Aspergillus laryngotracheobronchitis presenting as stridor in a patient with peripheral T cell lymphoma

Invasive aspergillosis is a serious opportunistic infection in immunocompromised patients. The case history is described of a 44 year old patient with peripheral T cell lymphoma who developed hoarseness and stridor after chemotherapy. Aspergillus fumigatus was isolated repeatedly from the sputum. Bronchoscopic examination showed symmetrical creamy-white exophytic lesions involving both vocal cords and the supraglottic area. There was diffuse tracheobronchitis with multiple raised cream-coloured plaques in the trachea which histologically consisted of numerous septate branching hyphae consistent with Aspergillus species. The lesions responded to systemic treatment with amphotericin B.     

Rb1 gene expression in B-cell lymphocytic leukaemia cases with deletion in the 13q14 region

Recent studies have been carried out to delineate further the role of the Rb1 gene in B-cell chronic lymphocytic leukaemia (B-CLL). The suggested role of the Rb1 gene in this disease was based on cytogenetic data. CLL patients (40 in toto) were examined using cytogenetic and molecular biological methods. R-banding analysis of metaphase chromosomes revealed aberrations in only seven cases containing either the Rb1 gene or a chromosome 13 monosomy. No evident differences were found by RT-PCR analysis of Rb1 gene expression. The amounts of the RT-PCR products obtained appeared to be approximately equal in all cases, and was independent of the clinical stage, immunophenotypes and LPS or TPA stimulation.     

Molecular linkage of the human alpha 1-antitrypsin and corticosteroid-binding globulin genes on chromosome 14q32.1

The genes encoding alpha 1-antitrypsin (alpha 1AT; gene symbol PI) and corticosteroid-binding globulin (CBG) are part of a cluster of structurally related serine protease inhibitor (serpin) genes on human Chromosome (Chr) 14q32.1. This cluster also includes the genes encoding alpha 1-antichymotrypsin (AACT) and protein C inhibitor (PCI), as well as an alpha 1-antitrypsin-related sequence (ATR; gene symbol PIL). In this report we present a detailed restriction map of a 110-kb region of genomic DNA that includes the alpha 1AT, ATR, and CBG genes. Gene order in this interval is tel-alpha 1AT-ATR-CBG-cen, and all three genes are transcribed in a distal-to-proximal orientation. Within the gene cluster, ATR is approximately 12 kb downstream of alpha 1AT, and CBG is about 57 kb downstream of alpha 1AT. Repetitive DNA sequences have been mapped throughout the interval, and several new restriction site polymorphisms in the region are described.     

Adult T cell leukaemia lymphoma in a non-aboriginal Australian woman with no apparent risk factors

OBJECTIVE: To present a case of adult T cell leukaemia lymphoma (ATLL) in a non-Aboriginal Australian woman with no apparent risk factor. CLINICAL FEATURES: A 43-year-old Australian woman of European descent presented with a febrile illness associated with generalised lymphadenopathy and splenomegaly. INVESTIGATIONS: There was lymphocytosis in the peripheral blood with a T helper cell phenotype. There were also lytic bone lesions with associated hypercalcaemia. HTLV-1 antibody was detected by agglutination assay and confirmed by western blot test. TREATMENT AND OUTCOME: After initial response to CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisolone), she relapsed and died with central nervous system involvement eight months after the initial diagnosis. CONCLUSION: To our knowledge this is only the third case of ATLL in a non-Aboriginal person in Australia.     

Expressed sequences as candidates for a novel tumor suppressor gene at band 13q14 in B-cell chronic lymphocytic leukemia and mantle cell lymphoma

Deletions affecting the interval between the RB1 gene and marker D13S25 at band 13q14 are the most frequent genetic abnormalities of B-cell chronic lymphocytic leukemia (B-CLL) and indicate the presence of a novel tumor suppressor gene in this region. In the current study, a high resolution physical map of fragments spanning one megabasepair (Mb) of genomic DNA at the critical 13q14 segment was constructed. To define the minimal region of loss within the RB1 and D13S25 interval, we screened 322 B-CLLs for deletions at either of the two loci. Thirty mantle cell lymphomas (MCLs) were included in the analysis because we observed a 13q14 deletion pattern similar to B-CLL in this disease. The incidence of 13q14 deletions was 51% in B-CLL and 70% in MCL, respectively. No frequent loss of the BRCA2 gene at band 13q12 was found. Detailed deletion mapping at band 13q14 with probes from the RB1-D13S25 interval lead to the identification of a critical deletion region 400 kb in size. Within this region two segments were most frequently affected, one at D13S272 120 kb in size and another 240 kb distal of D13S272 80 kb in size. From these two segments expressed sequences were identified as candidates for the putative 13q14 tumor suppressor gene involved in the pathogenesis of B-CLL and MCL.     

