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Biomedical subjects

M Hall

Publications and source records attributed to M Hall.

At least 37 records · Page 2Linked to original sources

The gapped xylem mutant identifies a common regulatory step in secondary cell wall deposition.

The phenotype of the novel gapped xylem (gpx) mutant is described. gpx plants exhibit gaps in the xylem in positions where xylem elements would normally be located. These gaps are not part of the transpiration stream and result in gpx plants having fewer functional xylem elements. The gaps are due to the absence of a secondary cell wall in developing xylem elements, resulting in complete degradation of these elements during cell death, and illustrate the importance of the secondary cell wall in retaining a functional xylem element following programmed cell death. Consequently the gpx phenotype suggests that the processes of secondary cell wall formation and cell death are independently regulated in developing xylem. gpx plants also exhibit a highly irregular pattern of secondary cell wall thickening in interfascicular cells, with some cells apparently undergoing little or no secondary cell wall deposition. Secondary cell wall deposition in plants involves the co-ordinate regulation of several complex metabolic pathways. The gpx mutant identifies a key step involved in regulating the deposition of secondary cell wall material in both xylem and interfascicular cells, and suggests that a common regulatory step controls secondary cell wall formation in these diverse cell types. The gpx mutant offers a unique opportunity to elucidate the mechanism by which the complex processes involved in secondary cell wall formation are co-ordinately regulated.

Arabidopsis↗

Sulfakinin neuropeptides in a crustacean. Isolation, identification andtissue localization in the tiger prawn Penaeus monodon.

The sulfakinin (SK) family of neuropeptides are characterized by a C-terminal octapeptide sequence that begins with two acidic residues (most commonly DD), and ends with YGHMRF-NH2, usually with the tyrosyl residue sulfated. So far, sulfakinins have only been identified in insects and the present study was initiated to investigate if the family is more widely distributed within the arthropods. Purification of an extract of the central nervous system of the giant tiger prawn Penaeus monodon has revealed three novel members of the sulfakinin peptide family. One of the peptides, Pem SKI, has the sequence <QFDEY(SO3H)GHMRF-NH2, where <Q denotes a pyroglutamic acid residue, and is for all criteria typical of insect sulfakinins, several of which also have an N-terminal pyroglutamic acid. Tyrosyl O-sulfation was verified by mass spectrometry. The two other peptides have a hitherto unknown L/M variation at position three from the C-terminus. One of these, Pem SKII, has a particularly glycine-rich N-terminus, AGGSGGVGGEYDDYGHLRF-NH2. The other, Pem SKIII, is a truncated form of Pem SKII, with the sequence VGGEYDDYGHLRF-NH2. Mass spectrometry of the latter two peptides indicated that only one of the two tyrosyl residues is sulfated. By analogy, it is suggested that the sulfation is located at the residue in position six from the C-terminus. A small amount of a nonsulfated variant of Pem SKII was also present in the extract. Immunocytochemical studies with sulfakinin antisera show a sparse neuronal distribution pattern, similar to that of insects. A prominent pair of large (approximately 25 micrometer) cells and 6-8 pairs of smaller (approximately 10 micrometer) cells are present in the protocerebrum. The larger cells have prominent neurites that give rise to varicosities in the centre of the brain. Their axons exit the brain via the circumoesophageal connectives and continue along the intersegmental connectives. Each of the thoracic and abdominal ganglia has sulfakinin-immunoreactive arborizations as a result of branching from the intersegmental nerves. This distribution pattern strongly suggests a role in neurotransmission or neuromodulation, although it remains to be elucidated what the exact role(s) is. However, on account of the conservation of peptide structure during the evolutionary period spanning the insect/crustacean lineage, especially between Pem SKI and insect sulfakinins, it may be assumed that the sulfakinins have a significant physiological role.

Amino Acid Sequence↗

Alzheimer's disease due to an intronic presenilin-1 (PSEN1 intron 4) mutation: A clinicopathological study.

