Biomedical subjects

J M Palmer

Publications and source records attributed to J M Palmer.

At least 19 recordsLinked to original sources

PubMed1995

A genetic model of melanoma tumorigenesis based on allelic losses.

Previous karyotypic studies have indicated a possible series of non-random chromosomal events involved in progression of melanoma. We sought to verify and augment this model of melanocyte tumorigenesis by studying allelic deletions of markers mapping to these regions in 30 matched pairs of melanoma and constitutional DNA samples. Polymorphic loci on chromosomes 1, 7, 10, 11, 17, and 21 were analyzed and data combined with those previously obtained for chromosome arms 6q and 9p in the same series of tumours. The most frequent and earliest deletions were found on 9p (57%) and 10q (32%). With the exception of one case, no sample had loss of markers on another chromosome without concomitant loss of markers on 9p or 10q. Losses on 6q were also a frequent (31%) and early event whereas losses of loci on distal 1p (22%) or 11q (26%) occurred only in metastatic melanomas. A "background" rate (0-17%) of allele loss was seen on chromosomes 7, 17, and 21. These data strongly support the previous model based on karyotypic findings in melanocytic lesions. However, we have been able to further, augment that model by delimiting the regions of loss on 10q, to that distal to D10S254, and on 1p, to between D1S243 and D1S160.

Alleles↗

PubMed1995

Subcellular localization of pyruvate dehydrogenase dihydrolipoamide acetyltransferase in human intrahepatic biliary epithelial cells.

In previous histological studies, biliary epithelial cells (BEC) in the liver of patients with primary biliary cirrhosis (PBC), but not controls, reacted strongly with antibodies specific for the major autoantigen associated with PBC, the E2 component of pyruvate dehydrogenase complex (PDC-E2). In this study we have used transmission electron microscopy (TEM) to document the precise subcellular localization of PDC-E2 in BEC. Two antibodies which recognize PDC-E2 were used: affinity-purified anti-PDC-E2 raised in rabbits; and human antibody from the serum of patients with PBC, affinity-purified against human heart PDC. The intracellular localization of antibody binding was determined by laser scanning confocal microscopy and TEM. Both antibodies bound to the inner membrane of mitochondria in BEC isolated from both patients with PBC and controls, but binding to the external aspect of the plasma membrane was observed only in BEC from patients with PBC. Surface antigen expression in PBC may make BEC immunological targets.

Adult↗

PubMed1995

Altered neuropeptide content and cholinergic enzymatic activity in the inflamed guinea pig jejunum during parasitism.

We investigated the effects of an enteric infection with the parasitic nematode, Trichinella spiralis, on peptidergic and cholinergic neural pathways of the guinea pig jejunum. The content of the enteric neuropeptides, substance P (SP) and vasoactive intestinal peptide (VIP), and the activities of the key cholinergic enzymes, acetylcholinesterase (AChE) and choline acetyltransferase (ChAT), were measured and compared in extracts of jejunal muscularis externa (ME) obtained from uninfected jejunum and T. spiralis-inflamed jejunum. Significant decreases were detected in both SP immunoreactivity and AChE activity on days 6 and 10 postinfection (PI) in nematode-infected guinea pig jejunum compared to uninfected controls. The maximum changes observed for SP and AChE both occurred on day 10 PI and were evident as decreases of 37% and 48%, respectively, from the mean uninfected control values for SP and AChE. In contrast, VIP immunoreactivity and ChAT activity showed no significant changes during the enteric phase of T. spiralis infection. Nematode-evoked histopathological changes in jejunal tissues from infected animals were associated with significant increases in myeloperoxidase (MPO) activity, an index of inflammation intensity, which occurred on day 6 PI (885% of mean control) and day 10 PI (469% of mean control) coinciding temporally with the significant decrease in SP content and AChE activity during infection. Thus, intestinal motor disturbances observed in mammalian hosts during enteric nematode infections involve inflammation-generated changes in the neurohumoral control of smooth muscle function.

Acetylcholinesterase↗

PubMed1995

Diuretic enhanced duplex Doppler sonography in 33 children presenting with hydronephrosis: a study of test sensitivity, specificity and precision.

