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Biomedical subjects

G Acs

Publications and source records attributed to G Acs.

At least 19 recordsLinked to original sources

Lymphatic vessel density is significantly increased in melanoma.

BACKGROUND: Melanoma is well known for its ability to involve regional lymph nodes in the early stage. However, the presence of lymphangiogenesis in melanoma is still controversial due to lack of lymphatic-specific markers. The purpose of this study was to determine the intra- and peritumoral lymphatic vessel density (LVD) using a novel lymphatic vessel-specific marker D2-40 and compare it to general vessel density (GVD) as determined by CD31 immunostaining in a series of melanocytic lesions. METHODS: The intra- and peritumoral GVD and LVD were examined by immunohistochemistry using D2-40 and CD31 antibodies in a series of melanocytic lesions. RESULTS: We found significantly higher intratumoral LVD in melanomas as compared to either common acquired or dysplastic nevi (p < 0.01). Although peritumoral LVD in melanoma and malignant melanoma in situ was higher compared to nevi, the difference did not reach statistical significance (p = 0.059). There was no significant difference in GVD among the various groups of melanocytic lesions. CONCLUSIONS: Our results show that intratumoral LVD is significantly increased in melanomas compared to benign nevi. The higher intratumoral lymphatic density in invasive melanomas suggests that melanoma cells might promote lymphangiogenesis. In addition, assessment of intratumoral LVD may be potentially useful in the differential diagnosis of melanocytic lesions.

Antibodies, Monoclonal↗

Systemic and regional hemorheological consequences of warm and cold hind limb ischemia-reperfusion in a canine model.

We have studied systemic and regional changes in hemorheological parameters after complete acute limb ischemia and reperfusion (I/R) in 24 mongrel dogs. Unilateral cooled and non-cooled vascular ischemia (3 h)-reperfusion (4 h), and sham-operations were performed. Blood samples were collected from the excluded region, during reperfusion and for 5 days. Whole blood and plasma viscosity (WBV, PV), relative cell transit time (RCTT) of erythrocytes, fibrinogen level and hematological parameters were determined. In I/R groups WBV of excluded blood was significantly higher compared to the base (p < 0.05), and RCTT increased during the reperfusion. On 2nd-3rd days RCTT increased significantly in both I/R groups. In each group PV and fibrinogen showed continuous increase during the postoperative period, prominently in cooled I/R group, and furthermore WBV corrected for hematocrit (40%) was the highest in cooled I/R group. These suggest that surgical acute limb I/R may cause hemorheological changes, which are more serious after cooling. (Grants: OTKA-T032571, 6003/1/2001/ETT.)

Animals↗

Erythropoietin and erythropoietin receptor expression in human cancer.

Erythropoietin (EPO) stimulates the growth of erythroblasts in the bone marrow (C. Lacombe and P. Mayeux, NEPHROL: DIAL: TRANSPLANT:, 14 (SUPPL: 2): 22-28, 1999). We report basal and hypoxia-stimulated expression of EPO and its receptor, EPOR, in human breast cancer cells, and we demonstrate EPO-stimulated tyrosine phosphorylation and the proliferation of these cells in vitro. In 50 clinical specimens of breast carcinoma, we report high levels of EPO and EPOR associated with malignant cells and tumor vasculature but not with normal breast, benign papilloma, or fibrocystic tissue. Hypoxic tumor regions display the highest levels of EPO and EPOR expression. Enhanced EPO signaling may contribute to the promotion of human cancer by tissue hypoxia.

Biopsy↗

Diabetic mastopathy in men: imaging findings in two patients.

The classic imaging findings of diabetic mastopathy, an uncommon entity manifesting in patients with a history of long-standing insulin-dependent diabetes mellitus, have been reported in the literature in women but not, to the authors' knowledge, in men. Two men with diabetic mastopathy presented with palpable breast masses. The clinical histories of the men in whom this condition was diagnosed were similar to those reported for women with the condition. The mammographic findings in both men, at presentation, were suggestive of gynecomastia.

Adult↗

Differential expression of E-cadherin in lobular and ductal neoplasms of the breast and its biologic and diagnostic implications.

