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Biomedical subjects

M Maher

Publications and source records attributed to M Maher.

At least 19 recordsLinked to original sources
PubMed1992

I-Rel: a novel rel-related protein that inhibits NF-kappa B transcriptional activity.

The NF-kappa B transcription factor complex is comprised of two subunits, p50 and p65, that share significant homology to the rel oncogene. We have isolated a cDNA encoding a novel 66-kD rel-related protein, designated I-Rel. Unlike other rel-related proteins, I-Rel does not interact with DNA. I-Rel forms heterodimers with p50, however, and greatly attenuates its DNA-binding activity--an effect probably resulting from the presence of a domain inhibitory to DNA binding present within the 121 amino-terminal residues of I-Rel. In contrast, I-Rel does not associate with p65. Transfection experiments demonstrate that I-Rel suppresses NF-kappa B-induced transcription, probably through its association with p50. Expression of I-Rel mRNA is induced by mitogenic stimulation and accumulates after the appearance of p50 transcripts. Our findings suggest that p50 and I-Rel are components of a feedback pathway where expression of I-Rel may modulate indirectly the expression of genes responsive to the NF-kappa B transcription factor complex.

Amino Acid Sequence↗
PubMed1992

Control of arteriolar resistance in heart failure. Partial attenuation of specific phosphodiesterase inhibitor-mediated vasodilation by digitalis glycosides.

BACKGROUND: The vasodilatory response to local specific type III phosphodiesterase inhibition with amrinone was evaluated before and immediately after local administration of digoxin in 14 patients with severe congestive heart failure (CHF). METHODS AND RESULTS: A 3F polyethylene catheter was inserted into the common femoral artery for drug administration and pressure monitoring. Mean blood flow velocity (MBFV) was continuously determined in the superficial femoral artery by transcutaneous Doppler ultrasonography. After intra-arterial administration of 10 mg amrinone, group MBFV increased from 7.7 +/- 1.4 to 16.0 +/- 2.1 cm/sec (p less than 0.05, n = 10). Local administration of 20 micrograms digoxin, which was infused over 20 minutes, did not alter group MBFV (i.e., 8.2 +/- 1.6 versus 7.6 +/- 1.5 cm/sec; p = NS, n = 10). The second administration of 10 mg amrinone, which immediately followed completion of local digoxin infusion, increased group MBFV but to a lesser extent than that produced by the first amrinone administration (i.e., 11.9 +/- 1.9 versus 16.0 +/- 2.1 cm/sec; p less than 0.05, n = 10). When placebo was administered instead of digoxin, group MBFV was similar after the first and second administrations of amrinone (i.e., 15.3 +/- 3.3 versus 15.6 +/- 3.8 cm/sec; p = NS, n = 4). CONCLUSIONS: Although local administration of digoxin did not significantly alter baseline vascular tone in patients with CHF, it substantially decreased the direct vasodilatory effect induced by specific type III phosphodiesterase with amrinone.

Aged↗
PubMed1992

Portal vein thrombosis following sclerotherapy.

We present the case of a woman with idiopathic portal hypertension who underwent sclerotherapy for bleeding esophageal varices. She had a rebleed 27 months after complete eradication of esophageal varices. Endoscopy showed bleeding gastric varices. Ultrasonography, and later splenoportography, revealed a large thrombus in the right branch of the portal vein causing gross dilation of the portal and splenic vein. A proximal splenorenal shunt was done to decompress the portal system and hence gastric varices. Repeat endoscopy 4 weeks after surgery revealed complete disappearance of the gastric varices, while ultrasonography at 38 weeks showed marked decompression of the portal system with complete disappearance of the thrombus from the right branch of the portal vein. No new thrombus formation was seen.

Adult↗
PubMed1991

Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NF-kappa B.

The sequence reported in our 22 March 1991 report "Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NFkappaB" [Science 251, 1490 (1991)], contained some errors. Resequencing under strong denaturing conditions revealed three insertions at nucleotide positions 1194, 1212, and 1220, which changed the AA sequence from RSAR-PRLGP to QISQASALAP (residues 372 to 380), thus accounting for some of the divergence in this region. A corrected sequence has been sent to GenBank.