PURPOSE: We assessed the value of diuretic enhanced Doppler sonography in the diagnosis of pediatric renal obstruction as well as its reproducibility, sensitivity and specificity. MATERIALS AND METHODS: We studied 33 children (68 kidneys) by standard diagnostic techniques and diuretic Doppler sonography. A total of 20 obstructed kidneys was compared to 48 without obstruction and we performed surgery on 13. An average of 2.3 resistive index measurements were made per test and 436 total resistive index values were assessed by Student's t distribution and chi-square analysis before and after surgical repair. The assessor was blinded to the clinical diagnosis. RESULTS: The obstructed mean resistive index before (0.71) and after (0.74) furosemide administration differed significantly from the nonobstructed mean resistive index (0.65, p < 0.02). Postoperative mean resistive index (0.68) was not affected by the diuretic and did not differ from the mean resistive index of nonobstructed kidneys. Resistive index test sensitivity was 76% and specificity was 88%. The precision for 3 values per test was +/- 0.11. CONCLUSIONS: When at least 3 values are obtained per test, diuretic Doppler sonography predicts the actual resistive index average with 98% confidence limits 90% of the time.

Adolescent↗

PubMed1994

Neuroimmune communication in the submucous plexus of guinea pig colon after infection with Trichinella spiralis.

BACKGROUND/AIMS: Enteric neuroimmune communication in gastrointestinal hypersensitivity responses includes antigen detection by mast cells and release of chemical messages to the enteric nervous system. The aim of this study was to analyze the electrical and synaptic behavior of neurons in the colonic submucous plexus during exposure to Trichinella spiralis antigen in animals infected earlier with the parasite. METHODS: Microelectrodes were used to record in submucous neurons of guinea pig distal colon during application of Trichinella antigen. RESULTS: Neurons in sensitized animals were more excitable than in controls. Hyperexcitability was seen as a greater probability of spontaneous action potential discharge and repetitive firing to depolarizing current or exposure to acetylcholine. Application of histaminergic antagonists reversed the augmented excitability, suggesting endogenously released histamine as a responsible factor. Antigenic exposure increased neuronal excitability and suppressed nicotinic transmission at fast cholinergic synapses only in sensitized animals. Effects on excitability, but not presynaptic inhibitory effects, were blocked by cimetidine. CONCLUSIONS: Signaling between mucosal mast cells and the enteric nervous system is involved in colonic anaphylactic responses to sensitizing antigens. Histamine is a paracrine signal in the communication pathway.

Action Potentials↗

PubMed1992

A controlled trial of prednisolone treatment in primary biliary cirrhosis. Three-year results.

The results of a 3-year, placebo-controlled trial of prednisolone treatment in primary biliary cirrhosis (PBC) are presented. The active (n = 19) and placebo (n = 17) arms were initially well matched for age, menopausal status and disease severity. At 3 years hepatic symptoms were relatively improved in the prednisolone group. Hepatic mortality was 3/19 (prednisolone), 5/17 (placebo) (p = n.s.). For all liver blood tests the trend favoured prednisolone treatment, though the differences were only significant for alkaline phosphatase and protein. All immunoglobulins fell significantly. Quantitative ELISA determination of antimitochondrial antibody showed a significant fall in the prednisolone group compared with placebo (p less than 0.001 at 1 year, p less than 0.05 at 3 years). Deterioration in histology (appearance of cirrhosis) was more common in the placebo group. Overall hepatic function (hepatic mortality, doubling in bilirubin, 6 milligrams fall in albumin, de novo appearance of cirrhosis or symptoms of portal hypertension) was significantly worse in the placebo group (p less than 0.01). After 3 years no significant differences could be detected in bone mineral content (single photon absorptiometry of radius and femur) between the two groups or in comparison with other PBC patients. Thus, after 3 years, prednisolone treatment was associated with a better overall hepatic outcome and little evidence of increased bone loss.

Absorptiometry, Photon↗

PubMed1992

Exclusion of the familial melanoma locus (MLM) from the PND/D1S47 and MYCL1 regions of chromosome arm 1p in 7 Australian pedigrees.

Familial melanoma (MLM) is sometimes found associated with the dysplastic nevus syndrome (DNS). Considerable controversy exists over the possible assignment of a cutaneous malignant melanoma/dysplastic nevus gene, designated CMM, to the distal short arm of chromosome 1, linked to the PND and D1S47 loci. To date, no support for linkage of MLM alone to these markers has been found; likewise no study has been able to exclude the entire region between PND and D1S47 from linkage to MLM. We have carried out linkage studies between markers on 1p and MLM in seven Australian kindreds; three of these are the largest reported worldwide. We have been able to exclude localization of an MLM gene from a 40-cM region that spans the interval between D1S47 and PND and extends approximately 15 cM on either side of these markers. In addition, we can exclude a region of about 20 cM around the MYCL1/D1S57 loci.

