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K Kyriacou

Publications and source records attributed to K Kyriacou.

At least 19 recordsLinked to original sources
PubMed2006

Novel germline mutations in the APC gene of Cypriot patients with familial and sporadic adenomatous polyposis.

Familial adenomatous polyposis (FAP) is one of the two commonest familial syndromes that predispose to colorectal cancer. FAP is caused by mutations in the adenomatous polyposis coli (APC) tumour suppressor gene that has a high penetrance. The disease is characterized by the occurrence of hundreds to thousands of colorectal polyps, which if left untreated give rise to colorectal cancer. In Cyprus, there are no molecular data available as yet on families with FAP. This work presents the results of APC analysis in our population for the first time. The APC gene was analyzed in 33 DNA samples from 20 individuals belonging to four FAP families and 13 patients with sporadic polyposis. We identified three truncating mutations, four missense mutations and 11 polymorphisms. It is of interest that two of the three truncating mutations, 2307delA and Q1242X, are novel, which supports the existence of a unique genetic pool in the Cypriot population. This ethnic molecular study in addition to highlighting population heterogeneity also contributes to phenotype-genotype associations that are essential for the clinical management of FAP families in Cyprus.

Adenomatous Polyposis Coli↗
PubMed2003

A comparative morphological study in 33 cases of respiratory chain encephalomyopathies.

Mitochondrial encephalomyopathies (ME) are clinically and genetically heterogeneous syndromes ranging from pure myopathies to complex multisystem disorders. This phenotypic and genotypic variability, coupled with the lack of a laboratory gold standard marker for the diseases, makes diagnosis a challenging process. Mitochondrial DNA analysis and biochemical assay of muscle homogenates are quite specific diagnostically but have low sensitivity in unselected cases suspected of ME. We decided to evaluate four routine morphological methods in 33 cases of definite or probable ME in an effort to assess the reliability of each of these techniques in diagnosing ME.

Adult↗
PubMed2001

Alpha-thalassaemia prenatal diagnosis by two PCR-based methods.

In Cyprus all couples carrying alpha0-thalassaemia mutations are detected in the course of the thalassaemia carrier screening program and prenatal diagnosis is offered to all of them. Prenatal diagnosis for alpha-thalassaemia is routinely done by two independent molecular methods. With the first method, the mutations of the parents are directly determined by gap-PCR and then the chorionic villus sample (CVS) is examined for the presence of these mutations. With the other method, a (CA)n repeat polymorphic site located between the psialpha1- and alpha2-globin genes is used for determining the presence or absence of the normal and mutant alleles. In the period from 1995 to 1999, molecular analysis of 46 couples in which haematological data were consistent with deletion of two alpha-globin genes in both partners indicated that only 13 of them were actually at risk for haemoglobin (Hb) Bart's hydrops fetalis and prenatal diagnosis was provided in 16 pregnancies. The molecular diagnosis was possible in all cases with the use of both gap-PCR and (CA)n repeat polymorphisms analysis. No misdiagnosed cases for alpha-thalassaemia have been reported to date.

Adult↗
PubMed2001

A multi-center study in order to further define the molecular basis of beta-thalassemia in Thailand, Pakistan, Sri Lanka, Mauritius, Syria, and India, and to develop a simple molecular diagnostic strategy by amplification refractory mutation system-polymerase chain reaction.

The spectrum of the beta-thalassemia mutations of Thailand, Pakistan, India, Sri Lanka, Mauritius and Syria has been further characterized by a multi-center study of 1,235 transfusion-dependent patients, and the mutations discovered used to assess the fidelity of a simple diagnostic strategy. A total of 44 beta-thalassemia mutations were identified either by allele-specific oligonucleotide hybridization, amplification with allele-specific primers, or DNA sequencing of amplified product. The results confirm and extend earlier findings for Thailand, Pakistan, India, Mauritius and Syria. This is the first detailed report of the spectrum of mutations for Sri Lanka. Two novel mutations were identified, codon 55 (-A) and IVS-I-129 (A-->C), both found in Sri Lankan patients. Two beta-thalassemia mutations were found to coexist in one beta-globin gene: Sri Lankan patients homozygous for the beta0 codon 16 (-C) frameshift were also homozygous for the beta+ codon 10 (C-->A) mutation. Studies of Sri Lankan, Pakistani, and Indian carriers suggest the codon 10 (C-->A) mutation is just a rare polymorphism on an ancestral allele, on which the beta0 codon 16 (-C) mutation has arisen. Each country was found to have only a few common mutations accounting for 70% or more of the beta-thalassemia alleles. A panel of primers to diagnose the majority of the mutations by the amplification refractory mutation system was developed, enabling a simple molecular diagnostic strategy to be introduced for each country participating in the multi-center study.

