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Biomedical subjects

D J Brown

Publications and source records attributed to D J Brown.

At least 163 records · Page 9Linked to original sources

The psychosocial approach to rehabilitation of the spinal cord injured patient.

The development of a liaison psychiatry service to the Austin Hospital Spinal Injuries Unit highlighted the need for a psychosocial approach to patients rehabilitation. Increasingly we recognised that psychological factors influenced the course of the patient's acute illness and rehabilitation; this led to the formation of a psychosocial group under the leadership of the liaison psychiatrist. Membership of this group includes the liaison psychiatrist, psychiatry registrar, clinical psychologist, social workers, visiting nurse, chaplains and the rehabilitation registrar. The psychosocial approach advocates the consideration of psychosocial management in all aspects of patient care. In this paper we describe the structure and function of the psychosocial team in the management of patients in the Spinal Injuries Unit at the Austin Hospital.

Family↗

Redundancy of signal and anchor functions in the NH2-terminal uncharged region of influenza virus neuraminidase, a class II membrane glycoprotein.

Class II membrane glycoproteins share a common topology of the NH2 terminus inside and the COOH terminus outside the cell. Their transport to the cell surface is initiated by the function of a single hydrophobic domain near the NH2 terminus. This functional domain serves both as an uncleaved signal sequence and as a transmembrane anchor. We examined the signal and anchor functions of influenza virus neuraminidase, a prototype class II membrane glycoprotein, by deletion analysis of its long, uncharged amino-terminal region. The results presented here show that the entire stretch of 29 uncharged amino acids (7 to 35) is not required for either a signal sequence or an anchor sequence function. On the basis of translocation and membrane stability data for different mutants, we suggest that the first 20 amino acid residues (7 to 27) are likely to provide the hydrophobic core for these functions and that within this putative subdomain some sequences are more efficient than the other sequences in providing a translocation function. Finally, it appears that neuraminidase and its mutant proteins are translocated with the proper orientation, regardless of the characteristics of the flanking sequences.

Amino Acid Sequence↗

Effect of lactate on glucose incorporation into fetal lung phospholipids.

Fetal rabbit lung explants were incubated with 3.0 mM glucose and varying levels of lactate. An increase in lactate concentrations resulted in a decrease in glucose incorporation into total disaturated phosphatidylcholine. Glucose utilization for surfactant phosphatidylcholine synthesis was also reduced by approximately 35% in the presence of 5.0 mM lactate. The decreased incorporation of glucose occurred in the fatty acid portion of both total tissue disaturated phosphatidylcholine and surfactant phosphatidylcholine. The effect of lactate on glucose incorporation into pulmonary phospholipids was not affected by the presence of pyruvate in concentrations up to 500 microM. Pyruvate alone produced only a slight decrease in glucose utilization for lung phospholipid production. These data indicate that glucose and lactate are competitive substrates for late gestation surfactant phospholipid fatty acid synthesis, and that lactate is potentially a very important substrate for fetal lung development.

Age Factors↗

Evidence for lactate utilization for fetal lung glycogen synthesis.

Fetal rabbit lungs from 23 day gestation animals were used to investigate the potential role of lactate as a substrate for fetal lung glycogen synthesis. Fetal lactate dehydrogenase activity was approximately twice that found in the adult lung, while the activity of phosphoenolpyruvate carboxykinase was elevated fourfold over the adult value. Pyruvate carboxylase activities were similar in both fetal and adult lungs. Studies employing fetal lung explants in organ culture indicated that the presence of both glucose and lactate may be necessary for glycogen accumulation in the developing fetal lung. These data support the hypothesis that lactate is an important precursor for fetal lung glycogen.

Animals↗

Old and new techniques together resolve a problem of infection by Salmonella typhimurium.

Isolates of Salmonella typhimurium, recovered over a 9-month period from a child with gastroenteritis, were characterized by biotyping, phage-typing and plasmid-profile analysis. Because the data from the different methods were discrepant, it was difficult to establish whether her infection was due to a single strain that had changed character in vivo or was due to recurrent infections with different, unrelated strains. Restriction-enzyme fingerprinting of the plasmids from the different isolates provided an explanation for the initial discrepancy and high-lighted a source of potential confusion in epidemiological studies.

