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M W Thomas

Publications and source records attributed to M W Thomas.

At least 19 recordsLinked to original sources
PubMed1999

Comprehensive mutation analysis of TSC1 and TSC2-and phenotypic correlations in 150 families with tuberous sclerosis.

Tuberous sclerosis (TSC [MIM 191090 and MIM 191100]) is an autosomal dominant disorder characterized by hamartomas in many organs. Two thirds of cases are sporadic and are thought to represent new mutations. TSC is caused by mutations affecting either of the presumed tumor-suppressor genes, TSC1 and TSC2. Both appear to function as tumor suppressors, because somatic loss or intragenic mutation of the corresponding wild-type allele is seen in the associated hamartomas. Here we report the first comprehensive mutation analysis of TSC1 and TSC2 in a cohort of 150 unrelated TSC patients and their families, using heteroduplex and SSCP analysis of all coding exons and using pulsed-field gel electrophoresis and conventional Southern blot analysis and long PCR to screen for large rearrangements. Mutations were characterized in 120 (80%) of the 150 cases, affecting TSC1 in 22 cases and TSC2 in 98 cases. TSC1 mutations were significantly underrepresented in sporadic cases (P=. 000185). Twenty-two patients had TSC2 missense mutations that were found predominantly in the GAP-related domain (eight cases) and in a small region encoded in exons 16 and 17, between nucleotides 1849 and 1859 (eight cases), consistent with the presence of residues performing key functions at these sites. In contrast, all TSC1 mutations were predicted to be truncating, consistent with a structural or adapter role for the encoded protein. Intellectual disability was significantly more frequent in TSC2 sporadic cases than in TSC1 sporadic cases (P=.0145). These data provide the first representative picture of the distribution and spectrum of mutations across the TSC1 and TSC2 loci in clinically ascertained TSC and support a difference in severity of TSC1- and TSC2-associated disease.

Blotting, Southern↗
PubMed1998

Cataracts.

Explore the source record for details and available documents.

Adolescent↗
PubMed1996

Normative values for isometric muscle force measurements obtained with hand-held dynamometers.

BACKGROUND AND PURPOSE: The extent of a patient's impairment can be established by comparing measurements of that patient's performance with normative values obtained from apparently unimpaired individuals. Only a few studies have described normative values for muscle strength measured by hand-held dynamometry. The purpose of this study of older adults, therefore, was to obtain normative values of maximum voluntary isometric force using hand-held dynamometers. SUBJECTS: One hundred fifty-six asymptomatic adults (77 men, 70 women) participated in this study. The subjects' mean age was 64.4 years (SD=8.3, range=50-79). The male subjects' mean age was 64.5 years (SD=8.4, range=50-79), and the female subjects' mean age was 64.3 years (SD=8.2, range=50-79). METHODS: Gender, age, dominant side, height, weight, and activity level were recorded. Eight upper-extremity movements (shoulder flexion, extension, abduction, and medial and lateral rotation; elbow flexion and extension; and wrist extension) and five lower-extremity movements (hip flexion and abduction, knee flexion and extension, and ankle dorsiflexion) were resisted by one of three experienced testers using a strain-gauge hand-held dynamometer. RESULTS: Gender, age, and weight were identified as independent predictors of force for all muscle actions on both the dominant and nondominant sides. These variables were used, therefore, to create regression equations and normative values for the force of each muscle action. CONCLUSION AND DISCUSSION: The reference values provided may allow clinicians who follow the described testing protocol to estimate the severity of force-generating impairments in patients aged 50 to 79 years.

Aged↗
PubMed1994

A new method for the diagnosis of Trichomonas gallinae infection by culture.

Diagnosis of Trichomonas gallinae infection can reliably be made by the demonstration of organisms in material taken from a bird's mouth and crop. This can be examined directly or incubated in a growth medium until organisms are numerous enough to be easily found in aliquots examined with the microscope. We compared two methods of culture diagnosis of Trichomonas gallinae infection in pigeons. A commercially available kit, In-Pouch TF, proved as sensitive for this purpose as in vitro Diamond's medium, but had practical advantages over the usual in vitro system.

Animals↗
PubMed1990

Thymidine kinase in breast cancer.

