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Biomedical subjects

D R Martin

Publications and source records attributed to D R Martin.

At least 91 records · Page 5Linked to original sources

Sodium handling by deep nephrons and the terminal collecting duct in glomerulonephritis.

The present study was designed to characterize the effects of anti-glomerular basement membrane (anti-GBM) glomerulonephritis (GN) on sodium handling by surface nephrons, deep nephrons and the terminal collecting duct segment. Studies were performed in rats during hydropenia and volume expansion. In hydropenia, the glomerular filtration rate (GFR) and sodium excretion tended to be lower in rats with GN than in controls. However, the major differences between the control and GN animals were seen in volume expansion. In the volume expanded groups fractional excretion of sodium was greater in controls (3.20 +/- 0.51%) than in GN (1.20 +/- 0.36%, P less than 0.01). Despite this, delivery to end proximal sites was similar in the two groups in absolute terms and higher in the expanded GN group compared to the expanded controls. Absolute sodium delivery to the bend of the loop of Henle in the expanded GN rats was decreased in absolute terms but increased in fractional terms compared to expanded controls. However, fractional delivery of sodium to the base of the terminal collecting duct was less in GN (3.71 +/- 1.39%) than in controls (7.19 +/- 0.96%, P less than 0.002). In both groups, fractional delivery between tip of the collecting duct fell compared to base (P less than 0.05) but delivery to the tip was again greater in controls (5.49 +/- 1.08%) than in GN (1.51 +/- 0.47%). In GN 62.6 +/- 5.0% of delivered sodium was reabsorbed between collecting duct sites, nearly twofold that of controls (28.8 +/- 9.4%, P less than 0.01). Thus, fractional sodium reabsorption in the collecting duct was enhanced by GN.

Animals↗

Age-related changes in binaural processing: I. Evoked potential findings.

Possible age-related effects of speech competition in one ear on the late auditory (LAEP) and P300 event-related potentials recorded at the other ear were investigated with female volunteers. In each of the age categories of 20 to 34, 35 to 49, 50 to 64, and 65 to 80 years, 10 subjects were tested. While contralateral speech competition produced no significant amplitude or latency changes in the earlier auditory brainstem or middle latency responses, several age- and competition-related effects were observed with the later-occurring LAEP and P300 responses. With contralateral competition, the two oldest groups exhibited significantly larger reductions in the N1-P2 peak-to-peak amplitude of the LAEP than did the two youngest groups. While significant decreases in P300 amplitude also occurred with the competition, the magnitude of this effect was not age-related. In addition, small but statistically significant increases in the latency of all three major components, N1 and P2 of the LAEP, and P300, occurred in the presence of contralateral competition. These effects also did not differ among the four age groups. Thus, the LAEP appears to be sensitive to some form of age-related change in binaural processing or attention, although the P300, while sensitive to contralateral competition, did not reflect an age-related component in this effect.

Adult↗

Age-related changes in binaural processing: II. Behavioral findings.

In the preceding report in this journal, the authors presented evidence for an electrophysiologic correlate of impaired binaural processing or attention in elderly listeners. In the present experiment, the subjects tested in the earlier study were administered a Dichotic Digits Recognition task in which they were required, in separate sessions, to repeat all digits heard in both ears (channel capacity measure), or to report the digits in one ear while ignoring the digits in the opposite ear (selective attention measure). With both measures, older subjects performed significantly poorer than did younger subjects. Although similar age-related decrements in performance were observed with the behavioral and electrophysiologic tests, no significant correlations were found in the performances on the two types of tests. This suggests that, while both behavioral and electrophysiologic tests can reveal age-related decrements in binaural processing, they do not necessarily reflect the same underlying neural processes.

Adult↗

Opacity factor from group A streptococci is an apoproteinase.

Opacity factor (OF) is an enzyme, elaborated by certain serotypes of group A streptococci, which produces opalescence in mammalian sera. OF has been designated a lipoproteinase. Lipoproteins are complex structures and many enzymes are involved in their catalysis. We therefore set out to establish which of the many enzymes OF could be. Results showed that OF rendered high density lipoprotein (HDL) insoluble, accounting for the opalescence in serum, and altered its electrophoretic mobility. Electron microscopy revealed that OF caused an aggregation of HDL and an alteration in molecule shape. OF specifically split apoprotein AI of HDL into two fragments demonstrable by SDS-PAGE. We therefore designate OF as an apoproteinase.

Apolipoprotein A-I↗

Characterisation of opacity factor from group-A streptococci.