Amino Acid Sequence↗
PubMed1991

Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NF-kappa B.

A DNA probe that spanned a domain conserved among the proto-oncogene c-rel, the Drosophila morphogen dorsal, and the p50 DNA binding subunit of NF-kappa B was generated from Jurkat T cell complementary DNA with the polymerase chain reaction (PCR) and degenerate oligonucleotides. This probe was used to identify a rel-related complementary DNA that hybridized to a 2.6-kilobase messenger RNA present in human T and B lymphocytes. In vitro transcription and translation of the complementary DNA resulted in the synthesis of a protein with an apparent molecular size of 65 kilodaltons (kD). The translated protein showed weak DNA binding with a specificity for the kappa B binding motif. This protein-DNA complex comigrated with the complex obtained with the purified human p65 NF-kappa B subunit and binding was inhibited by I kappa B-alpha and -beta proteins. In addition, the 65-kD protein associated with the p50 subunit of NF-kappa B and the kappa B probe to form a complex with the same electrophoretic mobility as the NF-kappa B-DNA complex. Therefore the rel-related 65-kD protein may represent the p65 subunit of the active NF-kappa B transcription factor complex.

Amino Acid Sequence↗
PubMed1991

The early results of internal fixation of displaced acetabular fractures.

The treatment of choice today for displaced acetabular fractures is anatomical reconstruction by open reduction and internal fixation. Nineteen patients with 20 displaced acetabular fractures treated by this method have been reviewed. A satisfactory outcome was obtained in all but one patient. The surgery is amongst the most demanding in orthopaedics. Specialised radiographic techniques are essential in defining the personality of the fracture and in planning the reconstructive surgery.

Acetabulum↗
PubMed1991

The acute pancreatotoxic effects of the plant nitrile 1-cyano-2-hydroxy-3-butene.

The effects of synthetic 1-cyano-2-hydroxy-3-butene (CHB), a racemic mixture of the (R)- and (S)-enantiomers, were studied in adult male rats. The compound given by gavage in olive oil at doses of 25-200 mg/kg causes toxic effects on the pancreas that resemble those seen when naturally occurring CHB is given to rats. At 6 h after dosing, pancreatic edema is seen with doses of 100 mg/kg and greater. The edema fluid had a high protein content, indicating a marked increase in macromolecular permeability of the pancreatic microcirculation. A loss of zymogen granules from the acinar cells and a lacy supranuclear vacuolation of the acinar cell cytoplasm was observed. At 4 h after dosing, pancreatic nonprotein thiols were depleted and rebounded at 24 h to three times control values. At 120 h nonprotein thiol levels decreased but were still elevated compared with control values. Glutathione-S-transferase activity in the pancreas had a similar pattern of change with initial reduction, followed by elevation at 24 h. In rats with pancreatic and biliary fistulas, intraduodenal CHB caused a transient early stimulation of pancreatic juice secretion followed by a return to control values in the case of the lower doses of CHB and depression of flows at larger doses. All doses of CHB caused a dose-related depression of protein concentration in pancreatic juice. Pancreatic juice flow was almost abolished at doses of 200 mg/kg. CHB caused a dose-dependent choleresis accompanied by a marked reduction in bile acid concentrations in bile.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1991

Is the vagotomy complete?

Incomplete vagotomy is the single most common cause of ulcer recurrence. Completeness of vagotomy was assessed postoperatively in 17 patients using the congo red test. Various types of vagotomies included truncal vagotomy and gastrojejenostomy in 6, highly selective vagotomy in 5, truncal vagotomy and pyloroplasty in 3 and selective vagotomy with gastrojejenostomy in 3 cases. Congo red test was positive in 13 cases, with 9 of these showing evidence of incomplete vagotomy manifesting as erosions, duodenitis, stomal ulceration or ulcer recurrence.

Adolescent↗
PubMed1991

Grosse-Kempf intramedullary nailing of femoral fractures.