We describe 21 affected individuals from a kindred with early-onset autosomal dominant familial Alzheimer's disease caused by an intronic presenilin-1 mutation (in intron 4). Mean age at onset of symptoms was 37.4 years [95% confidence interval (CI): 36.6-38.2 years], mean age at death was 44.7 years (95% CI: 43.1-46.3 years) and mean duration of illness was 7.3 years (95% CI: 5.9-8.7 years). Myoclonus and seizures were prominent features of this pedigree. In the four cases for whom neuropsychometric data were available, verbal memory impairment preceded visual memory deficits; naming was relatively preserved until late in the disease. One of these four cases underwent serial volumetric MRI scans demonstrating in vivo brain tissue loss of 3.9% (38.9 ml, annualized rate of atrophy: 1. 7%) over 22 months of follow-up. The four individuals who had necropsies demonstrated the neuropathological hallmarks of Alzheimer's disease. Apolipoprotein E (APOE) status was assessed in five individuals: the case with the youngest age at onset at 33 years of age was found to be homozygous epsilon4/epsilon4, > 1 SD below the mean age of onset for those of known APOE genotype (36.4 +/- 2.3 years, mean +/- SD), and > 2 SDs below the mean age of onset for the pedigree as a whole (37.4 +/- 1.7 years, mean +/- SD). APOE genotype may therefore modulate age at onset in this pedigree.

Adult↗

Are differences in interleukin 10 production associated with joint damage?

OBJECTIVE: Constitutive differences between individuals in cytokine production may determine the variation in the course of inflammatory arthritis. METHODS: The association between interleukin 10 (IL-10) production and joint destruction was studied by comparing IL-10 mRNA content in synovial biopsies from seven patients with destructive joint disease and six patients with non-destructive joint disease. The IL-10 mRNA content was 0.4 +/- 0.6 arbitrary units in erosive joints compared with 2.3 +/- 1.2 arbitrary units in non-erosive joints (P: < 0.03, Mann-Whitney U:-test). As this difference suggested that IL-10 production was associated with joint destruction, we tested whether the IL-10 locus determined the extent of joint damage. RESULTS: Innate differences in IL-10 production are locus-dependent. In line with these data, we showed that innate differences in IL-10 protein production were also present as differences in IL-10 mRNA levels. We tested if polymorphisms in the promoter of IL-10 were associated with the extent of joint damage. DISCUSSION: In a cohort study of female rheumatoid arthritis patients followed for 12 yr, the extent of joint destruction differed significantly between patients with different IL-10 genotypes. In patients with the -1082AA genotype who were studied prospectively, the mean increase in radiographic damage score (modified Sharp score of X-rays of hands and feet) during the first 6 yr was 9 +/- 9 per yr vs 19 +/- 16 per yr for patients with the genotype -1082GG (P: < 0.02). In line with these data, cultures of endotoxin-stimulated whole blood from 158 donors showed that the presence of the allele associated with less joint destruction correlated with slightly higher IL-10 production. CONCLUSIONS: Both the immunogenetic and the synovial biopsies suggest that a variation in IL-10 production is associated with joint destruction.

Adult↗

Guidelines in gynaecology: evaluation in menorrhagia and in urinary incontinence.

OBJECTIVE: To evaluate the effectiveness of national guidelines and local protocols in improving hospital care (process and outcome) for women with menorrhagia and for women with urinary incontinence. DESIGN: 2 x 2 balanced incomplete block controlled before and after study. SETTING: Gynaecology units in four district general hospitals across Scotland. INTERVENTION: National guidelines were adapted locally to protocols, which were disseminated at specific local educational meetings and implemented by placing a copy of the appropriate protocol in women's hospital casenotes prior to consultation. POPULATION: Four hundred and ninety-seven women with menorrhagia and 449 women with urinary Incontinence. MAIN OUTCOME MEASURES: Process of care within six key areas of clinical practice: initial hospital assessment; appropriate use of hospital investigations; inappropriate use of hospital investigations; appropriate first line treatments; appropriate pre-surgery assessment; and use of surgical treatments. Outcome of care using condition-specific outcome measures and four domains of SF-36 at zero, six and twelve months following intervention. RESULTS: There were significant improvements with the introduction of guidelines and protocols in two (initial hospital assessment and appropriate pre-surgery assessment) of the six key areas of clinical practice assessed. In the other areas there were no significant improvements or deteriorations observed. There was no evidence of effect of guidelines and protocols on the condition-specific outcome measures or on the four domains of the SF-36. CONCLUSIONS: There were only very modest benefits observed from the introduction of guidelines and protocols on the hospital management of the two conditions. The reasons for this lack of impact of the guidelines is unclear. Experience of this study raises important methodological issues for future research in this area.

