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C J Lips

Publications and source records attributed to C J Lips.

At least 127 records · Page 7Linked to original sources
PubMed1989

Living with a hereditary form of cancer: experiences and needs of MEN 2 patients and their families.

Unlike the purely medical research done in multiple endocrine neoplasia type 2 (MEN 2) families, little work has been done on the psychosocial aspects of the disease. To assess the severely stressful influences and the consequences of that stress on the family network, a small-scale survey was carried out during a national meeting. The goal of the study was to obtain more information about the experiences and needs of MEN 2 patients and their relatives. Of the 59 respondents, 85% were satisfied with the medical information provided, 81% were satisfied with the medical knowledge of the specialist, but only 12% were satisfied with the medical knowledge of the general practitioner regarding MEN 2. Furthermore, 63% of the parents had difficulties in talking about the disease with their children. The need expressed for contact with fellow sufferers and their families is expected to lead to the establishment of an interest group for MEN 2 families.

Adolescent↗
PubMed1989

Evolutionary pathways of the calcitonin (CALC) genes.

Recombinant DNA techniques have made it possible to establish the structure of various genes encoding polypeptide hormones. Comparison of nucleotide sequences of the calcitonin (CALC) genes in man has revealed surprising similarities and variations. These findings and the homologies among the sequences in different species offered an opportunity for speculation about relationships between these genes and about their evolutionary origin. The first gene (CALC-I) directing the synthesis of calcitonin (CT) or CT gene-related peptide (CGRP) comprises six exons and gives rise to two mRNAs by an alternative RNA-processing mechanism. The homology between CGRP and CT reflects their common origin. The human genome contains a second gene (CALC-II) that is structurally related to the CALC-I gene. The CALC-II RNA transcripts do not appear to be differentially processed, as only preproCGRP-II mRNA and not preproCT-II is detected. The first and second CT/CGRP genes probably have evolved from a common ancestor gene early in evolution. Meanwhile, a third genomic locus containing nucleotide sequences highly homologous to exons 2 and 3 of both CALC genes was detected and probably generated by duplication of a part of CALC-II. This locus is not likely to encode a CT- or CGRP-related polypeptide hormone. The CALC genes and this last (pseudo) gene are located on the short arm of chromosome 11. Recently, islet- or insulinoma-amyloid polypeptide (IAPP) was isolated as a major constituent of amyloid present in human insulinoma and in pancreatic islet amyloid in noninsulin-dependent diabetes mellitus. IAPP shows 46% amino acid sequence homology with human CGRP-II.(ABSTRACT TRUNCATED AT 250 WORDS)

Amyloid↗
PubMed1988

Islet amyloid polypeptide: identification and chromosomal localization of the human gene.

Islet or insulinoma amyloid polypeptide (IAPP) is a 37 amino acid polypeptide isolated from pancreatic amyloid. Here, we describe the isolation and partial characterization of the human gene encoding IAPP. The DNA sequence predicts that IAPP is excised from a larger precursor protein and that its carboxy-terminus is probably amidated. The predicted normally occurring IAPP is identical to the reported polypeptides isolated from pancreatic amyloid, except for the amidated carboxy-terminus. IAPP specific polyadenylated RNAs of 1.6 kb and 2.1 kb are present in human insulinoma RNA. The human IAPP gene is located on chromosome 12.

Amino Acid Sequence↗
PubMed1988

A third human CALC (pseudo)gene on chromosome 11.

A genomic locus in man (CALC-III) containing nucleotide sequences highly homologous to both exon 2 and exon 3 of the CALC-I and -II genes, is described in this paper. The CALC-I gene produces calcitonin (CT) (encoded by exon 4) or calcitonin gene-related peptide (CGRP) (encoded by exon 5) in a tissue-specific fashion. The CALC-II gene produces a second human CGRP, but probably not a second CT. The CALC-III gene does not seem to encode a CT- or CGRP-related polypeptide hormone and is probably a pseudogene. Like the other two CALC genes, the CALC-III gene is located on human chromosome 11.

Bacteriophage lambda↗
PubMed1988

Expression of insulin-like growth factor-I and -II genes in human smooth muscle tumours.

