Search PubMed⌕ Search

Biomedical subjects

P Morris

Publications and source records attributed to P Morris.

At least 73 records · Page 4Linked to original sources
PubMed1996

Retrorsine in breast milk influences copper handling in suckling rat pups.

AIMS: To explore the hypothesis that a second xenobiotic agent is required with excess copper to produce Indian Childhood Cirrhosis, this study investigated the effect of the pyrrolizidine alkaloid retrorsine fed to the mother during the suckling period upon the serial changes in neonatal copper status. METHODS: Female Wistar rats with new-born litters were fed either a control or a retrorsine (50 mg/kg) diet. At 0, 4, 8, 11, 15, 18 and 21 days, pups from each litter were weighed, sacrificed and their livers removed for copper, DNA and metallothionein analysis. Serum samples were assayed for caeruloplasmin oxidase activity and albumin. RESULTS: 1) Higher than adult level of hepatic copper in normal rats which rose post-natally before declining from day 11 after birth, 2) raised hepatic copper concentrations and total copper in the retrorsine group from day 15; levels were higher than adult at birth, 3) reduced serum caeruloplasmin oxidase activity and albumin levels in retrorsine group, but both groups lower than adult, 4) lower hepatic metallothionein levels in retrorsine group, but both groups higher than adult, and 5) reduced liver DNA in the retrorsine group when expressed as total DNA and per gram of tissue. These changes were not secondary to under-nutrition as a small study on under-nourished rat neonates showed that copper handling is not significantly altered when compared to well-nourished rats. CONCLUSIONS: Retrorsine passing to rat neonates via breast milk causes: 1) the accumulation of hepatic copper, 2) impairment of the rise in serum caeruloplasmin, which could indicate a decline in synthesis or failure of copper incorporation into the apo-protein, 3) a decrease in hepatic metallothionein and serum albumin levels, again suggesting diminished protein synthesis, and 4) reduced hepatic DNA indicative of decreased cell number but increased cell size. Accumulation of liver copper but reduction of copper-binding proteins could result in free copper and explain the synergistic hepatotoxicity of copper and retrorsine.

Animals↗
PubMed1996

The incidence of minor sequelae following anaesthesia in children.

A survey was performed to estimate the incidence of the minor sequelae of anaesthesia in children. During an eight-month period 266 children, aged five years and over, were personally interviewed by an anaesthetist following recovery from anaesthesia. At interview the child was questioned to ascertain any morbidity suffered and record was made of the operation performed and the anaesthetic administered. Data were then evaluated, using multivariate analysis, to identify risk factors for the more common sequelae. This study revealed a higher incidence of the minor sequelae of anaesthesia in children than had previously been reported. The three most common sequelae recorded were nausea (48.1%), vomiting (35.0%), and sore throat (31.4%).

Anesthesia↗
PubMed1996

Approaches to studies on neuronal/glial relationships by 13C-MRS analysis.

The use of different 13C-labelled precursors alone or in combination ([1-13C]glucose, [2-13C]glucose, [1-13C]acetate, [2-13C]acetate and [1,2-13C2]acetate) to study neuronal/glial metabolic relationships by MRS is discussed. Glutamine and citrate resonances represent glial metabolism if a combination of [1-13C]glucose + [2-13C]acetate is used, but only for short time periods. A combination of [2-13C]glucose + [2-13C]acetate will label -COO- groups from glucose and -CH2 groups from acetate, respectively, which distinguish well in theory. However, this approach is severely limited by the long T1S of -COO- groups and low S/N. Contributions of the anaplerotic pathway can be assessed using [2-13C]glucose, but again can be limited by the long T1S of -COO- groups. Labelling of glycerol-3-phosphate (believed to be produced in glia) from [1-13C]glucose is difficult to see under normal conditions but has proved useful in, e.g., hypoxia. We believe the most promising approach is the use of [1-13C] glucose with [1,2-13C2]acetate, by analysis of the multiplets ('isotopomers') of the amino acid resonances.

