PubMed Health⌕ Search

Biomedical subjects

L Jackson

Publications and source records attributed to L Jackson.

At least 55 records · Page 3Linked to original sources
PubMed1999

Pathogenesis of Cryptococcus neoformans is associated with quantitative differences in multiple virulence factors.

Two isolates of Cryptococcus neoformans were previously described as being highly divergent in their level of capsule synthesis in vivo and in their virulence for mice. The highly virulent isolate (NU-2) produced more capsule than a weakly virulent isolate (184A) in vitro under tissue culture conditions and in vivo. This investigation was done to determine if there were differences between the two isolates in other factors that might also contribute to virulence. Growth rate was not a factor as NU-2 grew more slowly than 184A. Based on PCR fingerprinting the two isolates were genetically different providing an opportunity to examine differences in multiple virulence traits. Quantitative analysis revealed that NU-2 expressed significantly more melanin and mannitol than did 184A. Although the isolates expressed the same capsular chemotype, NU-2 produced an additional structure reporter group (SRG) under tissue culture conditions that was not present when grown in glucose salts/urea/basal medium (GSU). Capsular polysaccharide SRGs of 184A were unaffected by shifting the growth conditions from GSU to tissue culture conditions. Our results suggest that pathogenesis of a C. neoformans strain is dictated by the quantitative expression of the strain's combined virulence traits. Regulators of the expression of these genes may be playing key roles in virulence.

Chromatography, Gas↗
PubMed1999

International, collaborative assessment of 146,000 prenatal karyotypes: expected limitations if only chromosome-specific probes and fluorescent in-situ hybridization are used.

The development of chromosome-specific probes (CSP) and fluorescent in-situ hybridization (FISH) has allowed for very rapid identification of selected numerical abnormalities. We attempt here to determine, in principle, what percentage of abnormalities would be detectable if only CSP-FISH were performed without karyotype for prenatal diagnosis. A total of 146 128 consecutive karyotypes for prenatal diagnosis from eight centres in four countries for 5 years were compared with predicted detection if probes for chromosomes 13, 18, 21, X and Y were used, and assuming 100% detection efficiency. A total of 4163 abnormalities (2.85%) were found including 2889 (69. 4%) (trisomy 21, trisomy 18, trisomy 13, numerical sex chromosome abnormalities, and triploidies) which were considered detectable by FISH. Of these, 1274 were mosaics, translocations, deletions, inversions, rings, and markers which would not be considered detectable. CSP-FISH is a useful adjunct to karyotype for high risk situations, and may be appropriate in low risk screening, but should not be seen as a replacement for karyotype as too many structural chromosome abnormalities will be missed.

Chromosome Aberrations↗
PubMed1999

Mechanisms for induction of L-selectin loss from T lymphocytes by a cryptococcal polysaccharide, glucuronoxylomannan.

Disseminated cryptococcosis is accompanied by cryptococcal polysaccharides in the serum and the lack of cellular infiltrates in infected tissues. Cryptococcal polysaccharides given intravenously to mice inhibit the influx of T lymphocytes into the sites of cell-mediated immune response. The focus here was to determine whether cryptococcal polysaccharides modulate the expression of molecules, such as L-selectin, that are important in extravasation of T cells. Cryptococcal glucuronoxylomannan (GXM), but not galactoxylomannan or mannoprotein, was found to cause loss of L-selectin from freshly isolated human T cells of both CD4 and CD8 subsets and from Jurkat cells. With the signaling-pathway inhibitors staurosporine (which inhibits protein kinase C) and herbimycin A (which inhibits protein tyrosine kinases), we showed that GXM or the cryptococcal culture filtrate antigen CneF directly induces L-selectin loss from CD4(+) and CD8(+) T cells via a herbimycin A-sensitive pathway(s) presumably involving one or more protein tyrosine kinases but not via a pathway involving protein kinase C. Loss of L-selectin from the T cells before the T cells have a chance to bind to L-selectin ligands on endothelial cells would be expected to prevent T-cell migration into inflamed tissues and/or lymph organs.

