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Biomedical subjects

A Kajdacsy-Balla

Publications and source records attributed to A Kajdacsy-Balla.

At least 19 recordsLinked to original sources
PubMed2001

Cigarette smoking is strongly associated with mutation of the K-ras gene in patients with primary adenocarcinoma of the lung.

BACKGROUND: The majority of lung carcinoma cases occur in current or former smokers. K-ras gene mutations are common in lung adenocarcinoma and have been associated with cigarette smoking, asbestos exposure, and female gender. METHODS: In the current study, the authors examined the contribution of cigarette smoking to K-ras gene mutations in patients with primary lung adenocarcinoma. Smoking histories were obtained from 106 prospectively enrolled patients with primary adenocarcinoma of the lung. RESULTS: K-ras mutations were detected in the primary tumor using an allele-specific ligation assay. Ninety-two of the 106 patients (87%) with lung adenocarcinoma were smokers. Nonsmokers with this tumor were more likely to be women (11 of 14; 79%), whereas the majority of smokers (57%) were men. K-ras mutations were detected in 40 of 106 tumors (38%) and were significantly more common in smokers compared with nonsmokers (43% vs. 0%; P = 0.001). CONCLUSIONS: The results of the current study confirm and extend previous observations that smokers with adenocarcinoma of the lung are more likely to have K-ras mutant tumors compared with nonsmokers. The strong link between cigarette smoking and K-ras mutations in adenocarcinoma of the lung supports the role of specific tobacco carcinogens in the etiology of this malignancy.

Adenocarcinoma↗
PubMed2001

Laryngotracheal reconstruction in canines: fixation of autologous costochondral grafts using polylactic and polyglycolic acid miniplates.

OBJECTIVE: To examine the feasibility of a new method of laryngotracheal reconstruction (LTR) that uses a bioabsorbable plating system consisting of polylactic and polyglycolic acid and provides some advantages over currently used methods. DESIGN AND INTERVENTIONS: Anterior subglottic stenosis was created in 10 beagles that then underwent LTR using an autologous costochondral graft. External laryngotracheal framework and cartilage grafts were secured using a sheet and screws made from a copolymer composed of polylactic and polyglycolic acid. Animals were humanely killed at 40, 60, and 90 days, and specimens were submitted for pathological examination. Histologic analysis included evaluation for inflammatory reaction, polylactic and polyglycolic acid incorporation into cartilage, cartilage necrosis, cartilage remodeling, and graft epithelialization. RESULTS: All animals underwent LTR after creation of a subglottic stenosis without episodes of airway compromise. After LTR, all airways were returned to prestenosis diameter without significant complication, and all animals were immediately extubated after surgery without difficulty. After the animals were killed, distraction of the stenotic cricoid area was demonstrated in 100% of the cases. Significant necrosis was noted in 2 of 10 grafts grossly; however, histologic analysis demonstrated significant areas of viable cartilage, areas of cartilage remodeling, and good epithelialization despite graft necrosis. Complete epithelialization of grafts was noted in the other 8 specimens. CONCLUSIONS: Using a canine model, we demonstrated a bioabsorbable plating system that offers an effective method for LTR. This model has the advantages of providing external support to the operated laryngeal and tracheal framework, elimination of the difficulties of suture placement, and potential future failure while offering rigid external fixation of a cartilage graft.

Absorbable Implants↗
PubMed2001

Antigenic characterization of medullary carcinoma of the breast: HLA-DR expression in lymph node positive cases.

Medullary carcinoma of the breast has attracted attention because of its relatively good prognosis, in spite of its high cytologic grade. It has, by definition, a consistent, florid tumor infiltrating lymphocyte (TIL) population, probably the result of cytotoxic T-lymphocytes recognizing tumor cells in an HLA-DR-restricted manner. HLA-DR tends to be more highly expressed on primary medullary carcinoma cells than on ductal carcinoma cells; however, the MHC-class II antigenicity of the tumor cells themselves has not been analyzed extensively, and as yet there has been no comparative study of HLA-DR expression in medullary and ductal carcinomas metastatic to lymph nodes. Eleven cases of medullary carcinoma and 15 cases of ductal carcinoma, primaries, and respective lymph node metastases were analyzed by immunoperoxidase staining for HLA-DR and lymphocytes antigens. Polymerase chain reaction (PCR) analysis to identify HLA-DR subtypes from the paraffin blocks was performed on selected cases of primaries and nodal metastases of both tumor types. Immunoperoxidase staining for HLA-DR antigen revealed a marked difference in antigen expression between medullary and ductal carcinomas. In the medullary carcinomas, the mean percentage of cells staining for HLA-DR was 74.5% in the primary tumors and 67.3% in the nodal metastases. For the ductal carcinomas, the mean percentage of cells staining was 17.7% in the primaries and 7% in the metastases. There was a tendency for the level of HLA-DR expression to remain high in medullary carcinoma metastatic to nodes, whereas whatever HLA-DR was present within ductal primaries tended to diminish when cells metastasized to regional nodes. PCR analysis of the HLA-DR within the two tumor types revealed no emerging subtype or variant that could be associated with either the medullary or the ductal carcinomas. Medullary carcinoma cells express much greater quantities of HLA-DR, on the whole, than ductal carcinomas. Expression of HLA-DR is retained on medullary carcinoma cells that have spread to lymph nodes, whereas the smaller quantities of HLA-DR present within ductal primaries tend to diminish even further when the tumor cells are found in lymph nodes. No discernible HLA-DR mutations or predominant subtypes emerged on PCR analysis, and the authors therefore conclude that it is the quantity and not the quality of HLA-DR expression in medullary carcinoma that maintains the characteristic TIL infiltrate, not seen in ductal carcinomas.