Extracellular opacity factor (OF) from group-A Streptococcus M-type 22 was purified by ammonium sulphate precipitation followed by ion-exchange on DE-52 cellulose and gel filtration on sephacryl S-400. OF was eluted near the void volume and shown to be heterogenous by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Antiserum to ammonium sulphate-purified OF from a cell-free culture supernate was prepared in rabbits. All preparations of OF from supernate and cell-extract were inhibited by the antiserum. No M protein was detected in the OF samples from various purification steps. The purified OF showed activity at a broad pH range with optimal activity at pH 6; it was inactivated considerably at high temperatures. Enzyme activity was inhibited by pepstatin A, but was unaffected by serine proteinase inhibitor, aprotinin, ethylene diamine trichloroacetic acid, N-ethylmaleimide, iodoacetamide and mercaptoethanol. This suggests that OF is an aspartic proteinase.

Chromatography, Ion Exchange↗

Three peptides from the ANF prohormone NH(2)-terminus are natriuretic and/or kaliuretic.

The present investigation was designed to determine whether peptides derived from the NH(2)-terminal portion of the 126-amino acid prohormone (pro) of atrial natriuretic factor (ANF) have natriuretic and diuretic properties similar to ANF. Three peptides consisting of amino acids 1-30 [(proANF-(1-30)], 31-67 [proANF-(31-67)], and 79-98 (proANF-(79-98)] of the ANF prohormone were tested and compared with the COOH-terminus peptide (ANF) with respect to their ability to increase urine volume, urine sodium and potassium excretion, and glomerular filtration rate (GFR) in anesthetized Munich-Wistar rats. Each of these peptides except proANF-(79-98) caused a significant diuresis (P less than 0.05) when infused at their respective 100 ng.kg body wt-1.min-1 concentrations for 120 min. ProANFs-(1-30), (31-67), (79-98), and (99-126) (ANF) increased sodium excretion by 231, 973, 167, and 1,405%, respectively. The fractional excretion of sodium compared with control was significant at P less than 0.05, P less than 0.01, and P less than 0.05 for proANFs (1-30), (31-67), and (99-126), respectively. ProANF-(79-98) did not significantly increase the fractional excretion of sodium, but it was the only peptide from the NH(2)-terminus of the prohormone that significantly increased the fractional excretion of potassium's ProANF-(31-67) did not increase urinary potassium excretion. ProANF-(1-30), (79-98), and ANF significantly (P less than 0.05) increased urinary potassium excretion. None of these peptides significantly enhanced GFR. In conclusion, three peptides from the NH(2)-terminus of the ANF prohormone as well as ANF (the COOH-terminus) have either natriuretic, kaliuretic, and/or diuretic properties, but the respective ability of each of these peptides to produce these effects varies considerably.

Animals↗

In vivo administration of histoincompatible lymphocytes leads to rapid functional deletion of cytotoxic T lymphocyte precursors.

It is well established that a single intravenous injection of F1 lymphocytes can rapidly and specifically reduce the ability of a parental recipient to generate CTL against donor alloantigens in a subsequent MLR. By fluorescently labeling the injected cells, we have been able to identify, and if desired, remove them in cell suspensions prepared from recipient spleen and lymph node. The injected cells, whether F1 or syngeneic, appeared to form part of the normal recirculating pool. Removal of injected F1 cells from responder lymph node or spleen cell suspensions had no effect on the response reduction observed in the 5-d in vitro MLR (typically 80% reduction for responder cells taken 2 d after injection of F1 cells). When the frequency of CTL precursors (CTLp) was measured by limiting dilution, it was reduced to the same degree as the MLR response, implying that response reduction is due to a reduction in the number of activatable CTL in the responder cell suspension. An equal mixture of responder cells from treated (i.e., F1 injected) and control mice gave a measured CTLp frequency equivalent to the average of the separate frequencies, implying the absence of suppressor cells active in vitro. Labeled F1 cells recovered from a first recipient could be used to induce response reduction in a second recipient. The results are discussed in terms of APCs that functionally delete rather than stimulate CTLp that recognize them (i.e., a "veto mechanism"). These experiments appear to rule out a role for in vivo-induced suppressor cells up to 8 d after injection of semiallogeneic cells but do not address the question of whether they are induced at later times.

Animals↗

Methicillin-resistant Staphylococcus aureus: an increasing threat in New Zealand hospitals.

During the three years 1985 to 1987 an increasing number of methicillin-resistant Staphylococcus aureus (MRSA) strains were identified in New Zealand each year. A total of 66 strains of MRSA were identified among isolates received from 418 patients and health personnel. The majority (337/418, 80.6%) of the isolates were from two independent large outbreaks of MRSA. All strains of MRSA were sensitive to vancomycin, rifampicin and fusidic acid. An overseas origin, usually Australia, was identified for 48.4% of strains. The majority of isolates were from patients whose host defences had been breached. Postoperative and cutaneous wounds were the commonest sites of acquisition.