The insulin-like growth factors I and II (IGF-I and -II) are polypeptides which play an important role in growth and development of the organism. In the present report we describe the detection of human IGF-I RNAs (both type Ia and type Ib) and IGF-II RNAs in benign (leiomyoma) and malignant (leiomyosarcoma) tumours from smooth muscle origin, using Northern blot hybridization analysis. In normal smooth muscle tissue of the uterus we found low levels of IGF-I RNAs only. In the tumours the same IGF-I RNA species were detected as in adult non-tumour tissues (uterus, liver). For transcription of the IGF-II gene in these tumours, two promoters are used which are expressed in fetal liver, but not in adult liver. The presence of IGF-I and IGF-II RNAs was also established by nucleotide sequence analysis of recombinant DNA clones isolated from cDNA libraries derived from two leiomyosarcomas. The nucleotide sequences of these cDNA clones, together covering the entire coding regions of IGF-Ia and IGF-II var RNA, predict that IGFs encoded by the tumour RNAs do not differ in amino acid sequence from the corresponding polypeptides isolated from serum. In those tissues containing IGF-I RNAs, IGF-I immunoreactivity was also demonstrated.

Exons↗
PubMed1988

Evolutionary pathways of the calcitonin genes.

Since the development of molecular biology, knowledge about polypeptide hormones has increased rapidly. Recombinant DNA techniques have made it possible to establish the structure of genes encoding polypeptide hormones. The results have provided insight into the mechanisms underlying the increasing diversity of polypeptide hormones. Comparison of nucleotide sequences of various genes has revealed surprising similarities and variations. The calcitonin (CT) genes offered an opportunity for speculation about the evolutionary origin on one hand and relationships between these genes on the other.

Animals↗
PubMed1987

Expression of insulin-like growth factor-I and -II genes in rat medullary thyroid carcinoma.

Several types of cancer cells produce polypeptide growth factors and often the same cells have functional receptors for the released growth factor (autocrine secretion). We have studied expression of genes encoding somatomedin-C/insulin-like growth factor-I (Sm-C/IGF-I) and IGF-II, in rat medullary thyroid carcinomas (MTCs) in different stages of tumour differentiation. RNAs hybridizing specifically to an IGF-I cDNA probe were detected in 6 out of 7 differentiated MTCs and IGF-II related RNAs were demonstrated in 5 out of these 7 differentiated MTCs. In 5 anaplastic MTCs no IGF RNAs were detected, except for a small amount of IGF-II related RNA in one tumour.

Carcinoma↗
PubMed1987

Expression of the second calcitonin/calcitonin gene-related peptide gene in Ewing sarcoma cell lines.

The existence of two closely related calcitonin (CT)/CT gene-related peptide (CGRP) genes has been recognized in rat and man. In man, expression of the CALC-I gene produces CT and/or CGRP-I mRNA, whereas CGRP-II mRNA is transcribed from the CALC-II gene. Until recently, expression of the CALC-II gene had been detected only in a metastasis of medullary thyroid carcinoma. In this study, expression of the CALC-II gene was demonstrated by Northern blot hybridization analysis in four of six cell lines established from different Ewing sarcomas, a malignant neoplasm of bone. Expression of the CALC-I gene was not detected in any of the six cell lines. A presumed large mol wt immunoreactive precursor of CGRP-II and small amounts of mature CGRP-II, but no CT, were found in medium from IARC/EW 1 cells. Nucleotide sequence analysis of cloned cDNA from this cell line confirmed the production of CGRP-II mRNA. CALC-II gene expression in Ewing sarcoma might be useful for studies concerning regulation of gene expression in the CALC gene family and possibly for tumor classification.

Base Sequence↗
PubMed1986

Structure and expression of the human calcitonin/CGRP genes.

Recently, we have reported the isolation of cDNA encoding a second human calcitonin gene-related peptide (hCGRP-II) [(1985) FEBS Lett. 183, 403-407]. In this report we describe the isolation and characterization of the gene encoding hCGRP-II. This gene, designated CALC-II, is structurally closely related to the known CALC-I gene encoding human calcitonin (hCT) and hCGRP-I. In contrast to CALC-I, CALC-II does not seem to be alternatively expressed. The formation of a second, hCT-like mRNA by differential splicing of CALC-II transcripts is unlikely in view of the structure of CALC-II, and could not be demonstrated in tissues known to express CALC-I and CALC-II.

Amino Acid Sequence↗
PubMed1986

Model for alternative RNA processing in human calcitonin gene expression.

