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C J Lips

Publications and source records attributed to C J Lips.

At least 91 records · Page 5Linked to original sources
PubMed1993

Detection of calcitonin and calcitonin gene-related peptide mRNA in human medullary thyroid carcinoma. A retrospective study.

In situ hybridization finds many applications in modern pathology. In many cases, special attention is paid to the processing of the tissues prior to in situ hybridization. In order to investigate the value of RNA in situ hybridization (RISH) in retrospective studies, we performed RISH for calcitonin and calcitonin gene-related peptide (CGRP)-I and -II mRNA in eight medullary thyroid carcinomas processed in 1981-1983. RISH was successful with radioactive calcitonin and CGRP-I probes. With biotinylated probes, only calcitonin-specific probes gave adequate results. The concentrations of CGRP mRNA were probably too low to be detected by non-radioactive RISH. The results of RISH were correlated with the immunohistochemical localization of the polypeptides. The results matched in all cases except one, where hybridization for calcitonin mRNA was found, but no immunoreactive calcitonin polypeptide. We conclude that RISH can be successfully used for retrospective analysis, even after long storage of tissue embedded in paraffin.

Calcitonin↗
PubMed1993

Plasma concentrations of islet amyloid polypeptide after glucagon administration in type 2 diabetic patients and non-diabetic subjects.

Islet amyloid polypeptide (IAPP) is the main constituent of pancreatic islet amyloid, observed in the pancreases from patients with Type 2 diabetes mellitus. IAPP is synthesized by the pancreatic beta-cells. In order to study the secretion characteristics of IAPP in Type 2 diabetes mellitus, plasma IAPP was measured during a provocation test with glucagon in 33 Type 2 diabetic patients and 18 non-diabetic subjects. The median fasting IAPP level was 5.7 (range 1.1-13.1) pmol l-1 in the 27 patients treated with oral hypoglycaemic agents and 2.7 (1.9-5.9) in the 6 patients on insulin. In the non-diabetic group fasting IAPP was 5.7 (2.2-10.1). Six minutes after glucagon administration median IAPP rose to 9.4 (1.7-31.0) and 6.1 (5.1-10.2) in the respective diabetic groups, and to 16.8 (4.0-41.0) in the non-diabetic subjects (p << 0.05). The correlation coefficient between change in IAPP and change in C-peptide was 0.68 in the diabetic group. We conclude that intravenous administration of glucagon stimulates IAPP release from the beta-cell. This provocation test is easy to perform and can be used on a large scale in the study of IAPP secretion in Type 2 diabetes mellitus.

Adult↗
PubMed1993

The clinical implications of a positive calcitonin test for C-cell hyperplasia in genetically unaffected members of an MEN2A kindred.

C-cell hyperplasia precedes the development of medullary thyroid carcinoma in multiple endocrine neoplasia type 2A (MEN2A). Identification of abnormal calcitonin levels after a provocative stimulus is a technique that has been widely used to diagnose this preneoplastic condition in an early stage during the development of medullary thyroid carcinoma, when total thyroidectomy is likely to be curative. In a MEN2A kindred, we identified seven individuals with abnormal calcitonin test results, whose carrier state was questionable. Five of these people were thyroidectomized, and C-cell hyperplasia was diagnosed. Four of these individuals were the offspring of a mother who is at risk for the development of MEN2A but who has had normal calcitonin test results throughout the years and of a father who is not at risk but who has had abnormal test results over a period of 10 years, without evidence of progressive elevation. None of these people developed other manifestations of MEN2A. DNA analysis using markers linked to the MEN2A gene demonstrated, with > 99% likelihood, that none of the individuals who could be genotyped was a gene carrier. C-cell hyperplasia due to some mechanism other than the presence of the MEN2A gene may also occur in MEN2A kindreds. DNA analysis offers an important additional tool for proper diagnosis in the clinical management of MEN2A families.

Adolescent↗
PubMed1993

[Type II multiple endocrine neoplasms (MEN IIB): an unusual cause of constipation. A plea for early thyroidectomy].

We present a 5 year old girl who was diagnosed to have multiple endocrine neoplasia syndrome type IIB (MEN IIB). She presented with serious constipation and had the distinct features of MEN IIB. 100% of the patients with MEN IIB develop medullary thyreoïd carcinoma (MTC). MTC in MEN IIB is known to behave in a very aggressive way. Microscopically MTC was already present in this patient despite of normal calcitonin stimulation tests. Accordingly we plead for a more radical management relating to thyreoïdectomy in MEN IIB.

