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Biomedical subjects

C Williams

Publications and source records attributed to C Williams.

At least 469 records · Page 26Linked to original sources

Responses of asthmatic and non-asthmatic athletes to prolonged treadmill running.

Metabolic and cardio-respiratory responses of four asthmatic and four non-asthmatic athletes to two hours of treadmill running at 70 percent of maximal oxygen uptake are compared. The asthmatic group had pre-exercise airflow obstruction, as indicated by the lower forced expiratory volume in one second (FEV1) even after medication (2.90 +/- 0.661) compared to the non-asthmatic group (4.09 +/- 1.331). Changes in blood lactate, glucose and catecholamine concentrations as a result of the two hour run were similar for the two groups. However, the pattern of breathing was different. The asthmatics had a slower breathing frequency but a similar tidal volume to the non-asthmatics. Both groups had an increase in the ventilation rate over the two hour run. For the non-asthmatic group, this increase in ventilation was achieved by an increase in the breathing frequency (p less than 0.01), whereas tidal volume was reduced (p less than 0.05). The increase in the ventilation rate over the two hour run for the asthmatic group was brought about by a small increase in breathing frequency (p less than 0.05), whereas tidal volume was not changed. This maintenance of the tidal volume by the asthmatic athletes during endurance running may compensate for the airflow obstruction, and so allow successful participation in endurance running.

Adaptation, Physiological↗

Value of physiological measurement in sport.

The value of physiological measurement in sport lies in the opportunity it provides to learn more about the responses of individuals to the demands of exercise, the particular physiological characteristics which allow some individuals to become successful at some sports, but not others, and the physiological adaptations to training which underlie improvements in human performance. In this paper, running has been used to illustrate the value of making physiological measurements on sportsmen and women because it is an activity which is common to many sports. Sports can be divided into two broad groups, namely the 'endurance sports' and, what may be called, the 'multiple sprint' sports. The focus of attention of this brief overview is the physiological measurements which provide a general description of the 'fitness' for these sports.

Anaerobic Threshold↗

Seeding the tumor.

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Brachytherapy↗

Focal dystonia following soft tissue injury: three case reports with long-term outcome.

Three cases of focal dystonia are described which followed upper extremity injuries. Each patient developed a dystonic posturing in that limb; two patients improved when their initial condition was addressed. Various authors have proposed that focal dystonia represents a limited form of generalized dystonia, which is believed to result from a disturbance of striatopallidal-thalamic input to the supplementary motor area (SMA)--a vital executive area for motor control. An alternative hypothesis is offered; that is, a similar dysfunction of the SMA could be the result of altered sensory information from a painful limb disturbing the crucial integration between sensory input and motor performance. The following three examples of such integration are provided: (1) the long loop or transcortical reflex, (2) input of distinctive somatosensory neurons to the SMA, and (3) the projection of proprioceptive and tactile sensory input into peripheral receptive fields of the motor cortex.

Adolescent↗

Two-needle calculation of recirculation compared with the standard three-needle method.

A two-needle method for calculating recirculation was compared with the standard three-needle method, substituting the standard phlebotomy of a remote vessel during dialysis with blood obtained from the dialyzer inlet needle 15 minutes after the termination of dialysis. Twenty patients were studied prospectively. There was no significant difference between corrected blood flow calculated with the standard and two-needle methods. The BUN obtained from the inlet line needle 15 minutes after conclusion of the treatment did not differ significantly from the BUN concentration in the specimen from a contralateral arm drawn five minutes before termination of dialysis. Recirculation calculated by the two-needle method correlated well with the results obtained with the standard three-needle method. The two-needle method provides a convenient alternative to the standard three-needle method of determining recirculation.

Aged↗

[Delayed acute measles encephalitis].

Delayed acute encephalitis is a rare complication of measles that may occur either in immunodepressed patients or in patients without overt immunodepression. In the present series of 8 cases, diagnosis was made on CSF/serum measles antibody titre and/or intranuclear paramyxovirus nucleocapsides identified by electron microscopy in the central nervous system cells. The disease is characterized by the association of focal defects (monoparesis, hemiparesis, aphasia, a.s.o.) with periodic myoclonic jerks without major impairment of consciousness. The encephalitis lasted 2 to 4 weeks and 3 patients died. With the exception of 1 case, all the patients had severe sequelae after a follow-up of 1 to 9 years. The EEG showed diffuse polymorphous delta waves, with a predominance on the side opposite to the myoclonias and pseudoperiodic complexes in all cases. CT scan was abnormal in 4 of 6 cases, showing hypodense areas. Antiviral or immunogenic therapeutic trials were administered to 5 patients without clear improvement. Sensitive methods of antibody dosage seem to be useful for the early diagnosis of the disease.

