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Biomedical subjects

J L Smith

Publications and source records attributed to J L Smith.

At least 19 recordsLinked to original sources

Overexpression of oskar directs ectopic activation of nanos and presumptive pole cell formation in Drosophila embryos.

In Drosophila, a small group of maternal effect genes, including oskar, defines a shared pathway leading to the provision of two determinants at the posterior pole of the embryo. One determinant is the posterior body patterning morphogen nanos, and the other directs germ cell formation. Overexpression of oskar causes the shared pathway to be hyperactivated, with excess nanos activity present throughout the embryo and a superabundance of posterior pole cells. In addition, presumptive pole cells appear at a novel anterior position. Strikingly, formation of these ectopic pole cells is enhanced in nanos mutants. This observation may reflect competition between nanos and the germ cell determinant for a shared and limiting precursor.

Animals

T-cell receptor variable (V) gene usage by lymphoid populations in T-cell lymphoma.

A panel of monoclonal antibodies specific for TcR V gene families was used to study TcR V region expression in 28 cases of malignant and reactive T-cell expansions including four cases of mixed cellularity Hodgkin's disease (HD) and five reactive cases. TcR V beta 5 gene products were represented in three cases of lymphoblastic malignancy (V beta 5.1, V beta 5.2) and two cases of peripheral T-cell lymphoma (PTCL) (V beta 5.1). In the PTCL cases, the expanded family was found in the absence of clonal TcR gene rearrangements and in one of these cases with Ig JH and Ck clonal gene rearrangements consistent with the presence of a phenotypically and histologically undetectable clonal B-cell population. In a third PTCL case not investigated for genotype, the TCR V alpha 12 family was overrepresented. Expanded TcR V alpha 2 and V beta 5.1 families were identified in HD and V beta 8 and V beta 5.2/V beta 5.3 families in a reactive lymph node and CD3 and CD8-positive blood lymphocytosis respectively. Further study of PTCL and related entities are needed to establish whether expanded TcR families are common in those cases that fail to exhibit clonal TcR gene rearrangement.

Antibodies, Monoclonal

Urinary trypsin levels observed in pancreas transplant patients with duodenocystostomies promote in vitro fibrinolysis and in vivo bacterial adherence to urothelial surfaces.

This study evaluated the role of activated urinary trypsin in mediating the increased incidence of infectious and hemorrhagic lower urinary tract complications in pancreas transplant patients with pancreatico-duodenocystostomies (PDC). The effect of trypsin concentrations corresponding to those observed in the urine of PDC patients were studied using an in vitro assay of clot lysis and an in vivo assay of bacterial-urinary tract adherence. Results were compared with those of parallel assays performed using urine from a pancreas transplant patient with a duodenocystostomy and control human urine. All trypsin concentrations studied demonstrated fibrinolytic activity. Fibrinolysis increased as a direct function of both trypsin concentration and duration of substrate exposure (P < 0.0001). Fibrin lysis resulting from the urine of the transplant patient was 4.6 times greater than that predicted based upon assays of total trypsin content in the sample. Fibrinolytic activity in control urine specimens was 0.16% of that observed in transplant urine specimens. Exposure of the rat urinary bladder to 200 micrograms/ml trypsin concentrations, or transplant urine, resulted in a significant increase in bacterial adherence over that seen in control urine from treated animals (P < 0.05). These findings demonstrate a significant effect of urinary trypsin on physiologic processes involved in hemostasis and the prevention of urinary tract infection. Active urinary trypsin may play an etiologic role in hemorrhagic and infectious lower urinary tract complications observed in patients with a PDC.

Animals

Single cervical exostosis. Report of a case and review of the literature.

The authors present a rare case of solitary cervical osteochondroma. Because of its rarity and its predilection for the atlantoaxial area, the diagnosis may be overlooked in evaluating patients having cervical myelopathy. Surgical decompression usually improves the patient's neurologic status.

Adult

Compound (primordial) adnexal carcinoma arising in a systematized compound epithelial nevus.

A distinctive systematized epithelial nevus and associated multifocal carcinomas of the microcystic and sclerosing sweat duct type affected the lower extremities of a 9-year-old girl. The carcinomas were well differentiated and were both adenosyringomatous and microcystic. They qualify as microcystic and compound. In both the epithelial nevi and the carcinoma, primordial potentials are recapitulated.

Biopsy

Prevalence of glioblastoma multiforme in subjects with prior therapeutic radiation.

This retrospective study profiled subjects with glioblastoma multiforme (GBM) who had previously received therapeutic radiation. A chart review was conducted of 100 adult patients diagnosed with GBM and referred to a major medical center in the southwestern United States. Seventeen patients received previous radiation therapy with an average dose of 48.5 Grey (Gy) and an average latency period of 15 years between initial therapy and GBM diagnosis. Of these 17, four white females fit all four attribution criteria for radiation-induced GBM. Two had been treated with radiation for prolactinomas, one for pinealoma and one for squamous cell cancer of the ethmoid sinus. The addition of these four case studies to the previously published descriptions of 80 cases of gliomas, 36 of which were GBM, subsequent to radiation therapy provides additional support for considering therapeutic radiation as a risk factor for GBM development.

Academic Medical Centers

Use of paraffin wax embedded bone marrow trephine biopsy specimens as a source of archival DNA.

