Biomedical subjects
Publications and source records attributed to K Ballas.
Pilonidal sinus of the interdigital web space of the hand is a rare occupational disease which occurs in hairdressers and professionals working with animals. This paper reports such a sinus in the hand of a male hairdresser and reviews the treatment of this condition.
OBJECTIVE: Colorectal emergency requiring radical surgery is becoming increasingly frequent in the elderly and problems remain as regards the best management policy. Our long-time experience is presented in this study. PATIENTS AND METHODS: In the last 23 years, 105 elderly patients, aged > or = 65 years, with colorectal disease underwent an emergency operation in our Surgical Department. Forty-five patients (mean age 72 years) had benign disease and 60 patients (mean age 76.5 years) colorectal carcinoma. RESULTS: The carcinoma was located in the left colon (68%), right colon (18%) and rectum (14%). Mostly, patients with malignant cancer presented with obstructive ileus, and patients with benign tumours with perforation and peritonitis, with a predominance of diverticulitis. A resection operation either with primary anastomosis or Hartmann's procedure was performed in 75% of cases; in the rest, only palliation was resorted to. Forty-three percent of the patients with colorectal cancer emergency were > or = 80 years of age. The mean morbidity was 25% and mortality 17%, which make up to 33% and 26.6% for benign disease, and 20% and 10% for malignant cancer, respectively. The mortality rate was higher in patients with perforation than those with obstruction. CONCLUSION: Advanced age is not a contraindication to radical surgery in case of colorectal emergency in the elderly. In the majority, a resection operation is feasible. In high-risk patients, colostomy is a life-saving alternative.
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The zoonotic ascarid Toxocara has been suggested as a possible etiologic agent of asthma. We conducted a clinic-based case-control study to examine whether the zoonotic infection acquired by ingesting Toxocara eggs is associated with asthma in children. Blood samples were collected from children aged 2-15 years, 95 of whom had asthma and 229 of whom did not have asthma. Risk factors for asthma and Toxocara infection were assessed by a questionnaire given to each child's parent or legal guardian. Blood samples were tested for the presence of Toxocara antibodies, using an enzyme-linked immunosorbent assay. No significant association was found between Toxocara infection and asthma. Significant associations were found between asthma and risk factors and between Toxocara infection and risk factors. High prevalence of Toxocara infection was noted among Hispanic children of Puerto Rican descent.
Cells from patients with MDS-derived AML display heterogeneous proliferative responses to transforming growth factor beta (TGF beta). We analyzed growth inhibition and SMAD2 phosphorylation by TGF beta in CD34+ cells from nine patients, as compared to normal controls. While TGF beta consistently inhibited thymidine incorporation of normal cells (41% of control, P < 0.05), cells from patients with AML were growth-inhibited in only four of seven cases (40%), whereas TGF beta stimulated thymidine incorporation in the three other samples (166%). Remarkably, TPO reverted the stimulatory effect of TGF beta to profound growth inhibition. Upon exposure to TGF beta, SMAD2 protein was phosphorylated in normal CD34+ cells (n = 3), CD34+ leukemic blasts from all examined patients with AML (n = 4), and in the myeloid leukemic cell lines M-07e and HEL. TGF beta inhibited TPO-mediated thymidine incorporation, cell proliferation and survival in all samples analyzed. In M-07e cells and CD34+ cells from healthy donors, this inhibition was enhanced by an antagonist of JAK2 (AG490), but not a MEK-1 antagonist (PD098059). Conversely, in CD34+ cells from a patient with AML, both AG490 and PD098059 significantly enhanced TGF beta-mediated suppression of TPO-induced thymidine incorporation. Thus, in MDS-derived AML, altered responses to TGF beta may be due to defects downstream of SMAD2 and may involve MAPK activation.