Acetates↗
PubMed1996

Colon perforation, bilateral pneumothoraces, pneumopericardium, pneumomediastinum, and subcutaneous emphysema complicating endoscopic polypectomy: anatomic and management considerations.

A case of colonoscopic polypectomy complicated by perforation, pneumoperitoneum, bilateral pneumothoraces, pneumopericardium, pneumomediastinum, and subcutaneous emphysema is presented. The anatomic basis for the various clinical presentations of extraluminal air following colonoscopy as well as the option of conservative therapy of select cases of perforation is discussed.

Aged↗
PubMed1995

A regulatory mechanism that detects premature nonsense codons in T-cell receptor transcripts in vivo is reversed by protein synthesis inhibitors in vitro.

Gene rearrangement during the ontogeny of T- and B-cells generates an enormous repertoire of T-cell receptor (TCR) and immunoglobulin (Ig) genes. Because of the error-prone nature of this rearrangement process, two-thirds of rearranged TCR and Ig genes are expected to be out-of-frame and thus contain premature terminations codons (ptcs). We performed sequence analysis of reverse transcriptase-polymerase chain reaction products from fetal and adult thymus and found that newly transcribed TCR-beta pre-mRNAs (intron-bearing) are frequently derived from ptc-bearing genes but such transcripts rarely accumulate as mature (fully spliced) TCR-beta transcripts. Transfection studies in the SL12.4 T-cell line showed that the presence of a ptc in any of several TCR-beta exons triggered a decrease in mRNA levels. Ptc-bearing TCR-beta transcripts were selectively depressed in levels in a cell clone that contained both an in-frame and an out-of-frame gene, thus demonstrating the allelic specificity of this down-regulatory response. Protein synthesis inhibitors with different mechanism of action (anisomysin, cycloheximide, emetine, pactamycin, puromycin, and polio virus) all reversed the down-regulatory response. Ptc-bearing transcripts were induced within 0.5 h after cycloheximide treatment. The reversal by protein synthesis inhibitors was not restricted to lymphoid cells, as shown with TCR-beta and beta-globin constructs transfected in HeLa cells. Collectively, the data suggest that the ptc-mediated mRNA decay pathway requires an unstable protein, a ribosome, or a ribosome-like entity. Protein synthesis inhibitors may be useful tools toward elucidating the molecular mechanism of ptc-mediated mRNA decay, an enigmatic response that can occur in the nuclear fraction of mammalian cells.

Animals↗
PubMed1995

Analysis of HLA-DMB mutants and -DMB genomic structure.

The HLA-DM locus encodes class II-like A and B chains and apparently regulates the antigen presentation function of conventional major histocompatibility complex (MHC) class II molecules. Here we describe the HLA-DMB mutations in three presentation defective B lymphoblastoid cells lines (B-LCL), 7.19.6, 10.6.6, and 10.78.6, which express DMB transcripts of abnormal length. Mutant 7.19.6 has a C-->T point mutation that introduces a 5' splice site into exon 3 of DMB. The independently derived mutants, 10.6.6 and 10.78.6, each harbor a G-->A mutation in exon 3 and also lack an identical downstream segment of RNA. Mapping of DMB intron/exon borders, using a genomic clone, revealed that the segment missing in mutants 10.6.6 and 10.78.6 represents the fourth exon of DMB; no mutations were found within exon 4 in either 10.6.6 or 10.78.6, however. In addition, the DMB gene was found to have a six exon genomic structure, typical of MHC class II B genes.

Amino Acid Sequence↗
PubMed1995

Effect of gestational age on levels of serum alkaline phosphatase isoenzymes in healthy pregnant women.