AIMS: To evaluate the use of DNA extracted from paraffin wax embedded trephine biopsy specimens as a source of archival nucleic acid for Southern hybridisation studies and polymerase chain reaction (PCR) amplification. METHODS: DNA was extracted simultaneously from paraffin wax embedded bone marrow trephine and lymph node biopsy specimens after incubation of tissue sections for one to five days in lysis mix and proteinase K with periodic sampling. DNA from 10 trephine biopsy specimens was subjected to PCR amplification using HLA-DPB primers to determine whether the extracted nucleic acid was of sufficient quality to permit amplification. RESULTS: For most specimens the greatest yield of high molecular weight DNA was seen after five days' incubation. Unlike lymph node material the quality of extracted nucleic acid and the quantity obtained from trephines was insufficient for Southern blot analysis. PCR amplification using HLA-DPB primers yielded positive results in six out of 10 trephine biopsy specimens. CONCLUSIONS: DNA extracted from paraffin wax embedded trephine biopsy specimens is largely degraded and unsuitable for Southern analysis but serves as a useful source of archival nucleic acid for PCR amplification.

Biopsy

Pneumocandins from Zalerion arboricola. III. Structure elucidation.

Pneumocandin B0 (6) and six related lipopeptides are antifungal and anti-Pneumocystis carinii agents from mutants of Zalerion arboricola, whose structures were determined mainly on the basis of spectroscopic analysis. They belong, along with pneumocandin A0 (L-671,329) previously isolated from these laboratories, to the echinocandin class of antifungal agents. The product from base-catalyzed ring opening involving the hemiaminal position of the dihydroxyornithine residue of B0, has been clearly defined as 6b. Modifications were limited to the 3-hydroxy-4-methylproline, 3,4-dihydroxyhomotyrosine and 4,5-dihydroxyornithine residues of pneumocandin A0.

Anti-Bacterial Agents

oskar mRNA is localized to the posterior pole of the Drosophila oocyte.

Mutants of the maternal posterior-group genes of Drosophila lack posterior body pattern elements and germ cells, both of which form through the action of determinants localized to the posterior pole of the oocyte. We report that transcripts of one of these genes, oskar, become localized to the posterior pole of oocytes shortly after the oocyte begins to differentiate visibly. Analysis of various posterior-group mutants reveals that localization of oskar mRNA is an early step in the posterior localization pathway. In addition, we find that nonsense oskar mutations disrupt osk mRNA localization, while missense oskar mutations do not.

Amino Acid Sequence

Malignant blue nevus.

To elucidate the histologic features and biologic behavior of malignant blue nevus (MBN), 12 cases were analyzed in which the tumor showed no junctional activity and arose in a blue nevus background. Seven patients were men and five were women; their mean age was 48.8 years. Eight lesions were on the scalp, and no patient had a family history of melanoma. The histologic appearance of most lesions was a nodule or nodules of malignant cells in a blue nevus. Mitoses were present in all lesions with atypical forms in eight; however the mitotic rate exceeded two per ten high-power fields in only one lesion. Four lesions had necrosis, and four had a heavily pigmented malignant component. Four patients had recurrences; ten patients had metastases, and eight died of their disease. Therefore MBN is an aggressive neoplasm.

Adult

Further evidence of extrinsic forces in bending of the neural plate.

Bending of the neural plate has long been considered to be driven by principally intrinsic forces generated by wedging of neurepithelial cells. Our previous studies have shown that during neural fold elevation, significant neurepithelial cell wedging occurs only within the median hinge point (MHP), the midline region of neural plate anchored to the notochord. We have also shown that neural fold elevation can still occur when MHP cells are prevented from becoming wedge-shaped but fails to occur when the neural plate is separated from lateral nonneurepithelial tissues, even though MHP cells still become wedge-shaped and the midline neural plate still furrows. Together, these results suggest that neural fold elevation, rather than being driven by neurepithelial cell wedging, is driven, at least in part, by extrinsic forces generated by lateral nonneurepithelial tissues. However, it could be argued that in the absence of localized neurepithelial cell wedging, compensatory and atypical cell wedging occurred uniformly throughout the neural plate, providing forces adequate for neural fold elevation. Likewise, it could be argued that in the process of separating the neural plate from lateral nonneurepithelial tissues, the neural plate was damaged to the extent that the neural folds were unable to elevate. To investigate the validity of these arguments, we removed the following tissues microsurgically prior to neural fold elevation: MHP cells, varying amounts of lateral neurepithelial cells (L cells), and the tissues directly underlying these two populations of neurepithelial cells. We found that the neural folds still formed and underwent elevation, convergence, and fusion, resulting in an essentially normal neural tube, even though MHP cells, the underlying notochord, and some L cells were absent for long craniocaudal distances. These results demonstrate that microsurgery alone does not damage the neural plate sufficiently to prevent neural fold elevation, convergence, and fusion. Moreover, the fact that each of the two persisting remnants of lateral neurepithelium generally remained straight and consistently changed their orientation from horizontal to vertical rather than curling suggests very strongly that bending of the neural plate in these embryos is not the result of compensatory and atypical cell wedging. Finally, the results provide further direct evidence of extrinsic forces in bending because the two remnants of lateral neurepithelium, which were oriented horizontally at the time of tissue extirpation, could not have become oriented vertically in the absence of such forces.

Aging

Crystallization and preliminary characterization of mitogillin, a ribosomal ribonuclease from Aspergillus restrictus.

Mitogillin is a ribonuclease secreted by the fungus Aspergillus restrictus. The substrate for mitogillin is a short, universally conserved, sequence in ribosomal RNA. Cleavage of this sequence inactivates protein synthesis. Mitogillin was crystallized by a two-chamber vapor/liquid diffusion method using ethanol as the precipitant. This method has wider potential in the use of volatile organic solvents as precipitants. Crystals of mitogillin diffract X-rays to lattice d-spacings of at least 1.6 A, and belong to the monoclinic space group P2(1), with a = 50.4 A, b = 82.4 A, c = 38.2 A and beta = 99.8 degrees.

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