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M J Walsh

Publications and source records attributed to M J Walsh.

At least 73 records · Page 4Linked to original sources
PubMed1987

Regulation of types I, III, and IV procollagen mRNA synthesis in glucocorticoid-mediated intestinal development.

Administration of dexamethasone (0.8 mg/kg) to 9-day-old rats once daily for 3 consecutive days caused precocious induction of adult specific disaccharidase activity in the small intestine. Maturation-specific disaccharidase activity was accompanied by decreased amounts of types I and III collagen and decreased procollagen type I and III mRNA levels. Conversely, type IV procollagen, fibronectin, and laminin amounts and their respective mRNA levels were increased. In vitro transcription of nuclei isolated from small intestine and colon of suckling rats indicated a decreased rate of synthesis of procollagen types I and III mRNAs and an increased rate of synthesis of procollagen type IV mRNAs and laminin mRNAs after dexamethasone treatment. The data suggest that glucocorticoids mediate a differential regulation of interstitial and basement membrane collagen gene expression in the developing rat intestine.

Animals↗
PubMed1987

Isoelectric point restriction of cerebrospinal fluid and serum IgG antibodies to measles virus polypeptides in multiple sclerosis.

Thirty consecutive isoelectric point (pI)-discrete IgG fractions were isolated from multiple sclerosis (MS) cerebrospinal fluid (CSF) and used to immune precipitate measles virus (MV) polypeptides. Most basic fractions were enriched in activity against nucleocapsid protein (NP), and to a lesser extent against hemagglutinin (H) protein; intermediate fractions were enriched in activity against H and fusion (F) proteins; and more anodic pI fractions were almost exclusively enriched in activity against the large (L) protein of MV. In MS there are marked differences between CSF and autologous serum in regard to antibody activity to MV. In contrast, there were similar profiles of antibody response to MV proteins in SSPE CSF and serum.

Chemical Precipitation↗
PubMed1986

Temporal invariance and clonal uniformity of brain and cerebrospinal IgG, IgA, and IgM in multiple sclerosis.

Elevated cerebrospinal fluid (CSF) IgG and oligoclonal IgG bands on electrophoresis are valuable clinical markers for B cell proliferation in the brains of patients with multiple sclerosis (MS). Using two-dimensional electrophoresis, (2DE) we have established that the humoral immune response in MS brain is characterized by finite clonal complexity for the major Ig classes. An important question is whether this immune response is clonally stable or varies with time, related to the development of new lesions and random entry of B cells into the MS brain. To investigate this, we performed serial electrophoretic studies on CSF obtained from 19 patients with MS; the intervals ranged from 7 to 12 yr, with a mean of 8 yr. These analyses included studies of IgG, IgA, and IgM, and revealed that the humoral immune response in MS is clonally stable over long periods. Spontaneous fluctuations or reduction in CSF IgG levels by drugs did not qualitatively affect B cell clonal proliferation in MS brain, in that dominant bands and spots were not obliterated. It has been asserted that IgG synthesis in MS is nonsense antibody because the spectotypes of IgG isolated from different regions of MS brains differ. Factors other than clonal heterogeneity could account for differences found using one-dimensional analysis. B cell clonal products resolve into unique and well-resolved spots by 2DE; the method is uniquely suitable for analysis of restricted immune responses. Therefore, Ig were isolated from 11 regions of three MS brains and the 2DE patterns were compared. The similarity of the 2DE patterns indicate unequivocally that major clones are distributed uniformly although some clones are more prominent in some brain areas. IgA and IgM isolated from the same areas also showed similar patterns. Furthermore, the patterns of light and heavy chains in brain regions differed from serum but were similar to the autologous CSF, providing new evidence that CSF IgG in MS derives from synthesis in situ. Our results indicate that, once initiated, B cell clonal proliferation persists indefinitely and is little altered qualitatively at a clonal level over time, even when CSF IgG levels change or are altered by drugs. Our results are consistent with allotype and idiotype analysis of Ig production in MS and conflict with nonsense antibody proposals of the origin and nature of in situ synthesized Ig in MS.

Blood-Brain Barrier↗
PubMed1986

Immunoglobulin heavy chain associated protein in multiple sclerosis cerebrospinal fluid.

Immunoglobulins G, A, and M (IgG, IgA and IgM) were isolated from multiple sclerosis (MS) cerebrospinal fluid (CSF) and sera by Protein A-Sepharose (PAS) affinity chromatography or using solid-phase immunoabsorbents. An isoelectric point heterogeneous protein with apparent mol. wt of 74,000-80,000 was seen consistently when CSF Igs were immunoaffinity purified but was never seen when PAS was used for Ig purification. Control experiments exclude the binding of this protein non-specifically either to Sepharose or to Igs or to other CSF proteins. Analysis of purified Igs under non-reducing conditions leads to some reduction in staining pattern indicating that a portion of the protein may be disulfide linked to itself or to other CSF proteins. Immunoblot analysis of CSF Igs separated on 2-DE gels is consistent with a portion of the total CSF Ig protein existing as "free" heavy (H)-chains. PAS requires dimeric Fc fragment of Ig for binding; the differences in 2-DE gels of PAS and immunoaffinity purified Igs may be due to interaction of the 74,000-80,000 protein with "free" H-chain, which nevertheless, still leaves this complex available for binding by anti-H chain antisera. It has been previously suggested that the cytotoxicity of "free" H-chains is abrogated in the absence of the complementary L-chains by H-chain binding proteins; the protein reported here has features similar to these proteins reported previously and may be involved in some way in regulating Ig production in the MS central nervous system.