Child, Preschool↗
PubMed1992

Characterization of the human islet amyloid polypeptide/amylin gene transcripts: identification of a new polyadenylation site.

Islet amyloid polypeptide (IAPP) or Amylin is synthesized by the pancreatic beta-cells. IAPP is the major component of islet amyloid in the pancreas of patients with non-insulin-dependent diabetes mellitus. We report the composition and complete nucleotide sequence of the two human IAPP mRNAs of 1.6 and 2.1 kb. A new polyadenylation site was identified and shown to be used in generation of the 2.1 kb RNA. A previously identified polyadenylation signal is assigned to the 1.6 kb RNA. We exactly determined the major transcription start site, which is used in generation of these mRNAs. Lower abundance RNAs containing sequences located further upstream in the IAPP gene were also detected.

Amyloid↗
PubMed1992

Expression and CpG methylation of the insulin-like growth factor II gene in human smooth muscle tumors.

Previously we have shown that expression of the insulin-like growth factor II (IGF-II) gene in 36 normal smooth muscle tissues (myometria) and 26 benign smooth muscle tumors (leiomyomas) was detectable by Northern blot analysis but that the RNA levels were low. In 9 of 20 malignant smooth muscle tumors (leiomyosarcomas) IGF-II gene expression was also low or absent, while in 11 of 20 the IGF-II gene was abundantly expressed. In 32 of these tissues we have now studied the DNA methylation state of the IGF-II gene. For the analysis of overall methylation of the gene the restriction endonucleases HpaII and MspI were used. In normal smooth muscle and in leiomyomas the IGF-II gene appeared to be methylated. In leiomyosarcomas with low IGF-II gene expression the DNA was partly demethylated. In leiomyosarcomas with abundant IGF-II gene expression overall methylation of the DNA tended to be low. In addition, we have studied the methylation state of one particular CpG site in the IGF-II gene with the restriction endonuclease AvaII. The results of the latter analysis confirm the analysis with HpaII and MspI. In conclusion, in malignant smooth muscle tumors the data indicate an inverse correlation between CpG methylation and expression of the IGF-II gene.

Base Sequence↗
PubMed1992

Islet amyloid polypeptide (IAPP) is synthesized in the islets of Langerhans. Detection of IAPP polypeptide and IAPP mRNA by combined in situ hybridization and immunohistochemistry in rat pancreas.

We investigated the localization of IAPP mRNA by means of in situ hybridization in tissue sections of rat pancreas. A 35S-labeled, IAPP-specific DNA probe--hybridized specifically in the islets of Langerhans. This localization was confirmed by immunohistochemical localization of insulin and IAPP polypeptides on adjacent tissue sections. Moreover, combined in situ hybridization of IAPP mRNA and immunohistochemistry of insulin and IAPP polypeptide on the same section, using insulin as specific marker shows the presence of IAPP mRNA in the islets of Langerhans.

Amyloid↗
PubMed1992

Expression of the first calcitonin/CGRP gene in spontaneous and transplanted rat medullary thyroid carcinoma: a comparison of dot-blot analysis, in situ hybridization, and immunohistochemistry.

Calcitonin (CT) and calcitonin gene-related peptide (CGRP) are encoded by a single gene, the CALC-I gene. They are expressed in the thyroid and in the nervous system by alternative splicing of the pre-messenger RNA derived from the CALC-I gene. In medullary thyroid carcinoma (MTC), a malignancy derived from the calcitonin-producing C-cells in the thyroid, production of calcitonin and CGRP is a common feature. We investigated the CT and CGRP production of four spontaneous MTCs transplanted three to four times and 14 MTC lines transplanted for several years in WAG/Rij rats, a strain with hereditary MTC. The expression of CT and CGRP in the spontaneous and in the transplanted tumors was studied by means of RNA in situ hybridization (RISH), dot-blot analysis, and immunohistochemistry. A down-regulation of CT production in transplanted compared with spontaneous tumors was observed, but an inverse relation between CT and CGRP mRNA content in both spontaneous and transplanted tumors was not observed. In this study, RISH proved to be as sensitive as dot-blot analysis to detect gene expression in tissue samples. The different approaches of analyzing the gene expression in tissue samples (the cellular localization of gene expression by ISH vs the analysis of an extract of a total tissue sample with dot-blot analysis) showed that each technique is equal in value and that they are complementary to each other.

