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Biomedical subjects

K Kock

Publications and source records attributed to K Kock.

At least 19 recordsLinked to original sources
PubMed2006

Restriction of GAGE protein expression to subpopulations of cancer cells is independent of genotype and may limit the use of GAGE proteins as targets for cancer immunotherapy.

The GAGE cancer testis antigen gene family encodes products that can be recognized by autologous T cells, and GAGE proteins have been suggested as potential targets for cancer immunotherapy. Analysis of GAGE expression in tumours has primarily been performed at the level of gene transcription, whereas little is known about GAGE expression at the protein level. To evaluate the potential of GAGE proteins as targets for cancer-specific immunotherapy, we studied the expression of these proteins in normal and malignant cells/tissues using a novel panel of monoclonal antibodies. Immunohistochemical analysis of more than 250 cancer specimens demonstrated that GAGE proteins were frequently expressed in numerous cancer types and correlated with the expression of the cancer testis antigens MAGE-A1 and NY-ESO-1. Significant intercellular and subcellular differences in GAGE protein levels were observed, and most GAGE-positive tumours also contained cancer cells lacking GAGE expression. Studies of genetically homogenous cell lines with similar intercellular heterogeneous GAGE expression showed that GAGE expression was not associated with a specific genotype, but defined a phenotypically distinct population of cells. Surprisingly, in normal tissues we found that GAGE proteins were not restricted to testis, but were also present in a subset of oocytes of resting primordial follicles and in maturing oocytes. This is the first time that a cancer testis antigen has been reported in postfoetal oocytes. The lack of GAGE expression in a subset of cancer cells within GAGE-positive tumours has decisive implications for the development of GAGE-targeted cancer therapy.

Animals↗
PubMed1997

Interannual variation in condition of the mackerel icefish

Mackerel icefish Champsocephalus gunnari are widespread on the South Georgia (54° S, 36° W) shelf. Analysis of condition indicated a strong interannual variation. High condition indices, indicative of good feeding conditions, were present when krill were abundant in the region. Years when krill were scarce and condition index was consequently low, were consistent with years when indices from land-based krill predators also indicated that krill were scarce.

Journal Article↗
PubMed1994

Structural organization of the genes for rat von Ebner's gland proteins 1 and 2 reveals their close relationship to lipocalins.

The rat von Ebner's gland protein 1 (VEGP 1) is a secretory protein, which is abundantly expressed in the small acinar von Ebner's salivary glands of the tongue. Based on the primary structure of this protein we have previously suggested that it is a member of the lipocalin superfamily of lipophilic-ligand carrier proteins. Although the physiological role of VEGP 1 is not clear, it might be involved in sensory or protective functions in the taste epithelium. Here, we report the purification of VEGP 1 and of a closely related secretory polypeptide, VEGP 2, the isolation of a cDNA clone encoding VEGP 2, and the isolation and structural characterization of the genes for both proteins. Protein purification by gel-filtration and anion-exchange chromatography using Mono Q revealed the presence of two different immunoreactive VEGP species. N-terminal sequence determination of peptide fragments isolated after protease Asp-N digestion allowed the identification of a new VEGP, named VEGP 2, in addition to the previously characterized VEGP 1. The complete VEGP 2 sequence was deduced from a cDNA clone isolated from a von Ebner's gland cDNA library. The VEGP 2 cDNA encodes a protein of 177 amino acids and is 94% identical to VEGP 1. DNA sequence analysis of the rat VEGP 1 and 2 genes isolated from rat genomic libraries revealed that both span about 4.5 kb and contain seven exons. The VEGP 1 and 2 genes are non-allelic distinct genes in the rat genome and probably arose by gene duplication. The high degree of nucleotide sequence identity in introns A-C (94-100%) points to a recent gene conversion event that included the 5' part of the genes. The genomic organization of the rat VEGP genes closely resembles that found in other lipocalins such as beta-lactoglobulin, mouse urinary proteins (MUPs) and prostaglandin D synthase, and therefore provides clear evidence that VEGPs belong to this superfamily of proteins.

