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K Tory

Publications and source records attributed to K Tory.

At least 19 recordsLinked to original sources
PubMed2004

Effect of propranolol on heart rate variability in patients with end-stage renal disease: a double-blind, placebo-controlled, randomized crossover pilot trial.

BACKGROUND: Low heart rate variability (HRV) is an independent risk factor of cardiac mortality in patients with end-stage renal disease (ESRD). It has been explained by uremic parasympathetic neuropathy. Sympathetic overactivity can also reduce HRV. Our aim was to determine whether there is vagal activity in ESRD patients that is masked by sympathetic activity. METHODS: The effect of propranolol on HRV was examined in 13 patients with ESRD, aged 20.1 +/- 7.6 years without diabetes. All patients were given intravenous propranolol (0.05 mg/kg) once and placebo once in a randomized, double-blind way, with an interval of 6.6 days (mean, range: 2-9). Propranolol was administered before hemodialysis treatment, after 40 minutes supine resting period. HRV was registered for 10 minutes, during supine, before and after the injection. Patients' HRV data were compared to that of 29 age-matched healthy controls. RESULTS: Initially, both high-(HFV) and low-frequency (LFV) bands of heart rate variability were lower in ESRD patients compared to controls (p < 0.001 for both). Propranolol resulted in a significant increase of HFV (propranolol: AlgHFV = 0.182 (0.027 - 0.337), placebo: deltalgHFV = -0.029 (-0.128 - +0.070); p = 0.032). Elevation of LFV was not significant. Six patients had an elevated plasma norepinephrine and/or epinephrine level. Plasma dopamine level was elevated in all but 1 patient (mean: 432 pmol/l, 95% CI: 320-543) and showed an inverse relationship with the increase of IgHFV secondary to propranolol (r = -0.66, p = 0.014). CONCLUSIONS: Low HFV of ESRD patients can be improved by beta-adrenergic blockade. It demonstrates that there is some vagal activity in ESRD that is masked by sympathetic activity. Therefore, altered sympathovagal balance of ESRD patients should be taken into consideration in the assessment of vagal uremic neuropathy.

Adolescent↗
PubMed2003

BGP-15, a hydroximic acid derivative, protects against cisplatin- or taxol-induced peripheral neuropathy in rats.

The neuroprotective effect of BGP-15 against peripheral sensory neuropathy was studied in rats that were exposed to short-term cisplatin or taxol administration. The changes of nerve conduction velocity were determined in situ after treating the Wistar rats with BGP-15 (50, 100, and 200 mg/kg po daily doses throughout the experiment), cisplatin (1.5 mg/kg ip daily dose for 5 days), or taxol (5.0 mg/kg ip daily dose every other day in a 10-day interval) alone or giving the test compound in combination with cisplatin or taxol. Electrophysiological recordings were carried out in vivo by stimulating the sciatic nerve at both sciatic notch and ankle site. Neither motor nor sensory nerve conduction velocity was altered by any dose level of BGP-15 tested. Both anticancer drugs decreased the sensory nerve conduction velocity (SNCV). BGP-15 treatment prevented the impairment of SNCV either in part or totally in the cisplatin- or taxol-treated groups. This neuroprotective potential of BGP-15 could be well correlated with its recently described poly(ADP-ribose) polymerase- inhibitory effect and its ability to protect against the damages induced by the increased level of reactive oxygen species in response to anticancer treatment.

Animals↗
PubMed2001

Signs of autonomic neuropathy in childhood uremia.

To evaluate the presence of autonomic neuropathy in childhood uremia, cardiovascular autonomic reflexes were examined in children with chronic renal failure. Cardiovascular autonomic reflexes of 10 uremic patients on chronic dialysis and 10 transplanted patients were compared to assess the effect of transplantation on autonomic neuropathy. Resting heart rate, heart rate changes induced by deep breathing, by Valsalva maneuver, and following standing up, and blood pressure change induced by handgrip test were examined. Of the 10 uremic children, 4 showed early involvement and 2 had definite involvement of autonomic neuropathy. Only 1 of the 10 transplanted patients showed early signs of autonomic neuropathy. Autonomic tests demonstrated predominantly parasympathetic dysfunction. In conclusion, cardiovascular autonomic neuropathy is not rare in children and adolescents and young adults with chronic renal failure. In contrast, the prevalence is very low in transplanted patients with similar uremic precedents. Efforts should be made to prevent or delay this uremia-related complication.

Adolescent↗
PubMed2001

Monitoring cardiovascular changes during hemodialysis in children.

