Biomedical subjects

L Grimelius

Publications and source records attributed to L Grimelius.

At least 73 records · Page 4Linked to original sources

PubMed1996

Reproductive history and cigarette smoking as risk factors for thyroid cancer in women: a population-based case-control study.

A population-based case-control study was conducted in Northern Norway and Central Sweden to investigate hormonal and reproductive factors and cigarette smoking as determinants of papillary and follicular thyroid carcinoma in women. Information on 191 histologically confirmed cases and 341 age-matched controls was included. No clear association was found with regard to the number of live births, number of pregnancies, a history of incomplete pregnancies, or the use of oral contraceptives or hormonal replacement therapy. However, an early first childbirth (before 20 years of age, or less than 5 years after menarche) was associated with an increased risk of thyroid cancer. There was an increased risk of thyroid cancer among women with a history of artificial menopause compared to those with a spontaneous menopause [odds ratio (OR), 2.52; 95% confidence interval (CI), 0.96-6.62], which was more pronounced for the papillary carcinoma and after adjustment for age at menopause and use of replacement therapy. Cigarette smokers had a decreased risk of borderline statistical significance compared to nonsmokers (OR, 0.69; 95% CI, 0.47-1.01), particularly among premenopausal women (OR, 0.60; 95% CI, 0.38-0.96). This negative association persisted after adjustment for parity, hormonal treatments, and education. Women who started smoking before the age of 15 experienced a marked reduction in risk (OR, 0.38%; 95% CI, 0.18-0.80¿). Moreover, there was a suggestion of a dose-response effect with the amount of cigarettes smoked daily and with duration of the habit. Both the increased risk of artificial menopause and the negative association with smoking are compatible with a relation between levels of estrogens and thyroid cancer among women.

Adenocarcinoma, Follicular↗

PubMed1995

Medical diagnostic x rays and thyroid cancer.

BACKGROUND: Diagnostic x rays are the largest man-made source of exposure to ionizing radiation for the general population. Whether there are meaningful cancer risks associated with such exposures is unclear. Most previous case-control studies have relied on recalled histories of x rays, and there is concern that completeness and accuracy of recall might differ between cancer case and control subjects. PURPOSE: The present study used information recorded prospectively in hospital charts to address the relationship between medical diagnostic x rays and risk of thyroid cancer. METHODS: The Swedish Cancer Registry and the Uppsala-Orebro Regional Cancer Registry were used to identify persons with papillary or follicular thyroid cancer diagnosed from January 1, 1980, through December 31, 1992, among residents of the Uppsala Health Care Region. After histopathologic review, there were 484 such case subjects available for study. An equal number of age-, sex-, and county of residence-matched control subjects from the general population were randomly selected on the basis of the Swedish Registry of the Total Population. Lifetime residential histories were compiled, and radiology records were searched at all Swedish hospital serving regions where study subjects ever maintained an official residence. Approximate radiation doses to the thyroid gland for specific types of x-ray examinations were assigned on the basis of mean values of measurements made in Sweden in 1973-1975 and in the United States in 1970. Odds ratios were used to evaluate the association between diagnostic radiography and risk of thyroid cancer. RESULTS: A total of 3853 medical diagnostic x rays were ascertained among thyroid cancer case subjects and 4039 among the matched control subjects. There were no tendency for case subjects to have had more of the types of x-ray procedure associated with higher radiation dose to the thyroid gland (i.e., those involving the head or neck area). This finding was true even when analysis was restricted to x rays occurring before 1960, when doses likely were higher than in more recent years, and for examinations occurring in childhood and adolescence, when susceptibility to radiation-induced thyroid cancer is greatest. The relative risk of thyroid cancer was not significantly associated with estimated cumulative dose to the thyroid gland from diagnostic x rays (two-sided P for trend = .80). CONCLUSION: These data indicate that the risk of thyroid cancer due to medical diagnostic x rays, if any, is very small.

Adenocarcinoma, Follicular↗

PubMed1995

Is residence in areas of endemic goiter a risk factor for thyroid cancer?