Acute Disease↗

The smaller human VH gene families display remarkably little polymorphism.

We report the nucleotide sequence of 30 distinct human VH gene segments from the VHIV, VHV and VHVI gene families. When these sequences were compared to previously published sequences from these smaller human VH families a surprisingly low level of polymorphism was noted. Two VHIV gene segments from unrelated individuals were identical to two previously published VHIV sequences. Five VHV sequences were identical and seven VHVI gene segments were identical. Where differences were found between the sequences, allele specific oligonucleotide probes were used to verify the germline nature of the change and to test for segregation in several large kindreds. These data provide evidence that at least some human VH gene segments are remarkably stable.

Alleles↗

Transepithelial transport of drugs by the multidrug transporter in cultured Madin-Darby canine kidney cell epithelia.

We studied transepithelial transport of 3H-labeled hydrophobic cationic drugs in epithelia formed by wild-type and by drug-resistant Madin-Darby canine kidney (MDCk) cells that had been infected with a retrovirus carrying the multidrug-resistance (MDR1) cDNA which encodes the P-glycoprotein. P-glycoprotein is an ATP consuming plasma membrane multidrug transporter responsible for the efflux of cytotoxic chemotherapeutic drugs from resistant cancer cells. Wild-type MDCK cells have small amounts of P-glycoprotein detected by immunoprecipitation. Net transepithelial transport across wild-type MDCK epithelia was demonstrated. Basal to apical flux of 100 nM vinblastine was about six times higher than apical to basal flux. Addition of unlabeled vinblastine reduced basal to apical flux of tracer and increased apical to basal flux of tracer, a pattern expected if there is a saturable pump that extrudes vinblastine at the apical plasma membrane. Daunomycin, vincristine, and actinomycin D were also actively transported and at 20 microM these agents inhibited transport of vinblastine, suggesting that wild-type MDCK cells have a common transporter for all these drugs. Vinblastine transport was also inhibited by 20 microM verapamil, which inhibits the multidrug transporter and reverses multidrug-resistance in non-polarized cells. Net transepithelial transport of all these cytotoxic drugs and of verapamil was much higher in epithelia formed by MDCK cells infected with a human MDR1 virus (MDR-MDCK) which is expressed on the apical surface of MDR-MDCK monolayers. Because the transport of these cytotoxic drugs and verapamil is increased in MDR-MDCK epithelia compared to wild-type MDCK epithelia, transport in both these cell populations can be attributed to P-glycoprotein. These results are consistent with a role for P-glycoprotein in multidrug secretory transport across the epithelium of the proximal tubule since P-glycoprotein is normally expressed on the apical membrane of proximal tubule cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Genetic analysis of DNA from single human oocytes: a model for preimplantation diagnosis of cystic fibrosis.

Gene sequences in human oocytes were studied to investigate the possibility of diagnosing inherited or sporadic genetic disease before implantation after in vitro fertilisation. By specific amplification the possibility of analysing the DNA from single human oocytes for a specific gene was shown, and genotypes for markers closely linked to cystic fibrosis and Duchenne muscular dystrophy were determined. Single oocytes were used to approximate the total amount of DNA present in a single cell taken for biopsy from a 4-16 cell blastocyst. With a new technique for specific DNA amplification, the polymerase chain reaction, these data can be obtained within several hours of cell isolation. Extreme care must be taken to avoid any contamination of the sample with DNA from other sources. With this technique genotyping for single gene disorders is feasible with an accuracy and on a time scale that would allow implantation of the zygote after in vitro fertilisation without freezing.

Base Sequence↗

A 113-amino acid fragment of CD4 produced in Escherichia coli blocks human immunodeficiency virus-induced cell fusion.

A gene encoding a 113-amino acid, NH2-terminal fragment of CD4, rsT4.113, was constructed and expressed in Escherichia coli under the control of the tryptophan operon promoter. Following induction, rsT4.113 is produced at 5-10% of total E. coli protein, and it is found in inclusion bodies. The protein is purified in two steps under denaturing and reducing conditions. Solubilized rsT4.113 is first purified on a column of Q-Sepharose to remove low molecular weight contaminants and then purified to greater than 95% homogeneity by gel filtration. Renaturation of rsT4.113 is achieved at approximately 20% yield by dilution and dialysis. High performance liquid chromatography analysis of renatured rsT4.113 reveals a less than 15% contaminant of reduced protein. Purified and renatured rsT4.113 contains epitopes for both OKT4a and Leu3a, anti-CD4 monoclonal antibodies which block CD4-gp 120 association, but lacks measurable affinity toward a nonblocking anti-CD4 monoclonal antibody, OKT4. By comparison to a longer form (375 amino acids) of recombinant soluble T4 produced in mammalian cells that contains the entire extracellular domain, rsT4.113 has a comparable affinity for binding to OKT4a and Leu3a in a radioimmunoassay. Analysis of antiviral activity of rsT4.113 demonstrates that the E. coli-derived protein inhibits human immunodeficiency virus-induced syncytium formation with an IC50 of 5-10 micrograms/ml. These data demonstrate that the human immunodeficiency virus-binding domain of CD4 is localized within the NH2-terminal 113 amino acids of CD4 and is contained within a structure homologous to the kappa variable-like domain of immunoglobulins.