We studied the pattern of E-cadherin expression in 183 invasive carcinomas (100 ductal, 42 lobular, 41 with mixed ductal and lobular features) and 198 in situ carcinomas (131 ductal, 53 lobular, 14 in situ with ductal and lobular features) by immunohistochemistry. We found a highly significant correlation of E-cadherin membrane expression with the histologic phenotype of the tumors. While moderate to strong membrane expression of E-cadherin was seen in all invasive and in situ ductal carcinomas, 41 of 42 invasive and 50 of 53 in situ lobular carcinomas showed complete loss of expression. All in situ carcinomas diagnosed histologically as showing mixed ductal and lobular features demonstrated complete loss of staining. Invasive carcinomas with ductal and lobular features showed 3 staining patterns: (1) complete or almost complete lack of membrane staining similar to that seen in lobular carcinomas, (2) uniform membrane expression throughout the tumor similar to ductal carcinomas, and (3) focal loss of E-cadherin staining, which correlated well with the histologic impression of focal lobular features. In tumors with histologically equivocal features, immunohistochemical detection of E-cadherin expression can be a useful diagnostic tool for the differentiation of ductal and lobular carcinomas of the breast.

Breast Neoplasms↗

Loss of membrane expression of E-cadherin in leukemic erythroblasts.

CONTEXT: The special societal relationships existing between various cell types in bone marrow suggests that there may be a link between the adhesive characteristics of hematopoietic cells and their maturation. Egress of the developing hematopoietic cells is also a highly regulated process governed by adhesive interactions. In leukemia, immature blasts are not retained within the marrow, suggesting a breakdown of adhesive mechanisms. Recent reports suggest that E-cadherin, an epithelial adhesion molecule, is expressed on erythroid precursors and megakaryocytes, but not on other hematopoietic marrow elements. OBJECTIVE: To characterize the expression pattern of E-cadherin in normal and leukemic erythroid precursors by immunohistochemistry in paraffin-embedded tissue and bone marrow aspirate smears. METHODS: Five normal bone marrow specimens from rib resections, 15 trephine bone marrow biopsy specimens, and 6 bone marrow aspirate smears from the iliac crest of patients with no known leukemia were selected. Fourteen bone marrow biopsy specimens from patients with erythroleukemia were also studied. Immunoperoxidase staining of paraffin-embedded tissue and air-dried aspirate smears for E-cadherin (1:200 dilution, HECD-1 clone) was performed using the avidin-biotin peroxidase technique. RESULTS: In paraffin-embedded bone marrow biopsy and rib specimens and in air-dried bone marrow aspirate smears, strong membrane expression of E-cadherin was seen in the normal erythroid precursors in all cases. In contrast, no membrane expression of E-cadherin was present in any of the bone marrow biopsy specimens from patients with erythroleukemia. CONCLUSIONS: Immunohistochemical detection of membrane expression of E-cadherin may be a useful tool for identification of erythroid precursors. Cells of erythroleukemia lack membrane expression of E-cadherin, in contrast to their normal counterparts. Further studies are needed to define the potential role of E-cadherin in the maturation of erythroid precursors and to ascertain the significance of loss of membrane expression of E-cadherin in erythroleukemia.

Biopsy↗

Cytomorphology of high-grade neuroendocrine carcinoma of the urinary tract.

High-grade neuroendocrine carcinoma of the bladder is a rare malignant tumor with poor prognosis. We present the cytomorphologic features of six retrospectively identified cases which displayed high-grade tumors with neuroendocrine differentiation in bladder washings. Cytology specimens showed small-to-medium-sized tumor cells with powdery chromatin, inconspicuous nucleoli, and ill-defined nuclear membranes. Tumor fragments showed prominent nuclear molding and single-cell necrosis. All cases also revealed a varying proportion of tumor cells resembling the usual transitional-cell carcinoma. Biopsy specimens from five cases demonstrated high-grade transitional-cell carcinoma with areas resembling small-cell carcinoma. In one case the entire tumor consisted of classic small-cell carcinoma and failed to show any areas of transitional-cell differentiation. All cases were positive for neuroendocrine markers. Neuroendocrine carcinomas of the urinary bladder are rare, with cytological features similar to high-grade neuroendocrine carcinomas seen in other organs. They can be accurately diagnosed cytologically, and an awareness of the cytomorphologic features is important.