Hemodialysis (HD) causes rapid volume shifts and circulatory changes. In chronic renal failure (CRF) Na+/K+ATP-ase is depressed, whereas endogenous digoxin-like factor (EDLF) is elevated. Our aim was to characterize HD-induced cardiovascular adaptation and its possible links to Na+/K+ATP-ase and EDLF. Eleven children with CRF on HD (aged 14.7 +/- 3.7 years) and 11 healthy children were investigated for basic circulatory parameters. Thoracic impedance (Zo) and circulatory parameters were monitored by impedance cardiography (ICG) during HD. Erythrocyte Na+/K+ATP-ase and EDLF were measured before and after HD. Up to the loss of 6% of total body weight, Zo rose linearly with fluid removal, above this no further increase occurred. Heart rate and mean arterial pressure (MAP) were inversely related (r = -0.97); MAP rose in the first and decreased in the second part of HD. Systemic vascular resistance paralleled MAP, whereas stroke volume rapidly decreased, but stabilized in the second part of HD. The ratio of preejection period/ventricular ejection time (PEP/VET) correlated positively with HD duration (r = 0.92), suggesting diminished cardiac filling. Cardiac index (CI) remained stable. EDLF was high in uremia accompanied by depressed Na+/K+ATP-ase (P < 0.05 and P < 0.01, respectively). Following HD Na+/K+ATP-ase normalized. Correlation between Na+/K+ATP-ase activity and MAP was linear (r = 0.85). In conclusion, ICG during HD provides detailed information concerning circulatory adaptation resulting in stable CI, suggesting that the dialysis-induced hypovolemia is compensated by the centralization of the blood volume. Changes of Na+/K+ATP-ase indicate that dialyzable blood pressure-regulating substance(s) inhibit(s) the pump. However, lack of further correlation between Na+/K+ATP-ase, EDLF, and cardiovascular parameters indicates the complexity of the regulatory processes.

Adolescent↗
PubMed2000

Clinical relevance of immunohistochemical expression of p53-targeted gene products mdm-2, p21 and bcl-2 in breast carcinoma.

The present study was designed to investigate the clinical/prognostic relevance of immunohistochemical expression of p53-targeted genes mdm-2, p21WAF1 and bcl-2 alone and in combination with p53 for the indirect assessment of p53 gene status in breast cancer. 141 archival breast carcinomas were immunostained, and the putative mutational status of the p53 gene was defined in 21 of them, as a control for immunohistochemistry, using the polymerase chain reaction single-strand conformational polymorphism (PCR-SSCP) analysis. Genetic changes of p53 correlated significantly with p53 protein overexpression (p = 0.01) but did not do so with any of the related molecules. Immunohistochemical p53 status was directly correlated with mdm-2 (p = 0.0001), p21 (p = 0.0004) and inversely with bcl-2 (p = 0.005) expression. bcl-2 proved to be an independent marker of prognosis, p53 only in the group of node-positive carcinomas, whereas bcl-2-/p53+ tumours revealed the worst prognosis. Mdm-2 and p21 expression was of prognostic significance neither alone nor in combination. We conclude that the detection of down-stream regulators of p53 does not increase the efficacy of immunohistochemistry in assessing the functional status of p53 in breast cancer; however, their combined analysis may help to select subgroups of patients at the extremes of risk for recurrence, or those with greater chances for survival.

Adult↗
PubMed1999

Diagnostic relevance of chromosomal in-situ hybridization in Merkel cell carcinoma: targeted interphase cytogenetic tumour analyses.

AIMS: To resolve the conflicting diagnoses of five pathologists (which included well-differentiated neuroendocrine carcinoma, malignant carcinoid, undifferentiated small-cell carcinoma, primitive neuroectodermal tumour, metastases of small-cell lung carcinoma (SCLC) and Merkel cell carcinoma (MCC)), and tumour-free lungs after necropsy, we investigated an alarmingly metastasizing MCC in a 32-year-old Caucasian man using chromosomal in-situ hybridization (CISH). Differences in incidence and course in males and females also prompted targeted analyses for chromosomes X and Y. The lesion was also analysed for p53 gene mutations. METHODS AND RESULTS: Paraffin sections of the thorax, buccal lymph nodes and scalp tumours were stained with haematoxylin and eosin. Immunohistochemistry was performed with antibodies against pancytokeratin, keratin 20, neuron-specific enolase (NSE), chromogranin, neurofilaments and vimentin, among others. Sections (5-6 microm) of the tumours were analysed with alpha-satellite probes for chromosomes 1, 6, 7, 11, 12, 17, 18, X and Y using CrSH; and exons 5-9 of the p53 gene were examined by polymerase chain reaction and single strand conformation polymorphism (PCR-SSCP) methods. Although positive for pancytokeratin, keratin 20, chromogranin, NSE, synaptophysin and vimentin, the similarity in antigen profiles expressed by SCLC and MCC prevented a definitive tumour diagnosis. Chromosomal in-situ hybridization, however, revealed trisomies 1 and 11, two frequent aberrations in MCC, and trisomy 18. Moreover, 71% of the tumour cells had two to three copies of X, whereas 98% of the cell nuclei in the hair follicles and normal epidermis (purported Merkel cell origins) displayed one X chromosome. No mutations were detected in the five exons of the p53 gene examined. CONCLUSIONS: Had CISH been performed earlier, treatment may have been tailored specifically to suit MCC, since MCC and SCLC have different therapeutic strategies. Finally, chromosome X may be of prognostic relevance in MCC, which apparently predominates in females and yet shows poorer prognosis in males, and hence be worthy of further investigation.