Cerebrospinal Fluid Proteins↗
PubMed1986

Effect of early treatment with nifedipine in suspected acute myocardial infarction.

In this single centre prospective, double blind study, 98 patients with suspected acute myocardial infarction (AMI) were randomized, within six hours, to nifedipine 10 mg (46 patients) or placebo (52 patients) both administered sublingually. The delay time from onset of chest pain to treatment was 3.33 +/- 0.2 hours (mean +/- SEM) and 3.28 +/- 0.18 hours for the nifedipine and placebo treated groups, respectively. Treatment was continued orally for 3 days. AMI was confirmed in 28 patients given nifedipine and 23 patients given placebo. Infarct sizing by CK-MB isoenzyme release was possible, for technical reasons, in only 23 patients on nifedipine and 17 patients on placebo. CK-MB isoenzyme release was 710 +/- 104 IU l-1 and 655 +/- 118 IU l-1 for the nifedipine and placebo treated groups respectively (P greater than 0.05). In the acute coronary insufficiency (ACI) group--18 patients given nifedipine and 29 patients given placebo--there was no significant difference in duration of admission, urgent cardiac readmission or progression to AMI within one month. Study withdrawal occurred in 15.3%--8 nifedipine and 7 placebo. Overall, one month mortality was 10.2% with 5 deaths in both the nifedipine and placebo treated groups. Early treatment with nifedipine did not reduce enzymatically determined infarct size or one month mortality in patients with AMI, or reduce one month morbidity or mortality in patients with ACI.

Acute Disease↗
PubMed1986

Percutaneous transluminal coronary angioplasty in unstable angina: comparison with stable angina.

Percutaneous transluminal coronary angioplasty was performed in 25 patients with unstable angina and in a similar group of 25 patients with stable angina. The frequency of single, double, and triple vessel disease was identical in each group. Technical success was achieved in 22 (81%) out of 27 attempts in those with unstable angina and in 14 (52%) out of 27 attempts in those with stable angina. Vessel occlusion occurred in nine patients, necessitating emergency bypass surgery in four. There was evidence of myocardial infarction in three patients in each group and one patient in the unstable group subsequently died. Twenty eight of 32 successfully treated patients were followed up by means of repeat coronary arteriography, exercise electrocardiography, and clinical assessment after a mean (SD) interval of 14 (7) months. There was angiographic evidence of restenosis in 32% (seven of 22) of lesions in the unstable group and 44% (four of nine) of lesions in the stable group. There were no late infarctions or deaths during the follow up period. These results support the growing evidence that angioplasty can be carried out safely and effectively in patients with unstable angina.

Angina Pectoris↗
PubMed1985

The basis of intra-blood-brain-barrier IgG synthesis.

We hold that the intra-blood-brain-barrier (BBB) IgG synthesis (SYN) rate can be quantitated reliably and validly. Although several formulas distinguish patients with multiple sclerosis from normal controls equally well, only the SYN rate formula has been validated in humans using isotopic tracer techniques. Our formula for the IgG SYN rate is reducible to Reiber's formula; therefore, both can be used to quantify the IgG SYN rate in a manner not possible using the IgG index. Although our SYN rate formula has been validated for a modest range of BBB abnormalities (cerebrospinal fluid/serum albumin ratios), there is evidence to suggest that it may be used even in patients having severe BBB damage. We question the acceptance of unique cerebrospinal fluid IgG bands as indisputable evidence of intra-BBB IgG SYN in the presence of a modest to severely damaged BBB. Finally, the utility of quantitation and detection of intra-BBB IgG SYN by standardized methods in a group of asymptomatic, normal individuals compared with a group of patients with clinical definite multiple sclerosis is presented.

Blood-Brain Barrier↗
PubMed1985

Immunoglobulin G, A, and M--clonal restriction in multiple sclerosis cerebrospinal fluid and serum--analysis by two-dimensional electrophoresis.