Asia↗
PubMed2000

AM-FM texture segmentation in electron microscopic muscle imaging.

This paper describes the application of an amplitude modulation-frequency modulation (AM-FM) image representation in segmenting electron micrographs of skeletal muscle for the recognition of: 1) normal sarcomere ultrastructural pattern and 2) abnormal regions that occur in sarcomeres in various myopathies. A total of 26 electron micrographs from different myopathies were used for this study. It is shown that the AM-FM image representation can identify normal repetitive structures and sarcomeres, with a good degree of accuracy. This system can also detect abnormalities in sarcomeres which alter the normal regular pattern, as seen in muscle pathology, with a recognition accuracy of 75%-84% as compared to a human expert.

Humans↗
PubMed2000

Hb Bart's levels in cord blood and alpha-thalassemia mutations in Cyprus.

The purpose of this study was to examine the frequency of alpha-thalassemia in the population of Cyprus using cord blood samples. The levels of Hb Bart's were compared with the hematological indices and the results correlated with the presence of alpha-thalassemia mutations. The protocols for the polymerase chain reaction detection of the six most common alpha-globin mutations encountered in Cyprus were optimized, and the frequency of each mutation was determined through the screening of 495 random cord blood samples. The total allele frequency for the mutations examined was 10.6%, of which 1% is due to the triplication of the alpha-globin genes. The -alpha(3.7 kb) deletion accounts for 72.8% of all detectable mutations, while the--MED-I and -(alpha)-20.5 kb mutations account for 7.8%. The level of Hb Bart's and the MCV and MCH values in cord blood samples were found to correlate closely with the severity of alpha-thalassemia, although the -alpha(3.7 kb) deletion and perhaps other mild alpha-thalassemia mutations may not give detectable Hb Bart's levels. A reasonably accurate estimate of the alpha-thalassemia carrier frequency may be obtained from cord blood studies if Hb Bart's estimates are combined with hematological indices. When molecular methods are added, these give the best way to use cord bloods to survey populations for alpha-thalassemia.

Alleles↗
PubMed2000

Molecular characterization of beta-thalassemia in Syria.

This study concerns the determination of beta-thalassemia alleles and other hemoglobin variants in 82 patients from Syria. We have characterized 146 chromosomes and found 17 different beta-thalassemia mutations, and one beta-globin chain variant that gives rise to the abnormal Hb S. The eight most common beta-thalassemia mutations were the IVS-I-110 (G-->A), IVS-I-1 (G-->A), codon 5 (-CT), -30 (T-->A), codon 39 (C-->T), IVS-I-6 (T-->C), IVS-II-1 (G-->A), and codon 15 (TGG-->TAG). These mutations accounted for almost 75% of the total beta-thalassemia chromosomes. We identified 34 different genotypes with a high level of homozygosity. The various beta-thalassemia mutations were characterized using gene amplification with specific oligonucleotide primers, restriction enzyme analysis, denaturing gradient gel electrophoresis and direct sequencing. By combining these three approaches we were able to detect mutations in almost 90% of the chromosomes studied. Our findings provide a sound foundation on which to base a preventive program for thalassemia and we believe that the data that we present will facilitate the improvement of medical services such as carrier screening, genetic counseling, and prenatal diagnosis. Furthermore a detailed knowledge of the molecular pathology of beta-thalassemia will strongly improve the prenatal diagnosis services in Syria.

Adolescent↗
PubMed2000

A novel form of distal hereditary motor neuronopathy maps to chromosome 9p21.1-p12.

Distal hereditary motor neuronopathies (dHMNs) form a heterogeneous group of rare disorders characterized by distal weakness and wasting in the limbs with no significant sensory involvement. Harding has classified dHMNs into seven categories based on clinical and genetic criteria. We report a novel form of autosomal recessive dHMN in 7 consanguineous families located in the Jerash region of Jordan. Onset of the disease is between 6 and 10 years of age and is characterized by weakness and atrophy of the lower limbs associated with pyramidal features. Within 2 years, symptoms progress to the upper limbs. Neurophysiological studies typically show normal conduction velocities, reduced compound motor action potential amplitudes, normal sensory nerve action potentials, and chronic neurogenic changes on needle electromyography. No significant abnormalities are seen on sural nerve biopsy. We call this novel form of dHMN Jerash hereditary motor neuronopathy. We studied the families at the molecular genetic level and mapped the Jerash hereditary motor neuronopathy gene to an approximately 0.54-cM region on chromosome 9p21.1-p12, flanked by microsatellite polymorphic marker loci D9S1845 and D9S1791. A maximum LOD score of 19.80 at theta = 0.001 was obtained between the disease and locus D9S1878.