Breast Neoplasms↗
PubMed2000

Metalloproteinase levels are decreased in symptomatic carotid plaques.

BACKGROUND: Matrix metalloproteinase enzymes (MMP) have been identified in carotid atherosclerotic plaques, but their role in the development of clinical symptoms remains ill defined. We correlated the activity and levels of metalloproteinase enzymes and their inhibitors in human carotid plaques to ischemic neurologic events. METHODS: Carotid plaques were collected at the time of endarterectomy from 23 patients with carotid stenosis. Sixteen patients were asymptomatic and 7 patients had symptoms of stroke or transient ischemic attack within 6 weeks of surgery. Protein was extracted from the plaques, proteolytic activity was determined by gelatin zymography, and pro-MMP and tissue inhibitor of metalloproteinase (TIMP) enzyme content were measured by ELISA assay. Macrophage accumulation in the plaque was determined using immunohistochemistry. RESULTS: Plaques from symptomatic patients had decreased proteolytic activity on substrate gel zymography at the 62- and 92-kDa regions (corresponding to active MMP-2 and pro-MMP-9). A decrease in pro-MMP-9 (8.21 +/- 2.35 vs 17.42 +/- 3.14 ng, P < 0. 05) and an increase in TIMP-2 protein (12.62 +/- 0.58 vs 10.56 +/- 0. 77 ng, P < 0.05) were noted on ELISA in plaques from symptomatic patients. No difference was noted in macrophage accumulation in the plaques between the two groups. CONCLUSIONS: Plaques from patients who present with ischemic neurologic symptoms have decreased proteolytic activity associated with decreased pro-MMP-9 and increased TIMP-2 protein levels. These data suggest that metalloproteinase enzymes are not responsible for plaque instability in the carotid circulation and may in fact promote plaque stability.

Aged↗
PubMed2000

The role of constitutive NF-kappaB activity in PC-3 human prostate cancer cell invasive behavior.

The purpose of this study was to determine if increased NF-kappaB activity of highly invasive PC-3 cells contributed to their invasive behavior. Increased NF-kappaB activity has been observed in several malignant tumors and it may have an important role in tumorigenesis, progression and chemotherapy resistance. By serial selection, we obtained invasion variant PC-3 cell sublines. The PC-3 High Invasive cells invade readily through a Matrigel reconstituted basement membrane while PC-3 Low Invasive cells have low baseline invasion activity. In these studies, we discovered that NF-kappaB DNA binding activity was increased in PC-3 High Invasive cells when compared to PC-3 Low Invasive cells by electrophoretic mobility shift assay (EMSA). Gel supershift assays showed a 4-fold increase in p65 containing complexes and a 2.2-fold increase in the p50 containing complexes in the PC-3 High Invasive cells. Luciferase reporter assays showed that NF-kappaB dependent transcription activity was increased 10.2 +/- 2.5-fold in the highly invasive cells (P < 0.002). The PC-3 High Invasive cells showed a constitutive increase in phospho-IkappaB alpha and introduction of the super-repressor IkappaB alpha S32/36A inhibited NF-kappaB activity to 19.2 +/- 2.5 percent of control transfected cells (P < or = 0.001). The IkappaBa super-repressor reduced the basement membrane invasion of PC-3 High Invasive cells from 6.2 +/- 1.1 to 3.8 +/- 0.4 percent (P < 0.002) with no decrease in cell viability or proliferation. These results demonstrate that increased NF-kappaB activity contributed directly to the invasive behavior of PC-3 High Invasive prostate cancer cells.