Alpha-Globulins↗
PubMed1994

Denatonium bitter tasting among transgenic mice expressing rat von Ebner's gland protein.

Von Ebner's gland protein (VEGP) is a secretory protein, which is abundantly expressed in the small von Ebner's salivary glands of the tongue. VEGP as component of the perireceptor environment around taste papillae might function as transporter of hydrophobic molecules, for example bitter substances. Here we report a new approach to investigate the physiological role of VEGP by expression of the cloned rat VEGP gene in transgenic mice. Taste papillae of mice, in contrast to rats, do not contain VEGP. The founder mouse 4345 and three offspring carry the transgene as shown by PCR analysis and saliva of the transgenic mice contains high amounts of VEGP. In two-bottle preference tests, transgenic and nontransgenic siblings show significantly different capabilities to taste the bitter compound denatonium benzoate at 10 microM. The reduced sensitivity of transgenic mice to denatonium benzoate points to a clearance function of VEGP the specificity of which for taste compounds and other molecules remains to be seen.

Animals↗
PubMed1994

Ectopic pregnancy and its associated endometrial changes.

Three hundred and sixty-five women were operated for ectopic pregnancy at the Department of Gynecology and Obstetrics, Odense University Hospital in a 13-year period. In all cases, the diagnosis was verified by histological examination. In 245 cases there was curettage material available for histological examination. The slides were reviewed by one pathologist. The most common types of endometrium associated with ectopy were decidual reaction (42%), secretory endometrium (22%) followed by proliferative endometrium (12%). The endometrial changes classically considered as suggestive of ectopic pregnancy were found only in 53% of the cases. The histological examination of all this curettage material reveals a wide variety of endometrial histologies associated with ectopy: any type of endometrium without trophoblasts may be associated with ectopic pregnancy.

Abortion, Spontaneous↗
PubMed1993

Molecular cloning of human von Ebner's gland protein, a member of the lipocalin superfamily highly expressed in lingual salivary glands.

Von Ebner's glands (VEG) are small lingual salivary glands. Their ducts open into trenches of circumvallate and foliate papillae, thus influencing the milieu where the interaction between taste receptor cells and sapid molecules takes place. The major secretions of human VEG is a protein with a molecular mass of 18 kDa. The human VEG protein crossreacts with antibodies raised against the rat VEG protein, indicating sequence similarity between the rat and human VEG proteins. This was subsequently confirmed by N-terminal protein sequencing. A cDNA clone, isolated from a human VEG library, contained an insert of 735 bp including an open reading frame that encodes the human VEG protein of 176 amino acids. Comparison of the human and rat VEG proteins revealed an overall identity of 60%. Immunocytochemistry, in situ hybridization and in vitro translation studies demonstrated the human VEG protein to be highly and exclusively expressed in VEG. The VEG proteins are members of the lipocalin protein superfamily and, together with the rat odorant binding protein II, they constitute a new subfamily. Sequence similarity to proteins such as the retinol binding protein and the odorant binding protein which are lipophilic ligand carriers, suggests a possible function for the human VEG protein in taste perception.

Amino Acid Sequence↗
PubMed1993

Perireceptor events in taste.

The microenvironment at chemical receptor sites is important for ligand-receptor interaction as it can influence the entry, residence time or exit of odorant and sapid molecules. The perireceptor milieu at apical taste cell microvilli consists of taste pore mucus and secretions from salivary glands. The majority of taste buds are sheltered in epithelial folds of the foliate and circumvallate papillae where saliva is provided predominantly by the lingual von Ebner's glands (VEGs). To investigate possible saliva-tastant interactions, we have characterized a prominent 18 kDa secretory protein expressed in human, rat and pig VEGs. The human and rat VEG proteins share 60% sequence identity and, by virtue of their protein and gene structure, can be assigned to the lipocalin superfamily of lipophilic ligand carrier proteins. VEG proteins might function as transporters of hydrophobic molecules, for example bitter substances, like the nasal odorant-binding proteins that belong to the same protein family. Because binding experiments using various bitter substances have so far failed, and in light of the species-specific expression, other functions for VEG proteins must be considered. These include the protection of taste epithelia, pheromone transport and lipid binding.