The association between an indicator of iodine deficiency and differentiated thyroid cancer has been investigated in a population-based case-control study. This included all incident cases (N = 484) of papillary and follicular thyroid cancer diagnosed during the years 1980-1992 in a Swedish Health Care Region among residents born in Sweden, and as many individually matched controls. Cases were included after a uniform review of their histopathological specimens. Residence in areas where goiter had been severely endemic in the 1930s was used as exposure indicator. Odds ratios (OR) and 95% confidence intervals as estimates of relative risk were calculated as a measure of association using logistic regression. A trend toward an association was found with a duration of residence in goiter areas between 21 and 40 years, most prominent among follicular cancer cases and in the group diagnosed at age > or = 50 years compared to not exposed. Exposure for the first time during adolescence (between 11 and 20 years) was associated with an increased risk of papillary cancer. This was especially evident among women, both when compared to not exposed and to those exposed during the first year of life; the association was strengthened after adjustment for duration of residence. These findings support the hypothesis of distinct causation patterns from iodine deficiency to the 2 most common histological types of thyroid cancer.

Adolescent↗

PubMed1995

The expression profile of alternatively spliced neuronal c-src RNA distinguishes between human tumours of the sympatho-adrenal lineage.

Human neuronal and neuroendocrine tumour specimens and cell lines were analysed regarding proteins and transcripts coded by the proto-oncogene c-src. At the protein level, most of the neuroblastomas and phaeochromocytomas expressed the neuronal c-src form, pp60c-srcN. None of the other neuroendocrine tumours, i.e. paragangliomas, neuroendocrine pancreatic tumours, or carcinoid tumours and small-cell lung carcinomas of different types, appeared to express the neuronal form. In the brain, c-src is transcribed into 3 differently spliced mRNA variants, c-src, c-srcNI, and c-srcNI+NII. The expression of these transcripts was analysed by PCR amplification of fragments covering the mini-exons I and NII of the corresponding cDNAs. The PCR products were analysed by Southern hybridization and characterized by determination of their sequences. Neuroblastomas, paragangliomas, retinoblastomas and the phaeochromocytomas expressed neuronal c-src splice variants. However, whereas neuroblastomas and retinoblastomas contained all 3 transcripts, the phaeochromocytomas and paragangliomas expressed, with 2 exceptions, only the c-src and the c-srcNI+NII mRNA species. To assess whether neuroblastomas display adrenal chromaffin characteristics, they were analysed regarding expression of the chromaffin marker enzyme, phenylethanolamine-N-methyl transferase. Whereas phaeochromocytomas were positive, all neuroblastomas were immuno-chemically negative for this enzyme. These results and the c-src expression profile suggest that neuroblastomas, including those with an adrenal location, do not originate from the adrenal chromaffin differentiation lineage. The data further suggest neuronal c-srcNI mRNA as a marker for sympathetic neuronal cells of the sympatho-adrenal lineage.

Adrenal Gland Neoplasms↗

PubMed1995

Allelotyping of follicular thyroid tumors.

To elucidate further the genetic mechanisms for follicular thyroid tumor development and progression, we allelotyped follicular thyroid tumors and other thyroid lesions from 92 patients. In general, a low frequency of loss of heterozygosity (LOH) was found, the highest being for chromosomes 3q, 10q, 11p, 11q, 13q, and 22q (10%-15%). However, detailed study of LOH of these chromosome arms with regard to the different histopathological diagnoses indicates that a locus on chromosome 10q may be involved in follicular thyroid tumor progression. In addition, the majority of Hürthle cell adenomas showed LOH on either chromosome 3q or 18q, in contrast to the other tumor types. This discrepancy in genetic alterations may contribute to the divergent clinical features occurring in these tumors.

Adenocarcinoma, Follicular↗

PubMed1995

Argyrophilic nucleolar organizer regions. A revised version of the Ag-NOR-staining technique.