Adolescent↗
PubMed2000

Content-based retrieval of breast cancer biopsy slides.

The Biopsy Analysis Support System (BASS), previously used for image analysis of immunohistochemically stained sections of breast carcinoma, has been extended to include indexing and content-based retrieval of biopsy slide images from a database of 57 captured cases. Images from histopathological biopsy slides are described and these are accessed in terms of the properties of either individual nuclei or groups of cell nuclei present in the slide. Visual similarity of cases is specified in terms of a diagnostic index, commonly known as the H-score, which incorporates the heterogeneity of nuclear staining intensity, as well as the percentage of nuclei staining at specific intensities. The system provides a platform that can be exploited in telepathology and teleconsultation, but further research is needed to explore its full potential and accuracy in a diagnostic clinical environment.

Breast Neoplasms↗
PubMed1999

Distal hereditary motor neuronopathy of the Jerash type.

A novel form of autosomal recessive distal hereditary motor neuronopathy (distal HMN) is reported. The presence of pyramidal signs within the early stages of the disease with persistence of knee hyperreflexia form distinctive clinical features. We have mapped the HMN-J gene to chromosome 9p21.1-p12, within an estimated interval of 1.2-Mb.

Chromosome Mapping↗
PubMed1998

Medullary cystic kidney disease with hyperuricemia and gout in a large Cypriot family: no allelism with nephronophthisis type 1.

We describe a large Cypriot family with an interstitial type of nephropathy, inherited as an autosomal dominant trait that led to end stage renal failure between 51 to 78 years of age (mean 62.2 years). Twenty-three people are known to be affected, but several younger relatives with normal renal function may remain undiagnosed because of the absence of precise clinical and laboratory diagnostic criteria. This nephropathy is associated with medullary renal cysts, hypertension, hyperuricemia, and gout. Several relatives have typical medullary cystic disease (MCD), while in the others the findings are compatible with this diagnosis. Due to the similarity of clinical and pathologic findings, earlier reports had suggested that MCD may be allelic to autosomal recessive familial juvenile nephronophthisis, which was mapped recently to chromosome band 2q13. Linkage analysis of the present family with a closely linked marker excluded linkage to the above locus. Linkage was also excluded to the PKD1 locus of adult polycystic kidney disease type 1, and up to 5 cM on either side, on chromosome 16. We suggest that because of the element of hyperuricemia and gout found in this family, although with reduced penetrance, it may represent a variant of autosomal dominant MCD of the adult type. This variability may be the result of allelic or locus heterogeneity. Molecular genetic approaches including linkage analysis on appropriate families will certainly assist in classifying such related genetically heterogeneous disorders.

Adult↗
PubMed1996

Computer-aided classification of breast cancer nuclei.

Breast cancer is the most common malignancy affecting the female population in industrialized countries. Prognostic factors, such as steroid receptors visualized in biopsy slides, provide critical information to oncologists regarding the hormonal status of the individual tumors. These factors influence the choice of treatment and help in predicting patient survival and probability of recurrence. The objective of this paper is to introduce a new computer-aided system for the classification of breast cancer nuclei based on neural networks. Currently, medical experts assess steroid receptors in breast cancer biopsy slides mostly manually using four- or five-level grading schemes. These schemes are based on the assessment of two parameters: number of nuclei positive and their staining intensity. Available computerized systems define their own grading schemes based on automated measurements of low-level features, such as optical density, texture, area, and others. However, the findings produced by these systems may not be readily comprehensible by the majority of medical experts who have been accustomed to manual assessment schemes. Moreover, findings from one system cannot be directly compared to findings obtained from other computerized systems. To date, no standardized assessment scheme exists for computerized systems, while interobserver and intraobserver variabilities limit the utility of the routinely used manual assessment schemes. In this paper a new system for computer-aided biopsy analysis is introduced. Here, we focus on the system's nuclear classification module. The input to this module consists of a set of six local and global features: optical density, two chromaticity indices, a variance based texture measure, global nuclei density mean, and variance. The output of the nuclei classification module consists of a membership label in a zero to four grading scheme for each detected nucleus. The classification module is based on a feedforward neural network trained in a supervised fashion to classify the nuclear feature vectors. The sample data comprises 3015 nuclei from 28 images that were classified by a human expert. A Sammon plot visualization of the six dimensional input feature space shows that the classification problem is quite difficult. The neural network used in the classification module achieved 72% accuracy. Our result indicate that by using a nuclear classification module such as the one introduced in this paper it is possible to translate low-level system measurements into a vocabulary that is familiar to medical experts. Thus, a contribution is made to the standardization of grading schemes in addition to improving the accuracy in grading breast cancer nuclei.