Aged↗

Duodenal carcinoid tumor: report of a case diagnosed by endoscopic ultrasound-guided fine-needle aspiration biopsy with immunocytochemical correlation.

Fine-needle aspiration biopsy is a reliable and accurate method for the endoscopic diagnosis of gastrointestinal malignancies and it is particularly well suited for evaluation of submucosal lesions. We report the cytopathologic findings of a case of malignant carcinoid tumor of a 44-year-old male who presented with melena and a nonhealing duodenal ulcer. Endoscopic ultrasound examination revealed a submucosal lesion in the pyloric region. Fine-needle aspiration revealed abundant cellularity with tumor cells arranged in sheets and loose groups and dispersed single cells in a clean background. Papillary fragments, capillaries cuffed by tumor cells, and rosette formation were also noted. The cells were moderate in size, round to oval, with a small subpopulation of spindle-shaped cells. The nuclei were uniform, round to oval, with smooth nuclear borders. The chromatin pattern was finely granular with a salt-and-pepper appearance. The cytoplasm of the cells was small to moderate in amount, pale, and showed fine granularity. The differential diagnosis included a neuroendocrine neoplasm vs. an epithelioid gastrointestinal stromal tumor. The tumor cells were focally positive for chromogranin and negative for CD34, supporting the diagnosis of a neuroendocrine neoplasm. The differential diagnosis of primary gastrointestinal carcinoid tumors from gastrointestinal stromal tumors can be very difficult in cytologic material. In cases when diagnostic material is scant, or only present on one smear, the use of smear division and cell transfer in order to perform immunocytochemical stains may be of considerable value to confirm the neuroendocrine nature of the neoplasms.

Adult↗

Causes of death of patients with multiple injuries in Debrecen, Hungary.

OBJECTIVE: To find out the main causes of death of people who had multiple severe injuries. DESIGN: Retrospective study. SETTING: Teaching hospital, Hungary. SUBJECTS: 86 people with severe multiple injuries, of whom 59 died and had necropsies. MAIN OUTCOME MEASURE: Establishment of a database. RESULTS: Consumption of alcohol was a common precursor. Head and chest injuries predominated. More pedestrians than people in vehicles were killed, and there were 8 suicides and 3 murders. There were no gunshot injuries. CONCLUSIONS: Reduction of deaths from multiple injuries is as much a socioeconomic as a medical matter.

Alcohol Drinking↗

The effect of disabilities on exits from AFDC.

The Personal Responsibility and Work Opportunity Reconciliation Act (PRWORA) of 1996 replaces AFDC, the largest means-tested cast assistance program for low-income families, with the Temporary Assistance for Needy Families (TANF) block grant. Unlike AFDC, assistance under TANF is limited to five years in a lifetime, and states are required to move families from the assistance rolls into jobs. But not all adult welfare recipients can easily move to work because either they themselves are disabled or they have a child with disabilities requiring special care. This article examines the extent and impact of disability among families on AFDC to gain insight into the potential impact of changes under TANF. Using data from the 1990 Survey of Income and Program Participation (SIPP), we find that in nearly 30 percent of the families on AFDC either the mother or child has a disability. Furthermore, we find that having a disability significantly lowers the probability that a woman leaves AFDC for work but not for other reasons, such as a change in living arrangements. Finally, we find little evidence that having a child with a disability affects the probability of leaving AFDC for any reason.

Adolescent↗

Characterization of functional vanilloid receptors expressed by mast cells.

Capsaicin and its ultrapotent analog resiniferatoxin (RTX) act through specific vanilloid receptors on sensory neurons. The C-type receptor is coupled to 45Ca uptake, whereas the R-type is detectable by [3H]RTX binding. We describe here specific vanilloid responses in murine mast cells (MCs). In the MC lines and in bone marrow-derived mast cells, capsaicin and RTX induced 45Ca uptake similarly to that observed for cultured rat dorsal root ganglion neurons (DRGs). This response was antagonized by the antagonists capsazepine and ruthenium red. As in DRGs, pretreatment of MCs with capsaicin or RTX induced desensitization to subsequent stimulation of 45Ca uptake. The potency for desensitization by RTX in the MCs corresponded to that for 45Ca uptake, whereas in DRGs it occurred at significantly lower concentrations corresponding to that for the high-affinity [3H]RTX binding site. Consistent with this difference, in MCs we were unable to detect [3H]RTX binding. Vanilloids were noncytotoxic to the MCs, in contrast to the DRGs. Although vanilloids did not cause degranulation in MCs, in the P815 clone capsaicin evoked selective interleukin-4 release. We conclude that certain MCs possess vanilloid receptors, but only the C-type that functions as a channel. Our finding that MCs can respond directly to capsaicin necessitates a reevaluation of the in vivo pathway of inflammation in response to vanilloids.

