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Biomedical subjects

C L Jackson

Publications and source records attributed to C L Jackson.

At least 55 records · Page 3Linked to original sources
PubMed1996

45,X/46,XY mosaicism: the role of ultrasound in prenatal diagnosis and counselling.

The purpose of this study was to assess the benefit of ultrasound evaluation for fetuses with prenatally diagnosed 45,X/46,XY mosaicism. The charts of all patients who underwent chorionic villus sampling and/or amniocentesis between 1 March 1990 and 31 October 1995 were screened for 45,X/46,XY mosaicism. Cases were divided on the basis of the results of the confirmatory amniocentesis into two groups: (1) confined placental mosaicism (n = 4); and (2) true fetal 45,X/46,XY mosaicism (n = 4). All patients underwent high-resolution detailed ultrasound study between 16 and 22 weeks. If the initial ultrasound study failed to visualize fetal genitalia, scanning was repeated in 2 weeks. Chromosome analysis was carried out on the newborn's skin to confirm the prenatal result. Six cases were found to have 45,X/46,XY mosaicism on chorionic villus sampling. Amniocentesis indicated a normal 46,XY male karyotype for three fetuses and true fetal 45,X/46,XY mosaicism for two cases. One patient declined follow-up amniocentesis. At birth, this newborn was documented to have normal male genitalia and a 46,XY karyotype. An additional two cases underwent amniocentesis only and were documented to have 45,X/46,XY mosaicism. High-resolution detailed ultrasound study between 16 and 22 weeks revealed seven fetuses with normal male genitalia and one fetus with ambiguous genitalia. Of the four neonates with true 45,X/46,XY mosaicism this was the only one found to have ambiguous genitalia. We conclude that the work-up of patients with 45,X/46,XY mosaicism should include ultrasound study to look for ambiguous genitalia. This allows appropriate counselling regarding the natural history of the condition and aids in the planning for management in the postnatal period.

Amniocentesis↗
PubMed1996

Splenic marginal zone cell lymphoma. An immunophenotypic and molecular study of five cases.

Splenic marginal zone cell lymphoma (SMZCL) is a recently described clinicopathologic entity, that is reported to overlap with splenic B-cell lymphoma with villous lymphocytes. The authors describe the clinicopathologic, immunophenotypic, and molecular findings in five cases of SMZCL. There were two males and three females, with a mean age of 68.4 years, who presented with peripheral blood cytopenias and splenomegaly. One patient had an absolute lymphocytosis with many villous lymphocytes. With clinical follow-up of 9 to 37 months, two patients are alive and three patients died of unrelated causes. Splenectomy was done in each patient and the spleens were large, 970-2,400 g. Histologically, the SMZCLs preferentially replaced the marginal and mantle zones with partial or complete replacement of germinal centers in the white pump. The neoplastic cells were predominantly small to medium in size with oval or slightly irregular nuclei and relatively abundant pale or eosinophilic cytoplasm. Immunophenotypic studies demonstrated that the neoplastic cells expressed monotypic immunoglobulin, IgD in four tumors, pan-B-cell antigens, and bcl-2. The tumor cells were negative for the CD2, CD3, CD5, CD10, CD11c, CD25, CD35, CD38, CD45RO, and CD68 antigens, and tartrate-resistant acid phosphatase. Southern blot hybridization revealed immunoglobulin gene rearrangements in all tumors. The major breakpoint region of the bcl-2 gene and the T-cell receptor beta chain gene were in the germline configuration. Polymerase chain reaction studies did not identify the t(14;18) or t(11;14). All cases were negative for p53 protein and single-stranded conformational polymorphism analysis for p53 gene mutations was negative. Our results support the concept that SMZCL is a clinically indolent, low grade B-cell lymphoma that probably arises from splenic marginal zone lymphocytes.

Aged↗
PubMed1996

Stage IE non-Hodgkin's lymphoma involving the dura: A clinicopathologic study of five cases.