Oncogene rearrangement in non-Hodgkin's lymphoma with a 14q+ chromosome of unknown origin

Southern blot analysis was performed with a panel of DNA probes to detect rearrangements of c-myc, bcl-1, bcl-2 and bcl-3 in 14 cases of B-cell non-Hodgkin's lymphoma (NHL) with a clonal cytogenetic rearrangement involving the chromosome 14q32 locus and no known donor chromosome [t(14;?)(q32;?)]. In our experience, 21% of all chromosomal abnormalities involving the 14q32 locus in B-cell NHL are of this type. We found oncogene rearrangements in five of the 14 cases: bcl-1 rearrangement on one mantle zone lymphoma, bcl-2 rearrangements in two follicular lymphomas, and c-myc rearrangements in two small noncleaved cell lymphomas. We conclude that a 14q32+ abnormality of unknown origin is a relatively frequent karyotypic finding in B-cell NHL. In one third of the cases, known oncogenes that have been previously described in reciprocal translocations involving the immunoglobulin heavy chain locus were shown to be involved in the 14q32+ abnormality. The translocations in the other cases are likely to have involved one of the above oncogenes with breakpoints not revealed by the probes employed, other known oncogenes, or oncogenes that have not yet been identified.     

T cell receptor gene deletion circles identify recent thymic emigrants in the peripheral T cell pool

Progenitor cells undergo T cell receptor (TCR) gene rearrangements during their intrathymic differentiation to become T cells. Rearrangements of the variable (V), diversity (D), and joining (J) segments of the TCR genes result in deletion of the intervening chromosomal DNA and the formation of circular episomes as a byproduct. Detection of these extrachromosomal excision circles in T cells located in the peripheral lymphoid tissues has been viewed as evidence for the existence of extrathymic T cell generation. Because all of the T cells in chickens apparently are generated in the thymus, we have employed this avian model to determine the fate of the V(D)J deletion circles. In normal animals we identified TCR Vgamma-Jgamma and Vbeta-Dbeta deletion circles in the blood, spleen, and intestines, as well as in the thymus. Thymectomy resulted in the gradual loss of these DNA deletion circles in all of the peripheral lymphoid tissues. A quantitative PCR analysis of Vgamma1-Jgamma1 and Vbeta1-Dbeta deletion circles in splenic gamma delta and Vbeta1(+) alphabeta T cells indicated that their numbers progressively decline after thymectomy with a half-life of approximately 2 weeks. Although TCR deletion circles therefore cannot be regarded as reliable indicators of in situ V(D)J rearrangement, measuring their levels in peripheral T cell samples can provide a valuable index of newly generated T cells entering the T cell pool.     

Sequence analysis of thyroid transcription factor-1 gene reveals absence of mutations in patients with thyroid dysgenesis but presence of polymorphisms in the 5'' flanking region and intron

The purpose of this study was to determine the optimal scanning technique for lesion detection in a small bowel phantom and to evaluate the virtual endoscopy (VE) technique in patients. A small bowel phantom with a fold thickness of 7 mm and length of 115 cm was prepared with nine round lesions (3 x 1 mm, 2 x 2 mm, 2 x 3 mm, 2 x 4 mm). Spiral CT parameters were 7/7/4, 3/5/2, 3/5/1, 1.5/3/1 (slice thickness/table feed/reconstruction interval). VE was done using volume rendering technique with 1 cm distance between images and 120 degrees viewing angle. Two masked readers were asked to determine the number and location of the lesions. Seven patients underwent an abdominal CT during one breathhold after placement of a duodenal tube and filling of the small bowel with methyl cellulose contrast solution. VE images were compared with the axial slices with respect to detectability of pathology. With the 7/7/4 protocol only the 4-mm lesions were visualised with fuzzy contours. The 3/5/2 protocol showed both 4-mm lesions, one 3-mm lesion and one false positive lesion. The 3/5/1 protocol showed both 4-mm and both 3-mm (one uncertain) lesions with improved sharpness, and no false positive lesions. One 2-mm and one 1-mm lesion were additionally seen with the 1.5/3/1 protocol. Path definition was difficult in sharp turns or kinks in the lumen. In all patients, no difference was found between VE and axial slices for bowel pathology; however, axial slices showed 'outside' information that was not included in VE. We conclude that the 3/5/2 protocol may be regarded as an optimal compromise between lesion detection, coverage during one breathhold, and number of reconstructed images in patients; round lesions of 4 mm in diameter can be detected with high certainty.     

