Biomedical subjects

Peter Horvath

Publications and source records attributed to Peter Horvath.

6 recordsLinked to original sources

PubMed2026

Deep visual multi-omics profiling links morphology and molecular programs in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma exhibits striking intra-tumoral heterogeneity at morphological and genetic levels, complicating treatment and contributing to disease progression. CcRCCs with rhabdoid differentiation are highly aggressive tumors characterized by distinct histopathologies. However, the relationship between morphology, underlying molecular alterations, and tumor behavior remains largely unclear. Here, we present Deep Visual Multi-Omics, an approach integrating digital pathology, morphology-guided single-cell isolation, and ultra-sensitive multi-omics profiling to link cell morphologies to their molecular underpinnings. Across five tumors, we profiled ~40,000 AI-classified and expert-curated cells. We identified progressive molecular dysregulation across cells with increasing histopathological grade coexisting within heterogeneous tumors as well as distinct molecular alterations associated with aggressive rhabdoid ccRCC cells, including signatures consistent with enhanced FOXM1-driven proliferation, altered cell-matrix interactions, and a putative immunomodulatory phenotype. Notably, rhabdoid cells exhibited elevated expression of IFN-beta, PD-L1, CD38, ITGB2, and integrin signaling, suggesting that they themselves may act as a source of signals influencing the local immune microenvironment. Besides providing new insights into the biology of ccRCC and highlighting avenues for future translational studies, this illustrates the potential of Deep Visual Multi-omics to dissect cancer heterogeneity and characterize high-risk cell populations.

Humans↗

PubMed2006

Regulation of the activity and fatty acid specificity of lecithin-cholesterol acyltransferase by sphingomyelin and its metabolites, ceramide and ceramide phosphate.

Sphingomyelin (SM), the second most abundant phospholipid in plasma lipoproteins, was previously shown to be a physiological inhibitor of the lecithin-cholesterol acyltransferase (LCAT) reaction. In this study, we investigated the effects of its metabolites, ceramide and ceramide phosphate, on the activity and fatty acid specificity of LCAT in vitro. Treatment of SM-containing substrate with SMase C, which hydrolyzes SM to ceramide, abolished the inhibitory effect of SM, whereas treatment with SMase D, which hydrolyzes it to ceramide phosphate, increased the level of inhibition. Although incorporation of ceramide into the substrate in the absence of SM activated the LCAT reaction only modestly, its co-incorporation with SM neutralized the inhibitory effect of SM. Ceramide phosphate, on the other hand, inhibited the LCAT reaction more strongly than SM. The effects of the sphingolipids on the phospholipase A and cholesterol esterification reactions of the enzyme were similar, indicating that they regulate the binding of phosphatidylcholine (PC) to the active site, rather than the esterification step. Incorporation of ceramide into the substrate stimulated the synthesis of unsaturated cholesteryl esters at the expense of saturated esters. However, these effects on fatty acid specificity disappeared when the PC substrates were incorporated into an inert diether PC matrix, suggesting that ceramide increases the availability of polyunsaturated PCs to the enzyme by altering the macromolecular structure of the substrate particle. Since the plasma ceramide levels are increased during inflammation, these results indicate that the activity and fatty acid specificity of LCAT may be altered during the inflammatory response.

Bacterial Toxins↗

PubMed2006

Greek Cypriot attitudes toward Turkish Cypriots and Turkish immigrants.

The authors examined the attitudes of 106 Greek Cypriots toward Turkish Cypriots and Turkish immigrants on Cyprus. The authors examined Greek Cypriot attitudes, willingness to cohabit with Turkish Cypriots and Turkish immigrants, and the reasons behind their attitudes in terms of their social-identity perceptions, victimization experiences, and human-rights concerns. A series of repeated measures analyses of variance showed that Greek Cypriots were more willing to cohabit with and had less negative attitudes toward Turkish Cypriots than they were with and toward Turkish immigrants. Women felt more victimized by Turkish Cypriots and Turkish immigrants than did men. Perceived differences in social identity predicted unwillingness to cohabit with Turkish Cypriots. Feelings of victimization predicted negative attitudes toward Turkish Cypriots. Differences in social identity and victimization experiences predicted unwillingness to cohabit with Turkish immigrants. Differences in social identity predicted negative attitudes toward Turkish immigrants. The authors discussed the findings in terms of support for realistic group conflict theories of attitudes and their implications for the coexistence of these ethnic groups in Cyprus and of other ethnic groups in multicultural societies.