OBJECTIVE AND DESIGN: Non-Hodgkin's lymphomas rarely present as a localized mass involving the dura. In this report we describe the clinical, histologic, and immunohistochemical features of five cases of stage IE non-Hodgkin's lymphoma involving the dura. PATIENTS: Four women and one man, 36 to 67 years of age (median 50.6 years). RESULTS: Myelography and magnetic resonance imaging scans revealed discrete expansile masses involving the dura of the cervical, thoracic, and lumbar regions of the spinal cord and the frontal lobe of the brain. Histologically, the tumors were classified in the Working Formulation as small lymphocytic (2), diffuse large cell (2), and large cell immunoblastic (1) (anaplastic large cell lymphoma). Four tumors were of B-cell lineage and the anaplastic large-cell lymphoma was of T-cell lineage. The two small lymphocytic neoplasms had immunoglobulin heavy-chain gene rearrangements as shown by either Southern blot hybridization or the polymerase chain reaction. Four patients underwent decompression laminectomy; three received spinal radiation; two received chemotherapy (one intrathecal, one systemic) for lymphocytosis of the cerebrospinal fluid. The dural mass overlying the frontal lobe was excised and focally irradiated. Clinical follow-up was available for all patients. Four patients were alive 12 to 40 months after diagnosis and showed no evidence of recurrent or disseminated disease. The patient with anaplastic large-cell lymphoma died 10 days after laminectomy, secondary to pulmonary thromboemboli. CONCLUSIONS: We conclude that non-Hodgkin's lymphomas of varied histologic types and of either B- or T-cell lineage may rarely present as a stage IE dural mass. These lesions appear to have a good initial response to treatment; however, longer clinical follow-up is necessary to assess the incidence of relapse and final outcome.

Adult↗
PubMed1995

Effects of brefeldin A on the three-dimensional structure of the Golgi apparatus in a sensitive strain of Saccharomyces cerevisiae.

BACKGROUND: Brefeldin A (BFA), when added to the medium of cultured mammalian cells, induces a reversible block of secretion and disrupts the Golgi apparatus whereas Golgi enzyme markers appear to redistribute into the endoplasmic reticulum (ER). It has been shown in addition that in mammalian cells, BFA would prevent the assembly of coatomer proteins (COP) onto membranes by inhibiting the GTP-dependent interaction of the ADP-ribosylation factor (ARF) with such membranes. The purpose of the present study is to analyze, by stereoelectron microscopy, the structural modifications of Golgi elements and of the ER-Golgi relationship in a BFA-sensitive yeast mutant, S. cerevisiae erg6. METHODS: S. cerevisiae erg6 cells were placed in a medium containing 100 micrograms/ml BFA dissolved in 1% alcohol and collected after exposures of 0.5, 1.5, 5, 10, 15, 20, 30, and 70 min to the drug. Yeasts placed in a BFA-free medium but containing 1% alcohol served as controls. After fixation in 2% glutaraldehyde, the cells were postfixed in reduced osmium and embedded in Epon. Then 0.08-0.2 microns thick sections stained with lead citrate were examined with the electron microscope. Photographs of the thicker sections, tilted at +/- 15 degrees from the 0 degree position of the goniometric stage, were used to prepare stereopairs from which the three-dimensional configuration of the organelles was visualized. Since BFA is known to prevent the interaction of ARF with membranes, the phenotype of the arf1 mutant deficient in this protein was also examined for comparative purposes. RESULTS: In control cells, as in wild-type strains, two types of Golgi elements were observed: small networks of fine tubules seen close and occasionally connected to ER cisternae and coarser tubular networks showing nodular distensions having a size comparable to that of secretion granules. The latter networks were considered as trans-Golgi elements and the former as cis-Golgi elements. Several networks of both types were distributed throughout the cytoplasm. At short time intervals (0.5-5 min) of BFA treatment, the trans-Golgi elements disappeared from the cytoplasm, while the ER-connected cis-Golgi elements developed and formed large spheroidal masses frequently showing concentrically arranged fine tubular networks. Such spheroidal, cage-like structures later disappeared, and after 30 min Golgi elements were no longer identifiable, while ER cisternae assumed pleomorphic configurations as the cells showed signs of degeneration. S. cerevisiae arf1 mutants presented a phenotype similar to that of BFA-treated S. cerevisiae erg6. CONCLUSIONS: It is therefore concluded that soon after exposure to BFA there is, in this sensitive yeast mutant, a transitory hypertrophy of the ER-connected cis-Golgi network presumably resulting from a block at the exit end of this compartment. At longer time intervals (i.e., after 30 min) the Golgi elements are no longer formed, and the cells present signs of cell degeneration.

ADP-Ribosylation Factor 1↗
PubMed1994

Pattern of mutant p53 expression in human astrocytomas suggests the existence of alternate pathways of tumorigenesis.