Biopsy↗
PubMed1995

Pregnancy with spermatozoa from a globozoospermic man after intracytoplasmic sperm injection treatment.

We present a case of third trimester pregnancy occurring in a 29 year old woman after intracytoplasmic sperm injection (ICSI) treatment with spermatozoa from a globozoospermic man. We believe this is the first reported case. A 37 year old man was diagnosed with globozoospermia with normal sperm count and motility. In-vitro fertilization and subzonal insemination treatments failed to achieve fertilization of any eggs. The ICSI method produced 50% fertilization, 75% cleavage rate and a singleton pregnancy with a female fetus. No pregnancy or fetal abnormalities have been noted after > 7 months of gestation.

Adult↗
PubMed1988

Structural and functional studies of the effects of sympathetic nerve stimulation on rabbit submandibular salivary glands.

Continuous sympathetic stimulation at 8-10 Hz caused intense vasoconstriction in the gland, so stimulation was generally given in an interrupted pattern to minimize this detrimental effect on secretion. Only a small increase in fluid secretion occurred; it became thick and tended to block the cannula; therefore in later experiments the main duct was not cannulated. After sympathetic stimulation there was substantial degranulation of acinar cells. However, as this was accompanied by little movement of water, the secreted mucosubstance distended the ductal lumina. The granular tubule cells were unchanged by sympathetic stimulation. Use of selective blocking agents revealed that the sympathetically-evoked secretion of acinar mucin was mediated mainly via beta-adrenoreceptor activation. As stimulation of the sympathetic nerves alone caused little additional formation of fluid, the effects of superimposing continuous low frequency sympathetic stimulation onto a background of low parasympathetic secretion were compared with similar parasympathetic stimulation alone of the contralateral gland. These double nerve stimulations did not augment the volume of fluid secreted, or cause morphological changes additional to those from parasympathetic stimulation alone. Nevertheless, it is likely that, under natural reflex conditions, sympathetic impulses can increase the amount of acinar mucosubstance secreted.

Animals↗
PubMed1988

Morphological changes in the rabbit submandibular gland after parasympathetic or sympathetic denervation.

Selective denervation was used to obtain further information about the relative roles of the nerves supplying the gland. Parasympathetic denervation soon caused atrophy in both acinar and granular tubule cells, and a substantial reduction in gland wet weight. The secretory cells had several unusual features, and striated duct cells tended to accumulate glycogen. Three to four weeks after pre-ganglionic parasympathectomy, the parenchymal cells were less abnormal but still smaller than in the control, unoperated gland. Thus, parasympathetic impulses are required to maintain normal parenchymal cells. Chronic sympathectomy caused little or no detectable changes in the secretory cells, and there was no significant change in wet weight. Nevertheless, pre-ganglionic sympathetic axotomy reduced the reflex secretion of acinar mucosubstances in response to feeding. Thus, sympathetic impulses normally contribute to the reflex secretion of acinar mucosubstance from these glands.

Animals↗
PubMed1988

"Paralytic' secretion after parasympathectomy of rabbit submandibular glands includes a cholinergic component.

Chronic parasympathetic decentralization of submandibular glands in rabbits has been studied after 3 weeks, in acute experiments under urethane anaesthesia. A "paralytic' secretion occurred from the supersensitive denervated glands and it was not attributable to an increase in the "spontaneous' flow, that is present in normal glands. The "paralytic' secretion was completely inhibited by atropine, after which a "spontaneous' flow, that was similar to the contralateral glands, persisted. The alpha-adrenergic blocker dihydroergotamine, when given before atropine, reduced the "paralytic' secretion by 50-75% but when this drug was given after atropine it had no additional effect. The beta-adrenergic blocker propanolol did not cause a reduction in the "paralytic' secretion. Superior cervical ganglionectomy, in contrast, did not give rise to a significant "paralytic' flow. The results suggest that acetylcholine, released spontaneously from terminals of postganglionic parasympathetic nerves, plays an essential part in the "paralytic' secretion that occurs from rabbit submandibular glands after preganglionic denervation. Circulating catecholamines make a secondary contribution, acting synergistically with the acetylcholine on the supersensitive secretory cells.

Animals↗