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Biomedical subjects

J A Walker

Publications and source records attributed to J A Walker.

At least 73 records · Page 4Linked to original sources
PubMed1993

Corpus callosotomy: a quantitative study of the extent of resection, seizure control, and neuropsychological outcome.

Corpus callosotomy is valuable for controlling medically intractable generalized seizures in appropriate patients, but postoperative development of language disorders, neuropsychological impairment, and motor dysfunction have all been noted. The extent of callosum resection has been implicated as a possible determinant of outcome, but this hypothesis has not been formally tested. Analysis of the records of all patients who underwent corpus callosotomy at the University of California, San Francisco, from 1986 to 1991 showed that, of 15 patients who underwent anterior or complete callosotomy, seven were entirely or nearly seizure-free, four had at least a 50% reduction in seizure frequency, and four had no change. To determine callosal size and extent of callosotomy, preoperative and postoperative magnetic resonance images were measured with computer-based planimetry. Seizure outcome was not significantly associated with preoperative callosal size or extent of callosotomy. Intelligence quotient scores did not change significantly after callosotomy. No severe neuropsychological deficits developed after anterior or complete callosotomy, even in patients with mixed cerebral dominance or bilateral language representation. These results indicate that division of the anterior one-half to two-thirds of the corpus callosum is nearly as effective as more extensive anterior sectioning or complete callosotomy in reducing drop-attack and generalized tonic-clonic seizures in appropriate patients, and that the extent of callosotomy is not an important factor on outcome when at least 50% to 65% of the callosum is divided. Mixed cerebral dominance and other unusual patterns of language and memory organization do not appear to increase the postoperative risk for neuropsychological deficits, regardless of the extent of anterior section.

Adolescent↗
PubMed1993

Regulation of apoptosis in thymocytes.

Programmed cell death, or apoptosis, is tightly regulated during the development of T lymphocytes. Several studies have indicated that in normal mice, thymocyte are sensitive to apoptosis primarily during a brief period relatively late in the CD4+8+ maturation stage, when both positive and negative selection are thought to occur. One factor regulating sensitivity to apoptosis may be the expression and signalling capacity of the TcR/CD3 complex on developing thymocytes. In the present study, we report that sensitivity to apoptosis in immature thymocytes may also be regulated by a mechanism that can prevent induction of apoptosis in many thymocytes. This protective mechanism is induced by TcR/CD3 engagement and cross-linking, as well as by agents that mimic TcR/CD3-dependent phosphoinositol bisphosphate hydrolysis and activate Ca++ fluxes and Protein Kinase C. Cyclosporin A (CsA) inhibits the protective mechanism, permitting the induction of apoptosis by TcR/CD3 or TcR/CD3-mimicking stimuli in otherwise resistant thymocytes. In contrast, mature naive T cells do not undergo apoptosis following stimulation by these agents, even in the presence of CsA, suggesting that in mature naive T-cells the apoptotic machinery itself is normally no longer inducible. We discuss the possible implications of these results for regulation of T-cell development. In this study we also demonstrate that CsA can inhibit the ability of accessory cells to trigger thymocyte apoptosis in accessory cell-dependent assays, which may explain previous reports that CsA can inhibit the induction of thymic clonal deletion in vivo.

Animals↗
PubMed1992

Location and character of the cellular enzyme that cleaves the hemagglutinin of a virulent avian influenza virus.

H.-D. Klenk, W. Garten, and R. Rott (1984, EMBO J. 3, 2911-2915) have reported that hemagglutinin (HA) cleavage of virulent avian influenza viruses occurs in later steps of its intracellular transport and that the cleavage enzyme is calcium dependent and has a neutral pH optimum. The precise intracellular location of the HA cleavage, however, has never been established. Furthermore, because Klenk et al. used the whole cell lysate to examine the cleavage activity and the amino acid sequencing of the cleaved product was not done, the identity of the cleavage enzyme remains to be established. We therefore attempted to systematically characterize the HA cleavage of the virulent avian virus A/tern/South Africa/61 (H5N3). Using an inhibitor of glycoprotein transport (Brefeldin A) and temporal markers of glycoprotein processing, we found that the endoprotease responsible for the HA cleavage acts after the acquisition of endo-N-acetylglucosaminidase H resistance but before the addition of galactose to the molecule, and thus is located in the medial and/or trans Golgi. This observation was directly confirmed by in vitro experiments using rat liver subcellular membrane fractions containing Golgi complex. A fraction rich in galactosyltransferase (a trans Golgi marker) demonstrated the highest HA cleavage activity. The endoprotease in this fraction cleaved only the HA of the virulent avian influenza virus but not that of an avirulent virus. Through amino-terminal sequencing of the HA2 produced by digestion with the endoprotease in the rat Golgi fraction, we established that HA cleavage by the protease occurs at the authentic site. Further studies using the rat Golgi fraction showed that the HA cleavage enzyme is calcium dependent and has a low pH (6.0) optimum. Thus, the pH optimum of the enzyme in the Golgi fraction differs from that in whole cell lysate reported previously.