Silver staining techniques developed to demonstrate argyrophilic nucleolar organizer regions (Ag-NORs) have been widely applied in a variety of cell kinetic studies, using the mean number of AgNORs in tumour cells as a marker for malignancy of certain types of neoplasms. However, the AgNOR techniques currently available are not entirely satisfactory, as unspecific silver precipitates readily form in the sections. On the other hand, the contrast staining may be so weak as to render identification of the AgNORs difficult. In the present study, some of the key factors influencing the outcome of AgNOR staining were evaluated in a more systematic way. A modified AgNOR staining procedure is now proposed, giving highly contrasting AgNORs with minimal unspecific silver precipitation, thus facilitating both manual and computerized counting. The new technique involves the use of microwave irradiation in order to shorten the processing time, the use of gelatin as a protective colloid, and a Farmer's solution to optimize the specificity of the technique.

Adrenal Cortex Neoplasms↗

PubMed1995

The distribution of endocrine cell types of the gastrointestinal mucosa in genetically diabetic (db/db) mice.

BACKGROUND/AIMS: Genetically diabetic (db/db) mice are a model for non-insulin-dependent diabetes in humans. The gastrointestinal tracts in 12-week-old db/db and nondiabetic control (db/+) mice were studied with particular emphasis on the endocrine cells. METHODS: Immunocytochemical and quantification techniques were used to localize and determine the number of cells containing serotonin and various regulatory peptides. RESULTS: In the antrum, the gastrin- and serotonin-immunoreactive cells were increased in number. In the large intestine, the enteroglucagon and the peptide tyrosine-immunoreactive cells were increased in number, whereas there were fewer serotonin-immunoreactive cells. There were also fewer somatostatin-immunoreactive cells in most gastrointestinal regions. In diabetic mice, the intestine was longer and its mucosa thicker than in control mice. CONCLUSIONS: The results indicate that the genetic diabetic (db/db) condition exerts a significant influence on the gastrointestinal tract and on the endocrine cell systems studied. The observed alterations may reflect the effect of indirect factors rather than the diabetes per se.

Animals↗

PubMed1995

Prognostic value of bcl-2 immunoreactivity in medullary thyroid carcinoma.

Bcl-2 expression has been evaluated immunocytochemically in a series of 33 medullary thyroid carcinomas (MTC) with long-term (mean, 10.3 years) follow-up. Twenty-six of 33 cases showed intense bcl-2 immunoreactivity in more than 25% neoplastic cells. Bcl-2 immunoreactivity did not correlate with several clinicopathologic parameters including sex and age of the patients, sporadic or familial disease, tumor size and stage, amount of amyloid stroma, and immunoreactivity for calcitonin, chromogranin A, proliferating cell nuclear antigen (PCNA), N-myc, and p53. Lack of bcl-2 immunoreactivity, however, correlated significantly (P = .0001) with a shorter survival. Indeed, the seven patients with tumors devoid of bcl-2 immunoreactivity all died of disease within 8 years from the diagnosis. In multivariate analysis, lack of bcl-2 immunoreactivity was an independent predictor of worse prognosis (P = .001 for disease-free survival and P = .0001 for overall survival). None of the other clinicopathologic variable investigated proved to be an independent prognostic parameter. It is concluded that down-regulation of bcl-2 expression in MTC may identify a subset of tumors with a more aggressive clinical course.

Adolescent↗

PubMed1995

Histopathological diagnosis of parathyroid diseases.

Hyperparathyroidism is the predominant disease of the parathyroid gland. This disease is nowadays quite common and is often diagnosed at an earlier stage, mainly by means of serum calcium determinations on wide indications. This means that when detected, the glandular abnormalities may be less advanced, which could hamper differentiation of adenoma from chief cell hyperplasia, and of normal glands from slightly hyperplastic ones. Normal glands and pathological glands both show wide variations in size, cellular composition and arrangement, as described in this article. The usefulness of applying fat staining to distinguish between normal and abnormal glands is also reported. It is important to bear in mind that the parathyroid diagnosis is in fact an indirect diagnosis based on the assessment of an associated gland or glands.

Humans↗

PubMed1995

Intracellular degradation of the C-peptide of proinsulin, in a human insulinoma: identification of sites of cleavage and evidence for a role for cathepsin B.