Amino Acid Sequence↗
PubMed1992

Postnatal development of von Ebner's glands: accumulation of a protein of the lipocalin superfamily in taste papillae of rat tongue.

Antibodies produced against rat von Ebner's gland (VEG) protein, a recently characterized member of a lipophilic ligand carrier protein family, detect this protein immunocytochemically in von Ebner's gland acini and show that it is present at high concentrations in the clefts of circumvallate and foliate papillae. During embryonic development, von Ebner's gland anlagen are innervated (as shown immunocytochemically using neuronal specific antibodies) as early as embryonic day 20, before lateral glandular outgrowth and VEG protein can be observed. Expression of the VEG protein as determined by in situ hybridization and immunocytochemistry begins at postnatal day-2 cells in differentiating and branching off from von Ebner's gland ducts, and sharply increases with further enlargement and maturation of the gland. The close temporal correlation of von Ebner's gland innervation and VEG protein expression with papilla innervation and taste-bud development suggests a functional relationship of both structures. VEG protein might control access of lipophilic sapid molecules, such as bitter substances, to the gustatory receptors.

Amino Acid Sequence↗
PubMed1992

Germ cell neoplasms in three intersex patients with 46,XY karyotype.

This report presents 3 cases with gonadoblastoma mixed with other germ cell tumours in intersex patients, all with a 46,XY karyotype. One 11-year-old patient was a true hermaphrodite, the others, aged 13 and 18, respectively, had both gonadal dysgenesis. Different clinical courses have been noted. Two patients had gonadoblastoma combined with dysgerminoma; in one of them a teratoma was also found. In the third case gonadoblastoma was transformed into teratocarcinoma. The malignant degeneration was more serious in the 2 pubertal patients. Thus, we recommend early and prophylactic gonadectomy.

Adolescent↗
PubMed1992

Selection bias in genetic-epidemiological studies of cleft lip and palate.

The possible impact of selection bias in genetic and epidemiological studies of cleft lip and palate was studied, using three nationwide ascertainment sources and an autopsy study in a 10% sample of the Danish population. A total of 670 cases were identified. Two national record systems, when used together, were found suitable for ascertaining facial cleft in live births. More than 95% ascertainment was obtained by means of surgical files for cleft lip (with or without cleft palate) without associated malformations/syndromes. However, surgical files could be a poor source for studying isolated cleft palate (CP) (only a 60% and biased ascertainment), and they cannot be used to study the prevalence of associated malformations or syndromes in facial cleft cases. The male:female ratio was 0.88 in surgically treated cases of CP and was 1.5 in nonoperated CP cases, making the overall sex ratio for CP 1.1 (95% confidence limits 0.86-1.4) The sex ratio for CP without associated malformation was 1.1 (95% confidence limits 0.84-1.6). One of the major test criteria in CP multifactorial threshold models (higher CP liability among male CP relatives) must be reconsidered, if other investigations confirm that a CP sex-ratio reversal to male predominance occurs when high ascertainment is achieved.

Cleft Lip↗
PubMed1991

Autopsied cases of drowning in Denmark 1987-1989.

In the 3-year period 1987-1989, 219 drowning cases were submitted to medico-legal autopsy in Denmark. The demographic data including the manner of death and the external findings are reported. In 74 accident cases analysis for blood-alcohol concentration was performed. In 53% a concentration of more than 0.1% was found. In 91 drowning cases (age more than 18 years and where the time interval in the water was less than 24 h) the average weight of both lungs was 1.411 g, compared to 994 g in 20 control cases. In 7% of the drowning cases the weight was less than 1.000 g, so called dry lungs. Finally the weight of the lungs and the amount of pleural transsudate in relation to the time interval in the water were registered in 198 cases. For a longer time interval in the water the weight of the lungs decreased, while the amount of pleural transsudate increased. By adding these two parameters, the combined weight was between 1.000 and 2.200 g in more than 75% of the cases as long as the interval in the water was less than 30 days.