Adult↗

Characterisation using microphysiometry of CRF receptor pharmacology.

We have assessed the utility of the Cytosensor microphysiometer for studying the pharmacology of recombinant CRF receptors. Chinese hamster ovary cells stably expressing the human CRF1 or CRF2 receptor were perfused in the Cytosensor with bicarbonate-free Hams F12 (pH 7.4) containing 0.2% bovine serum albumin. The rank order of potencies of agonist peptides were CRF = sauvagine = urocortin = urotensin at CRF1 (pEC50 values 11.16 +/- 0.17, 11.37 +/- 0.14, 11.43 +/- 0.09 and 11.46 +/- 0.13; n = 4), and urocortin = sauvagine > urotensin > CRF at CRF2 (pEC50 values 10.88 +/- 0.12, 10.44 +/- 0.05, 9.36 +/- 0.12 and 8.53 +/- 0.07; n = 7-9). alpha-Helical CRF (9-41) was a competitive antagonist at the CRF2 receptor (pK(B) = 6.99 +/- 0.08, n = 4), but was a partial agonist at the CRF1 receptor (pEC50 = 6.85 +/- 0.08, Emax = 33%, n = 3). CP 154,526 was a competitive antagonist at the CRF1 receptor (pK(B) = 8.17 +/- 0.05, n = 6), but was inactive at the CRF2 receptor. These data are consistent with established CRF receptor pharmacology and show that the Cytosensor is a viable method for assessing the functional activity of CRF-receptor agonists and antagonists.

Acid-Base Equilibrium↗

High sensitivity immunoassays using particulate fluorescent labels.

The use of polystyrene fluorescent microspheres as sensitive labels in direct-detection (not enzymatically amplified) heterogeneous equilibrium "sandwich" immunoassays in 96-well plates is described. With mouse IgG as a model antigen, a fluorescent particulate label is more sensitive than a corresponding soluble reporter. The limit of detection of mouse IgG in the multiparametrically optimized assay was 0.2 ng/ml (7.6 x 10(8) antigens/ml) for the particulate reporter and 50 ng/ml (1.9 x 10(11) antigens/ml) for the soluble reporter. The sensitivities of assays using the particulate label were dependent on the surface densities of the capture and reporter antibodies and the concentration of reporter beads. Sensitivity was improved by adding the preformed reporter antibody/fluorescent microsphere complex to trapped antigen on the well surfaces instead of sequentially adding the reporter antibody and then the fluorescent microspheres. Maximal (equilibrium) binding of the particulate reporter to captured antigen occurred after 20 h with a concentration of 1.4 x 10(9) reporter beads/ml. Thus, particulate fluorescent labels provide high sensitivity in direct-detection immunoassays.

Animals↗

The crayfish plasma clotting protein: a vitellogenin-related protein responsible for clot formation in crustacean blood.

Coagulation in crayfish blood is based on the transglutaminase-mediated crosslinking of a specific plasma clotting protein. Here we report the cloning of the subunit of this clotting protein from a crayfish hepatopancreas cDNA library. The ORF encodes a protein of 1,721 amino acids, including a signal peptide of 15 amino acids. Sequence analysis reveals that the clotting protein is homologous to vitellogenins, which are proteins found in vitellogenic females of egg-laying animals. The clotting protein and vitellogenins are all lipoproteins and share a limited sequence similarity to certain other lipoproteins (e.g., mammalian apolipoprotein B and microsomal triglyceride transfer protein) and contain a stretch with similarity to the D domain of mammalian von Willebrand factor. The crayfish clotting protein is present in both sexes, unlike the female-specific vitellogenins. Electron microscopy was used to visualize individual clotting protein molecules and to study the transglutaminase-mediated clotting reaction. In the presence of an endogenous transglutaminase, the purified clotting protein molecules rapidly assemble into long, flexible chains that occasionally branch.