Adult↗
PubMed1999

Analysis of p53 mutation and cyclin D1 expression in breast tumors.

P53 and cyclin D1 are interacting regulatory genes and both are frequently altered in breast cancer. We analysed p53 mutation by SSCP and sequencing methods as well as p53 protein accumulation immunohistochemically in 34 consecutively operated breast tumors. None of 4 fibroadenomas revealed p53 mutation or p53 protein accumulation. Mutation of p53 was present in 7 carcinomas. Immunohistochemistry revealed accumulation of p53 protein in 6 carcinomas and there was a significant correlation between p53 mutation and protein accumulation. Overexpression of cyclin D1 protein was observed in 11 carcinomas by immunohistochemistry and no correlation was observed between cyclin D1 overexpression and p53 mutation or accumulation. Our data support the concept that the p53-cyclin D1 signal pathway and the cyclin D1 cascade are disregulated in breast cancer.

Breast Neoplasms↗
PubMed1999

Evaluation of the tyrosine kinase domain of the Met proto-oncogene in sporadic ovarian carcinomas*.

Most of the ovarian cancers originate from the ovarian surface epithelium derived from the coelomic mesothelium. The Met proto-oncogene encodes a transmembrane tyrosine kinase receptor (Met) that has the capacity to regulate cell proliferation and differentation and it is activated by hepatocyte growth factor. Trisomy of chromosome 7 and Met protein overexpression have been were observed in ovarian carcinomas, the papillary renal cancers and other solid tumors. Frequent mutations of Met proto-oncogene have been found in hereditary papillary renal cancer (HPRC) and most of the mutations are located in the tyrosine kinase domain. The aim of this study to perform a mutation analysis of exons 17 19 of Met proto-oncogene in epithelial ovarian tumors (EOTs). We have examined 24 tumor samples from patients, operated with EOTs. Mutation was detected in exon 18 in only one sample of 24 EOTs. Our results indicate that mutations located in the Met proto-oncogene is not a common event in EOT. It is not clear whether the mutation plays a role in the tumorigenesis or progression of EOT or not.

Adenocarcinoma, Mucinous↗
PubMed1998

Molecular assessment of p53 abnormalities at the invasive front of oral squamous cell carcinomas.

BACKGROUND: The prognostic significance of the invasive tumor front in squamous cell carcinomas has recently been recognized. The aim of the present study was to investigate possible molecular mechanisms underlying the significance of this area in oral squamous cell carcinomas. METHODS: We used immunohistochemical and molecular genetic techniques to investigate whether p53 alterations at the invasive tumor front could determine the aggressiveness of oral cancers. RESULTS: p53 Overexpression was detected in 52% to 56% (four different p53 antibodies) of 100 carcinomas studied. The concordance rate between results of immunohistochemistry and genetic analysis was 60%. No correlation was found between p53 status of the tumors and clinicopathologic parameters analyzed statistically. CONCLUSIONS: p53 Alterations have no prognostic impact in oral squamous cell carcinomas and apparently do not represent a molecular basis for the biologic significance of the invasive tumor front. The detection of discordant p53 aberrations between primary and second primary carcinomas in some patients provide evidence for their independent origin, with possible impact on prevention and therapy.

Adult↗
PubMed1998

Frequent loss of chromosome 12 in human epithelial ovarian tumors: a chromosomal in situ hybridization study.