Antibodies, Monoclonal↗
PubMed1999

The impact of hospital restructuring on social work services: a case study of a large, university-affiliated hospital in Canada.

The study investigates the impact of organizational restructuring on social work practice at a large, university-affiliated hospital. The article first reviews relevant literature on the patient-focused care model and presents an overview of the study setting. Several hypotheses are then presented that informed the research process. Workload measurement, interview, and questionnaire data are analyzed to test these hypotheses. The results indicate that the shift to program management has had some intended effects, particularly regarding increases in direct services supporting patients. Social workers reported somewhat lower levels of job satisfaction than expected, which partly reflects the dismantling of the professional infrastructure. Finally, the authors discuss implications for the future of the social work profession under the program management model.

Allied Health Personnel↗
PubMed1997

Dubowitz syndrome in a boy without developmental delay: further evidence for phenotypic variability.

Dubowitz syndrome is an autosomal recessive condition characterized by pre- and postnatal growth retardation, eczema, telecanthus, epicanthal folds, blepharophimosis, ptosis, and broadening of the bridge and tip of the nose. The initial patients described had varying degrees of mental retardation and there is little information about long-term developmental outcome. We present a boy with Dubowitz syndrome who does not have developmental delays, providing additional evidence that the phenotype includes normal neurodevelopmental status.

Abnormalities, Multiple↗
PubMed1997

Locally advanced breast cancer: early results of a randomised trial of multimodal therapy versus initial hormone therapy.

The aim of this study was to investigate initial treatment of locally advanced breast cancer. Patients were randomised to "multimodal" therapy (pre-operative chemotherapy, Patey mastectomy, flap irradiation and adjuvant hormone therapy) (n = 55), or initial "hormone" therapy (n = 53) with further therapy upon tumour progression. The objective response to chemotherapy was 57% (31/54) after four cycles. Of patients on hormone therapy, 36% (19/53) had an objective response and 32% (17/53) disease stasis at a 6 month assessment. At a median 30 months follow-up, there was no notable difference in development of metastases or survival: only 6 patients have uncontrolled loco-regional relapse (4 "hormonal", 2 "multimodal"). The number of treatments per patient required for this loco-regional control was lower in the "hormone" group (mean 2.13 versus 4.20 in the "multimodal" group). This small study has shown that the use of consecutive therapies, with the aim of tumour control, does not appear to compromise outcome in comparison with initial "multi-modal" therapy. Adopting such a policy may allow some patients to avoid unnecessary treatments.

Adult↗
PubMed1997

Specificities of anti-sialyl-Tn and anti-Tn monoclonal antibodies generated using novel clustered synthetic glycopeptide epitopes.

The fine specificities of MAbs generated using novel synthetic clustered STn and Tn glycopeptides as immunogens were compared with the anti-TAG-72 antibodies B72.3 and CC49. Hapten inhibition experiments demonstrated the specificity of several of the MAbs for STn and Tn expressed on ovine submaxillary mucin and tumor derived MUC-1 mucin. Amongst the STn specific MAbs only the B195.3 MAb shows absolute dependence on the presence of sialic acid and specificity to the simple disaccharide NANAA alpha2-6-GalNAc. Identification of tumor associated carbohydrate epitopes in cluster and monomer configurations are possible using MAbs detecting the defined structure specificities described herein.

Animals↗
PubMed1997

Submicroscopic deletions at 16p13.3 in Rubinstein-Taybi syndrome: frequency and clinical manifestations in a North American population.