IL-18 is a regulator of NK cell function which utilizes the serine-threonine IL-1R-associated kinase signal transduction pathway and may activate additional not yet characterized signaling pathways. Here we evaluated IL-18-mediated signal transduction using the human NK cell line NK92 as a model. NK92 cells were shown by RT-PCR to express all three IL-18 receptor chains (IL-18R, accessory protein-like chain, IL-18-binding protein). Stimulation by IL-18 strongly enhanced tyrosine phosphorylation of STAT3 and of the mitogen-activated protein kinases (MAPK) p44erk-1and p42erk-2. In contrast, STAT5 was not activated. The cytolytic activity of NK92 against K562 target cells, which was augmented in a dose-dependent manner by IL-18 in the presence of trace amounts of IL-2, was suppressed by the specific inhibitors of MAPK pathways (PD098059 and SB203580). Similarly, the stimulatory effect of IL-18 on IFN-gamma protein production, given in conjunction with IL-2, was counteracted by inhibition of MAPK. IL-18 alone failed to stimulate IFN-gamma protein production despite inducing expression of IFN-gamma mRNA. IL-2 alone stimulated neither IFN-gamma mRNA expression nor IFN-gamma protein production. IL-18 did not stimulate proliferation of NK92 cells, either alone or in combination with IL-2 or IL-12. Inhibition of the MAPK pathway did not significantly alter the IL-2- and IL-12-induced proliferation of NK92 cells, whereas the Janus kinase/STAT pathway inhibitor AG490 strongly suppressed proliferation. MAPK activation appears to play a prominent role in IL-18 signaling, being involved in transcription and translation of IL-18-induced IFN-gamma mRNA and IL-18-induced cytolytic effects. In contrast, proliferation of NK92 cells is not affected by MAPK p44erk-1 and p42erk-2.
The human interleukin(IL)-18 is a key regulator of interferon(IFN)-gamma production and T-cell differentiation. Here we report the complete genomic structure and characterization of the 5'untranslated promoter region of the human IL-18 gene. The gene is composed of six exons and five introns, spanning approximately 19. 5kb. Promoter activity of the 5'-flanking region was investigated with a luciferase reporter gene assay. Transient transfection studies demonstrate a constitutive expression of the IL-18 gene in monocytic U937 and THP-1 cells. For this constitutive expression at least 92 base pairs of the promoter region are essential as shown by consecutive 5' promoter deletions in both cell types. DNA protein binding experiments revealed specific binding of activated signal transducer and activator of transcription factor-5 (STAT5) but not of STAT3 to three consensus sequences upstream in the promoter region. Cotransfection of STAT5 resulted in increased induction of the IL-18 promoter in the U937 and THP-1 cells.
We here summarize the analysis of 126 DNA samples from patients with hematopoietic neoplasias and solid tumors and from various tumor cell lines that were screened in the tumorigenicity assay. Thirty-eight samples were able to induce tumors after transfection in NIH/3T3 cells and injection into nude mice. Southern-blot analysis with a panel of oncogene probes revealed human ras genes in the vast majority of cases (25 N-ras, 2 K-ras, 1 H-ras) but also activated FGF4, dbl, ret and mas genes respectively. DNA samples from the 6 remaining transfectants were cloned into EMBL-3 phages and screened with a human specific repetitive Alu probe. Direct hybridization of a transfectant cDNA library allowed cloning of the ufo oncogene. Application of the exon-trapping technique to alu-positive phage DNA from the other transfectants enabled us to isolate tre, cot, B-raf, p85beta/HUMORF8 and a novel oncogene.