The enzyme thymidine kinase is associated with DNA synthesis. Thymidine kinase serum levels were studied in normal controls (n = 20), patients with primary breast cancer (n = 60), patients with systemic breast cancer (n = 20) and as a non-cancer disease control group in patients with inflammatory gastrointestinal disorders (n = 20). Comparison of pretreatment values in the cancer patients with the normal controls showed a significant difference between the three groups in relation to stage of disease: mean values 4.22 (+/- 1.08), 6.22 (+/- 2.24) and 9.79 (+/- 7.56) pmol ml-1 h-1 for normal controls, operable breast cancer and systemic breast cancer respectively (P less than 0.005; analysis of variance). Patients with systemic breast cancer had a significantly elevated serum thymidine kinase level compared to controls (P less than 0.01) and patients with primary operable cancer (P less than 0.05). Patients with primary operable cancer had significantly higher serum thymidine kinase levels over normal controls (P less than 0.01). Mean serum TK in patients with inflammatory gastrointestinal diseases was similar to normal controls but significantly less than both patients with primary operable breast cancer and patients with systemic breast cancer. Twenty patients with operable breast cancer were followed up after primary surgery by serial 3-monthly thymidine kinase levels in the disease free interval. Four patients have developed systemic recurrence with a rise in the mean thymidine kinase value to 14.3 pmol ml-1 h-1. Ten patients with advanced breast cancer had serial thymidine kinase levels measured 2-monthly during the first 6 months of primary hormone therapy. The serum values fell in all five responders (mean 9.12-4.78 pmol ml-1 h-1) and rose in all five progressors (mean 8.62-38.5 pmol ml-1 h-1). Serum thymidine kinase reflects stage of disease in breast cancer. Serial thymidine kinase levels in patients with systemic breast cancer reflected response to systemic therapy.

Breast Neoplasms↗
PubMed1990

Purging of T-lymphocytes with magnetic affinity colloid.

There is a well-documented correlation between the number of T-lymphocytes in the bone marrow graft and subsequent development of acute graft-versus-host disease after allogeneic bone marrow transplantation. The incidence of acute graft-versus-host disease may be decreased with elimination of mature T-lymphocytes from the bone marrow graft. We have developed an immunomagnetic separation procedure using an avidin-based magnetic affinity cobalt colloid. Bone marrow cells were incubated with a combination of CD2, CD3, CD4, and CD8 monoclonal antibodies. The cells were washed and then incubated with the biotinylated, affinity-purified IgG fraction of goat anti-mouse immunoglobulins followed by an avidin-based magnetic affinity colloid. The cells were then run through a high-magnetic gradient separation column utilizing an external samarium cobalt magnet. The number of residual T-lymphocytes was assessed by limiting dilution analysis of clonogenic T-lymphocytes. This procedure produces an approximately 1.7-log reduction of antibody-reactive cells with 45% recovery of hematopoietic progenitors (granulocyte-macrophage colony-forming cells, GM-CFC). This causes a reduction of T-lymphocytes in the bone marrow graft to approximately 5 x 10(5) cells/kg body weight.

Antibodies, Monoclonal↗
PubMed1989

Internal fixation of femoral capital physeal injuries in dogs: 40 cases (1979-1987).

Fractures of the femoral capital physis were stabilized with small pins or a lag screw in 36 dogs (4 bilateral injuries). Radiography was used to monitor the development of osteoarthritis in affected joints and narrowing of the femoral neck. More radiographic signs of arthritis (P less than 0.05) developed in the coxofemoral joints of dogs that were less than or equal to 4 months old when injured, compared with those in dogs greater than 4 months old. Of 40 capital physeal injuries, 35% had concurrent ipsilateral coxofemoral joint injuries and developed more radiographic signs of arthritis (P less than 0.05) than did those that had no other coxofemoral injury. Narrowing of the femoral neck developed in 70% of the healing capital physeal repairs, but in most dogs, narrowing was not associated with segmental collapse of the femoral neck. Neither time interval from injury to surgical fixation nor surgical approach used had an effect (P greater than 0.05) on the development of narrowing of the femoral neck.

Age Factors↗
PubMed1987

Magnetic affinity colloid (MAC) cell separation of leukemia cells from autologous bone marrow aspirates.

A colloidal suspension of Co2B with avidin irreversibly adsorbed to the surface has been used with biotinylated antibodies and lectins to eliminate specific cell populations from mixtures with peripheral blood or bone marrows. Using the monoclonal antibodies CF-1 and PM-81 with this magnetic affinity colloid (MAC), we can eliminate five logs of K562 cells from mixtures with peripheral blood or marrow cells as determined by a linear limiting dilution clonogenic assay. We have also used this separation to eliminate clonogenic leukemia cells from fresh samples of peripheral blood and bone marrow from relapsed acute leukemia patients. Using CF-1 alone or in combination with PM-81, we eliminated two logs of colonies and clusters of leukemia cells from the fresh samples. The same antibodies used with MAC separation of hematologically normal marrows allow recovery of greater than 30% of the hematopoietic progenitors.

Bone Marrow Cells↗
PubMed1985

Identification of dipeptidyl peptidase IV as a protein shared by the plasma membrane of hepatocytes and liver biomatrix.