Accidents↗
PubMed1991

Zygosity, placental membranes and Weinberg's rule in a Danish consecutive twin series.

The usual assumption that monochorionic twins are monozygotic has recently been questioned, based on blood group discordance in 3 of 12 monochorionic pairs. Therefore, this study evaluates the validity of zygosity diagnosis based on examination of placental membranes, and at the same time evaluates Weinberg's differential rule in a Danish consecutive twin series. All twin pairs, 265 like-sexed and 87 unlike-sexed pairs, born at Odense University Hospital, Denmark, from 1 January 1980 through 31 August 1988, were ascertained. In 229 like-sexed pairs, zygosity was determined by serological methods, and in 190 of these, the fetal membranes could be reliably classified. Fifty-nine monochorionic twin pairs were identified and none of those pairs were discordant for any genetic markers. Therefore, we conclude that monochorionic twins can be considered monozygotic. The distribution of monozygotic and dizygotic pairs was in accordance with Weinberg's rule.

Female↗
PubMed1990

An epidemiological study of congenital anorectal malformations: 15 Danish birth cohorts followed for 7 years.

In the county of Fyn (about 500,000 inhabitants) which is a well defined and representative 10% sample of the total Danish population, 15 total birth cohorts were scrutinized for the occurrence of anorectal malformations (ARM). All the patients were followed until the age of 7 or death. In a total of 96,073 births, 29 cases were observed; one concordant monozygotic pair was counted as one case. The study showed the point prevalence at birth to be 3.0 per 10,000; almost the same frequency has been found in Sweden whereas other figures from Europe and North America are lower. Children with ARM have in general a poor prognosis, largely due to the many associated anomalies. In this material, 11 of 12 isolated ARM cases survived until age 7, but five of these had significant handicaps. Out of 17 probands with associated anomalies, only seven survived until age 7, all of them having some handicap. This group of patients spent at least 15 times more days in hospital than an age-matched group from the same region until age 7, and they underwent a considerable number of operations. The study showed an increased frequency of chromosome anomalies among children with ARM.

Abnormalities, Multiple↗
PubMed1989

Micromelic bone dysplasia with cloverleaf skull.

Micromelic bone dysplasia with cloverleaf skull is a well-described entity with short, straight tubular bones, hydrocephalus and cloverleaf deformity of the skull, narrow chest and platyspondyly. A further two unrelated patients are presented, in whom the shape of the head varied. Both cases also showed a narrow foramen magnum, hypoplastic cerebellum, atrial septal defect, hypoplastic adrenals, and ureteric malformations. The findings in the skeleton show similarities to other types of generalised bone dysplasias but are distinguishable from these. This well-defined bone dysplasia should probably be regarded as a separate entity. Visceral malformations may be associated.

Abnormalities, Multiple↗
PubMed1987

Endoscopic fine-needle aspiration cytology of the stomach. A new diagnostic procedure.

In order to improve the diagnosis of submucosal gastric malignancies, a new method of endoscopic fine-needle aspiration cytology was evaluated. The method is compared with conventional forceps biopsy and brush cytology, and technical problems are discussed. It is concluded that endoscopic fine-needle aspiration cytology is a simple and safe procedure, but further development of the method and more clinical experience are required before the diagnostic capability of the method can be established.

Biopsy↗
PubMed1986

Microscopic appearance of the esophageal mucosa in a consecutive series of patients submitted to upper endoscopy. Correlation with gastroesophageal reflux symptoms and macroscopic findings.

The histologic finding of basal-layer hyperplasia and papillosis as consequences of gastroesophageal reflux still constitute an area of controversy. Consequently, a prospective study of symptoms and endoscopy and biopsy interpretation was undertaken in 200 patients consecutively submitted to upper endoscopy, whereof 12 were excluded. Complete agreement among all three variables was found in half of the patients and harmony between two of the variables in one fourth. In the last fourth the outcome was positive in one variable only, equally distributed among the symptoms, endoscopy, and histology. It is concluded that histology is of considerable value in gastroesophageal reflux disease.

Esophagoscopy↗