Biomedical subjects
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Hypoglossal neurinomas are rare. Only 46 cases have been reported. We report a case of dump-bell neurinoma with a large multilobulated intracranial component. The relevant literature is reviewed.
It is believed that platelets play a key role in the production of pre-eclamptic toxaemia and toxaemia of pregnancy. Toxaemia of pregnancy is described as a condition of chronic DIC where there is thrombocytopenia as well as raised fibrin degradation products. Since fibrinogen receptors are involved in the final stage of the platelet aggregation reaction, we wanted to investigate the platelet receptors for fibrinogen in normal and abnormal pregnancy. Thirty-six normal pregnant women (12 in their 2nd trimester, 24 in their 3rd trimester), 24 pregnant pre-eclamptic toxaemia cases and 16 non-pregnant controls were included in the present study. All patients with pre-eclamptic toxaemia had oedema, proteinuria and hypertension. Flow cytometric study of platelets was undertaken utilizing fluorescein isothiocyanate (FITC)-labelled anti-human fibrinogen antibody in unstimulated and ADP-stimulated (final concentration 0.02 M) platelets. The intensity of platelet fluorescence was classified into three groups and expressed in arbitrary units. The results indicate that there are a higher number of stimulated platelets expressing fibrinogen receptors in the circulation of patients with pre-eclampsia. Thus, it is possible to hypothesize that platelets showing increased fibrinogen receptors aggregate and form microthrombi in smaller vessels in women with pre-eclamptic toxaemia.
This article describes a participatory action research project addressing the problem of African American access to and use of hospice. Qualitative interviews conducted with six African American pastors resulted in the identification of major themes used for development of a scale to measure barriers to hospice. A subsequent quantitative study documenting these barriers was conducted with 127 African American and European Americans. Results of both studies, which were used to further social action efforts in the community, indicated the cultural barriers of differences in values regarding medical care and differences in spiritual beliefs between African Americans and European Americans. Results also indicated institutional barriers, including lack of knowledge of services, economic factors, lack of trust by African Americans in the health care system, and lack of diversity among health care staff. Implications for social work practice and policy are discussed.
We have cloned and sequenced a SEC7-related gene in Paramecium tetraurelia that contains an open reading frame for 1135 amino acids encoding a 133 kDa protein, PSec7. Sec7, first identified in vesicular trafficking mutants in yeast, and its phylogenetic homologues function as guanine-nucleotide exchange factors for small G-proteins such as ARF (ADP-ribosylation factor). The deduced amino acid sequence in PSec7 for the motifs that form the ARF binding site are more than 70% identical to yeast Sec7 and similarly identical to ARNO, the human ARF exchange factor, with correct positioning of the critical glutamic acid residue within the motif region. Overall, the identity of PSec7 to yeast Sec7 is 32%. The deduced amino acid sequence also has five sequences that resemble IQ motifs, EF hand binding domains found in all myosins, and two pleckstrin homology domains. Similar sequences are present in yeast Sec7 and other Sec7-related molecules. A protein kinase A phosphorylation site may also be present. Southern blots suggest that a single gene encodes PSec7. Northern blots show that the message encoding PSec7 is induced on deciliation, followed by ciliogenesis, which suggests a role for PSec7 in cilia such as transport or targeting of ciliary membrane components.
There is no standard treatment for patients with recurrent gliomas, and their prognosis remains poor. 2-Chlorodeoxyadenosine is a purine analogue that has significant activity in many low-grade lymphoproliferative disorders. The authors conducted a phase II study to determine the efficacy of 2-chlorodeoxyadenosine in patients with recurrent gliomas. Patients with a histologically confirmed primary brain tumor with evidence of progression after radiation therapy were eligible. Protocol treatment consisted of 2-chlorodeoxyadenosine 7.0 mg/m2 intravenously on days 1 through 5 every 28 days. For those with a history of prior nitrosourea therapy, the dose of 2-chlorodeoxyadenosine was reduced to 5.6 mg/m2 on days 1 through 5. Treatment was continued until progression or a maximum of 12 cycles. Fifteen patients with recurrent astrocytomas or oligoastrocytomas of all grades were entered in the study. Treatment was well tolerated. Major toxicities were myelosuppression and neurotoxicity. No responses were seen. The authors conclude that although 2-chlorodeoxyadenosine is well tolerated, no demonstrable activity in patients with recurrent gliomas was established.