Anti-Bacterial Agents↗

Elevated mRNA levels of major histocompatibility complex class II genes in lymphocytes of autoimmune BB rats.

The BB rat spontaneously develops autoimmune abnormalities such as insulin-dependent diabetes mellitus and thyroiditis. The autoimmunity of the BB rat is controlled in part by genes of the major histocompatibility complex (MHC), known as the RT1 complex in the rat, and accumulating evidence suggests the involvement of MHC class II molecules. The RT1 complex specifies two types of class II molecules, which are encoded by the loci RT1.B and RT1.D. We have determined the relative steady-state mRNA levels of the class II genes RT1.B beta, RT1.D alpha, and RT1.D beta in splenic lymphocytes from individual autoimmune BB rats of various ages and from age-matched histocompatible normal Wistar-Furth (WF) rats. The relative steady-state mRNA levels of the RT1.D alpha and RT1.D beta genes, but not of the RT1.B beta gene, were elevated approximately 2.5-fold in lymphocytes of prediabetic BB rats 45-75 days old in comparison with age-matched normal WF rats and older BB rats greater than 75 days old. In the diabetic and nondiabetic BB rats greater than 75 days old, the RT1.D alpha and RT1.D beta transcripts were found at lower normal levels, similar to that of WF rats. In contrast, the RT1.B beta transcripts were found at comparable levels in lymphocytes of the BB and WF rats at all ages examined. The increased steady-state mRNA levels of the RT1.D alpha and RT1.D beta genes in the prediabetic BB rats may reflect differences in the proportion of lymphocytes expressing these genes and thus differences in splenic lymphocyte populations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The complete sequence of the MHC class II chain RT.1D alpha u of the diabetic BB rat: mRNA levels of RT1.D alpha in lymphocytes.

The major histocompatibility complex of the rat (RT1 complex) encodes two sets of class II molecules referred to as RT1.B and RT1.D. The complete structure of the RT1.D alpha u chain of the diabetes prone BB rat was determined by the isolation and characterization of a full size cDNA. Comparisons of the nucleotide and protein sequences of RT1.D alpha with the analogous molecules, H-2 I-E alpha and HLA DR alpha, revealed that these alpha chains have been highly conserved during evolution. Southern blot analysis indicated an association of the RT1 haplotypes, 'u' and 'l', with Bam H1 DNA bands of 9.8 kb and 11.7 kb, respectively. The BB rat develops insulin dependent diabetes as an autoimmune abnormality. Accumulating evidence suggests a cellular mediated etiology and the involvement of class II molecules. The steady state levels of RT1.D alpha mRNA were measured in splenic lymphocytes of diabetes prone BB rats and age matched histocompatible normal nondiabetic WF rats by a RNase protection assay. Compared to WF rats, elevated transcripts of RT1.D alpha were found in lymphocytes of young BB rats (approximately 4x and approximately 2.5x greater at 20-40 and 40-75 d, respectively). In lymphocytes of older diabetic and nondiabetic BB rats (greater than 75 d) the levels of RT1.D alpha mRNA were lower than in the young BB rats and were found at the WF control levels. The increased steady state RT1.D alpha mRNA levels in the young BB rats may reflect differences in the proportion of splenic lymphocytes expressing this gene (activated lymphocytes), and thus differences in splenic lymphocyte populations. The steady state RT1.D alpha mRNA levels in lymphocytes of the normal rats were found to be relatively similar at all ages examined. The increased class II gene transcripts found in lymphocytes of young BB rats indicates that they possess a highly activated immune system.

Amino Acid Sequence↗

Outbreak of methicillin-resistant Staphylococcus aureus infection in a New Zealand hospital.

During a 17 month period from March 1985 to July 1986, 30 patients and four members of staff became infected or colonised with a single strain of methicillin-resistant Staphylococcus aureus (MRSA) during an outbreak which originated at Wellington Hospital. Initially, crossinfection occurred within the intensive care unit but infected or colonised patients became distributed to 14 hospital wards and to five other hospitals within New Zealand. MRSA septicaemia contributed to the death of two patients. The source of the epidemic strain of MRSA has not been established with certainty, but may have been introduced by a staff nurse known to be a carrier when employed at an Australian hospital. The investigation, management and eventual control of this first outbreak in New Zealand are described.