Animals↗
PubMed1992

Light chain nephropathy in a 19-month-old boy with AIDS.

A 19-month-old boy with AIDS developed clinically unexplainable proteinuria. Biopsied renal tissue was examined by light microscopy, transmission electron microscopy, and immunofluorescence. Findings included an increase of mesangial matrix with occasional nodular sclerosis, mesangial hypercellularity, and glomerular deposits of kappa and lambda light chains. There were deposits of kappa, but not lambda, light chains in the arteriolar walls, and around the tubular and interstitial capillary basement membranes. Quantitative urinary immunoelectrophoresis revealed an extremely high urinary concentration of kappa light chain. These changes are diagnostic of light chain nephropathy. The rarity of light chain nephropathy in childhood and its occurrence in a patient with AIDS make this case unusual.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Resection of dominant opercular gliosis in refractory partial epilepsy. Report of two cases.

Frontal opercular gliosis in the dominant hemisphere caused medically refractory partial epilepsy in two patients. Both patients were aphasic during their seizures, but otherwise had normal speech. Magnetic resonance images showed well-demarcated lesions resembling tumors in each patient; on heavily T2-weighted images, the lesions were hyperintense compared with normal brain. Cortical mapping with subdural grids localized speech to the area of the lesions; therefore, the resections were performed under local anesthesia and speech was tested throughout the procedure. Postoperatively, both patients were seizure-free and had no new neurological deficits. Well-demarcated lesions, even in the dominant operculum, can be safely removed in patients with medically refractory partial epilepsy.

Adolescent↗
PubMed1992

Attenuation of contraction-induced skeletal muscle injury by bromelain.

The proteolytic enzyme, bromelain, reportedly has therapeutic effects in the treatment of inflammation and soft tissue injuries. We tested the hypothesis that bromelain attenuates skeletal muscle injury induced by lengthening contractions. The left extensor digitorum longus (EDL) muscle of anesthetized hamsters was injured using a motorized foot pedal which repeatedly flexed/extended the foot through a range of 125 degrees. The EDL muscle was electrically stimulated for 400 ms during plantarflexion. Animals were assigned randomly to either a 0-d group (evaluated 3-h post-injury) or to untreated (UT) or bromelain-treated (T) groups, evaluated 3, 7, or 14 d post-injury. Following injury, T received 5 mg.kg-1 b.w. of bromelain, twice daily. Maximum isometric tetanic force (Po) was measured in vitro, then muscles were fixed, sectioned, and examined for evidence of fiber damage. The Po of injured muscles from T were higher than Po of injured muscles from UT at 3 (18.7 +/- 0.4 vs 16.5 +/- N.cm-2 and 14 d (20.5 +/- 0.6 vs 18.2 +/- 0.6 N.cm-2) (P less than 0.05), but not 7 d (19.5 +/-0.7 vs 17.7 +/- 0.8 N.cm-2). The Po of UT injured muscles were significantly lower than Po of contralateral control muscles at all time periods. Po of injured muscles from T were lower than Po from control muscles at 3 and 7 d (P less than 0.05), but not 14 d. The number of intact fibers of 3-d UT injured muscles was lower than the number of intact fibers in control muscles (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Parental attitudes toward pediatric organ donation: a survey.

We conducted a telephone survey of parents in the National Capital Region to assess their intention to donate their child's organs and to provide physicians with information that could help alleviate their concerns about approaching parents for consent. Of 339 parents who agreed to answer questions after being given details of their child's "death" 288 (85%) said that they would be willing to donate their child's organs. The degree of willingness was associated with the certainty of death, altruism and empathy toward children in need of an organ, previous discussion of organ donation with a family member and knowledge of an adolescent or adult child's attitude toward donation. Factors that inhibited the intention to donate included uncertainty of death, insufficient information from medical professionals and fear of multilation. The child's age was not significantly associated with intention to donate. Concordance between the results and actual donation rates in Canada and the United States supports the generalizability of the survey findings.

Adolescent↗
PubMed1990

Radiation-induced bilateral cystic temporal lobe necrosis: reversal of memory deficit after fenestration and internal shunting. Case report.

The authors report a case in which bilateral cystic temporal lobe necrosis developed after treatment of nasopharyngeal lymphoepithelioma with 7000 cGy of external beam radiation. The patient presented with an isolated memory deficit that was documented by neuropsychological testing. After fenestration and internal shunting of both cysts, there was striking resolution of the lesions and of the memory deficit.

Brain Diseases↗
PubMed1990

The effect of oral bases on enteral aluminum absorption.