The 16S-23S rDNA intergenic spacer region of organisms identical with or closely related to 'Tropheryma whippelii', the uncultivated causative agent of Whipple's disease, was analysed directly from 38 clinical specimens of 28 patients using a specific nested PCR followed by direct sequencing. As compared to the reference sequence in public databases, two novel 'T. whippelii' spacer types were recognized. In the absence of DNA-DNA hybridization data it is uncertain whether the three types found represent subtypes of a single species or three different but closely related species. Methods were developed to detect all three variants by single-strand conformation polymorphism analysis and by type-specific PCR assays, thus allowing the screening of large numbers of specimens. Further studies may provide a clue to the possible associations between the type of infecting strain and the various clinical presentations of Whipple's disease.
OBJECTIVE: There is one previously reported case linking ischemic colitis and orally administered nasal decongestants containing pseudoephedrine (MEDLINE 1974-1998). We aimed to document an association between pseudoephedrine ingestion and ischemic colitis. METHODS: We reviewed the cases of four women (ages, 37-50 yr) who presented with the sudden onset of colicky abdominal pain followed by hematochezia. Three patients had used medicine containing pseudoephedrine daily for approximately 1 wk before admission. The fourth patient had used pseudoephedrine chronically for 6 months. Two patients had no significant past medical history. One woman had presented 6 months earlier with ischemic colitis while taking both pseudoephedrine and hormone replacement therapy. This time she presented with ischemic colitis while not taking hormone replacement therapy, but still taking decongestants. Another woman had a history of ulcerative colitis, which had been quiescent for 10 yr. One patient had been a smoker; however, like the other patients she had no evidence of systemic vascular disease. On colonoscopy, all four patients had colitis, primarily affecting the splenic flexure in the anatomical watershed area. Other causes of segmental colitis, including infectious colitides, pseudomembranous colitis, and Crohn's disease, were not evident. Colonoscopic biopsies were consistent with ischemic injury. RESULTS: All cases responded to abstinence from pseudoephedrine and medical supportive therapy. None has had a relapse since discontinuing the pseudoephedrine (8-12 months). CONCLUSIONS: The vasoconstrictive action of pseudoephedrine may predispose susceptible patients to develop ischemic colitis in the watershed area of the splenic flexure. Perimenopausal women may be especially susceptible because of irregular ovulation. This may result in relative vasoconstriction when estrogen levels are low or a hypercoagulable state when estrogen levels are excessive.
A 38-year-old male presented with an extremely rare primary osteogenic sarcoma, unassociated with Paget's disease or late effects of radiation, involving the sella and sphenoid sinus region. Complete excision of the tumor was achieved through an extended frontobasal approach. Postoperatively, six cycles of combination chemotherapy (adriamycin, ifosphamide, and cisplatin) followed by a total of 55 Gy local radiotherapy in 33 fractions was given. Primary osteogenic sarcoma should be considered in the differential diagnosis of the central skull base tumors. Osteogenic sarcoma, in general, has a bad prognosis, and should be managed aggressively with multimodality treatment including gross total surgical resection, combination chemotherapy, and radiotherapy.
A 63-year-old man with multiple left atrial myxomas presenting with right hand weakness is described. Two-dimensional echocardiography obtained during the evaluation for his stroke showed a large left atrial mass. At surgery, two separate left atrial myxomas were excised. Pathology confirmed the diagnosis. Although left atrial myxomas are uncommon, they should be included in the differential diagnosis of stroke, especially in patients who present without cardiovascular or cerebrovascular risk factors. The absence of cardiac symptoms and signs does not rule out a cardiac myxoma.