Animals↗

The effect of dental rehabilitation on the body weight of children with failure to thrive: case reports.

Four case reports of children with nursing caries and failure to thrive are presented. Without regard to the condition of the dentition, the various cases could be classified as organic, mixed, or nonorganic in etiology. After dental rehabilitation, all patients exhibited an acceleration of weight velocity that resulted in weights above the 5th percentile. During the period of observation, the weight velocity continued to increase with time, consistent with the "catch-up" phenomenon of growth that is observed in nutritionally deprived children.

Bottle Feeding↗

Differential activation and desensitization of sensory neurons by resiniferatoxin.

Recently, with use of rat dorsal root ganglion (DRG) neurons we have been able to dissociate the binding affinities of vanilloids from their potencies to induce 45Ca uptake, which suggests the existence of distinct classes of the vanilloid receptor (). In the present study, we have demonstrated that the ultrapotent capsaicin analog resiniferatoxin (RTX) desensitized rat DRG neurons to the subsequent induction of 45Ca uptake by capsaicin and RTX with affinity and cooperativity similar to that found for [3H]RTX binding, contrasting with a approximately 10-fold weaker potency and lack of cooperativity to induce 45Ca uptake. Likewise, the competitive antagonist capsazepine inhibited RTX-induced desensitization with potency similar to that for inhibition of specific [3H]RTX binding, whereas the potency of capsazepine was approximately 10-fold higher for inhibiting RTX-induced 45Ca uptake. Finally, the noncompetitive antagonist ruthenium red inhibited both the RTX-induced desensitization and 45Ca uptake but showed approximately 60-fold selectivity for inhibiting RTX-induced desensitization. The RTX-induced desensitization was not associated with loss of specific [3H]RTX binding, suggesting lack of gross cell toxicity. In contrast to RTX, capsaicin caused desensitization with a potency corresponding to that for 45Ca uptake and did so in a noncooperative manner. Unlike the RTX-induced desensitization, the desensitization by capsaicin was blocked by ruthenium red only at doses that blocked 45Ca uptake and depended on external calcium. Our findings provide further support for the existence of vanilloid receptor subtypes on DRG neurons with distinct pharmacology and distinct patterns of desensitization.

Animals↗

Recent advances in understanding of vanilloid receptors: a therapeutic target for treatment of pain and inflammation in skin.

C-fiber sensory afferent neurons, which contain neuropeptides such as calcitonin-gene related peptide and substance P, mediate a wide variety of physiologic responses, including chemogenic pain, thermoregulation, and neurogenic inflammation. Capsaicin, the pungent constituent in red pepper, functions to activate and then, at higher doses and longer times, desensitize this class of neurons. This latter response provides the basis for the therapeutic application of capsaicin. A major advance in the field has been the identification of resiniferatoxin, a phorbol-related diterpene, as an analog of capsaicin that is ultrapotent but with differential selectivity. In particular, resiniferatoxin is only similar in potency for induction of pain but is much more effective for desensitization. Structure-activity analysis in whole animal experiments provides further evidence for dissociation of biologic endpoints, strongly arguing for the existence of vanilloid receptor subclasses. Using resiniferatoxin, we have been able to define specific, high-affinity receptors for capsaicin both in animal models such as rats and in man. Of great importance, the pharmacologic characterization in cultured dorsal root ganglion cells of the high-affinity resiniferatoxin-binding site and of the physiologic response believed to be directly coupled to the receptor, viz. calcium uptake, differed in structure-activity and in cooperativity. We conclude that multiple high-affinity vanilloid receptor subclasses mediate vanilloid response; moreover, the resiniferatoxin-selective subclass of vanilloid receptors is not the voltage-independent, cation-nonselective ion channel as previously believed. Optimization of ligands for the individual vanilloid receptor subclasses should revolutionize this therapeutic area.