Interleukin 18 (IL-18) is a recently identified cytokine, originally called interferon gamma inducing factor, due to its capacity to induce interferon gamma production in Th1 type cells. IL-18 is expressed by a wide variety of cell types including mononuclear phagocytes, osteoblasts, keratinocytes and adrenal cortex cells. To quantify human IL-18 mRNA expression in small-scale cell samples the authors developed a competitive reverse transcriptase polymerase chain reaction using a competitive template as an internal standard. This assay was demonstrated as a valid, sensitive and precise tool to quantify human IL-18 mRNA expression. IL-18 mRNA expression of primary peripheral blood monocytes, CD4(+)T cells, CD8(+)T cells, B cells and NK cells was assessed by competitive RT-PCR. Basal IL-18 expression could be detected in all types of peripheral blood mononuclear cells (PBMC). The kinetics of IL-18 mRNA expression in PBMC from healthy donors was defined in vitro after monocyte-specific (lipopolysaccharide LPS), T-cell-specific (anti-CD3) and polyclonal-unspecific stimulation (phytohaemagglutinin PHA). Only LPS led to a strong increase of IL-18 mRNA expression peaking after 2 h. These results indicate that IL-18 is expressed constitutionally by all major PBMC subtypes. However, only monocyte specific stimulation resulted in a significant induction of IL-18 mRNA expression suggesting activated monocytes e.g. in inflammation as the main source of IL-18 expression.
The tumor promoter phorbol 12-myristic 13-acetate inhibits the growth of human endothelial cells and induces the formation of capillary-like, tubular structures. We report the novel growth regulatory function of the immediate-early gene, edg-3, which is identical to the IkappaB alpha/MAD-3 gene. We employed phosphothioate oligonucleotides (PTO) directed against the translation initiation site of IkappaB alpha to inhibit its expression. The antisense IkappaB alpha PTO-treated cells exhibited an exaggerated growth response to fibroblast growth factor-1 (FGF-1). In contrast, IL-1-induced growth arrest response was not modulated. These data suggest that the early response gene IkappaB alpha is an endogenous regulator of endothelial cell growth in vitro.
A strategy employing gene-trap mutagenesis and site-specific recombination (Cre/loxP) has been developed to isolate genes that are transcriptionally activated during programmed cell death. Interleukin-3 (IL-3)-dependent hematopoietic precursor cells (FDCP1) expressing a reporter plasmid that codes for herpes simplex virus-thymidine kinase, neomycin phosphotransferase, and murine IL-3 were transduced with a retroviral gene-trap vector carrying coding sequences for Cre-recombinase (Cre) in the U3 region. Activation of Cre expression from integrations into active genes resulted in a permanent switching between the selectable marker genes that converted the FDCP1 cells to factor independence. Selection for autonomous growth yielded recombinants in which Cre sequences in the U3 region were expressed from upstream cellular promoters. Because the expression of the marker genes is independent of the trapped cellular promoter, genes could be identified that were transiently induced by IL-3 withdrawal.
Using a rapid dot-blot screening procedure based on DNA amplification and hybridization to synthetic oligonucleotide probes, we investigated 18 neuroblastomas in various clinical stages for the presence of ras mutations. In none of the samples was a mutation in the relevant codons 12, 13 or 61 of Ha-ras, Ki-ras or N-ras found. These data virtually exclude the participation of mutated ras genes in the genesis of neuroblastoma.
During lytic infection SV40 T antigen binds specifically to three different regions of the SV40 DNA to initiate DNA replication and to regulate early and late transcription. We constructed plasmids containing either 23-bp synthetic oligonucleotides representing site I or II or SV40 DNA fragments with combinations of binding sites II and III with or without SV40 specific flanking regions. These plasmids were used to determine which sequences are sufficient for specific binding to isolated regions II and III. Under identical conditions T antigen bound in a sensitive in vitro binding assay efficiently to site I but not to the corresponding oligonucleotide of site II. Binding to site II could only be observed in the presence of the adjacent 17-bp AT-rich region of the SV40 DNA. On account of the markedly low affinity for binding site II, T antigen concentrations were required which exceeded those necessary to achieve saturation of binding to site I. The very low affinity for isolated site III could be slightly raised by the same AT-rich region. An increased binding to site II at 37 degrees compared to 0 degree in the presence of this region points to an indirect influence on the DNA structure of the binding site.
Large cell anaplastic lymphoma (ALCL) is characterized mainly by the presence of large, atypical lymphoid cells with anaplastic nuclear morphology and positivity to Ki-1 antigen. We describe, to our knowledge, the fourth reported case of primary ALCL of the spleen. The patient, a 62 year old woman, presented symptoms resembling a splenic abscess.