Dendritic cells (DCs), antigen-presenting cells capable of priming naive T cells to specific antigens in an HLA-restricted fashion, have been demonstrated to induce protective T cell-mediated immunity in tumor-bearing animals. We performed this study to test the safety, feasibility, and clinical response of immunizations with in vitro-generated DCs, loaded with an HLA-A2-restricted peptide fragment of the tumor antigen carcinoembryonic antigen (CEA), for the treatment of patients with advanced CEA-expressing malignancies. Cell preparations enriched for autologous DCs were generated from the patients' plastic adherent peripheral blood mononuclear cells in serum-free media supplemented with granulocyte macrophage colony-stimulating factor and interleukin-4. Within the cell preparation, 66% of the cells expressed the phenotype typical for DCs (CD86high, HLA-DRhigh, and CD14low). The DCs were loaded with the CEA peptide CAP-1 and cryopreserved. Groups of three to six patients received four weekly or biweekly i.v. infusions of the CAP-1-loaded DC in escalating dose levels of 1 x 10(7), 3 x 10(7), and 1 x 10(8) cells/dose. A subset of the patients in the last group also received intradermal injections of 1 x 10(6) DCs. There were no toxicities directly referable to the treatments. One patient had a minor response, and one had stable disease. Skin punch biopsy at DC injection sites demonstrated pleomorphic infiltrates in the three patients evaluated. We conclude that it is feasible and safe to generate and administer large numbers of previously cryopreserved DCs loaded with CAP-1 peptide to patients with advanced malignancies.
This is a review of the positive biopsy rate of nonpalpable breast lesions detected on mammography. The histology of 130 hookwire excision biopsy from 1990 to 1995 and the cytology of 39 stereotactic fine needle aspiration cytology in 1995 were reviewed. The yearly positive biopsy rate of each procedure was determined. In 1990, the positive biopsy rate for hookwire excision biopsy was 15%, in 1991 20%, in 1992 11%, in 1993 17%, in 1994 33% and in 1995 39%. In 1995, the positive biopsy rate for stereotactic fine needle aspiration cytology was 21%. The positive biopsy rate for hookwire excision biopsy had improved from 15% in 1990 to 39% in 1995.
Drosophila neuroblasts are a model system for studying asymmetric cell division. Neuroblasts bud off a series of smaller progeny, called ganglion mother cells (GMCs). An essential regulator of GMC development is the Prospero homeodomain transcription factor: Prospero is asymmetrically localized to the basal cortex of the mitotic neuroblast and partitioned into the newborn GMC. Prospero is translocated into the GMC nucleus, where it is necessary to establish GMC-specific gene expression. Cortical localization of Prospero protein is observed only during mitosis; cortical localization requires entry into mitosis and cortical delocalization requires exit from mitosis. The tight correlation and functional requirement between mitosis and cortical Prospero localization suggests that mitosis-specific posttranslational modifications may be involved in regulating Prospero subcellular localization. Here we use monoclonals recognizing the N-terminal or C-terminal region of Prospero to explore its posttranslational regulation. One- and two-dimensional Western analysis reveal a complex pattern of Prospero isoforms; phosphatase assays show that there are several phosphoisoforms of Prospero. Developmental 2D Western blots, cell fractionation assays, and analysis of a missense prospero mutation show that cortical Prospero protein is highly phosphorylated compared to nuclear Prospero protein. Our results are consistent with two functions of Prospero phosphorylation: (i) phosphorylation may be required for Prospero cortical localization; or (ii) phosphorylation may be a consequence of Prospero cortical localization, in which case it may facilitate subsequent events, such as Prospero cortical release or nuclear localization.