The Grosse-Kempf nail is a versatile interlocking intramedullary nail with proximal and distal locking. The locking transfixion screws afford additional axial and rotational stability and have expanded the use of intramedullary fixation to include all types of femoral fractures distal to the lesser trochanter and to within 7 cm of the knee joint. Forty consecutive femoral shaft fractures treated by this method have been reviewed. Solid union occurred in 39 cases at six months from surgery. Complications were directly related to technical difficulties and fracture personality. The surgical technique is demanding and requires special expertise training and equipment, but the benefits to the patient are so great that this is now regarded as the method of choice for treating femoral shaft fractures in adults.

Adolescent↗
PubMed1991

Transhiatal oesophagectomy for carcinoma oesophagus. Early experience.

Over a period of eighteen months, (June, 89 to Dec, 90) 19 patients underwent Transhiatal Oesophagectomy for carcinoma. Thirteen were males and 6 females, age varying from 32 to 80 years with an average of 48.6 years. Dysphagia was present in all patients, the duration varied from 1.5 to 6 months, average 3.5 months. Pre-operative endoscopy and biopsy was done in all cases. Lesion was located in upper thoracic oesophagus in 6, middle 9 and lower 4. Histology revealed squamous cell carcinoma in 18 and adenocarcinoma in one. Transhiatal oesophagectomy without thoracotomy and cervical oesophagogastric anastomosis was carried out. The stomach was placed in the posterior mediastinum in 13 and retrosternal in 6 cases. Liver metastasis were present in 3, palpably enlarged nodes in 7 and the tumor was adherent to tissues in the mediastinum in 6 cases. Four patients died in hospital, 2 due to myocardial infarction, one due to massive haemetemesis, and the cause of death could not be established in one. Satisfactory relief of dysphagia was achieved in all cases. Oesophagectomy without thoracotomy is safe and better tolerated than the traditional trans-thoracic operations. The experience of one surgical unit is presented.

Adenocarcinoma↗
PubMed1990

Effects of lithium and rubidium on immune responses of rats.

Rats were treated with LiCl or RbCl in drinking water for 65 days. Spleen cells from both treated groups exhibited significantly greater proliferative responses to lipopolysaccharide (LPS) than those from untreated controls. Responses to concanavalin A (Con A) were not affected. Cytotoxic activities of natural killer (NK) cells from both treated groups were significantly less than those from untreated controls. In vitro, Li augmented responses of spleen cells to LPS, but the same doses of Rb suppressed the responses. Effects on responses to Con A were variable. Both Li and Rb alone had a small mitogenic effect on spleen cells.

Animals↗
PubMed1989

Utilization of hospital services by cardiovascular patients, Alberta, Canada.

Using hospital discharge records, and United States DRG (diagnosis related groups) data, we studied hospital utilization by cardiovascular patients, associated hospital expenditures, and the per capita cost of treating cardiovascular diseases in Alberta, Canada between 1971 and 1986. Expressed in constant 1984 Canadian dollars, the estimated total hospital cost increased from $84 million in 1971 to $131 million in 1986; during this period the Province of Alberta spent about $51 Canadian per resident each year for cardiovascular hospital services. It was noted that rural residents consumed a higher volume of resources per capita than their urban counterparts. A patient origin-destination analysis indicated an increasing dependence of rural patients on urban hospitals for secondary or tertiary care, underscoring the effects of medical technology on referral patterns.

Alberta↗
PubMed1987

Altered leucine metabolism in noncachectic sarcoma patients.

Leucine and whole body protein metabolism were quantitated in 26 human subjects (6 sarcoma patients, 20 age-matched normal controls) using a primed, continuous infusion of [13C]leucine. Plasma samples were analyzed every 15 min for enrichment of [13C]leucine. Plateau enrichment levels were then used to calculate whole-body protein turnover, synthesis, and breakdown rates. Exhaled gas samples were analyzed every 15 min for enrichment of 13CO2, and plateau enrichment levels (as well as CO2 production rates) were used to calculate leucine oxidation rates. Fasting plasma amino acid levels, serum albumin, and total protein levels were also determined. The 6 patients were otherwise healthy but had a large, localized high-grade sarcoma which had not been previously treated. No patient had weight loss. Amino acid, albumin, and total protein levels were equivalent in patients and controls. Whole-body protein turnover rates were significantly greater in sarcoma patients than age-matched controls (15%). Increased protein turnover rates resulted in increased whole-body protein synthesis and breakdown rates in sarcoma patients compared to controls. Leucine oxidation rates were not different in the 2 groups. The results suggest that in humans with high-grade sarcomas leucine metabolic abnormalities are specific to tumor growth and not malnutrition because abnormalities of turnover, synthesis, and breakdown occur prior to any weight loss or measurable change in blood amino acid or protein level.