The alternative RNA processing pathways in human calcitonin gene (CALC-I gene) expression were investigated using steady state RNA isolated from human medullary thyroid carcinoma (MTC) and from a culture line derived from this tumor. On Northern blots the mature 1.0 kilobases (Kb) calcitonin (CT) - and 1.1 Kb calcitonin gene-related peptide (CGRP) mRNAs were detected with CALCI gene specific probes as well as high molecular weight poly (A) containing RNAs of 2.1, 2.3, 3.3, 4.2, 5.0 and 5.7 Kb. The 5.7 Kb RNA was identified as the poly(A) tailed primary transcript containing sequences corresponding to all 6 exons and 5 introns of the CALC-I gene. From the composition of the other RNAs the splicing order of the different introns could be deduced. The results suggest the following model. First all introns not involved in alternative processing (introns 1, 2 and 5) are spliced from the 5.7 Kb RNA in rapid successive reactions yielding a 3.3 Kb RNA, which accumulates. From this 3.3 Kb RNA, the last common intermediate in the alternative processing pathway, CT mRNA is formed by splicing of intron 3 and poly(A) addition at exon 4, in this order or the reverse order via 2.3 Kb or 2.1 Kb RNA intermediates respectively. Alternatively, the whole intron 3-exon 4-intron 4 region is spliced from the 3.3 Kb RNA yielding CGRP mRNA. The temporal sequence of poly(A) addition at exons 4 and 6 may relate to the observed structural differences between the poly(A) addition signals at these sites. The ratio of CT- to CGRP mRNA may relate also to the differences in the primary structures of the intron 3- and intron 4 splice acceptor sites.

Base Sequence↗
PubMed1986

Detection of mRNA encoding calcitonin, calcitonin gene related peptide and proopiomelanocortin in human tumors.

Expression of the calcitonin (CT)/calcitonin gene related peptide (CGRP) gene and the proopiomelanocortin (POMC) gene has been demonstrated by Northern blot hybridization analysis of RNA extracted from human medullary thyroid carcinoma (MTC), pheochromocytoma and lung carcinoma. CT mRNA in these tumors could not be distinguished in size from CT mRNA isolated from normal human thyroid tissue. CGRP mRNA (previously demonstrated in 12 out of 12 lung tumor cell lines investigated) could not be detected in 13 primary lung tumors or 10 metastases thereof. The length of POMC mRNA in MTCs (present in all 4 metastases investigated but not in 7 primary tumors) and pheochromocytomas is about 100 nucleotides more than pituitary POMC RNA. In lung tumors 2 POMC RNA species can be detected, one of the same size as in pituitary tissue and one about 100 nucleotides larger.

Adenocarcinoma↗
PubMed1986

Clinical implications of estimation of intact parathyroid hormone (PTH) versus total immunoreactive PTH in normal subjects and hyperparathyroid patients.

We describe a clinical study comparing the value of measurements of intact human PTH [hPTH(1-84)] and total PTH immunoreactivity [hPTH-(1-84) plus fragments]. A two-step immunochemical method was used to separate plasma hPTH-(1-84) from all circulating PTH fragments. The first step involved extraction and concentration of plasma PTH using solid phase antiamino-terminal PTH antibodies. After elution, the PTH immunoextract was analyzed using a sensitive mid- and C-region immunoassay. Complete separation in the immunoextraction step was proven by Sephadex G-75 gel filtration. hPTH-(1-84) values in fasting patients showed a clear distinction between those with primary hyperparathyroidism and those with nonparathyroid hypercalcemia, in contrast with small overlap in total immunoreactive PTH values. The hPTH-(1-84) values increased faster and more substantially in response to long EDTA and calcium infusion tests, compared with total PTH immunoreactivity, in normal subjects. Infusion of EDTA (10 mg/kg BW) in 5 min) elicited a readily measurable response of hPTH-(1-84) between 5 and 10 min after starting the infusion. Ingestion of 1000 mg calcium caused a decrease in hPTH-(1-84) in 1 h or less. More than 50% of patients with terminal renal failure had normal hPTH-(1-84) values despite elevated total immunoreactive PTH concentrations. We conclude that the two-step hPTH-(1-84) assay is more specific and sensitive than most regional PTH assays. Measurements of hPTH-(1-84) levels may identify disorders of parathyroid function at an early stage and provide a useful tool for the study of parathyroid physiology.

Administration, Oral↗
PubMed1986

DNA methylation patterns of the calcitonin gene in human lung cancers and lymphomas.

Generalized hypomethylation of the genome and of specific genes has been described in human tumors. We now report that in human lung cancers, especially in the most aggressive form, small cell lung carcinoma, and in lymphomas, the 5'-region of the calcitonin (CT) gene exhibits methylation of increased numbers of CCGG sites in comparison with normal adult tissues. These unusual methylation patterns are found much less frequently in other tumor types examined. In the spectrum of the four major types of lung cancer (small cell, adeno-, squamous, and large cell carcinomas), the frequency of occurrence of hypermethylation in the 5'-region of the CT gene parallels that for presence of the neuroendocrine related biochemistry which characterizes small cell lung carcinoma. In medullary thyroid carcinoma, a tumor which expresses high levels of CT gene mRNA, the 5'-region of the CT gene is hypomethylated. Our findings provide a potential new molecular marker for two important human cancers (lung cancer and lymphomas) and suggest that there is a close relationship between abnormal CT gene methylation and developmental events for these tumors.

Calcitonin↗