OBJECTIVES: To confirm that the bone isoenzyme of alkaline phosphatase (ALP) contributes significantly to the increased ALP in normal pregnancy, and to determine the gestational age at which the increase occurs. METHODS: Cross-sectional determinations of serum total, bone and placental ALP were carried out in 67 normal pregnant women. The results were compared with those of 18 normal age-matched non-pregnant controls using Student's t-test. RESULTS: At both 31-32 weeks and 38 weeks of gestation, serum activities of bone ALP were increased significantly (P < 0.05 and P < 0.001, respectively) when compared with controls. The percentage contribution of bone ALP to the total was higher at 31-32 weeks and lower at 38 weeks when compared with the contribution from placental ALP. CONCLUSION: Knowledge of time of elevation of serum bone ALP activity in normal pregnancy will be helpful in the interpretation of elevated serum total ALP activity during pregnancy.

Adult↗
PubMed1995

High-field MRS studies in brain slices.

We are applying multi-nuclear high-field (500 MHz) MR spectroscopy of metabolising whole tissue preparations of the mammalian brain to studies on individual components of convulsions, which include prolonged depolarization, metabolic deprivation, and the effects of excitotoxins. The responses of glial cells and neurones can be partially distinguished by following labelling patterns of metabolic intermediates from 13C-labelled glucose or acetate (which enters only glial cells). This approach clearly confirmed our earlier indications that the metabolic response to depolarization (40 mM extracellular K+) occurs essentially in glial cells. Some evidence for metabolic shuttling between glia and neurones was obtained from the changes in C3/C4 ratios of glutamate and glutamine, and the C2/C3 of GABA. Mechanisms for metabolic support of neurones by glia may be of importance in neuronal protection under such metabolic stress as occurs in epilepsy. Changes in free intracellular divalent cations ([Ca2+]i and [Zn2+]i) were monitored using the 19F-MRS indicator, 5FBAPTA. Large increases in [Ca2+]i and decreases in PCr were produced by excitotoxins (glutamate and NMDA), depolarization or ischemia, but intracellular Zn2+ appeared only after exposure to the excitotoxins. The NMDA receptor blocker, MK801, removed all of the responses to NMDA, but only prevented the appearance of Zn2+ observed with glutamate. These results indicate that the damage caused to neurones by such insults as convulsions is not due simply to the presence of excessive excitotoxic glutamate.

Animals↗
PubMed1995

Risk factors for pneumothorax during percutaneous Hickman line insertion in patients with solid and haematological tumours.

The purpose of this study was to identify risk factors for pneumothorax during percutaneous subclavian Hickman line insertion in patients with haematological (HT) or solid tumours (ST). One hundred and twelve patients (55 HT, 57 ST) had 132 subclavian Hickman lines inserted under fluoroscopic control. Lines were inserted on the left on 116 occasions and the right in 16. Thirty-five single, 29 double and 68 triple lumen catheters were inserted. Variables included in the analysis were age, sex, side of insertion, catheter gauge and nutritional status as indicated by the body mass index (BMI kg/m2). Both univariate and logistic regression analyses were performed. There were ten pneumothoraces, all occurring in patients with STs. Univariate analysis revealed that patients with STs were older (median age 59 versus 36 years; P = 0.0001) and more cachectic (median BMI 21.9 versus 24.2 kg/m2; P = 0.03) than those with HTs, and the patients experiencing pneumothorax were older (median age 57 versus 44 years; P < 0.01) and more cachectic (median BMI 19.6 versus 24.0 kg/m2; P = 0.004) than those undergoing uncomplicated procedures. For patients with a BMI < 19 kg/m2 versus those with a BMI > 19 kg/m2, the pneumothorax rate was 5/8 versus 5/124 (P < 0.00001). Logistic regression analysis confirmed the significantly older age of the patients with STs (P < 0.001) and of those experiencing pneumothorax (P = 0.02). This analysis also confirmed the lower BMI of patients experiencing pneumothorax (P = 0.002). The patients' sex, the side of line insertion and the catheter gauge were not associated with pneumothorax on either the univariate or logistic regression analyses. From these data we conclude that pneumothorax complicating a subclavian Hickman line is significantly more likely in elderly patients with a low BMI. Such patients are more likely to have STs than HTs. In patients with a BMI < 19 kg/m2, the subclavian route should be used with caution.