Animals↗
PubMed1992

The natural course of multiple endocrine neoplasia type IIb. A study of 18 cases.

BACKGROUND: Multiple endocrine neoplasia (MEN) type IIb is an autosomal dominantly inherited disorder associated with medullary thyroid cancer, pheochromocytoma, and a characteristic phenotype. The present study was performed to investigate the natural course of the syndrome and to describe its expression. METHODS: The medical records of 18 patients with MEN IIb, seven male and 11 female, were reviewed. RESULTS: The mean age at diagnosis of MEN IIb was 18 years (range, 8 to 41 years). All 18 patients had medullary thyroid cancer. In three patients, medullary thyroid cancer was diagnosed via screening. In two of these patients, the calcitonin value normalized after thyroidectomy. One patient died of metastases from medullary thyroid cancer at the age of 20 years (median duration of follow-up, 10 years). Eight of the 18 patients had pheochromocytomas. All of our patients had neuromas and bumpy lips, and all but one had a marfanoid habitus. A large proportion of the patients had intestinal abnormalities (75%), thickened corneal nerves (69%), skeletal abnormalities (87%), and delayed puberty (43%). CONCLUSIONS: The course of medullary thyroid cancer in MEN IIb is not always as aggressive as is generally thought. Periodic examination of relatives who are at risk may lead to early diagnosis and curative treatment. Intestinal abnormalities, skeletal abnormalities, and delayed puberty are commonly found in association with MEN IIb.

Adolescent↗
PubMed1992

No constant relationship between islet amyloid polypeptide (IAPP) and insulin expression in insulinomas.

The relationship between insulin and islet amyloid polypeptide (IAPP) expression was studied at the level of RNA and peptide in 3 patients operated on for insulinoma. Two patients had a solitary tumour; one patient suffered from the MEN-I syndrome. In the 3 tumours, as in normal pancreas, the same 2 IAPP-specific mRNA species, approximately 1600 and 2100 nucleotides, respectively, were detected. In 2 patients, the IAPP mRNA concentration of the tumour was lower than the insulin mRNA concentration; in the third patient, however, the specific IAPP hybridization signal was at least equal to that for insulin. Amyloid deposits were found in one solitary tumour and in the tumour from the MEN-I patient, both staining strongly positive with anti-IAPP antibodies; cytoplasmatic IAPP was weak. In conclusion, at least in some insulinomas, no constant relationship exists between insulin and IAPP expression.

Adolescent↗
PubMed1991

[Neurofibromatosis and a tumor of Vater's papilla].

A male aged 57 is reported with neurofibromatosis presenting with a tumour in the periampullary region. Pathologic examination revealed a neuroendocrine tumour of the carcinoid type. A review of the literature suggests that neurofibromatosis patients are at significant risk for developing a periampullary tumour which is nearly always of neuroectodermal origin. To date, surgical excision is the only curative therapy. Therefore, early diagnosis is of major importance. In all patients with neurofibromatosis presenting with jaundice, gastrointestinal bleeding or abdominal pain, a periampullary tumour should be considered. A review is presented of the latest developments concerning the DNA-based mutation causing this disorder. In family members, DNA linkage studies should be carried out, and they should be periodically screened, e.g. with gastroduodenoscopy.

Ampulla of Vater↗
PubMed1991

Validation of an in vitro RNA processing system for CT/CGRP precursor mRNA.

The pre-mRNA encoding calcitonin (CT) and calcitonin gene-related peptide (CGRP) is differentially processed in a tissue-specific fashion to include or exclude the calcitonin-specific exon 4. A minigene containing a viral first exon and exons 4, 5, and 6 from the human CT/CGRP gene was correctly processed in transfected HeLa or F9 teratocarcinoma cells to produce mRNA that included or excluded exon 4, respectively. This processing decision could be reproduced in vitro using nuclear extracts from these two cell lines and an RNA precursor from a similar minigene. Supplementation of extract from HeLa cells with extract from F9 cells resulted in the F9 splicing pattern in which exon 4 was excluded. This model system may be useful for the purification of splicing factors important in the regulation of this splice choice.

Adenoviridae↗