Adult↗
PubMed1987

Requirements for activation of human peripheral blood T cells by mouse monoclonal antibodies to CD3.

The present study was undertaken in an attempt to reconcile the conflicting results concerning the signals required for the activation of human resting T cells by antibodies to the T-cell receptor/CD3 complex (Ti/CD3). For this purpose we have used highly purified peripheral blood T cells, depleted of monocytes and of preactivated Ia + T cells, to the extent that they were unable to proliferate to interleukin 2 (IL-2) alone or to optimal doses of phytohemagglutinin (PHA). To further minimize the contribution of contaminating monocytes, we used the anti-CD3 mAb, Leu-4, and cells from Leu-4 nonresponder subjects, whose monocytes we show completely fail to bind the Leu-4 mAb. The parameters of T-cell activation which we measured were rises in intracellular free calcium ion [Ca2+]i, IL-2 receptor expression IL-2 production, and cell proliferation. Our results indicate that induction of proliferation of resting T cells requires at least two signals. Signal one is best delivered by multivalent anti-CD3 mAb, such as Leu-4 mAb covalently linked to Sepharose 4B (Seph-Leu-4), or with Leu-4 mAb and anti-mouse IgG. These reagents crosslink the CD3 receptor complex on the T cell, and result in a rise in intracellular [Ca2+]i, in expression of receptors for IL-2, and in proliferation upon addition of IL-2. In contrast, purified T cells exposed to soluble Leu-4 mAb do not exhibit a rise in intracellular [Ca2+]i, do not express receptors for IL-2, and do not proliferate upon addition of IL-2, indicating that the valency of anti-CD3 mAb is critical for the delivery of the first activation signal to the T cell. The essential step of crosslinking of CD3 antigens on T cells by anti-CD3 mAb is normally mediated by monocytes which have bound anti-CD3 mAbs via their Fc receptors. Monocytes from Leu-4 nonresponder subjects, which we show fail to bind Leu-4 mAb, fail to crosslink CD3 antigens on T cells, resulting in failure of T-cell activation. The second signal needed for the proliferation of T cells whose Ti/CD3 complexes are crosslinked is IL-2. IL-2 production by such T cells required a monocyte delivered signal, which must be delivered to these T cells simultaneously with the crosslinking of their Ti/CD3 antigens. This IL-2-inductive signal can be delivered by both Leu-4 nonresponder and Leu-4 responder monocytes, indicating that delivery of this IL-2 inductive signal is independent of anti-CD3 mAb binding by monocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1987

Testicular function in type II hyperlipoproteinemic patients treated with lovastatin (mevinolin) or neomycin.

Steroid synthesis requires cholesterol derived from de novo synthesis or plasma lipoproteins. Low density lipoproteins appear to be the major contributor of cholesterol for steroid synthesis in man. Patients with disorders of low density lipoproteins or the low density lipoprotein receptor have reduced cortisol production in response to ACTH. Therapeutic agents designed to lower plasma cholesterol could, therefore, adversely affect steroid hormone production. Lovastatin (mevinolin) is a new hypolipidemic agent which blocks cholesterol synthesis by competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase. In beagle dogs, lovastatin at 40-180 times the clinically effective dose in man, has been associated with an increase in spontaneous testicular atrophy. Accordingly, the effect of lovastatin on testicular function and lipoprotein levels was studied in 16 hyperlipidemic men in a randomized, double blind, cross-over study with another hypolipidemic agent, neomycin. Serum testosterone, PRL, LH, and FSH; LHRH-stimulated LH and FSH concentrations; and testicular size were measured, and semen analyses were made. We found no evidence that lovastatin had adverse effects on testicular function despite significant alterations in plasma lipoprotein concentrations.

Adult↗