Amino Acid Sequence↗

Reduction of the occurrence of acute cellular rejection among renal allograft recipients treated with basiliximab, a chimeric anti-interleukin-2-receptor monoclonal antibody. United States Simulect Renal Study Group.

BACKGROUND: A double-blind, placebo-controlled phase III study was performed to assess whether basiliximab, a chimeric anti-interleukin-2 receptor monoclonal antibody, reduced the incidence of acute rejection episodes in renal allograft recipients. METHODS: A total of 348 patients were randomized into two demographically matched, equally sized groups treated with either basiliximab or placebo. The dose of basiliximab-20-mg infusions on day 0 and day 4-was selected to block detection of interleukin-2 receptor on 97% of peripheral blood lymphocytes for 30-45 days. All patients received immunosuppressive therapy with cyclosporine microemulsion (Neoral) and steroids. An intent-to-treat analysis of 1-year data assessed the incidence of posttransplant acute rejection episodes, patient and graft survival rates, and the safety and tolerability of basiliximab. RESULTS: Among the eligible 346 patients equally divided into the two treatment groups, basiliximab reduced the proportion of patients who experienced biopsy-confirmed acute rejection episodes by 28%: 61 (35.3%) basiliximab vs. 85 (49.1%) placebo (P=0.009). Graft losses occurred in 9 (5.2%) basiliximab-treated and 12 (6.9%) placebo-treated patients. Five (2.9%) deaths in the basiliximab group and seven (4.0%) in the placebo group occurred. Compared with placebo, a higher fraction of basiliximab patients produced urine in the operating room, and a significantly lower fraction had renal dysfunction in the first month (serum creatinine > or =5 mg(dl) and between 1 and 12 months (serum creatinine > or =3 mg/dl). During the first 12 months, 94 (54%) basiliximab-treated patients experienced serious adverse events, compared with 106 (61%) who received placebo. CONCLUSIONS: Prophylactic basiliximab therapy is well tolerated, has an adverse event profile comparable to placebo, and significantly reduces the number of acute rejection episodes in renal allograft patients within the first year after transplantation.

Acute Disease↗

Trophic effects of cardiotrophin-1 and interleukin-11 on rat dorsal root ganglion neurons in vitro.

Cardiotrophin-1 (CT-1) was originally isolated for its hypertrophy inducing effects on cardiac myocytes whereas interleukin-11 (IL-11) was identified due to its ability to stimulate an interleukin-6 (IL-6) dependent plasmocytoma cell line. Both cytokines are structurally and functionally related to a group of factors called neuropoietic cytokines, which also includes IL-6, ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), and oncostatin M. These factors have trophic effects on subsets of neurons. In the present study we examined the influence of CT-1 and IL-11 on newborn rat dorsal root ganglion neuron survival in vitro. Mouse CT-1 showed prominent trophic effects that were comparable to those of CNTF and LIF. Mouse IL-11 alone did not enhance neuronal survival, but soluble mouse IL-11 receptor alpha rendered neurons sensitive to IL-11. Surprisingly, soluble IL-11 receptor alpha even had slight neurotrophic effects by itself. These results suggest that CT-1 and IL-11 might also be involved in the physiological regulation of sensory neuron survival. Thus, they might, like CNTF, become tools for the therapeutic intervention in neurodegeneration due to disease, toxicity, and trauma.

Animals↗

Alpha-tocopherol inhibits oxidative stress induced by cholestanetriol and 25-hydroxycholesterol in porcine ovarian granulosa cells.