Attitude↗

PubMed2004

Decreased sensory neuropeptide release in isolated bronchi of rats with cisplatin-induced neuropathy.

We studied if attenuated neurogenic bronchoconstriction was associated with a change in sensory neuropeptide release in preparations from rats with cisplatin-induced neuropathy. Electrical field stimulation (100 stimuli, 20 V, 0.1 ms, 20 Hz) induced an increase in the release of somatostatin, calcitonin gene-related peptide (CGRP) and substance P determined by radioimmunoassay from baseline 0.18+/-0.01, 0.17+/-0.01 and 0.86+/-0.02, to 0.59+/-0.02, 1.77+/-0.04 and 5.96 fmol/mg wet tissue weight, respectively, in organ fluid of tracheal tubes from rats. This was significantly attenuated to post-stimulation values of 0.36+/-0.02, 0.45+/-0.02, 4.68+/-0.24 fmol/mg wet tissue weight for somatostatin, CGRP, and substance P, respectively, with a significant decrease in field stimulation-induced contraction of bronchial preparations from animals 11 days after a 5-day treatment period with cisplatin (1.5 mg/kg i.p. once a day). The cisplatin-treated animals developed sensory neuropathy characterized by a 40% decrease in femoral nerve conduction velocity. The results show that a decrease in tracheo-bronchial sensory neuropeptide release associates with feeble bronchomotor responses in rats with cisplatin-induced sensory neuropathy.

Animals↗

PubMed2002

Feeble bronchomotor responses in diabetic rats in association with decreased sensory neuropeptide release.

Type I diabetes is associated with a low incidence of asthma. We tested whether a decrease in sensory neuropeptide release is associated with an attenuated bronchoconstrictive response to field stimulation (FS; 100 stimuli, 20 V, 0.1 ms, 20 Hz) in streptozotocin (STZ)-induced diabetes. The organ fluid of the preparations were also tested for substance P, calcitonin gene-related peptide (CGRP), and somatostatin concentrations by RIA. Preparations were from either normal rats or those pretreated with 50 mg/kg STZ iv 8 wk before experiment. A group of STZ-treated animals was supplied with insulin delivery (4 IU/day sc) implants between 4 and 8 wk. A subgroup was formed to study the effect of capsaicin desensitization. The atropine-resistant contraction was attenuated by diabetes without capsaicin-sensitive relaxation response. Exogenous CGRP and substance P potentiated, whereas somatostatin inhibited (1 nM-10 microM) the FS-induced contractions in rings from either group. FS released somatostatin, CGRP, and substance P from 0.17 +/- 0.024, 0.15 +/- 0.022, and 1.65 +/- 0.093 to 0.58 +/- 0.032, 0.74 +/- 0.122, and 5.34 +/- 0.295 in preparations from normal, and from 0.19 +/- 0.016, 0.11 +/- 0.019, and 0.98 +/- 0.116 to 0.22 +/- 0.076, 0.34 +/- 0.099, and 1.84 +/- 0.316 fmol/mg wet wt in preparations from diabetic rats. Insulin supplementation restored neuropeptide release in rings from STZ-treated rats. The results show that the decreased FS-induced contractions occurred with a decrease in sensory neuropeptide release in STZ-diabetic rats.

Animals↗

PubMedDate not supplied

Clinical importance of accurate refractor vertex distance measurements prior to refractive surgery.

PURPOSE: To determine directly measured vertex distances in a consecutive series of patients refracted at a refractor and to examine the clinical importance of such a measurements for improving refractive surgical results. METHODS: Vertex distance measurements were obtained in 189 consecutive patients by using a new device capable of taking direct and accurate measurements behind a refractor. Eyelid thickness was measured with an industrial caliper in five patients. RESULTS: The average true vertex distance was 20.4 mm with a range of 10 to 34 mm. Eyelid thickness was 3 mm in all five patients. CONCLUSIONS: Precise measurement of true refractor vertex distance is important for accuracy of refractive surgical procedures. The practice of assuming an average vertex distance of 12 to 14 mm for all refractive patients underestimates the vertex distance in many patients refracted at the refractor, resulting in overcorrecting minus and undercorrecting plus refractions.

Eyeglasses↗