Bacteriophage Typing↗

Continuing care of the spinal cord injured.

The functions of a comprehensive Spinal Cord Unit do not cease with the discharge of the patient from in-patient treatment after rehabilitation; they extend to aftercare, both in medical follow-up and prevention and treatment of complications, and in ongoing support and education of the patient and his family. An effective aftercare service must offer a life-long commitment to patients, and the aftercare team must include members of the disciplines which were involved in the initial rehabilitation, and also often others. Although demanding of time, resources and money, good aftercare is cost-effective in terms of savings in the cost of out-patient treatment and of re-admissions to hospital for the treatment of complications, and in maintaining many patients in the community, often as contributing members of society.

Aftercare↗

Data collection on spinal cord injuries: urological outcome.

Analysis of 628 consecutive admissions to the Spinal Injuries Unit, Austin Hospital, between July 1978 and December, 1985 illustrates the value of a comprehensive data collection system which has been developed at the hospital since 1978. Some brief epidemiological data is presented, together with a detailed analysis of the urological outcome of patients with traumatic lesions whose discharge has been completed. A high rate of catheter-free status and urine sterility at discharge is reported, and factors affecting these results are analysed. The authors hope that an international system of data collection can be developed in the future to allow meaningful comparison of results between units.

Data Collection↗

The diagnosis and management of post traumatic syringomyelia.

We have reviewed 21 cases with the clinical diagnosis of Post Traumatic Syringomyelia (P.T.S.). Fifteen of these cases had proven syrinx formation on Contrast Computed Tomography (C.C.T.) and the other 6 had obviously abnormal cords. A much earlier onset of P.T.C.M. was found in complete spinal injuries than in incomplete ones. We have discussed the technique of contrast computed tomography used at this hospital, its value in the diagnosis of this condition and its ability to define actual spinal cord structure. Most cases (91%) benefitted from surgery and several had marked sensory improvement, which previously has been described as unusual. Syringo-cisternal shunting, a new technique for the drainage of cervical and upper thoracic syrinxes is described. A theory is proposed to explain why, in some patients with classical presentations of P.T.S., no syrinx was found on C.C.T., although abnormal cords were found in all cases. It is felt that these abnormal areas of spinal cord are responsible for the presenting symptomatology and may be precursors of syrinxes.

Adolescent↗

Fatty acids of rice coleoptiles in air and anoxia.

The metabolism of lipids, like that of other components, was adversely and strongly affected when rice (Oryza sativa L.) coleoptiles were grown anaerobically. In aerobic coleoptiles, the amounts of total fatty acid, phospholipid, and total lipid per coleoptile increased by 2.5- to 3-fold between days three and seven, whereas under anoxia, the increases were all less than 60%. The total amount of lipid at day seven in anoxia was less than 30% of that in air. In air, the total fatty acid content at day three was 25 nanomoles per coleoptile and this increased to over 71 nanomoles per coleoptile at day seven. All acids except 18:0 showed substantial increases. In anoxia, the corresponding values for total fatty acids were 24 nanomoles and 27 nanomoles. The small increases were confined to the saturated fatty acids; no significant increase occurred in unsaturated fatty acids. A minor fatty acid constituent (16:1) increased from 0.09 to 1.99 nanomoles per coleoptile between days three and seven in air. This component was never observed in any fatty acid preparation from anaerobic coleoptiles. The major phospholipids under all conditions were phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidic acid. A small amount of unidentified phosphoester, not present on thin layer chromatography plates from aerobic coleoptiles, was seen in extracts of anaerobic coleoptiles. The fatty acyl substituents of each of the phospholipids were analyzed at days three and seven in coleoptiles grown aerobically and in anoxia. Each phospholipid had its own distinctive fatty acid composition which remained fairly constant under all treatments; 16:0 and 18:2 were the most abundant fatty acids in every phospholipid class. In air, the percentages of total fatty acids that were in the phospholipids were 86% on day three and 87% on day seven. In anoxia, the values at the corresponding ages were 47 and 57%. Since no net synthesis of unsaturated fatty acids occurred in anaerobic conditions, the small increase in total unsaturated acids in the phospholipids between days three and seven must have occurred at the expense of fatty acids preexisting in the neutral lipid. No unusual pathways of biosynthesis or unusual precursors are required to explain the presence of unsaturated fatty acids in the rice coleoptile. The present study and results of experiments where coleoptiles were fed [(14)C]acetate (BB Vartapetian et al. 1978 Plant Sci Lett 13:321-328) clearly show that unsaturated fatty acid synthesis in rice coleoptiles requires O(2), as it does in other plants.