Virulence is a multifactorial trait which depends on the coordinated expression of many bacterial products, hence it is to be expected that the regulatory circuits that control the relevant genetic determinants are somehow interconnected. Two pleiotropic regulatory elements acting at different levels, the transcription factor PrfA which controls virulence gene expression and the potential chaperone ClpC which is involved in tolerance to environmental stress, are required for Listeria monocytogenes survival within the host. We analyzed the influence of PrfA on clpC expression in L. monocytogenes. clpC transcription is maximal under heat-shock conditions, i.e. at 42 degrees C, and is very weak or undetectable at 37 degrees C. In a prfA* mutant which constitutively overexpresses PrfA and PrfA-dependent virulence genes, clpC transcription dropped to basal levels during exponential growth at 42 degrees C. This repression was not observed during stationary phase, indicating growth phase-dependent regulation of clpC. Culture in charcoal-treated medium, which triggers in wild-type strains the transcriptional activation of the PrfA regulon, also caused a strong downregulation of clpC. Moreover, in a prfA deletion mutant, clpC transcription during exponential growth at 37 degrees C was clearly enhanced, reaching the same high levels of the wild-type at 42 degrees C. Overall, our results indicate that clpC expression is negatively controlled at the transcriptional level, directly or indirectly, by the central virulence regulator PrfA.
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The aim of this study was to determine whether biofilms of Porphyromonas gingivalis could proteolytically degrade the cytokines interleukin (IL)-1beta, IL-6, or IL-1 receptor antagonist (IL-1ra). Biofilms were grown on membrane filters on the surface of Wilkins-Chalgren blood agar. The biofilms were removed from the plates, and solutions containing 2.5 microg/ml of each cytokine were added. Following incubation for up to 4.0 h, supernatants from the biofilms were subjected to SDS-PAGE. The separated proteins were transferred by Western blotting to PVDF membranes and probed with peroxidase-conjugated antibodies recognizing both the intact cytokines and their degradation products. After 2 h, no intact IL-1beta, IL-6, or IL-1ra were detectable. Cytokine proteolysis also occurred in the presence of horse serum. These results demonstrate that biofilm-grown P. gingivalis can degrade both pro- and anti-inflammatory cytokines and so may be able to perturb cytokine networks in vivo by eliminating cytokines from the local environment.
Being motor nerves neurinomas originating from ocular nerves are very rare, unless associated with neurofibromatosis. Authors describe two cases of oculomotor nerve i.e. third nerve, Schwann cell tumours. One of them presented as a cavernous sinus mass in a middle aged lady while the other was a middle aged man with a large cisterno-cavernous tumour. Surgical approach is discussed and the relevant literature reviewed.
A very unusual case of sellar-sphenoid sinus hemangioblastoma without stigmata of von Hippel-Lindau disease is presented. Subtotal excision of tumor was done via an extended frontobasal approach. Diagnostic controversies between hemangioblastoma and angioblastic meningioma are discussed and the relevant literature reviewed.
The oral gram-negative bacterium Actinobacillus actinomycetemcomitans is a major pathogen in human periodontal disease. Saline extraction releases a range of surface-associated components from this bacterium, including one which exhibits potent anti-proliferative activity as assessed by its capacity to inhibit DNA synthesis by human and other mammalian cells. Cultures incubated with this bacterial fraction for a prolonged period comprise a high proportion of cells containing a 4n level of DNA. Studies using hydroxyurea-synchronized cultures showed that cells treated with the surface-associated fraction were arrested in the G2 phase of the cell cycle and did not enter mitosis. This G2/M blockade was observed only when the bacterial fraction was added to the cells during early S phase. Our data also suggest that the active bacterial component binds to surface receptors expressed by the human cells and may act by a novel mechanism which involves down-regulation of cyclin B1 expression. The anti-proliferative activity of the bacterial fraction, purified by a combination of ammonium sulphate precipitation, HPLC anion exchange and gel filtration, has been shown to be an 8 kDa protein, which we have called gapstatin. Purified gapstatin was shown to be responsible for the the inhibitory effects of the surface-associated fraction on mammalian cells.