Atrial Natriuretic Factor↗

PubMed1992

Linkage mapping of melanoma (MLM) using 172 microsatellite markers.

The incidence of malignant melanoma is currently increasing faster than any other cancer and in 5-12% of cases occurs in a familial context in which the disease cosegregates as an autosomal dominant trait. To identify the location of genes that predipose individuals to familial melanoma (MLM), we have carried out linkage analysis in three large Australian melanoma pedigrees using 172 microsatellite markers spread across all autosomes. Three additional smaller families were typed for 70 of the same markers. In five of the six families we found lod scores between 1.0 and 2.3, which may provide evidence for the location of melanoma genes in proximity to some of these markers. If this turns out to be the case, these data potentially demonstrate that MLM is genetically heterogeneous since there was no marker for which all families gave significantly high LODs. These data provide the foundation for an exclusion map for melanoma and, more importantly, high-light areas of the genome for others to substantiate the potential positions of some of the genes that may be responsible for susceptibility to MLM.

Chromosome Mapping↗

PubMed1992

Catalytic mechanisms and regulation of lignin peroxidase.

Lignin peroxidase (LiP) is a fungal haemoprotein similar to the lignin-synthesizing plant peroxidases, but it has a higher oxidation potential and oxidizes dimethoxylated aromatic compounds to radical cations. It catalyses the degradation of lignin models but in vitro the outcome is net lignin polymerization. LiP oxidizes veratryl alcohol to radical cations which are proposed to act by charge transfer to mediate in the oxidation of lignin. Phenolic compounds are, however, preferentially oxidized, but transiently inactivate the enzyme. Analysis of the catalytic cycle of LiP shows that in the presence of veratryl alcohol the steady-state turnover intermediate is Compound II. We propose that veratryl alcohol is oxidized by the enzyme intermediate Compound I to a radical cation which now participates in charge-transfer reactions with either veratryl alcohol or another reductant, when present. Reduction of Compound II to native state may involve a radical product of veratryl alcohol or radical product of charge transfer. Phenoxy radicals, by contrast, cannot engage in charge-transfer reactions and reaction of Compound II with H2O2 ensues to form the peroxidatically inactive intermediate, Compound III. Regulation of LiP activity by phenolic compounds suggests feedback control, since many of the products of lignin degradation are phenolic. Such control would lower the concentration of phenolics relative to oxygen and favour degradative ring-opening reactions.

Benzyl Alcohols↗

PubMed1992

Atrial natriuretic peptide inhibits fluid intake in hyperosmolar subjects.

1. The effect of atrial natriuretic peptide on osmotically stimulated thirst appreciation and consequent fluid intake was investigated in healthy man. 2. Six seated male subjects were studied on two occasions: synthetic alpha-human atrial natriuretic peptide (99-126) (2 pmol min-1 kg-1) or placebo (saline, 150 mmol/l NaCl) was infused intravenously for 105 min; 30 min after the start of atrial natriuretic peptide/placebo infusion, hypertonic saline (855 mmol/l NaCl) was infused (0.06 ml min-1 kg-1) for 60 min. Subjects were then allowed free access to water for the next 2 h; infusion of atrial natriuretic peptide/placebo continued for the first 15 min of the drinking period. 3. The plasma atrial natriuretic peptide concentration did not alter significantly during infusion of hypertonic saline and placebo; it rose to a steady state of 12.7 +/- 1.1 pmol/l (mean +/- SEM) during the infusion of atrial natriuretic peptide and hypertonic saline, and remained at this level during the first 15 min of the drinking period. During infusion of hypertonic saline and atrial natriuretic peptide or placebo, similar increases in plasma osmolality (P less than 0.001) and plasma vasopressin concentration (P less than 0.005) occurred. During infusion of hypertonic saline and atrial natriuretic peptide or placebo, thirst increased significantly over the time course of both studies (P less than 0.01), but the effect of atrial natriuretic peptide infusion compared with placebo infusion was to significantly decrease thirst at 60 min. 4. Drinking rapidly abolished thirst and vasopressin secretion before changes in plasma osmolality occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Antimicrobial susceptibility of anaerobic bacteria in Australia.