BACKGROUND: Clinical observations suggest that malignant astrocytomas may arise from well-differentiated, low-grade tumors that have undergone anaplastic progression or may develop de novo. Mutations that alter the function of the p53 gene product are thought to play a critical role in astrocytoma tumorigenesis. The authors studied the pattern of mutant p53 expression in astrocytomas to define its role in the formation of malignant tumors by these different pathways. METHODS: Tissues from 44 astrocytomas corresponding to Grades I-IV of the World Health Organization (WHO) classification were analyzed for the presence of mutations in exons 5, 7, and 8 of the p53 gene using single strand conformation polymorphism (SSCP) and sequence analysis of DNA amplified by the polymerase chain reaction. Immunostaining for mutant p53 proteins was performed on tissues fixed in formaldehyde solution and embedded in paraffin; the tissues were from these 44 astrocytomas and another 103 astrocytomas obtained from archival material. RESULTS: Tumors with mutant p53 genes were reliably identified by immunostaining for mutant p53 proteins. A higher percentage of astrocytomas of histologic Grades II-IV stained positively for p53 than were identified by mutational analysis. The average ages of patients with Grade III/IV astrocytomas with prominent (> 10%) p53 staining and those with sparse (< 10%) or no p53 staining were 44.5, 64.3, and 67.9 years, respectively (P < 0.0001). CONCLUSIONS: The pattern of mutant p53 expression is consistent with a role in driving the progression of low-grade astrocytomas to more malignant tumors. These results provide a genetic basis for the clinical observation that malignant astrocytomas resulting from anaplastic progression occur in a younger patient population than do malignant astrocytomas arising de novo.

Adult↗
PubMed1994

Ultrastructural modifications of vesicular and Golgi elements in the Saccharomyces cerevisiae sec21 mutant at permissive and non-permissive temperatures.

BACKGROUND: The secretory protein transit between cisternae of endoplasmic reticulum (ER) and Golgi elements is blocked when the yeast Saccharomyces cerevisiae sec21 mutant is shifted from the permissive (24 degrees C) to a non-permissive (37 degrees C) temperature, but 30-50 nm vesicles accumulate in the cytoplasm. At the semi-permissive temperature of 33 degrees C there is no complete block but rather a slowdown of the protein transport between ER and Golgi. The purpose of the present investigation is to analyze the structural expression of these events. METHODS: S. cerevisiae sec21 mutants were maintained for 90 min at semi-restrictive (33 degrees C) or restrictive (37 degrees C) temperatures and then progressively returned to 24 degrees C. Following fixation in glutaraldehyde and a postfixation in potassium ferrocyanide reduced osmium, 0.08 to 0.2 microns thick sections were cut from Epon embedded yeasts. Using the thicker sections, stereopairs of electron microscope photographs were prepared and used to visualize the three-dimensional configuration of the organelles. RESULTS: At permissive temperature, the Golgi elements appeared as isolated networks of membranous tubules dispersed throughout the cytoplasm. The diameter of these membranous tubules varied considerably from one Golgi element to another. Larger tubules showed at their intersections distensions with size and staining intensity comparable with that of the secretory granules seen at proximity of the Golgi networks or at the cell periphery. Small vesicles in the 30-50 nm size range were rarely if ever observed in cells grown at permissive temperature. Golgi networks and secretion granules were less conspicuous in mutant cells maintained at 33 degrees C and completely disappeared at 37 degrees C. In both cases, the main structural feature was the presence in the cytoplasm of numerous small vesicles and of short membranous tubules with a diameter identical to that of the small vesicles. As soon as 5 minutes after shifting mutants from 33 degrees C to 24 degrees C, the small vesicles disappeared from the cytoplasm, while secretory granules were actively produced in extensively developed Golgi network. When mutants were returned from 37 degrees C to 24 degrees C, the disappearance of small vesicles was more progressive and concomitant with the progressive reconstruction of Golgi networks. CONCLUSIONS: It is thus postulated that, in the above mentioned conditions, the small vesicles of the sec21 mutant did not act as intermediate carriers between the endoplasmic reticulum and a pre-existing Golgi apparatus, but rather fused together to produce newly formed Golgi networks.

Golgi Apparatus↗
PubMed1994

BFR1, a multicopy suppressor of brefeldin A-induced lethality, is implicated in secretion and nuclear segregation in Saccharomyces cerevisiae.