Amino Acid Sequence↗

Clinical, pathological, and biochemical studies on an infantile case of sulfatide/GM1 activator protein deficiency.

A 28-month-old black male died with severe complications of mental and motor deterioration, seizures, and aspiration. Autopsy demonstrated moderate liver enlargement, normal spleen and kidneys, small testes, and a grossly normal brain. Further examination showed irregular macrogyrae with evidence of a storage or sclerotic process. Thin layer chromatography of the lipids in formalin-fixed tissue demonstrated elevated levels of ceramide trihexoside and possibly sulfatides in liver and a decrease in the ratio of galactosylceramide to sulfatide in brain. Examination of the gangliosides in formalin-fixed brain indicated a slight increase in the percentage of GM1 ganglioside and a clear elevation in GM2 and GM3 gangliosides. Cultured skin fibroblasts had a normal activity for a large number of lysosomal enzymes including arylsulfatase A and galactocerebrosidase. When the cells were loaded with [14C]sulfatide only about 12% of the sulfatide was metabolized after 3 days. Extracts of the cells were subjected to SDS-PAGE and immunoblotting with antisphingolipid activator protein-1 (SAP-1) rabbit antiserum, and no cross-reacting material was detected confirming the diagnosis of metachromatic leukodystrophy caused by SAP-1 deficiency. This patient was clinically more severe than the other patients described previously with this deficiency. Further studies are underway to define the nature of the mutation in this patient.

Autopsy↗

Proteins of the acrosomal region in mouse sperm: immunological probes reveal post-testicular modifications.

Due to the central role the acrosomal region plays in sperm-egg interactions, monoclonal antibodies (mAbs) were used to identify components of this domain in mouse sperm. Several sperm proteins that localize specifically to the anterior acrosomal region are described here in terms of electrophoretic mobility, susceptibility to proteolytic degradation, and post-translational modification during epididymal transit. Six different mAbs were used, each recognizing a distinctive antigen (Ag) or set of Ags in cauda epididymal mouse sperm: a doublet of 185/200 Kd (M42 mAb); 150-160 Kd (M5 mAb); 105 Kd (W71 mAb); 21, 35, and 60 Kd (M41 mAb); 27 and 33 Kd (W33 mAb); and 57 and 86 Kd (W108 mAb). Previously reported work implicates two of these, M42 Ag and M5 Ag, as participants in sperm-zona interaction (Saling and Lakoski: Biol Reprod 33:527-536, 1985; Saling: Dev Biol 117:511-519, 1986; and Lakoski et al.: Biol Reprod 38:221-233, 1988). Recognition of some (M42, M5, W108), but not all (W33), of the Ags by their corresponding mAbs was affected by sperm incubation with proteases (trypsin or collagenase). Evidence of post-translational modification during epididymal maturation was suggested by altered electrophoretic mobility of several of the Ags (M42, M5, W33, and W108) accompanying sperm transit from proximal to distal epididymis. Retention of sperm within the caput epididymis prevented structural alterations for the four proteins examined, indicating that spatial rather than temporal factors are critical for Ag modification in maturing mouse sperm.

Acrosome↗

Blockade of histamine-stimulated alterations in cerebrovascular permeability by the H2-receptor antagonist cimetidine.

Histamine has been shown previously to cause dose-dependent systemic hypotension and concurrent alterations in the permeability of the blood-brain barrier of rats. The purpose of the present study was to determine whether histamine-induced changes in cerebrovascular permeability were mediated by the histamine H2-receptor. Wistar-Kyoto (control) and spontaneously hypertensive rats were pretreated with the histamine H2-receptor antagonist cimetidine (10 mg/kg), followed by saline or histamine (1.25, 2.5 or 5.0 micrograms/kg). Premedication with cimetidine did not block histamine-induced systemic hypotension. The permeability of the blood-brain barrier was measured with 131I-labelled serum albumin (RISA) or with 99mTc-sodium pertechnetate (TcO4-). In both control and spontaneously hypertensive animals, cimetidine prevented histamine-induced changes in the permeability of the blood-brain barrier to either tracer. These findings suggest that the H2-receptor is the prime mediator of histamine-stimulated alterations in cerebrovascular permeability.

Animals↗