The cytotoxicity of oxysterols including 7-ketocholesterol, alpha-epoxide, cholestanetriol and 25-hydroxycholesterol and the possible protecting effect of alpha-tocopherol on cholestanetriol and 25-hydroxycholesterol-induced cytotoxicity were investigated in primary cultures of porcine ovarian granulosa cells. Cell viability as determined by % trypan blue staining and mitochondrial function as determined using 3-[4,5-dimethylthiazol-2-yl]-2,5- diphenyltetrazolium bromide (MTT) reduction were decreased significantly after 24 h exposure to 2.5 microM alpha-epoxide, cholestanetriol and 25-hydroxycholesterol. 7-Ketocholesterol (2.5 microM) did not affect cell viability or mitochondrial function under the same culture conditions. The specific activities of catalase and superoxide dismutase, two antioxidant defense enzymes were increased significantly (p < 0.01) following 24 h exposure to 2.5 microM concentrations of cholestanetriol while only superoxide dismutase was increased in 25-hydroxycholesterol-treated cells (p < 0.001). Specific activity of glutathione peroxidase was unchanged relative to control cells. Levels of thiobarbituric acid reactive substances remained unchanged after exposure to 7-ketocholesterol, alpha-epoxide, cholestanetriol, 25-hydroxycholesterol and cholesterol. Administration of 1 microM alpha-tocopherol to the culture medium significantly improved cell viability and restored both superoxide dismutase and catalase activities to control levels in cholestanetriol -treated cells and only superoxide dismutase in 25-hydroxycholesterol-treated cells. These studies suggest that the cytotoxic nature of physiologically relevant concentrations of cholestanetriol and 25-hydroxycholesterol in granulosa cells is in part due to oxidative stress, but it may be reduced in the presence of alpha-tocopherol.

Animals↗

Management of coexisting coronary artery and asymptomatic carotid artery disease: report of a series of patients treated with coronary bypass alone.

BACKGROUND: A retrospective chart review of 94 patients with asymptomatic high-grade carotid stenosis undergoing coronary bypass (and valve replacement in some cases) was performed to determine whether significant carotid lesions can be safely ignored in patients undergoing cardiac surgical procedures. These operations were performed during a 2-year period. PATIENTS AND METHODS: There were 55 men and 39 women, with an age range of 37-89 years. Seventy-one patients had unilateral high-grade carotid stenosis, 17 patients had bilateral high-grade lesions, and six patients had unilateral high-grade stenosis and contralateral occlusion. Associated medical problems were recorded and short-term follow-up was obtained. RESULTS: There was one perioperative stroke and no deaths in this group of patients. CONCLUSIONS: Although these data indicate that high-grade carotid stenoses may be safely ignored during cardiac surgical procedures, a multicentre prospective randomized trial is needed to determine the appropriate treatment of the patient with coexisting carotid and coronary artery disease.

Aged↗

Kawasaki syndrome-like illness associated with infection caused by enterotoxin B-secreting Staphylococcus aureus.

Two children had symptoms and clinical signs that were characteristic of the diagnostic criteria for Kawasaki syndrome, temporally associated with Staphylococcus aureus bacteremia. One child initially had focal osteomyelitis that was evident clinically and radiographically, and radiographic evidence of multifocal osteomyelitis was noted at follow-up. The blood-borne S. aureus isolates from these two patients secreted staphylococcal enterotoxin B and were negative for toxic shock syndrome toxin. Staphylococcal and streptococcal superantigens may play a role in the pathogenesis of some cases of Kawasaki syndrome or Kawasaki syndrome-like illness.

Anti-Bacterial Agents↗

Radiographic pelvimetry for assessment of dystocia in bitches: a clinical study in two terrier breeds.

Radiographic pelvimetry was used to assess the role of pelvic anatomy in obstructive dystocia in bitches. Based on the history of previous whelpings, 20 Boston terrier and 14 Scottish terrier bitches were divided into two equal groups: normally whelping bitches and bitches with obstructive dystocia. Additional whelpings during the period of study were closely observed and the pups were immediately weighed and measured. The bitches were clinically examined and the pelvis was radiographed in ventrodorsal and lateral projections. Measurements from the radiographs showed a significantly smaller pelvic size in the bitches with obstructive dystocia compared to the normally whelping bitches. Fetal-pelvic disproportion in the Scottish terrier was mainly due to a dorsoventrally flattened pelvic canal, whereas in the Boston terrier it arose from the combination of a dorsoventrally flattened pelvic canal and big fetuses with large heads. These results suggest that radiographic pelvimetry could be used to predict a disposition for dystocia in individual bitches, and as a basis for selection of breeding animals.

Animals↗