An extract of a neuroendocrine tumor of the human pancreas contained a high concentration of insulin and the C-peptide of proinsulin, as determined by radioimmunoassay, together with somatostatin, calcitonin, and thymosin beta 4. Analysis of the molecular forms of the proinsulin-derived peptides by high-performance liquid chromatography demonstrated that insulin was stored in the tumor as the intact peptide. In contrast, metabolites of C-peptide, representing the (1-21), (1-23), (1-25) and (1-29) N-terminal fragments, were isolated from the extract in addition to intact C-peptide. Generation of these metabolites involves cleavage of Xaa-Leu or Leu-Xaa bonds. Previous immunohistochemical studies have identified cathepsin B in secretory granules and lysosomes of human insulinoma cells. Synthetic human C-peptide was rapidly cleaved by purified human cathepsin B, primarily at the site of leucine residues, to give several metabolites, including the (1-25) and (1-23) fragments. The data indicate that the C-peptide of proinsulin is selectively metabolized in the neoplastic B cell by a mechanism that involves proteolytic cleavages in the C-terminal region of the peptide.

Aged↗

PubMed1995

Mutations of codon 918 in the RET proto-oncogene correlate to poor prognosis in sporadic medullary thyroid carcinomas.

The hereditary multiple endocrine neoplasia syndromes types 2A and B (MEN 2A and B) were recently linked to germline mutations in the RET proto-oncogene, altering one of five cysteine residues in exon 10 or 11 (MEN 2A), or substituting a methionine for a threonine at codon 918 in exon 16 (MEN 2B). The latter mutation also occurs somatically in some sporadic medullary thyroid carcinomas (MTC), and has in a previous study been correlated with a less favorable clinical outcome. In the present study, 46 MTCs were selected for investigation of the codon 918 mutation. The mutation was found in 29 tumors (63%), and was significantly correlated with a poor outcome, with regard to distant metastasis or tumor recurrence (p < 10(-4)). Two tumors showed multifocal growth and C-cell hyperplasia, and these patients were therefore also investigated for germline mutations in exons 10, 11 and 16. The codon 918 mutation was found only in the tumors, thus of somatic origin. The RET codon 918 mutation may have prognostic impact, and therefore preoperative assessment may influence decision-making in the treatment of patients suffering from MTC.

Base Sequence↗

PubMed1995

IGF2 expression is a marker for paraganglionic/SIF cell differentiation in neuroblastoma.

Neuroblastoma is a childhood tumor of the sympathetic nervous system. Observations in the Beckwith-Wiedemann syndrome suggest that sympathetic embryonal cells with an abundant expression of the insulin-like growth factor 2 gene (IGF2) may be involved in the genesis of low-malignant infant neuroblastomas. We have therefore compared the cell type-specific IGF2 expression of the human sympathetic nervous system during early development with that of neuroblastoma. An abundant expression in normal sympathetic tissue was specific to extra-adrenal chromaffin cells, ie, paraganglia and small intensely fluorescent (SIF) cells, whereas sympathetic neuronal cells were IGF2-negative. A subpopulation of neuroblastomas expressed IGF2, which correlated with an early age at diagnosis, an extra-adrenal tumor origin, and severe hemodynamic signs of catecholamine secretion. Histologically IGF2-expressing tumors displayed a lobular growth pattern, and expression was restricted to the most mature and least proliferative cells. Typically, these cells were morphologically and histochemically similar to paraganglia/SIF cells and formed distinct ring-like zones in the center of the lobules around a core of apoptosis-like tumor cells. The similarities found between IGF2-expressing neuroblastoma cells and paraganglia/SIF cells in terms of histological features, anatomical origin, and age-dependent growth suggest a paraganglionic/SIF cell lineage of most infant tumors and also of extra-adrenal tumors diagnosed after infancy. Furthermore, since paraganglia/SIF cells undergo postnatal involution, the same cellular mechanism may be responsible for spontaneous regression in infant neuroblastoma.

Biomarkers, Tumor↗

PubMed1994

Prognostic value of N-myc immunoreactivity in medullary thyroid carcinoma.