Adolescent↗

Adult forms of the Ca2+ATPase of sarcoplasmic reticulum. Expression in developing skeletal muscle.

Two separate genes encode fast-twitch and slow-twitch/cardiac muscle forms of the Ca2+ ATPase of sarcoplasmic reticulum. Full length Ca2+ ATPase clones have been isolated from adult rabbit fast-twitch, slow-twitch, and cardiac muscles. Segments of these clones containing unique sequences have been used as probes to study developmental changes in Ca2+ ATPase transcripts. The fast-twitch Ca2+ ATPase transcript undergoes developmentally regulated alternative splicing in which a penultimate 42-base pair exon is retained in the adult transcript but is excised in the neonatal transcript. This additional exon shifts the exon encoding the neonatal carboxyl-terminal sequence, -Asp-Pro-Glu-Asp-Glu-Arg-Arg-Lys (Brandl, C. J., Green, N. M., Korczak, B., and MacLennan, D. H. (1986) Cell 44, 597-607) into a nontranslated region and results in the expression of an adult isoform with a carboxyl-terminal -Gly. The neonatal form of the fast-twitch Ca2+ ATPase represents 72% of the fast-twitch Ca2+ ATPase transcripts just prior to birth but only 17% by 14 days of age and 4% in adult fast-twitch muscle. Adult slow-twitch, adult cardiac, and neonatal skeletal muscles express an identical Ca2+ATPase mRNA transcript which is distinct from either of the fast-twitch forms. The slow-twitch/cardiac Ca2+ ATPase is the predominant form expressed in late fetal and early neonatal rabbit skeletal muscle, but this form is lost as the skeletal muscle differentiates into a fast-twitch state. Three or more alternative polyadenylation signals exist for this mRNA in all tissues with the most 3' signal predominating.

Aging↗

Heat shocking as a useful adjunct to routine phage typing of Staphylococcus aureus.

The heat shock technique (heating a culture at 55 degrees C for 3 min immediately before phage typing) has been used in our laboratory as an adjunct to routine phage typing for 2 years. This has enabled phage typing patterns to be determined on isolates otherwise recorded as untypable. The method is easily performed and standardized. Phage patterns were found to be reproducible and adequate discrimination was achieved. We found the technique provided significant information which was not available by conventional typing.

Bacteriological Techniques↗

Dissimilation of Carbon Monoxide to Acetic Acid by Glucose-Limited Cultures of Clostridium thermoaceticum.

Clostridium thermoaceticum was cultivated in glucose-limited media, and the dissimilation of CO to acetic acid was evaluated. We found that cultures catalyzed the rapid dissimilation of CO to acetic acid and CO(2), with the stoichiometry obtained for conversion approximating that predicted from the following reaction: 4CO + 2H(2)O --> CH(3)CO(2)H + 2CO(2). Growing cultures formed approximately 50 mmol (3 g) of CO-derived acetic acid per liter of culture, with the rate of maximal consumption approximating 9.1 mmol of CO consumed/h per liter of culture. In contrast, resting cells were found not to dissimilate CO to acetic acid. CO was incorporated, with equal distribution between the carboxyl and methyl carbons of acetic acid when the initial cultivation gas phase was 100% CO, whereas CO(2) preferentially entered the carboxyl carbon when the initial gas phase was 100% CO(2). Significantly, in the presence of saturating levels of CO, CO(2) preferentially entered the methyl carbon, whereas saturating levels of CO(2) yielded CO-derived labeling predominantly in the carboxyl carbon. These findings are discussed in relation to the path of carbon flow to acetic acid.

Journal Article↗

Scarlet fever.

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Humans↗

Autumn--the season for post-streptococcal acute glomerulonephritis in New Zealand.

Post-streptococcal acute glomerulonephritis, which may follow either streptococcal throat or skin infection, continues to be prevalent among New Zealand school children. Group A streptococci were cultured from 41 patients with acute glomerulonephritis between 1978 and 1983. The skin was the predominant site of infection (68%). Streptococci belonging to major pyoderma-associated nephritogenic serotypes 49, 57 and 60 accounted for 19/30 (63%) M-typable isolates. A seasonal peak in hospital admissions was observed during the months April, May and June. From April to July peak rates for streptococcal skin infection also occurred during a one year community study. In this study group A streptococci were recovered from 83% of skin lesions. The predominance of pyoderma-associated nephritogenic serotypes among acute glomerulonephritis patients and their relative absence in uncomplicated skin infection implies an association with acute glomerulonephritis. We believe that streptococcal skin infection may be an important factor in the epidemiology of acute glomerulonephritis in New Zealand.

Acute Disease↗