The short arm isochromosome of chromosome 12 and trisomy 12 are well-established chromosomal alterations in human ovarian germ cell tumors. However, numerical aberrations of chromosome 12 in epithelial ovarian tumors (EOTs) are highly controversial; both trisomy 12 and monosomy 12 have been observed. We performed chromosomal in situ hybridization in paraffin-embedded and formalin-fixed tissue sections of 31 EOTs. Twenty-five EOTs could be evaluated statistically (2 mucinous, 11 serous, 5 endometrioid, 3 borderline, and 4 other epithelial-type tumors) to examine the copy number of chromosome 12 and 15. The frequency distribution of hybridization signals with alpha-satellite centromeric DNA probes for chromosome 15 revealed disomy in all cases. However, we found the loss of chromosome 12 in 16 of 25 tumor samples. No correlation was found between the presence of monosomy 12 and the clinical stage of the tumors. Frequent loss of chromosome 12 may indicate that this chromosome is involved in the tumorigenesis of EOTs. Further studies are needed to clarify whether loss of chromosome 12 is an early or late event in ovarian carcinogenesis.

Carcinoma, Endometrioid↗
PubMed1997

NotI linking/jumping clones of human chromosome 3: mapping of the TFRC, RAB7 and HAUSP genes to regions rearranged in leukemia and deleted in solid tumors.

By applying the 'recognition mask' strategy to 300 mammalian sequences containing NotI sites we demonstrated that 5' ends of genes are highly enriched in NotI sites. A NotI linking clone NL2-252 (D3S1678) containing transferrin receptor (TFRC) gene was used as an initial point for chromosomal jumping. One of the jumping clones, J21-045 traverses 210 kbp and links NL2-252 to NL26 (D3S1632), a NotI linking clone containing highly polymorphic sequences. The TFRC gene was mapped to 3q29, close to the telomeric marker D3S2344, by linkage analysis, a panel of hybrid cell lines, GeneBridge 4 panel and FISH. Clone NLM-007 (D3S4302) was found to contain ras-homologous gene RAB7. By FISH and a panel of hybrid cell lines this gene was mapped to 3q21. This region is of particular interest due to frequent rearrangements in different types of leukemia. Clone L2-081 (D3S4283) containing new member of ubiquitin-specific proteases (HAUSP gene) was localized in 3p21 inspiring further investigation of involvement of this gene in development of lung and renal carcinomas.

Chromosome Mapping↗
PubMed1997

Intracellular calcium release is more efficient than calcium influx in stimulating mitochondrial NAD(P)H formation in adrenal glomerulosa cells.

We compared the effect on mitochondrial NAD(P)H formation of calcium release from intracellular stores with that of calcium influx from the extracellular space. Simultaneous measurements of cytoplasmic free calcium ion concentration and mitochondrial NAD(P)H were performed on fura-PE3-loaded single rat adrenal glomerulosa cells. The effects of equipotent stimuli in terms of the evoked Ca2+ response were compared. Angiotensin II (AII; 1 nM) induced a higher amplitude NAD(P)H response than K+ (5.6-7.6 mM). Vasopressin (1 microM) also induced a greater initial NAD(P)H formation than K+, although the Ca2+ signal evoked by the two agonists had similar amplitude. To examine the effect of Ca2+ release from internal stores we applied AII in Ca2+-free medium. We compared the effect on NAD(P)H formation of Ca2+ release with Ca2+ influx induced by K+, and with capacitative Ca2+ influx induced by AII. NAD(P)H formation in response to Ca2+ release was greater than that induced by Ca2+ influx, irrespective of whether induced by K+ or AII. Our results indicate that Ca2+, presumably released in the vicinity of mitochondria, activates mitochondrial dehydrogenases more efficiently than Ca2+ entering through the plasma membrane. These data confirm the biological significance of previous observations showing that Ca2+ released from inositol 1,4, 5-trisphosphate-sensitive internal stores increases mitochondrial matrix [Ca2+] to a greater extent than extracellular Ca2+.

Angiotensin II↗
PubMed1994

One-megabase yeast artificial chromosome and 400-kilobase cosmid-phage contigs containing the von Hippel-Lindau tumor suppressor and Ca(2+)-transporting adenosine triphosphatase isoform 2 genes.

We have isolated and ordered yeast artificial chromosomes (YACs) and cosmids surrounding the von Hippel-Lindau (VHL) tumor suppressor and plasma membrane Ca(2+)-transporting ATPase isoform 2 (PMCA-2) genes on chromosome 3p25-26. The YAC contig consists of six YACs and covers a region of 1 megabase. A cosmid-phage contig around VHL and PMCA-2 genes (400 kilobases) was established and integrated into the YAC map. Using these clones, we generated an EcoRI map of the 400-kilobase region. PMCA-2 and VHL complementary DNA were positioned entirely within the cosmid-phage contig as well as two polymorphic markers (D3S601 and D3S1317). This physical map of the cloned region will allow a detailed analysis of both the PMCA-2 and VHL genes. Some of the genomic clones may be useful for isolation of the full-length VHL complementary DNA.