BACKGROUND: The analysis of N-myc expression in some neuroendocrine tumors has been reported to provide prognostic information. To the authors' knowledge, no attempts have been made thus far to correlate N-myc expression with the clinical outcome of medullary thyroid carcinoma (MTC). METHODS: N-myc gene product immunoreactivity was evaluated in 34 patients with MTC with long term follow-up, using the OA-11-803 polyclonal antiserum. The results were related to patient age and sex, sporadic or familial disease, tumor size, stage, growth rate (as determined by proliferating cell nuclear antigen [PCNA] immunostaining), and to clinical outcome. RESULTS: Patients harboring tumors with greater than 10% neoplastic cells immunoreactive to the N-myc antiserum (58% of the cases investigated) had significantly greater tumor size (P = 0.031) than patients with fewer or no N-myc immunoreactive cells. Deregulated expression of N-myc protein in tumor cells was not due to gene amplification, as demonstrated by multiplex polymerase chain reaction (PCR). In univariate analysis, patients with more than 10% immunoreactive neoplastic cells showed a significantly shorter disease free survival than did the remaining patients (P = 0.002). Among the other clinicopathologic parameters evaluated, male sex (P = 0.039) and sporadic disease (P = 0.035) also were associated with shorter disease free survival. In multivariate analysis, N-myc immunoreactivity (P = 0.039) and male sex (p = 0.050) retained a significant correlation with poor prognosis. CONCLUSIONS: Our results suggest that immunoreactivity to the N-myc antiserum, but not tumor growth fraction as evaluated by PCNA immunostaining, is a novel and useful adjunct to predict clinical behavior of MTC.

Adolescent↗

PubMed1994

Multiple neuropeptide immunoreactivities in a renin-producing human paraganglioma.

BACKGROUND: A case of a renin-producing paraganglioma of adrenal origin with metastases to the retroperitoneal area, paravaginal area, and the ovary is reported with immunohistochemical findings indicating expression of multiple neuropeptide immunoreactivities. The patient was 23 years old at the time of diagnosis, and died from metastatic spread of the tumor 7 years later. METHODS: Tumor tissue was examined by light microscopy, indirect immunohistochemistry, and electron microscopy. RESULTS: The tumor tissue investigated contained several cells exhibiting opioid peptide-like immunoreactivities (i.e., enkephalin and dynorphin-like immunoreactivity [LI]). A lower number of cells displayed neuropeptide Y-, galanin-, somatostatin-, neurotensin-, substance P-, peptide histidine-isoleucine-, cholecystokinin-, renin-, and calbindin-LI. CONCLUSION: To the authors' knowledge, galanin, dynorphin, peptide histidine-isoleucine, cholecystokinin, and calbindin have not been reported previously to occur in paraganglioma, and renin has been reported to occur very rarely. A review of recent literature suggest that enkephalin-, neuropeptide Y-, and somatostatin-like immunoreactivities may be useful as diagnostic markers for paragangliomas.

Adrenal Gland Neoplasms↗

PubMed1994

Immunohistochemical localization of endothelin-1 in non-neoplastic and neoplastic adrenal gland tissue.

Endothelin (ET)-1 is a 21-amino acid peptide with potent vasopressor and vasocontrictive properties. Biochemical studies suggest that this peptide occurs in adrenal glands, where it influences steroid hormone production. However, we have found no report of the topographical distribution of this peptide. The localization of ET-1 immunoreactivity in non-neoplastic (37 cases) and neoplastic adrenal glands (48 cases) was investigated with a sensitive immunohistochemical technique applied to routinely processed tissue specimens. ET-1 immunoreactivity was regularly seen in the cortex, especially in the zona fasciculata and to a varying extent also in the other two zones, but not in the medulla. The immunoreactive material appeared in the cytoplasm mostly in the form of vacuolar structures but also as grains. Focally, the cell membrane also showed immunoreactive staining. In the zona reticularis the immunoreactivity appeared mainly as cytoplasmic grains. Most cortical adenomas displayed numerous immunoreactive cells. The immunoreactivity in the tumour tissue appeared in the same forms as in normal cortex, but the reactive products were generally fewer in number. No obvious differences in immunostaining were seen between the aldosterone- and cortisol-producing adenomas or the non-functioning ones. Three of the ten carcinomas contained immunoreactive cells, but they were few, appearing focally and the ET-1 immunoreactive structures were seen as 'dust-like' material. The difference in immunoreactivity between the benign and the malignant cortical neoplasms may be of diagnostic value. Functionally our results support a relationship between ET-1 and steroid regulation in non-neoplastic cortical tissue.