The histotypic organization of liver parenchyma involves specific intercellular contacts and interaction of hepatocytes with supporting biomatrix. Evidence from this laboratory identified a peptide (Hep105, apparent Mr 105 000) that is shared by the plasma membrane of rat hepatocytes and rat liver biomatrix. This report identifies Hep105 as a peptide component of dipeptidyl peptidase IV (DPPIV; EC 3.4.14.-). A monoclonal antibody (MAb 236.3) was shown to immunoprecipitate DPPIV from non-ionic detergent extracts of surface-labeled 125I hepatocytes. The immunoprecipitate contained two 125I-labeled peptides: Hep105 and a peptide of apparent Mr 150000 (Hep150). Proteolysis of 125I-labeled Hep105 and Hep150 by Staphylococcus aureus V8 protease yielded essentially identical patterns of 125I-labeled peptide degradation products, indicating that Hep105 and Hep150 are structurally related. Only Hep150 exhibited DPPIV activity on transblot analysis, an observation that is consistent with the interpretation that it is the monomeric form of the enzyme. Heating (100 degrees C, 5 min) of purified Hep150 in the presence of sodium dodecylsulfate (SDS) resulted in its conversion to Hep105 and the disappearance of any demonstrable enzymatic activity. 3H-labeled diisopropyl fluorophosphate was incorporated into Hep105, indicating that Hep105 contains the active site for DPPIV. Purified rat liver biomatrix was shown to possess significant DPPIV activity. Taken together, these data indicate that Hep105 s a peptide component of DPPIV.

Animals↗
PubMed1985

Role of calcium in cholecystokinin-stimulated phosphoinositide breakdown in exocrine pancreas.

In dispersed acini from guinea pig pancreas cholecystokinin octapeptide (CCK-OP) stimulated breakdown of the phosphoinositides phosphatidylinositol (PI) and its phosphorylated derivative, phosphatidylinositol 4,5-bisphosphate (PI-P2), as measured by a decrease in the mass of PI and decreases in the content of [3H]PI and [32P]PI-P2 in acini prelabeled with myo-[2-3H]inositol or H3(32)PO4. The breakdown occurred in the absence of extracellular Ca2+ and when the CCK-OP-induced rise in free intracellular Ca2+ ([Ca2+]i) was ablated by loading the acini with the Ca2+-selective indicator and chelator quin-2 in the absence of extracellular Ca2+. In contrast to CCK-OP, the calcium ionophore A23187 caused breakdown of PI and PI-P2 in the presence but not in the absence of extracellular Ca2+, although like CCK-OP A23187 stimulated 45Ca outflux, a measure of cellular Ca2+ mobilization, and amylase release during the first 5-10 min of incubation independent of extracellular Ca2+. In the absence of extracellular Ca2+ A23187 did not inhibit the ability of CCK-OP to cause PI breakdown. These results indicate that CCK-OP stimulates breakdown of PI and PI-P2 and that this breakdown is independent of extracellular Ca2+, mobilization of intracellular Ca2+, and the CCK-OP-induced rise in [Ca2+]i. These findings suggest that one of the initial events resulting from CCK-OP interaction with its receptor is phosphoinositide breakdown.

Aminoquinolines↗
PubMed1984

Growth hormone-releasing factor stimulates pancreatic enzyme secretion.

Growth hormone-releasing factors (GRF's) from two human pancreatic tumors (hpGRF's) that caused acromegaly and from the rat hypothalamus ( rhGRF ) were recently isolated and characterized. Although these peptides are potent growth hormone secretagogues, they have not until now been described to have actions outside the pituitary. These GRF's were shown to stimulate digestive enzyme secretion from an exocrine pancreatic preparation in vitro, rhGRF being more than 100 times as potent as hpGRF. Adenosine 3',5'-monophosphate mediates this action of the GRF's.

Amylases↗
PubMed1982

Effect of monensin on osmotic water flow across the toad bladder and its stimulation by vasopressin and cyclic AMP.

The effects of the sodium ionophore monensin on osmotic water flow across the urinary bladder of the toad Bufo marinus were studied. Monensin alone did not alter osmotic water flow; however, the ionophore inhibited the hydrosmotic response to vasopressin and cyclic AMP in a dose-dependent manner. The inhibitory effects of monensin were apparent when the ionophore was added to th serosal bathing solution but not when it was added to the mucosal bathing solution. The inhibitory effect of serosal monensin required the presence of sodium in the serosal bathing solution but not the presence of calcium in the bathing solutions. Thus, it appears that intracellular sodium concentration is a regulator of the magnitude of the hydrosmotic response to vasopressin and cyclic AMP.

Animals↗