Rubinstein-Taybi syndrome (RTS) is a well delineated multiple congenital anomaly syndrome characterised by mental retardation, broad thumbs and toes, short stature, and specific facial features. The recent localisation of the disorder to 16p13.3 and subsequent identification of a submicroscopic deletion of this region in RTS patients led us to screen a large cohort of affected subjects using the RT1 probe. Among 64 patients with clinical evidence of RTS, seven (11%) had a deletion. Another patient had a translocation of the region without evidence of a deletion. The features of coloboma, growth retardation, naevus flammeus, and hypotonia have a positive predictive value for the presence of an RT1 deletion. Because of the relatively low frequency of deletions in RTS, the RT1 probe is useful in diagnostic confirmation, but has limited use as a screening tool.

Adolescent↗
PubMed1997

Family physicians managing tuberculosis. Qualitative study of overcoming barriers.

OBJECTIVE: To identify the types of non-clinical barriers family physicians face in the management of TB, and to suggest strategies for overcoming these barriers. DESIGN: Qualitative study based on focus group discussions with family physicians and specialists in different types of practices. SETTING: Private practices, community health centres, and family practice units in hospitals. PARTICIPANTS: Family physicians and specialists working in different practice settings. METHOD: At least one specialist participated in each focus group in order to understand possible differences in non-clinical barriers to TB management between family physicians and specialists. MAIN FINDINGS: Physicians can identify many types of non-clinical obstacles to TB management. Some obstacles appear to be directly related to the organization of family practice medicine, while others stem from the type of patient population seen or the stigma associated with TB. Some physicians question whether or not patient "noncompliance" is in fact a barrier to TB management. Many family physicians believe that they have readily available to them the expert opinion needed to manage TB effectively. CONCLUSIONS: Some specific interventions, such as changes in TB guidelines, could overcome some of the obstacles identified. Differences among family physicians in the organization and nature of their practice, and in their understanding of their role in TB management, however, should be taken into account in developing interventions because such differences could influence both the need for, and receptivity to, any changes.

Attitude of Health Personnel↗
PubMed1996

Murine glomerulotropic monoclonal antibodies are highly oligoclonal and exhibit distinctive molecular features.

We recently produced a panel of seven glomerular-binding mAbs from a nephritic MRL-lpr mouse that bind to histones/nucleosomes (group I) or DNA (group II) adherent to glomerular basement membrane. To elucidate the molecular basis of their binding and ontogeny, we sequenced their variable (V) regions, analyzed the apparent somatic mutations, and predicted their three-dimensional structures. There were two clonally related sets (3 of 4 in group I, 3 of 3 in group II) both of the VHJ1558 family, and one mAb of the VH 7183 family. V region somatic mutations within clonally related sets had little effect on glomerular binding and did not appear to be selected for based on glomerular binding. The VH regions were most homologous with those from autoantibodies to histones, DNA, or IgG (i.e., rheumatoid factors), the Vkappa regions, with those from autoantibodies to small nuclear ribonucleoproteins (snRNP). The VH regions also exhibited an unusual VD junction (in the group I clonally related set) and an overall high content of charged amino acids (arginine, aspartic acid) in complementarity-determining regions (CDRs), particularly in CDR3. Molecular modeling studies suggested that the Fv regions of these mAbs converge to form a flat, open surface with a net positive charge. The CDR arginines in group I mAbs; appear to be located in Ag contact regions of the binding cleft. In sum, these data suggest that glomerulotropic mAbs are a highly restricted set of Abs with distinctive molecular features that may mediate their binding to glomeruli.

Amino Acid Sequence↗
PubMed1996

Limb defects and chorionic villus sampling: results from an international registry, 1992-94.