Journal Article↗

Biochemical maturation of fetal rat lung: a comprehensive study including surfactant determination.

The paper describes a comprehensive assessment of lung growth and biochemical maturation in the fetal and early postnatal rat. Fetal lung grew faster than whole body between gestational day 16.5 and term. Cell number increased quasi-exponentially, except for a slowing of cell growth between days 19.5 and 20.5 of gestation. By contrast, growth was limited during the two first postnatal days. Percentage of dry tissue and protein concentration increased in parallel during the whole period. Increases in whole lung tissue phosphatidylcholine were greatest between 20.5 and 21.5 days of gestation, whereas in isolated surfactant fraction, changes were most marked between 19.5 and 20.5 days. The most striking changes were a 19-fold increase in phosphatidylcholine and a 12.5-fold increase in the total phospholipid concentrations in the surfactant fraction between gestational day 19.5 and 1 day postpartum. Similar changes occurred in disaturated phosphatidylcholine (DSPC) concentration. During the same period, phospholipids of the residual (nonsurfactant) fraction increased only about 2-fold. These data indicate that analysis of an isolated surfactant fraction is advantageous in providing a very sensitive index of augmented phospholipid production during the process of fetal lung maturation. Evidence of biochemical maturation was detected earlier in females than in males, as indicated by a significantly larger surfactant fraction DSPC concentration in 19.5-day-old females; however, this difference was modest in degree and very transient, since it was no longer demonstrable in later stages.

Animals↗

Identification of the defects in the hemagglutinin gene of two temperature-sensitive mutants of A/WSN/33 influenza virus.

Two temperature-sensitive mutants of WSN influenza virus, ts-61S and ts-134, possess defects in the hemagglutinin (HA) gene. These defects are characterized as a defective intracellular transport of the HA at the nonpermissive temperature and a marked thermolability. The nucleic acid sequences of the HA gene of these two viruses, as well as a series of revertant viruses, were determined. The deduced amino acid sequences demonstrate that the HA of ts-61S varied from the wild type protein by three amino acids while that of ts-134 differed by two residues. For both mutants, analysis of revertant viruses indicated that the phenotype of transport inhibition at the nonpermissive temperature and heat lability were associated with a single amino acid change in the globular portion of the molecule. In the case of ts-61S, the critical change in the HA was the replacement of a serine residue at position 110 with that of a proline. The mutational defect in the HA of ts-134 was due to the substitution of a tyrosine residue at position 159 with that of a histidine residue. Four of five revertants of ts-134 were suppressor revertants, of which some of the compensatory changes did not restore thermostability to the HA.

Amino Acid Sequence↗

Influence of sexual preference and chronic hepatitis B virus infection on T lymphocyte subsets, natural killer activity, and suppressor cell activity.

To determine whether abnormalities of cell-mediated immunity are associated with chronic hepatitis B virus infection or with homosexuality, we studied 15 homo- and 11 heterosexual men with chronic hepatitis B virus infection, as well as 11 homo- and 16 heterosexual apparently healthy men. T lymphocyte subsets, natural killer activity, and suppressor cell activity were determined. Homosexual men had significantly lower peripheral blood T4/T8 ratios resulting from a significant increase in T8-positive (suppressor/cytotoxic) cells, and they also had lower natural killer activity. These effects of homosexuality were independent of chronic hepatitis B virus infection, which caused no significant changes independent of homosexuality, and they were not caused by infection with human immunodeficiency virus (formerly HTLV-III/LAV). Suppressor cell function was unaltered in this study. We conclude that studies of cellular immunity in hepatitis B virus infection must take male sexual preference into account.

Acquired Immunodeficiency Syndrome↗

Recognition of the cryptic plasmid, pSLT, by restriction fingerprinting and a study of its incidence in Scottish Salmonella isolates.