Base Sequence↗
PubMed1994

Development of papillary renal cell tumours is associated with loss of Y-chromosome-specific DNA sequences.

Twenty-two papillary renal cell tumours were analysed by Southern hybridization using eight DNA probes from homologous regions of the X and Y chromosomes and two Y-chromosome-specific DNA probes. Sixteen of the 19 papillary renal cell tumours of male patients showed the loss of Y-chromosome-specific sequences. No loss of heterozygosity was detected in three tumours that developed in females. The frequency of loss of the Y chromosome was established in 50 non-papillary renal cell carcinomas as well. Only seven of the 31 non-papillary renal cell carcinomas obtained from male patients had lost the Y-chromosome-specific sequences, whereas no allelic loss was found in 19 non-papillary tumours obtained from female patients. Papillary renal cell tumours show a strong male preponderance (6:1) and loss of Y chromosome in 84 per cent of the cases, whereas non-papillary renal cell carcinomas show only a slight male preponderance (1.5:1) and the Y chromosome is lost in only 22 per cent of the cases. These data suggest that a tumour suppressor gene is localized at one of the homologous regions of the X and Y chromosomes, the homozygous inactivation of which is associated with the development of papillary renal cell tumours.

Alleles↗
PubMed1994

Molecular genetic investigations of the mechanism of tumourigenesis in von Hippel-Lindau disease: analysis of allele loss in VHL tumours.

Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome characterised by the development of retinal and central nervous system haemangioblastomas, renal cell carcinoma (RCC), phaeochromocytoma and pancreatic tumours. The VHL disease gene maps to chromosome 3p25-p26. To investigate the mechanism of tumourigenesis in VHL disease, we analysed 24 paired blood/tumour DNA samples from 20 VHL patients for allele loss on chromosome 3p and in the region of tumour suppressor genes on chromosomes 5, 11, 13, 17 and 22. Nine out of 24 tumours showed loss of heterozygosity (LOH) at at least one locus on chromosome 3p and in each case the LOH included the region to which the VHL gene has been mapped. Chromosome 3p allele loss was found in four tumour types (RCC, haemangioblastoma, phaeochromocytoma and pancreatic tumour) suggesting a common mechanism of tumourigenesis in all types of tumour in VHL disease. The smallest region of overlap was between D3S1038 and D3S18, a region that corresponds to the target region for the VHL gene from genetic linkage studies. The parental origin of the chromosome 3p25-p26 allele loss could be determined in seven tumours from seven familial cases; in each tumour, the allele lost had been inherited from the unaffected parent. Our results suggest that the VHL disease gene functions as a recessive tumour suppressor gene and that inactivation of both alleles of the VHL gene is the critical event in the pathogenesis of VHL neoplasms. Four VHL tumours showed LOH on other chromosomes (5q21, 13q, 17q) indicating that homozygous VHL gene mutations may be required but may not be sufficient for tumourigenesis in VHL disease.

Alleles↗
PubMed1994

Hereditary papillary renal cell carcinoma.

We describe a 3 generation family with members affected with papillary renal cell carcinoma, an uncommon histological type of renal cell carcinoma. Multiple tumors of varying size were present in both kidneys of affected family members. The disorder was not linked to polymorphic markers on chromosome 3p and there was no loss of heterozygosity at loci on 3p in renal tumors. The results suggest the presence of a renal cell carcinoma gene not located on 3p that predisposes to renal cell carcinoma with a distinct histological appearance. The inherited disorder in this family appears to be different from recognized hereditary cancer syndromes.

Adolescent↗
PubMed1994

Mutations of the VHL tumour suppressor gene in renal carcinoma.

Multiple, bilateral renal carcinomas are a frequent occurrence in von Hippel-Lindau (VHL) disease. To elucidate the aetiological role of the VHL gene in human kidney tumorigenesis, localized and advanced tumours from 110 patients with sporadic renal carcinoma were analysed for VHL mutations and loss of heterozygosity (LOH). VHL mutations were identified in 57% of clear cell renal carcinomas analysed and LOH was observed in 98% of those samples. Moreover, VHL was mutated and lost in a renal tumour from a patient with familial renal carcinoma carrying the constitutional translocation, t(3;8)(p14;q24). The identification of VHL mutations in a majority of localized and advanced sporadic renal carcinomas and in a second form of hereditary renal carcinoma indicates that the VHL gene plays a critical part in the origin of this malignancy.

Adenocarcinoma, Clear Cell↗