Brefeldin A (BFA) blocks protein transport out of the Golgi apparatus and causes disassembly of this organelle in mammalian cells. The primary effect of BFA is the release of the non-clathrin coat from Golgi membranes and vesicles. We sought to elucidate the mechanism of BFA action using a genetic approach in Saccharomyces cerevisiae. When an erg6 S. cerevisiae strain is treated with BFA, cell growth is arrested, cells lose viability and secretory proteins are accumulated in the endoplasmic reticulum (ER) and early Golgi compartments. We demonstrate that the mutant sec21 (defective in the S. cerevisiae homolog of gamma-COP, a non-clathrin coat protein) is supersensitive to BFA. Hence BFA probably affects the same processes in S. cerevisiae as in mammalian cells. We used a multicopy genomic DNA library to search for multicopy suppressors of BFA-induced lethality. We identified one such gene, BFR1, that, in addition, partially suppresses the growth and secretion defects of the ER-to-Golgi secretion mutant sec17. A bfr1-delta 1::URA3 deletion strain is viable, but has defects in cell morphology and nuclear segregation, and the mutation accentuates the growth and secretion defects of a sec21 mutant.

Amino Acid Sequence↗
PubMed1994

Recognition and management of pregnant adolescents in the pediatric emergency department.

The early initiation of comprehensive prenatal care is essential to avoid the complications associated with the more than one million adolescent pregnancies in the United States each year. Pediatric emergency physicians can play an important role in the initial diagnosis and appropriate referral of pregnant teenagers. However, previous studies have shown that the diagnosis of pregnancy can be difficult. The goals of this study were to characterize the spectrum of presenting complaints and to evaluate the assessment and disposition of pregnant teenagers presenting to a pediatric emergency department (PED). We retrospectively reviewed the medical records of 94 adolescents who presented with 95 pregnancies to our PED over an 18-month period. The mean age was 15.7 years (range 12 to 19 years). Only 8% mentioned pregnancy in their chief complaint at triage, and a concern about pregnancy was revealed by only 36% during the history of present illness. Ten percent denied they were sexually active. The most frequent complaints were gastrointestinal (77%); other complaints were gynecologic, urinary, or nonspecific. A concurrent sexually transmitted disease (32%) or urinary tract infection (31%) was frequently clinically suspected. At disposition, 26% were transported to an general emergency department for urgent obstetric evaluation; others were referred to a primary caregiver (23%) or obstetrician (39%). Pregnant teenagers present to the PED with a wide variety of complaints that may suggest other diagnoses. A high index of suspicion is required to diagnose pregnancy in adolescent girls so that appropriate care and referral can be initiated.

Adolescent↗
PubMed1994

The quality of medical teaching and learning in rural settings: the learner's perspective.

During 1992-93, the authors produced a video-based teacher development resource kit for rural and isolated general practitioners and hospital medical personnel who are involved in medical teaching. As part of the development process, we surveyed 240 medical undergraduate students of the University of Queensland about their experiences and perceptions of teaching and learning in rural settings in Queensland. For approximately 90% of undergraduate learners, the experience with a rural medical practitioner was extremely positive. The major positive features identified by students were: being treated as a colleague; being allowed/encouraged to work independently; receiving feedback on their work; and being given ample 'hands-on' minor procedural experience and/or teaching. The 10% of students who reported unfavourably on their rural terms identified lack of opportunities to carry out solo consultations/work independently, lack of structure in teaching/learning experiences, and lack of hands-on experience as the major disappointments. The results demonstrate clearly how and why the majority of rural medical teachers in Queensland are effective facilitators of undergraduate learning.

Attitude↗
PubMed1993

Localization of the gene for the ciliary neurotrophic factor receptor (CNTFR) to human chromosome 9.

Ciliary neurotrophic factor (CNTF) has recently been found to be important for the survival of motor neurons and has shown activity in animal models of amyotrophic lateral sclerosis (ALS). CNTF therefore holds promise as a treatment for ALS, and it and its receptor (CNTFR) are candidates for a gene involved in familial ALS. The CNTFR gene was mapped to chromosome 9 by PCR on a panel of human/CHO somatic cell hybrids and localized to 9p13 by PCR on a panel of radiation hybrids.

Amyotrophic Lateral Sclerosis↗
PubMed1993

Cloning of a cDNA encoding a putative human very low density lipoprotein/apolipoprotein E receptor and assignment of the gene to chromosome 9pter-p23.