The susceptibilities of 900 clinical isolates of anaerobic bacteria to 14 antimicrobial agents were determined by an agar dilution technique. Chloramphenicol, imipenem and metronidazole were found to be active against virtually all of the strains; only a single Bacteroides fragilis isolate was resistant to both imipenem and metronidazole. The addition of clavulanic acid to amoxycillin and ticarcillin potentiated the activities of these agents against all anaerobes including members of the B. fragilis group. Ampicillin/sulbactam and clindamycin were the next most active agents, 91 and 89% of isolates respectively being susceptible. Seventy-three per cent of the bacteria tested were susceptible to cefoxitin and 65% to cefotetan, with the MICs of almost 50% of the isolates clustering between 16 and 32 mg/L. There was also clustering around the breakpoint (64 mg/L) of piperacillin. Azithromycin exhibited poor activity against the B. fragilis group; only 18% of isolates were susceptible to < or = 4 mg/L. However, 92% of non-B. fragilis Bacteroides group strains were susceptible to this agent. We conclude that imipenem, metronidazole, chloramphenicol, ticarcillin/clavulanate, co-amoxiclav and, to a lesser extent, ampicillin/sulbactam are suitable as empirical therapy for infections caused by anaerobic bacteria.

Anti-Bacterial Agents↗

PubMed1991

Neuropharmacology of the muscarinic antagonist telenzepine in myenteric ganglia of the guinea-pig small intestine.

Intracellular recording methods were used to investigate the actions of the putative M1 muscarinic receptor antagonist telenzepine on the electrical and synaptic behavior of myenteric neurons. Telenzepine had no effect on resting membrane potential, input resistance, excitability and antidromic potentials in both AH/type 2 and S/type 1 neurons, when applied in concentrations of 0.1-2000 nM, although higher concentrations (10-100 microM) did have a significant non-specific effect on the postsynaptic membrane. Micromolar concentrations of telenpzepine (1-2 microM) had no effect on excitatory responses to substance P, vasoactive intestinal peptide, the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium or the nicotinic action of acetylcholine. Nicotinic fast excitatory postsynaptic potentials were also unaffected by 2 microM telenzepine. In contrast, at submicromolar concentrations (100 nM), telenzepine abolished responses to either muscarine or the muscarinic component of the acetylcholine response. The excitatory effect of muscarine at postsynaptic M1 receptors was dose dependently inhibited by telenzepine (0.1-1000 nM) at concentrations which had no effect on the electrical properties of the cells. This effect was slowly reversible, usually requiring more than 60 min for significant recovery. The threshold dose of telenzepine as an antagonist of the muscarinic depolarization in AH/type 2 neurons was in the range of 0.1-1 nM. The IC50 concentration of telenzepine needed to abolish the response was 8.5 nM. A small proportion of stimulus-evoked slow excitatory postsynaptic potentials in both AH/type 2 and S/type 1 cells were abolished by 1 microM telenzepine, while the majority of them remained unaffected, indicating that some slow excitatory postsynaptic potentials are mediated by the muscarinic action of released acetylcholine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Diuretic Doppler sonography in postnatal hydronephrosis.

Renal resistive indexes were measured by Doppler sonography in 12 children undergoing other standard diagnostic studies to evaluate hydronephrosis. Measurement of renal resistive indexes was modified by prior placement of a bladder catheter, oral hydration and administration of 1 mg./kg. furosemide after baseline measurement. Renal resistive indexes were again measured at 10 and 30 minutes after diuretic. While diuretic administration had no measurable influence on 10 nonobstructed kidneys, the elevated 10-minute post-diuretic renal resistive indexes recorded in 10 obstructed kidneys differed significantly from the indexes recorded in the nonobstructed group (p less than 0.001). The highest elevations in renal resistive indexes were recorded in nonpaired kidneys, which included 7 of the 10 kidneys in the obstructed group. In the 3 unilaterally obstructed kidneys the 10-minute post-diuretic renal resistive indexes did not differ significantly. However, renal resistive indexes in these kidneys increased at least 15% over baseline readings after diuretic administration. Diuretic Doppler sonography appears to be another useful method for differentiating functionally significant hydronephrosis from nonobstructive hydronephrosis in children.

Child↗

PubMed1991

Neuroimmune regulation of colonic secretion in guinea pigs.