Base Sequence↗
PubMed1999

Primary ocular Epstein-Barr virus-associated non-Hodgkin's lymphoma in a patient with AIDS: a clinicopathologic report.

OBJECTIVE: To report an unusual case of chronic multifocal chorioretinitis with vitritis in a patient with acquired immunodeficiency syndrome (AIDS) that was resistant to antiviral and antitoxoplasmic medication and required a retinal biopsy for definitive diagnosis. METHODS: Vitreous biopsy, pars plana vitrectomy, and retinal biopsy were performed. The vitreous biopsy material was sent for bacterial, fungal, and viral culture, and the vitreous cassette was sent for cytology. The retinal biopsy material was divided and sent for polymerase chain reaction testing for toxoplasmosis and virology and pathologic tissue analysis. RESULTS: Vitreous cytology showed a mixed population of lymphocytes and histiocytes, but all other microbiologic and virologic studies were negative. Tissue analysis revealed an infiltrate of atypical mononuclear cells extending from the inner limiting membrane through the outer plexiform layer characteristic of a B cell, non-Hodgkin's lymphoma of the central nervous system (NHL-CNS). In situ hybridization for the Epstein-Barr virus (EBV) was positive. An extensive systemic evaluation did not show evidence of extraocular tumor. CONCLUSION: Although rare, primary ocular NHL-CNS can be seen in patients with AIDS, and its clinical presentation often closely resembles other disorders. To our knowledge, this case represents the first ocular NHL in which EBV is shown to be associated.

Adult↗
PubMed1999

Prostate-specific antigen expression and lipochrome pigment granules in the differential diagnosis of prostatic adenocarcinoma versus seminal vesicle-ejaculatory duct epithelium.

BACKGROUND: Lipochrome pigment granules (LPGs) and prostate-specific antigen (PSA) localization have been cited as helpful adjuncts in differentiating atypical histologic patterns of seminal vesicle-ejaculatory duct (SVED) from prostatic adenocarcinoma. However, LPGs have been described in both benign and neoplastic prostatic acini, and PSA expression within the intraprostatic SVED has not been fully explored. DESIGN: Fifty radical prostatectomy specimens were studied for LPGs and 9 cases for PSA expression. RESULTS: Two morphologic types of LPGs (type 1 and type 2) were observed. The reproducibility in classifying LPGs was evaluated by kappa statistics, which demonstrated a strong agreement between 4 observers. Type 1 was restricted to SVED in all 50 specimens. Type 2 was subclassified into 2A and 2B. Type 2 LPGs were observed in prostatic acini of different zones, high-grade prostatic intraepithelial neoplasia, prostatic adenocarcinoma, and occasionally with type 1 LPG in SVED. Focal reactivity for PSA in the distal portion of SVED near urethra was noted in 1 of 9 cases. CONCLUSION: Awareness about morphologic differences between the 2 types of LPGs could help to avoid a potential diagnostic pitfall of misinterpreting SVED epithelium for adenocarcinoma. Caution is recommended in interpreting PSA expression, since rare focal PSA reactivity was observed in the distal SVED.

Adenocarcinoma↗
PubMed1997

Identification of heavy drinkers using a combination of laboratory tests.

OBJECTIVE: This study derived and evaluated a model that used results of commonly performed laboratory tests to identify men who are heavy drinkers. METHOD: The results of 40 commonly available laboratory tests were obtained on a diverse sample of 426 heavy drinkers and 188 light drinkers. A logistic regression equation for identifying heavy drinkers was derived in a training data set of 411 subjects and tested in a validation data set of 203 subjects. RESULTS: Ten laboratory measurements were included in the final regression equation: chloride, sodium, ratio of direct to total bilirubin level, blood urea nitrogen, high density lipoproteins, monocyte count, phosphorus, platelets, aspartate aminotransferase, and mean corpuscular hemoglobin. In the validation data this model correctly identified 98% of the 161 heavy drinkers and 95% of the 42 light drinkers. Other models reported in previous literature were applied to these subjects and did not perform as well. The model performed better for subjects of lower socioeconomic status. CONCLUSIONS: The laboratory tests in our model may help identify heavy drinkers. The performance of models to identify heavy drinkers depends on the demographic characteristics of the subjects.

Adult↗
PubMed1996

Characterization of normal and malignant human hepatocytes by Raman microspectroscopy.