Function of the repeated sequence in the 3'' flanking region of the Escherichia coli rnpB gene on transcription termination and RNA processing

A retrospective study of telephone calls concerning poisoning due to pharmaceutical products, attended by the Toxicological Information Service in Seville (Spain), is presented. The years 1993 and 1994 were analized. Demographic data including the age and sex of the patient, route of exposure, cause, type of poisoning and the therapeutic group, was obtained. The great majority were cases of acute poisoning due to domestic accident, attempted suicide took second place. Ingestion was the principal route of entry, and more males than females were affected. 35.2% were children under two. In general, the medicines most frequently involved were those affecting the nervous system (28.1%)--principally analgesics, anxiolytics and antidepressants--followed by dermatological agents (13.7%)--such as antiseptics and disinfectants-and those affecting the respiratory (medicines to treat common cold, bronchodilators, antitussives) and digestive systems (laxatives, antiacids). It is hoped that with knowledge of data from as many poisons centres as possible, an improvement may gradually be seen in the prevention of the such poisoning in the future.     

A case of primary splenic large cell lymphoma with a t(9;14)(p13;q32)

Appropriately substituted 2,3-dihydro-7H-thiazolo[3,2-a]pyrimidin-7-ones 9-12 and 18 were considered as annulated analogues of HEPT (1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-thymine), and some of these compounds were also found active against HIV-1, the most active one being 2,3-dihydro-5-[(3,5-dimethylphenyl)methyl]-3-ethoxy-6-ethyl-7H- thiazolo[3,2-a]pyrimidin-7-one (10b). S-Alkylation of 5-alkyl-6-(arylmethyl)-2-thiouracils 1-4 was performed with 2-bromoacetaldehyde acetals to furnish the S-[bis(alkoxy)ethyl] derivatives 5-8 and with allyl bromide to furnish S-allyl derivatives 17. The target compounds 9-12 were obtained by an N1 regioselective intramolecular cyclization reaction of silylated 5-8 using trimethylsilyl trifluoromethanesulfonate (TMS triflate) as the catalyst. Treatment of the S-allyl derivatives 17 with bromine in dry methylene chloride afforded the 3-(bromomethyl) derivatives 18.     

Increased LFA-1-mediated homotypic cell adhesion is associated with the G1 growth arrest induced by rapamycin in a T cell lymphoma

The immunosuppressive macrolide, rapamycin, impedes the G1 to S cell cycle progression in cytokine-stimulated normal lymphocytes and in certain autonomously proliferating cell lines. Here, we found that the rapamycin-induced growth arrest augments homotypic aggregation in the YAC-1 T cell lymphoma. The growth arrest and increased aggregation were both blocked by the rapamycin antagonist, L-685,818, which interacts with the intracellular binding proteins mediating rapamycin's biochemical action. Moreover, rapamycin-induced aggregation was not seen in YAC-1 cells mutants selected for resistance to the drug's antiproliferative effect. Although the inhibition of G1/S progression induced by serum deprivation also resulted in increased cellular aggregation, cell cycle blockade in late G1 by mimosine, early S phase by hydroxyurea, or G2/M by nocodazole all failed to do so. Furthermore, the aggregation induced by rapamycin was blocked by antibodies to the alpha (CD11a) or beta (CD18) subunits of the integrin, LFA-1, or to its ligands, ICAM-1 and ICAM-2, and did not occur in LFA-1-deficient YAC mutants. However, the surface expression of LFA-1, ICAM-1, or ICAM-2 was not augmented in cells aggregated by rapamycin. Finally, the serine/threonine protein phosphatase inhibitor, okadaic acid, was found to abrogate rapamycin-induced aggregation. Therefore, rapamycin's impairment of YAC-1 cell growth in G1 is accompanied by enhanced LFA-1-mediated homotypic cell adhesion that may reflect an increase of the integrin's avidity for its ligands and may involve protein phosphorylation/dephosphorylation events. This suggests the existence of a link between cell cycle progression and "inside-out" LFA-1 signaling, possibly regulated by rapamycin's biochemical targets.