BACKGROUND: Several reports of limb defects occurring among infants exposed to chorionic villus sampling (CVS) during pregnancy resulted in concern about the safety of this procedure for prenatal diagnosis. To avoid publication bias and evaluate the true risk of limb defects in a CVS cohort, the World Health Organization initiated international registration of post-CVS limb defects in 1992. METHODS: From May, 1992, to May, 1994, 77 infants or fetuses with limb defects from 138 996 pregnancies having CVS were reported to the WHO CVS Registry. These cases were analysed by standardised methods-ie, exclusion of syndromes, inherited disorders, and defects occurring in previable fetuses. The included limb deficiencies were studied by pattern analysis. FINDINGS: Defects of the upper limbs were reported in 64.6%, of the lower limbs in 12.5%, and of both upper and lower limbs in 20.8% of cases. These figures are in agreement with the distribution of limb defects in several large population-based studies. Transverse limb defects occurred in 40.8% and longitudinal defects in 59.2%, compared with 42.7% and 57.3% in an unexposed population. INTERPRETATION: The analysis of this cohort did not show any differences from the background population in the overall frequency or pattern distribution of limb deficiencies. There was also no correlation between gestational age at CVS and severity of defects. Therefore these results do not indicate any increased risk of limb defects after CVS.

Arm↗
PubMed1996

Theileria annulata: altered gene expression and clonal selection during continuous in vitro culture.

Kept in continuous in vitro culture, the protozoan parasite Theileria annulata gradually loses virulence when inoculated into cattle. These attenuated cell lines form the basis of the in vitro live vaccines which have been used successfully to control tropical theileriosis in several endemic regions. In the study reported here, events occurring during in vitro culture of an Indian (Hisar) cell line, which may be associated with the reduction in virulence, have been investigated. Hybridization with two polymorphic DNA probes following Southern blotting showed that selection of particular parasite genotypes occurs very rapidly with culture; a novel hybridization pattern is observed with both probes after 50-100 passages in vitro. In addition to this selection process, immunofluorescence studies using a monoclonal antibody which specifically recognizes virulent T. annulata revealed alterations in antibody reactivity following in vitro culture. This loss of reactivity was observed in three cloned cell lines derived from the early, virulent Hisar line and implies that phenotypic changes resulting from alterations to parasite gene expression are taking place during the attenuation process. When considered with the results from in vivo infections with serial passages of this cell line, it can be proposed that both altered gene expression and selection may be involved in the loss of pathogenicity of T. annulata during continuous in vitro culture.

Animals↗
PubMed1996

Chorionic villus sampling safety. Report of World Health Organization/EURO meeting in association with the Seventh International Conference on Early Prenatal Diagnosis of Genetic Diseases, Tel-Aviv, Israel, May 21, 1994.

Accumulated experience of 138,996 cases of chorionic villus sampling shows that chorionic villus sampling is a safe procedure with an associated fetal loss rate comparable to that of amniocentesis. The chorionic villus sampling registry shows that chorionic villus sampling is currently performed primarily between 9 and 12 weeks' gestation and carried no increased risk of limb reduction defects: the overall incidence of limb reduction defects after chorionic villus sampling is 5.2 to 5.7 per 10,000, compared with 4.8 to 5.97 per 10,000 in the general population. Analysis of the pattern distribution of limb defects after chorionic villus sampling revealed no difference from the pattern in the general population. This applies specifically to transverse limb defects. Together with the overall incidence of limb reduction defects, these data provide no evidence for any risk for congenital malformation determined by chorionic villus sampling. Because chorionic villus sampling is currently performed generally after 8 completed weeks of pregnancy, few data are available for analysis of complications related to earlier procedures. Avoiding early chorionic villus sampling also excludes sampling in cases of early fetal death, which can be diagnosed reliably by ultrasonography at 9 weeks of pregnancy.

Chorionic Villi Sampling↗
PubMed1996

A rare variant of mirror hand: a case report.

Mirror hand is one of the rarest congenital differences of the upper extremity. Typically, there is absence of the radius, duplication of the ulna, and 7 digits in mirrored symmetry about the middle finger. We report a case of a rarer subset of hand duplication in which there is a normal radius and ulna and a hand with 8 digits. The patient underwent surgery to excise the radial 3 digits and to reconstruct the remaining radial digit to function as an opposable, 2 phalanx thumb. Wrist extension was augmented by transferring the digital extensors from the excised fingers to the radial wrist extensors.

Hand Deformities↗