Immunoglobulin G, A, and M (IgG, IgA, and IgM) were purified from multiple sclerosis (MS) cerebrospinal fluid (CSF) and sera and analyzed by two-dimensional electrophoresis. The light (L)-chains of MS CSF IgG were of limited diversity and dominated by about 30 major spots and many less intense spots. CSF IgG of patients with subacute sclerosing panencephalitis (SSPE) was dominated by 10 to 20 intense L-chain spots. L-chains from patients with fungal, syphilitic, and tuberculous infections of the central nervous system (CNS) ranged from 70 to in excess of 300 spots. The patterns of L-chains in MS CSF and autologous sera were different, indicating amplified synthesis of particular L-chains in MS CNS. Cathodic IgG fractions differing in isoelectric point by 0.1 to 0.3 pH units were isolated. SSPE CSF IgG fractions were dominated by a few L-chain spots, MS CSF fractions contained less than 20 spots, and MS serum fractions contained about 200 spots. MS CSF mu-chains were similar in isoelectric point range to serum but fractionated into discrete spots compared with a diffuse pattern in serum. MS CSF IgA alpha-chain spot overlapped in mobility with serum alpha-chains except a portion of the alpha-chain complex in CSF was shifted cathodically forming discrete spots. The CSF L-chains of both IgM and IgA were completely dissimilar to serum. These studies indicate major limited diversity and compartmentalized CNS synthesis of IgG, IgA, and IgM in MS. The restricted clonal pattern is proposed as consequent to B-cell stimulation by disease-related antigen(s) with limited epitope complexity. The dominance of a small number of L-chains supports results from idiotypic analysis suggesting finite clonal complexity of MS CSF IgG and indicates the feasibility of structural analysis of MS CSF L-chains, particularly amino acid sequence determinations.

Humans↗
PubMed1985

Pharmacokinetics and haemodynamic effects of tocainide in patients with acute myocardial infarction complicated by left ventricular failure.

The pharmacokinetics and haemodynamic effects of tocainide, an orally active structural analogue of lignocaine, were studied in patients with acute myocardial infarction complicated by left ventricular failure. Fourteen patients (mean age 65 years) with acute myocardial infarction complicated by mild left ventricular failure were studied, following a single dose of tocainide (250 mg) by intravenous infusion, over 30 min. Heart rate, systemic arterial pressure, pulmonary artery pressure and cardiac output were monitored. Plasma tocainide levels were estimated by gas chromatography. The mean plasma level of tocainide achieved was 2.95 micrograms/ml (15.37 mmol/l). The mean plasma half-life was 15.6 h. The mean cardiac index was reduced 5 min after completion of the infusion, from 2.24 1 min-1 m-2 (+/- 0.40) to 2.07 1 min-1 m-2 (+/- 0.29) (P less than 0.01). At 90 min the cardiac index had returned to pre-treatment levels. Small changes were seen in the heart rate, arterial blood pressure and the pulmonary artery pressure but these changes were not statistically significant. The pharmacokinetics of tocainide were not significantly altered in patients with acute myocardial infarction complicated by mild left ventricular failure.

Aged↗
PubMed1985

Subacute sclerosing panencephalitis: measles virus matrix protein nucleic acid sequences detected by in situ hybridization.

Subacute sclerosing panencephalitis (SSPE) is characterized by a hyperimmune state toward the polypeptides of measles virus except the matrix (M) protein. Using cloned (3H)-labeled complementary DNA probes for in situ hybridization, we found the M protein and nucleocapsid (NP) protein nucleotide sequences in glial cells and neurons of cryostat sections from two SSPE brains. In one SSPE brain, M protein was lacking, but the other measles polypeptides were present. IgG and IgM antibodies eluted from that brain lacked antibodies to M protein, but antibodies to other measles polypeptides were present. In SSPE brain, the viral M-protein defect is not a deletion of the M gene, but rather a block in gene expression.

Brain Chemistry↗
PubMed1984

Two-dimensional electrophoresis of cerebrospinal fluid and ventricular fluid proteins, identification of enriched and unique proteins, and comparison with serum.

The proteins of cerebrospinal fluid (CSF) and ventricular fluid have been analyzed by two-dimensional electrophoresis (2DE) and the patterns compared with autologous serum. Fourteen proteins were specifically identified by immunoprecipitation followed by 2DE, or by blotting 2DE gels to nitrocellulose and detection by peroxidase staining. Proteins in CSF and serum with high and low affinity for the ligands, protein A, Cibacron Blue, and concanavalin A, were also characterized by 2DE. The 2DE profiles of CSF and serum proteins were similar and indicated that a relatively nonselective filtration mechanism based on protein size is the major determinant for the overall pattern of CSF proteins. The classic CSF-enriched or CSF-specific proteins, beta-trace, prealbumin, transferrin, and beta-2-microglobulin, were identified according to 2DE coordinates. Charge differences between CSF and serum for transferrin and prealbumin were identified. In addition, a large number of additional CSF-enriched or CSF-specific proteins of high, intermediate, and low molecular weight, all predominantly anodic in mobility, were identified. Three acidic protein complexes, heterogeneous in charge and molecular weight, were characterized as constituents of normal CSF, and two of these are increased in patients with inflammatory diseases of the CNS. All three proteins and several other proteins unique to CSF bound to Cibacron Blue-Sepharose. The use of 2DE in conjunction with affinity chromatography and sensitive protein stains enlarged the number of proteins previously identified as unique to CSF. By a modified 2DE and silver staining procedure, most of these proteins were visible without prior concentration of CSF.

Adult↗