Physicochemical considerations suggest that citrate may potentiate gastrointestinal aluminum absorption via the formation of an aluminum citrate moiety. We tested this hypothesis and also studied whether sodium bicarbonate would have a similar effect. Eight healthy adults each partook of four oral regimens: aluminum alone, aluminum plus sodium bicarbonate, aluminum plus citrate (as Shohl's solution), and citrate alone. Twenty-four hour urine collections were obtained immediately preceding and during the second day of each medication period for determination of aluminum content. A significant but similar increment in urinary aluminum occurred with both aluminum alone and aluminum plus sodium bicarbonate, while only a small increment was noted with Shohl's solution alone. The rise in urinary aluminum obtained with aluminum plus Shohl's solution, however, was nearly eight times that seen with either aluminum alone or aluminum plus sodium bicarbonate (327 micrograms vs 45 micrograms and 41 micrograms, respectively). Citrate thus appears to augment gastrointestinal aluminum absorption markedly, an effect not shared by an equivalent dose of sodium bicarbonate. Citrate administration to patients with renal failure who are also taking aluminum-containing medication may be harmful.

Administration, Oral↗
PubMed1990

A rapid method for determining the relationship between cDNA clones.

We describe a technique for rapidly screening the inserts of plasmids for homology to each other by using DNA fragments isolated in agarose gels to probe Southern blots of DNA prepared by the "miniprep" alkaline lysis method. The procedure includes a technique for labeling DNA fragments in agarose gel slices without further purification. The protocol results in a significant savings in time and expense and a considerable increase in fragment yield over methods involving fragment purification from polyacrylamide or agarose gels.

Base Sequence↗
PubMed1989

Expression of the pneumolysin gene in Escherichia coli: rapid purification and biological properties.

The gene for pneumolysin, the thiol-activated toxin from Streptococcus pneumoniae, has been expressed in Escherichia coli. The recombinant protein has been purified using a rapid, high yield, purification procedure and has been shown to be identical with respect to N-terminal amino-acid sequence, specific activity, effect on human polymorphonuclear phagocytes and effect on human complement to the native toxin purified from the pneumococcus. This provides a large enough source of material to begin investigation of pneumolysin as a candidate for inclusion in a pneumococcal vaccine.

Amino Acid Sequence↗
PubMed1989

The anatomy of mental unity and volition: an alternate view.

The preceding paper, by Louis Tinnin, challenges us to consider that there is a brain agency responsible for mental unity, volition and consciousness, which the author labels a "governing mental system" (GMS), or "ego," and that the neural substrate for this GMS is Wernicke's Area. The primary evidence in support of this position comes from three sources: a review of brain and language development in normal and abnormal individuals (e.g., deaf children); studies of patients who have undergone corpus callosum section for intractable epilepsy; and some observations of memory processing during the intracarotid sodium amytal (Wada) procedure. Our comments address two issues. The first is an analysis of the adequacy of these three sources as evidence for Tinnin's position. The second is a description of an alternative model to account for the mental system we agree exists but do not yet understand.

Cerebral Cortex↗
PubMed1989

Pneumolysin, the thiol-activated toxin of Streptococcus pneumoniae, does not require a thiol group for in vitro activity.

The role of the single cysteine residue in the activity of the thiol-activated toxin pneumolysin was investigated using oligonucleotide-mediated, site-directed mutagenesis. Three modified toxins in which the cysteine residue was changed to an alanine, a serine, or a glycine residue were purified to homogeneity and examined for activity. The Cys-428----Ala modified toxin was indistinguishable from the wild-type recombinant toxin in terms of hemolytic activity and lytic and inhibitory effects on human polymorphonuclear leukocytes (PMN), indicating that the cysteine residue is not essential for toxin activity. The Cys-428----Ser and Cys-429----Gly modified toxins had reduced activity on erythrocytes and polymorphonuclear leukocytes, being 6 and 20 times less active than the wild type, respectively. However, all the modified toxins formed oligomers in erythrocyte membranes to the same extent as the wild-type recombinant toxin. This suggests that the cysteine residue at position 428 is involved in neither the binding of toxin to membranes nor its insertion into the membrane, and also that the formation of oligomers is not by itself sufficient for toxin activity.

Bacterial Proteins↗
PubMed1989

Cigarette smoking and non-fatal myocardial infarction in women: is the relation independent of coronary artery disease?

The relation of cigarette smoking to both coronary disease and non-fatal myocardial infarction was examined in a cross sectional study of 1053 women who underwent coronary arteriography. As compared with the 489 women who had never smoked cigarettes, ever-smokers (mean duration of smoking, 25 years) were 1.6 times as likely to have significant stenotic disease and were 1.9 times as likely to have suffered a myocardial infarction. These associations were strongest in women under 50 years of age, with odds ratios of 3.5 for coronary artery disease and 4.5 for myocardial infarction. Although the extent of stenotic disease and prior myocardial infarction were strongly associated, women who smoked cigarettes remained at increased risk of a myocardial infarction even after their increased coronary artery disease had been taken into account. For example, heavy smokers (greater than 30 pack-years) were 2.3 times as likely to have had a myocardial infarction as were non-smokers; controlling for the extent of stenotic disease (in addition to age and other risk factors) reduced the estimated relative risk to only 1.9. Stratified analyses showed that this increased risk for clinical disease among smokers was evident at all levels of occlusion, even among women with minimal stenotic disease. These results, collected at the time of arteriography, suggest that non-atherogenic mechanisms may be important in the aetiology of myocardial infarction among women who smoke cigarettes.

Coronary Artery Disease↗