Adrenal Gland Neoplasms↗

PubMed1994

Impact of familial amyloid associated polyneuropathy on duodenal endocrine cells.

Duodenal endocrine cells in 11 patients with familial amyloid associated polyneuropathy (FAP) were compared with those in 12 healthy volunteers by means of immunohistochemistry and morphometry. The total endocrine cell content, determined by the argyrophilic reaction and chromogranin A immunoreactivity, was significantly reduced in FAP patients compared with controls. There was a significant reduction in the serotonin, cholecystokinin/gastrin, and secretin immunoreactive cell content. A decreased cell content was also noted for somatostatin and gastric inhibitory polypeptide immunoreactive cells but this was not statistically significant. Amyloid deposits were noted in seven of the 11 biopsy specimens from FAP patients, but otherwise the duodenum was histologically normal in both groups. The reduction in endocrine cell content was not correlated with the degree of amyloid deposit in the duodenum. These findings indicate that patients with FAP have reduced intestinal endocrine cells. This does not seem to be related to amyloid deposits in the mucosa or to villous or crypt abnormalities. The observed changes in endocrine cells may contribute to the development of intestinal motility dysfunction and maldigestion in these patients.

Adult↗

PubMed1994

Clinical management of gastric carcinoid tumors.

Four types of gastric carcinoids have been identified: (1) multiple small body-fundus carcinoids associated with chronic atrophic gastritis type A (A-CAG); (2) sporadic solitary lesions without specific pathogenetic background (non-A-CAG); (3) carcinoidosis associated with Zollinger-Ellison/MEN 1 syndrome, and (4) rare tumors, e.g. gastrin cell tumors, neuroendocrine carcinomas and mixed endocrine-exocrine tumors. In a retrospective study of 15 patients with gastric carcinoids (11 A-CAG, 3 non-A-CAG and 1 gastrin cell tumor) over a 10-year period, the histopathological and clinical features were assessed. The A-CAG-type carcinoids were clinically silent with lymph node metastases in 2/11 cases but no hepatic metastases. The non-A-CAG-type carcinoids were malignant with disseminated disease, hormonal symptoms and increased urinary excretion of the main histamine metabolite, MeImAA. Five patients with A-CAG tumors were subjected to antrectomy to remove hypergastrinemia, which is thought to be of pathogenetic importance for these tumors. During the observation period (1.5-8 years) 1 patient developed recurrent tumors, while the other 4 showed persistent argyrophil cell hyperplasia. A prospective treatment protocol of these tumors is suggested with endoscopic removal of less numerous, small lesions as first-step therapy, followed by antrectomy at recurrence. Larger lesions should be excised in combination with antrectomy. Gastrectomy is reserved for the rare cases of invasive tumors with lymph node metastases. As evident from the outcome of patients with non-A-CAG tumors radical surgery should be performed whenever practicable.

Carcinoid Tumor↗

PubMed1994

Blood sampling procedures influence serum calcitonin concentrations in rats.

The aim of this study was to determine whether serum calcitonin (S-CT) in rats is influenced by the method of taking blood samples. Sampling during halothane anaesthesia, after repeated administration of anaesthesia after a 14-day interval, and sampling without the use of anaesthetics (i.e. after the rats were made unconscious by stunning), resulted in different S-CT values (P < or = 0.001), whereas Ca2+ levels were not affected. In thyroidectomized rats, the S-CT values after stunning were not significantly different whereas those in sham-operated rats were different (P < or = 0.01). The possibility that anaesthesia may suppress stunning-induced changes in S-CT was explored in three other groups of rats subjected to halothane anaesthesia, stunning and stunning under halothane anaesthesia respectively. Although the S-CT level was highest after stunning and lowest in halothane-anaesthetized rats (P < or = 0.001), anaesthesia did not suppress the effect of stunning on S-CT. In conclusion the effect of sampling procedures must be considered in studies on the levels of S-CT in rats.

Anesthesia↗