The plasmid pSLT is a cryptic plasmid of 60 megadaltons (Md) present in Salmonella typhimurium LT2. We present evidence that it has a characteristic fingerprint when digested with the restriction enzymes PstI and SmaI. Among a representative collection of S. typhimurium isolates it was present in 67% of strains and was widely distributed amongst different phage types (DT) with the exception of DT10 and U285. Furthermore, its prevalence among veterinary isolates was significantly higher than among human isolates. It was not found among any of the 96 strains representative of other salmonella serotypes currently prevalent and thus appears to be serotype-specific.

Chromosome Mapping↗

The distribution of plasmids among a representative collection of Scottish strains of Salmonellae.

The distribution of plasmids was studied in a representative collection of salmonella strains which comprised 98 Salmonella typhimurium and 96 other serotypes. Plasmids were detected in 72% of strains (mean 1.3 plasmids/strain) and individual strains harboured between 0 and 7 plasmids. They were more common among S. typhimurium than other serotypes (incidence 92 and 53%; mean 1.9 and 0.8 plasmids/strain respectively). Although a higher proportion of S. typhimurium (33%) were antibiotic-resistant compared to other serotypes (14%) the evidence presented indicated that R-plasmids were not responsible for the difference observed in the number and distribution of plasmids in these strains. These results were discussed in comparison with similar studies of Escherichia coli and other enteric genera.

DNA, Bacterial↗

Restriction enzyme fingerprinting of enterobacterial plasmids: a simple strategy with wide application.

Restriction enzyme fingerprints were generated from purified plasmid DNA from 324 clinical isolates that belonged to 7 enterobacterial genera and 88 single plasmids in Escherichia coli K 12 according to the following strategy. Purified plasmid DNA was digested with PstI. The number of fragments detected in a 0.8 agarose gel was used to determine which 2 of 6 restriction enzymes including PstI was most likely to provide a fingerprint comprising sufficient fragments to ensure specificity but sufficiently few to allow easy visual assessment and minimize coincidental matching. When PstI produced greater than 20 fragments, EcoRI and HindIII were used; when PstI generated less than 6 fragments Bsp 1286 and AvaII were used and SmaI was employed when between 6 and 20 fragments were obtained from PstI digests. Using a minimum of 12 fragments from a combination of 2 enzymes as the criterion for characterizing a strain/plasmid, satisfactory 2-enzyme fingerprints were obtained from 87% of the strains and plasmids studied using PstI and no more than two additional enzymes per strain. Of the remaining 54 strains, 51 harboured only small plasmids (less than 10 kb) and 3 produced satisfactory fingerprints when digested with a fourth enzyme.

Chromosome Mapping↗

Formation of influenza virus particles lacking hemagglutinin on the viral envelope.

We investigated the intracellular block in the transport of hemagglutinin (HA) and the role of HA in virus particle formation by using temperature-sensitive (ts) mutants (ts134 and ts61S) of influenza virus A/WSN/33. We found that at the nonpermissive temperature (39.5 degrees C), the exit of ts HA from the rough endoplasmic reticulum to the Golgi complex was blocked and that no additional block was apparent in either the exit from the Golgi complex or post-Golgi complex transport. When MDBK cells were infected with these mutant viruses, they produced noninfectious virus particles at 39.5 degrees C. The efficiency of particle formation at 39.5 degrees C was essentially the same for both wild-type (wt) and ts virus-infected cells. When compared with the wt virus produced at either 33 or 39.5 degrees C or the ts virus formed at 33 degrees C, these noninfectious virus particles were lighter in density and lacked spikes on the envelope. However, they contained the full complement of genomic RNA as well as all of the structural polypeptides of influenza virus with the exception of HA. In these spikeless particles, HA could not be detected at the limit of 0.2% of the HA present in wt virions. In contrast, neuraminidase appeared to be present in a twofold excess over the amount present in ts virus formed at 33 degrees C. These observations suggest that the presence of HA is not an obligatory requirement for the assembly and budding of influenza virus particles from infected cells. The implications of these results and the possible role of other viral proteins in influenza virus morphogenesis are discussed.

Biological Transport↗