The role of submucosal neurons in anaphylactic-like responses in colonic epithelium from immunized guinea pigs was examined 6-8 wk after inoculation with 2 x 10(3) infective Trichinella spiralis larvae. Serosal addition of T. spiralis antigen (20 micrograms/ml) to muscle-stripped segments of colon set up in flux chambers evoked a maximum increase in short-circuit current within 5 min in immune, but not nonimmune, guinea pigs. Quercetin, a membrane-stabilizing drug, and pyrilamine, a histamine H1 receptor antagonist, attenuated epithelial responses evoked by T. spiralis antigen. Antigen-induced epithelial responses were reduced by neural blockade with tetrodotoxin and by the muscarinic receptor antagonist atropine but not by blockade of nicotinic receptors with mecamylamine. Antigenic challenge of colonic mucosa from immune guinea pigs enhanced the secretory responses to endogenously released neurotransmitters evoked by electrical field stimulation and substance P. In the presence of antigen, the tetrodotoxin-insensitive component of the carbachol response was enhanced and was reversed by quercetin but not pyrilamine. The results suggest that submucosal cholinergic nerves play a role in mediating the rapid epithelial responses evoked by worm antigen in the colonic mucosa of T. spiralis-immune guinea pigs. Interaction of immunological mediators with neurotransmitters in the submucosal plexus augments the secretory mucosal response triggered by T. spiralis in immunized hosts.

Animals↗

PubMed1991

The undescended testicle.

Cryptorchidism results from a complex hereditary series of incompletely understood events involving the HPG axis. The incidence is indirectly related to birth weight and dramatically decreases during the first 3 months after birth. Many nonscrotal testes are retractile and require no therapy whatsoever. True cryptorchid testes develop identifiable histologic alterations within 2 years of parturition, and endocrine abnormalities are often detectable during infancy. Hormonal therapy with hCG is effective in causing descent in only a small percent of children with cryptorchidism. GnRH nasal spray is no different from placebo in double-blind studies in which retractile testes have been excluded. The results are best in low-lying testes and in older children, but a recognized late-failure rate requires continued surveillance. HCG therapy appears to be of little use in nonpalpable cryptorchid testes. The risk of testicular cancer is increased in men with a history of cryptorchidism and even includes the contralateral descended testes. This risk may be reduced by early orchidopexy. Fertility is impaired in men with cryptorchidism and is reported to be no better than 75% and 50%, respectively, in men who have undergone successful unilateral or bilateral orchidopexy. There is unconfirmed evidence that orchidopexy carried out before the age of 2 years may improve these fertility rates. It is recommended that all children with cryptorchid testes undergo treatment by the age of 1 or 2 years. The parents of children with a nonpalpable testis should be informed of the high rate of testicular absence. If hormonal therapy is to be used, it must be initiated at 10 months of age. Treatment failures must be identified quickly to allow prompt referral of these children to a pediatric urologist or surgeon for orchidopexy.

Cryptorchidism↗

PubMed1990

Radical intermediates in veratryl alcohol oxidation by ligninase. NMR evidence.

Proton nuclear magnetic resonance (NMR) spectra of veratryl alcohol (3,4-dimethoxybenzyl alcohol) were obtained during its oxidation by ligninase. It was observed that a substantial increase in the linewidths of the resonances occurred only in the presence of both the enzyme and hydrogen peroxide. Quenching the reaction by the addition of alkali immediately restored the normal linewidths of the resonances. Furthermore, inversion-recovery experiments showed a decrease in the longitudinal relaxation time of the substrate when the enzyme was actively turning over. Changes in both these NMR parameters are consistent with the generation of radical intermediates during the ligninase-catalysed oxidation of veratryl alcohol.

Agaricales↗

PubMed1990

Lignin peroxidase from Phanerochaete chrysosporium. Molecular and kinetic characterization of isozymes.

Five isozymes of lignin peroxidase from Phanerochaete chrysosporium were purified and their physical, molecular and kinetic properties determined. The isozymes differ from each other in terms of their isoelectric point, molecular mass, sugar content, spectral characteristics, substrate specificity and stability. The N-terminal sequence of amino acids was different for each isozyme suggesting they are different gene products. The isozyme with the highest carbohydrate level was most sensitive to changes in environmental factors. The kinetic behaviour of the isozymes varied clearly when tert-butyl hydroperoxide instead of hydrogen peroxide was used as the oxidant. Two out of five isozymes had very similar substrate specificity. The results are discussed in relation to the role which lignin peroxidase isozymes may play in lignin biodegradation.

Amino Acid Sequence↗

PubMed1990

Unraveling the complexities of transcription by RNA polymerase III.

The biosynthesis of proteins and nucleic acids in eukaryotes requires the participation of numerous small RNAs, many of which are products of RNA polymerase III transcription. How cells are able to coordinate the synthesis of these RNAs during growth and replication has been the subject of recent exciting and thought-provoking studies. We review the progress in this area, and focus upon shared properties between transcription systems having different functions.

Animals↗