Animals↗

The effect of acetaminophen on tooth movement in rabbits.

Orthodontic patients have reported the use of analgesics during therapy. However, common anti-inflammatory analgesics, such as aspirin and ibuprofen, have been shown to slow the rate of tooth movement. Acetaminophen, another common analgesic, does not possess anti-inflammatory properties. The effect of acetaminophen on tooth movement was studied using New Zealand white rabbits. Experimental animals were matched to a control animal of the same sex and weight. Under anesthesia, springs were ligated between the lower first molar and incisor, resulting in approximation of these teeth. Under blinded conditions, seven of the rabbits received 1000 mgs of acetaminophen daily. Seven control animals received water. The animals were sacrificed after 21 days. The movement of incisors and molars was measured. Results showed considerable movement within both the experimental and control groups, but no significant difference in tooth movement between them. Acetaminophen has no effect on the rate of tooth movement in rabbits undergoing orthodontic treatment.

Acetaminophen↗

Splenic autotransplantation after abdominal trauma in childhood. Clinical and experimental data.

Splenectomy is known to increase the risk of overwhelming bacterial infection. There is a decrease in immunoglobulin IgM and T-lymphocytes, primary antibody response to antigen challenge is impaired, altered opsonic function an Tuftsin deficiency are noted. Splenic autotransplantation has been suggested as a method of preserving function and this concept is supported by experiments in animals. Prior to operation on humans the technique was thoroughly elaborated and practised in animal experiments (dogs). After splenectomy, 6-8 thin segments (Furka's "spleen chip") are placed in between the plates of the major omentum. Within the period of ten years out of 52 patients 11 children (4 girls, 7 boys) suffered from abdominal trauma underwent total splenectomy, and than autotransplantation in the Kenézy Hospital in Debrecen, Hungary. In several patients the postoperative follow-up radionuclide imaging, IgM, and Tuftsin levels, and the haematological changes (leukocytes, differential blood count, platelet count, iron level in serum) unambiguously confirmed the function of the splenic tissue.

Abdominal Injuries↗

A novel agonist, phorbol 12-phenylacetate 13-acetate 20-homovanillate, abolishes positive cooperativity of binding by the vanilloid receptor.

Capsaicin binds to a specific recognition site, referred to as the vanilloid receptor, which it shares with the natural, ultrapotent agonist resiniferatoxin and with the competitive antagonist capsazepine. Upon binding to its receptor, capsaicin opens a cation channel leading to Ca2+ influx. The binding of capsaicin or resiniferatoxin by the vanilloid receptor follows a sigmoidal saturation curve, indicative of positive cooperativity. The biological significance of this positive cooperative behaviour is unknown, as is the mechanism responsible for it. We have developed a novel ligand, phorbol 12-phenylacetate 13-acetate 20-homovanillate (PPAHV), which binds to cultured rat sensory neurons (with a Ki of 3.1 +/- 0.4 microM), and induces Ca2+ uptake by them (with an ED50 of 1.8 +/- 0.3 microM) with similar affinities and in a non-cooperative manner (Hill coefficients are 0.99 and 1.06 for binding and Ca2+ uptake, respectively). The behaviour of PPAHV thus contrasts with resiniferatoxin or capsaicin not only in the lack of cooperativity but also in the relative potencies for resiniferatoxin binding versus Ca2+ uptake (resiniferatoxin is less potent and capsaicin is more potent for induction of Ca2+ uptake than for binding). In further experiments in which the concentration of [3H]resiniferatoxin was varied, 1 microM PPAHV likewise reduced the cooperativity index that characterizes resiniferatoxin binding to rat spinal cord membranes from 2.3 +/- 0.1 to 1.1 +/- 0.2; in parallel experiments, neither capsaicin nor capsazepine (both at a concentration of 2 microM) affected binding cooperativity. Moreover, PPAHV (1 microM) turned the bi-phasic dissociation curve of resiniferatoxin into a monophasic curve, eliminating the second, slow-dissociation phase. The present results suggest that positive cooperativity is a ligand-induced feature rather than an inherent property of vanilloid receptors. A comparison of the spectrum of biological activity of ligands which bind to vanilloid receptors with different degrees of cooperativity may provide an approach to explore the functional significance of this binding behaviour.

Animals↗