Raman microspectroscopy was used to characterize normal and malignant hepatocytes in both cultured cells and human liver tissues. Consistent spectral changes were observed, including intensity increases at 1040 and 1083 cm(-1) with malignancy. A loss of intensity at 1241 cm(-1) was also observed in cancer cells, but was obscured in tissues by the overlap of a 1253 cm(-1) band, thought to originate from heme proteins. Normal liver tissue also differed from both the malignant tumor and its accompanying cirrhotic tissue at 1182 cm(-1). These results demonstrate the potential usefulness of Raman spectroscopy in clinical diagnosis, and investigations into the source of the observed spectral changes will provide information on the underlying mechanisms of carcinogenesis.

Carcinoma, Hepatocellular↗
PubMed1996

Dose-response effect of in vivo administration of endotoxin on polymorphonuclear leukocytes oxidative burst.

In vitro, endotoxin primes polymorphonuclear leukocytes (PMNs) to respond with a greater oxidative burst. The purpose of the present study was to investigate the in vivo effect of a wide range of single endotoxin bolus doses using a rat model. PMNs were subsequently challenged in vitro with phorbol ester to produce reactive oxygen intermediates (ROI). Flow cytometric determination of ROI production by large doses induced a decrease in ROI production by the few PMNs that remained in the circulation. By 6 h after injection, ROI production had returned to basal levels after a high dose, and was still increasing after a low dose. Neutropenia occurred immediately after endotoxin injection. After 6 h, PMN counts returned to almost normal levels with a high dose, but rebound neutrophilia occurred with a small dose. In contrast to in vitro studies, in vivo injection showed a response pattern that varied widely with dose and time of observation.

Animals↗
PubMed1995

A new model for inducing total hepatic ischemia while preventing circulatory collapse secondary to splanchnic vascular congestion.

Animal models used to study liver ischemia are limited by the lethal effect of splanchnic venous engorgement from portal triad occlusion (PTO). We compared a passive porto-systemic shunt (PSS) to a pump-driven PSS. The passive and pumped PSS groups (n = 6) received 60 min of PTO followed by 2 h of reperfusion. A control group received all interventions, but no PTO, and remained stable throughout. During PTO, severe circulatory shock with intestinal ischemia occurred in the passive group, while the pumped group remained stable. During reperfusion, both shunted groups experienced varying degrees of metabolic acidosis with decreases in cardiac index, stroke volume, superior mesenteric artery flow, and increases in systemic and intestinal vascular resistance. The mortality rate for the passive group was 83% vs. 0% for the pumped group. These results suggest that pumped PSS prevents splanchnic engorgement and allows for reproducible, isolated total hepatic ischemia in vivo.

Animals↗
PubMed1993

Alcohol intake increases human immunodeficiency virus type 1 replication in human peripheral blood mononuclear cells.

The effects of alcohol consumption on various T lymphocyte subset functions and on the degree of susceptibility of peripheral blood mononuclear cells (PBMC) to human immunodeficiency virus (HIV) type 1 infection and replication in vitro were investigated. PBMC from 60 HIV-1-seronegative healthy volunteers were studied before and after ingestion of alcohol beverages. After alcohol consumption, there was significantly increased HIV-1 replication (P < .001) in PBMC, as determined by HIV-1 p24 antigen levels in the culture supernatants, than in cultures obtained before alcohol ingestion. There was a decreased ability of lymphocytes, obtained after alcohol consumption, to produce interleukin-2 and soluble immune response suppressor activity after stimulation with concanavalin A. The data show that alcohol ingestion increases HIV-1 replication in human PBMC infected with HIV-1 in cell culture. This may be due to alcohol-induced functional impairment of various subsets of lymphocytes in the peripheral blood. Thus, HIV-1 replication may be augmented by alcohol in HIV-1-infected individuals, and alcohol intake may increase an individual's risk for acquiring HIV-1 infection.

Adolescent↗
PubMed1993

Experimental model of congenital syphilis.

Female LSH hamsters infected with Treponema pallidum subsp, endemicum before pregnancy or during early pregnancy transmit a form of syphilis to the fetus that is similar to human congenital syphilis. The offspring develops rhinitis, skin rash, failure to thrive, and hepatosplenomegaly. T. pallidum is detectable in their livers, spleens, and nasal secretions. Immunoglobulin M antibodies are detected in the serum.

Animals↗
PubMed1992

Activation of human complement system in paracoccidioidomycosis.

Plasma samples of 14 patients with paracoccidioidomycosis were analysed for components that represent activation of the complement system. Most patients (12/13) showed significant titres of complement-fixing antibodies and 14/14 had increased C4d/C4 ratios. There was no conclusive correlation between these two immunological indices, however. Factor B values of patients were similar to normal donors and fragment Ba was not detected in any of the patients. These results indicate a classical complement pathway activation in the plasma of patients with paracoccidioidomycosis.

Adolescent↗