Adult↗
PubMed1995

Visual field loss in senile dementia of the Alzheimer's type.

BACKGROUND: Visual performance is impaired in patients with senile dementia of the Alzheimer's type (SDAT). We investigated the visual field topography of these deficits. METHODS: Humphrey automated perimetry (Program 30-2) was used to measure differential luminance sensitivity within the central 60 degrees of the visual field in SDAT patients (n = 61) and in visually and cognitively normal volunteer subjects of similar age (n = 61). Twenty-three SDAT patients were retested 18 months after the original examination. RESULTS: Reliable visual fields (by manufacturer's criteria) were obtained in 72.1% (44/61) of the control subjects and 55.7% (34/61) of the SDAT group. In the SDAT group, differential luminance sensitivity was significantly reduced relative to the control group. Visual sensitivity was reduced throughout the visual field, but deficits were most pronounced in the inferior visual field, where they presented most commonly as arcuate defects. Patients with more severe dementia exhibited greater reductions in visual sensitivity. On follow-up, 14 of 23 SDAT patients exhibited progression of visual field loss, whereas only two of 23 patients exhibited a regression of the visual field loss. CONCLUSIONS: Although automated perimetry requires considerable patient cooperation, many patients with SDAT can produce reliable visual field results. These patients exhibit significant reductions in global sensitivity. Visual field loss in SDAT is most pronounced in the inferonasal and inferotemporal arcuate regions of the visual field but also involves the central field.

Aged↗
PubMed1994

An essential role for HLA-DM in antigen presentation by class II major histocompatibility molecules.

In antigen-presenting cells, class II molecules of the major histocompatibility complex (MHC) bind peptides derived from endocytosed proteins. In certain B-lymphoblastoid cell mutants, MHC class II molecule-peptide complex formation is impaired, resulting in deficient antigen-presenting function. MHC deletion mutants with this defect map the responsible gene(s) to the class II region of the MHC. Here we report that multiple independent mutants with the class II presentation defect harbour lesions in HLA-DMB, an MHC-linked gene encoding a class II-like beta-chain. Expression of DMB complementary DNA in mutants lacking DMB messenger RNA restores the wild-type phenotype. These results establish HLA-DM as a critical regulatory molecule in class II-restricted antigen presentation and suggest that it functions at an intracellular site to promote class II molecule-peptide association.

Animals↗
PubMed1994

Synergistic liver toxicity of copper and retrorsine in the rat.

To investigate the possible synergy between copper and retrorsine (a pyrrolizidine alkaloid) as a cause of Indian Childhood Cirrhosis, four groups of male Wistar rats were fed the following diets from weaning: A. Normal diet; B. Copper loaded (2 g CuSO4/kg diet); C. Retrorsine supplemented (Expt 1:25 mg/kg body weight/week by gavage, Expt 2:25 mg/kg food initially then 15 mg/kg food after 4 weeks); and D. Copper and retrorsine as above. Serial plasma samples were assayed for aminotransferases, albumin and bilirubin. Liver samples at biopsy and sacrifice provided samples for copper analysis and histology. Results showed that copper and retrorsine together significantly increased liver damage compared with feeding either alone as assessed by: 1. Increased mortality rate; 2. Decreased plasma albumin and increased plasma bilirubin (mainly conjugated) indicative of hepatocyte dysfunction; 3. Massive liver copper accumulation, and 4. Increased liver damage histologically. Thus retrorsine caused liver copper accumulation, and together copper and retrorsine led to severe hepatic dysfunction, characterised by hypoalbuminaemia and conjugated hyperbilirubinaemia. Plant alkaloids secreted in milk by grazing animals and copper from brass vessels may together produce Indian Childhood Cirrhosis.

Animals↗