This indicates that the mechanism by which B cells generate immunoglobulin diversity is operational in some T cells. Lines that synthesize mu RNA without JH rearrangement may have activated the C mu gene directly or have undergone recombination at a more distant locus.

Animals↗

Use of indomethacin and its relationship to retinopathy of prematurity in very low birthweight infants.

The relationship between the use of indomethacin, a prostaglandin inhibitor, for closure of patent ductus arteriosus (PDA) and the occurrence of retinopathy of prematurity was investigated retrospectively. 63 preterm infants less than or equal to 1500 g who were less than or equal to 32 weeks' gestational age, appropriate weight for gestational age, with a diagnosis of PDA, and admitted during the first 24 hours of life were studied. Diagnosis of retinopathy was made by retinal examination when each infant was about 4 weeks. Diagnosis of PDA was made by clinical, radiological, and echocardiographic findings. 15 patients were treated with indomethacin because of severe congestive heart failure. There were no differences between gestational ages, birthweights, duration of oxygen therapy, or incidence of retinopathy in treated and untreated patients. We suggest that the use of indomethacin for PDA closure does not increase the incidence of retinopathy in very low birthweight infants.

Ductus Arteriosus, Patent↗

Hyaline membrane disease and intraventricular haemorrhage in small for gestational age infants.

19 small for gestational age (SGA) infants with gestational ages less than or equal to 32 weeks were matched with 19 appropriate for gestational age (AGA) preterm neonates with similar risk factors for intraventricular haemorrhage and hyaline membrane disease. Gestational age, 1- and 5-minute Apgar scores, type of delivery, survival rate, use of corticosteroids before delivery, sex, twinning, presence of premature rupture of membranes, and birth date were comparable in the two groups. Gestational age of both groups was 30 (+/- 1.8) weeks, and birthweights were 919 (+/- 202) g (SGA group) and 1268 (+/- 212) g (AGA group). The incidences of hyaline membrane disease and intraventricular haemorrhage were different: 74 and 42% respectively for AGA neonates, 5 and 11% respectively for SGA infants. We suggest that a stressful environment in utero may enhance maturation and prevent hyaline membrane disease and intraventricular haemorrhage.

Cerebral Hemorrhage↗

Bacterial colonization of radial artery catheters.

In 147 radial artery catheterizations performed, blanching or embolization was noted in 10.8% of the patients. Only a single episode of catheter-related septicemia was observed (0.6%) Mean duration of catheterization was 48 +/- 6 hours. Of 110 catheters cultured 25.4% grew bacteria; most organisms cultured were nonpathogenic. Duration of catheterization and intravascular infusion did not alter the incidence of catheter colonization.

Arteries↗

Hypochloremic metabolic alkalosis following tolazoline-induced gastric hypersecretion.

Gastric hypersecretion following administration of tolazoline resulted in severe hypochloremic alkalosis in an infant with persistent fetal circulation. An initial bolus injection of 2 mg/kg was followed by an infusion of 5 mg/kg/hr for 24 hours. The infusion was then maintained at 2 mg/kg/hr for the next four days. Volume of gastric secretions exceeded 25 ml/kg/24 hr. Weaning from tolazoline and replacement of chloride and potassium corrected the metabolic alkalosis.

Alkalosis↗

Cloned pairs of variable region genes for immunoglobulin heavy chains isolated from a clone library of the entire mouse genome.

To investigate the organization of immunoglobulin genes, we have constructed a clone library containing 10(6) randomly generated fragments of mouse embryo DNA, corresponding to eight equivalents of the genome. The cloning method involved methylation of embryo DNA at EcoRI recognition sites, partial digestion by EcoRI* endonclease activity, and direct ligation of the resulting large fragments to the lambda phage vector Charon 4A. The library was searched for sequences homologous to a cloned complementary DNA copy of a mu heavy chain mRNA. Nine clones bearing variable heavy chain (VH) sequences were isolated, representing at least eight distinct VH genes. Thus, multiple related VH genes are available in the genome to contribute to immunoglobulin diversity. Each of the two clones carries a pair of VH genes, one pair separated by 15 +/- 1 kilobase pairs of mouse DNA and the other by 14 +/- 2 kilobase pairs. This indicates that related VH genes are clustered and may occur in a tandem array having a repeating unit of 14--16 kilobase pairs. The large spacer sequences between VH genes cannot, however, be highly conserved.

Animals↗

Modern management of tetanus neonatorum.

Five infants with neonatal tetanus were managed with neuromuscular blockade and positive pressure ventilation. All survived. Tetanus was frequently confused with neonatal seizures at time of presentation. All infants were delivered at home. Mean age of onset of symptoms of poor suck, hypertonicity, and generalized spasms was 5.4 days with hospital admission at 6.4 days. Mean duration of mechanical ventilation was 34 days. Although hospital management of tetanus neonatorum may be expected to have a satisfactory outcome, it represents a costly and complex approach to a preventable disease.

Female↗

Medullary and carotid chemoreceptor interaction for mild stimuli.

The interaction of medullary and carotid chemoreceptors during mild stimulation was investigated in 44 experiments on 6 chloralose-urethane anesthetized mongrel dogs using a donor-perfused, bilateral carotid sinus preparation. The donor dog breathed hypoxic mixtures (average PaO2 of 78 mm Hg) and the experimental animal breathed hypercapnic mixtures (average PACO2 of 49 mm Hg) in order to separately or simultaneously stimulate both chemoreceptor areas at low levels. After 4 min, the changes of tidal volume (VT), respiratory rate (f) and minute ventilation (VI), as a percentage of the control value, were compared to test whether the sums of the changes for separate stimuli were the same as for simultaneous stimuli, i.e. additive chemoreceptor effects. The simultaneous stimuli had significantly (P less than 0.05) greater responses for VT (19% greater than 5%) and VI (42% greater than 13%), but not for f (23% = 9%). Stepwise multiple regression studies of the response/control ratios on the blood gas values showed that multiplicative interaction terms accounted for more of the variance than additive terms for VT, f and VI and yielded equations which had overall significant slopes. We conclude that this evidence demonstrates that the two chemoreceptor effects combine synergistically at low levels of stimulation.

Animals↗

Cluster analysis of respiratory time series.

We have investigated the respiratory control system with the hypothesis that, although many variables such as minute ventilation (VI), tidal volume (VT), breathing period (TT), inspiratory duration (TI), and expiratory duration (TE) may be observed, the controller functions more simply by manipulating only 2 or 3 of these. Thus, if tidal volume is the only independent variable, TI being determined by the "off-switch" threshold, these variables should have very similar time courses. Anesthetized dogs were subjected to CO2 breathing and carotid sinus perfusion to stimulate both chemoreceptors. The time series of the variables VI, VT, TT, TE, and TI as well as PACO2 were determined on a breath by breath basis. Derived characteristics of these time series were compared using Cluster Analysis and the latent dimensionality of respiratory control determined by Factor Analysis. The characteristics of the time series clustered into 4 groups: magnitude (of the response), speed, variability and relative change. One respiratory factor accounted for 86% of the variance for the variability characteristics, 2 factors for magnitude (91%) and relative change (85%) and 3 factors for speed (89%). The respiratory variables were analysed for each of the 4 groups of characteristics with the following results: VT and TI clustered together only for the magnitude and relative change characteristics where as TT and TE clustered closely for all four characteristics. One latent factor was associated with the [TT-TE] group and the other usually with PACO2.

Animals↗