We report the cloning of a 3656-bp cDNA encoding a putative human very low density lipoprotein (VLDL)/apolipoprotein E (ApoE) receptor. The gene encoding this protein was mapped to chromosome 9pter-p23. Northern analysis of human RNA identified cognate mRNAs of 6.0 and 3.8 kb with most abundant expression in heart and skeletal muscle, followed by kidney, placenta, pancreas, and brain. The pattern of expression generally paralleled that of lipoprotein lipase mRNA but differed from that of the low density lipoprotein (LDL) receptor and the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP), which are members of the same gene family. VLDL/ApoE receptor message was not detected in liver, whereas mRNAs for both LDL receptor and LRP were found in hepatic tissue. In mouse 3T3-L1 cells, VLDL/ApoE receptor mRNA was induced during the transformation of the cells into adipocytes. Expression was also detected in human choriocarcinoma cells, suggesting that at least part of the expression observed in placenta may be in trophoblasts, cells which would be exposed to maternal blood. Expression in brain may be related to high levels of ApoE expression in that organ, an observation of potential relevance to the recently hypothesized role for ApoE in late onset Alzheimer disease. Our results suggest that the putative VLDL/ApoE receptor could play a role in the uptake of triglyceride-rich lipoprotein particles by specific organs including striated and cardiac muscle and adipose tissue and in the transport of maternal lipids across the placenta. The findings presented here, together with recent observations from other laboratories, bring up the possibility that a single gene, the VLDL/ApoE receptor, may play a role in the pathogenesis of certain forms of atherosclerosis, Alzheimer disease, and obesity.

3T3 Cells↗
PubMed1993

Role of endogenous platelet-derived growth factor in arterial smooth muscle cell migration after balloon catheter injury.

The process of intimal thickening after de-endothelializing injury to the rat carotid artery is dependent on the migration of smooth muscle cells from the media. Recent reports have suggested that platelet-derived growth factor may be an important mediator of migration after injury. We have addressed this issue by directly determining smooth muscle cell migration in injured arteries of animals depleted of platelets and after administration of an antibody that blocks platelet-derived growth factor. Because there is a reported association between plasminogen activator synthesis and smooth muscle cell migration, we assayed the activity levels of plasminogen activators after arterial injury and also assessed the effect of a plasmin inhibitor on migration. The data suggest that platelet-derived growth factor, released by platelets at sites of arterial injury, is an endogenous mediator of smooth muscle cell migration; that plasmin generation, catalyzed by tissue-type plasminogen activator, is necessary for migration; and that one way in which platelet-derived growth factor may act is by stimulation of the synthesis of tissue-type plasminogen activator by smooth muscle cells.

Animals↗
PubMed1993

Basic fibroblast growth factor: its role in the control of smooth muscle cell migration.

The formation of an intimal lesion in an injured artery is the consequence of the replication and migration of smooth muscle cells. Recent studies have implicated basic fibroblast growth factor (bFGF) as an important mediator of replication in the arterial media, and platelet-derived growth factor as an important mediator of migration. However, the degree of arterial trauma produced during injury has a significant influence on the time of onset of intimal thickening, suggesting that factors released from damaged smooth muscle cells may affect migration. We have investigated the role of one of these factors, bFGF, in smooth muscle cell migration in vivo. We found that 1) deendothelialization of the rat carotid artery results in significantly more migration when it is accompanied by traumatic injury to the underlying smooth muscle; 2) the rate of migration in arteries that have been gently deendothelialized is significantly stimulated by systemic injection of bFGF; and 3) inhibition of bFGF with a blocking antibody significantly reduces the amount of migration after traumatic deendothelializing injury with a balloon catheter. These findings suggest that bFGF plays an important role in the mediation of smooth muscle cell migration after arterial injury.

Animals↗
PubMed1992

The role of plasminogen activation in smooth muscle cell migration after arterial injury.

The migration of smooth muscle cells from the media to the intima that occurs after balloon catheter injury to the rat common carotid artery has been quantified by an electron microscopic surveying technique. These vessels have also been assayed for plasminogen-activator activity, which was found to rise sharply 4 days after balloon injury. At this time point smooth muscle cells begin to migrate in appreciable numbers. In order to investigate whether there is a causal relationship between plasminogen-activator activity and smooth muscle cell migration, animals were dosed with tranexamic acid. This synthetic inhibitor of plasmin activity reduced smooth muscle cell migration by 73% (p < 0.05), indicating that plasmin activity is necessary for migration after balloon injury. Lisinopril, an inhibitor of angiotensin-converting enzyme, inhibited smooth muscle cell migration after balloon injury by 78% (p < 0.01) but did not influence plasminogen-activator activity. Taken together, these results show that plasmin is a necessary but not sufficient component in the pathway that leads to smooth muscle cell migration after balloon catheter injury in the rat.

Animals↗