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Biomedical subjects

L Grimelius

Publications and source records attributed to L Grimelius.

At least 109 records · Page 6Linked to original sources
PubMed1991

Oncoprotein immunoreactivity in human endocrine tumours.

Abnormally expressed oncogenes are implicated in neoplastic transformation. We have investigated a series of endocrine tumours using immunocytochemistry as a first screening tool to detect oncogene expression. Paraffin sections of 44 pulmonary small cell carcinomas, 15 pulmonary atypical carcinoids, 12 bronchial carcinoids, 28 medullary thyroid carcinomas, 27 phaeochromocytomas, and 17 insulinomas were immunostained with antibodies to c-erbB-2, c-myc, L-myc, and N-myc. Diffuse immunoreactivity was detectable for c-erbB-2 in 8 out of 44 (18 per cent) pulmonary small cell carcinomas, 3 out of 15 (20 per cent) pulmonary atypical carcinoids, and 6 out of 27 (22 per cent) phaeochromocytomas; for c-myc in 18 out of 44 (41 per cent) pulmonary small cell carcinomas and 5 out of 15 (33 per cent) pulmonary atypical carcinoids; for N-myc in 6 out of 28 (21 per cent) medullary thyroid carcinomas; and for L-myc in 4 out of 27 (15 per cent) phaeochromocytomas. There was considerable intratumoral and intertumoral heterogeneity and, in each tumour group, no relationship was found between tumour pattern, mitotic index, and oncoprotein immunoreactivity. These results suggest that oncogene products are present in a proportion of endocrine tumours, and that specific oncoproteins seem to be related to tumour type but not to other histopathological findings. Thus, oncoprotein detection may be a useful tool for identifying subsets of endocrine tumours that are not otherwise recognizable morphologically.

Endocrine System Diseases↗
PubMed1991

Paragangliomas: neuroendocrine features and cytometric DNA distribution patterns. A clinico-pathological study of 22 cases.

Paragangliomas from 22 patients with extraadrenal tumours of this type were studied. Neuroendocrine features were examined using immunohistochemical techniques. Twenty-two antisera raised against neuroendocrine "markers", regulatory peptides, serotonin and intermediate filament proteins were studied in this group and cytometric DNA assessments were made by means of image cytometry. One normal and 5 hyperplastic carotid bodies were used as controls in the DNA cytometric investigations. Clinical and/or histopathological evidence of "malignancy" was present in 5 cases. The tumour cells showed heterogeneity with regard to their expression of different peptides, and the immunohistochemical analyses did not permit differentiation between benign and malignant paragangliomas. An euploid nuclear DNA distribution pattern was found in all controls and in 17 of the tumours; all except 1 were clinico-pathologically benign. An aneuploid DNA pattern was observed in 5 of the cases and some malignant features were present in 4 of these cases. DNA data may give further information apart from that obtained from the histopathological findings which may be of value in predicting the biological behaviour of this tumour type.

Adult↗
PubMed1991

Phylogenetic aspects of pancreastatin- and chromogranin-like immunoreactive cells in the gastro-entero-pancreatic neuroendocrine system of vertebrates.

Using a battery of region-specific antisera raised against different amino acid sequences of pancreastatin (Pst) (Pst-1-6, Pst-1-17, Pst-14-49, Pst-33-49) as well as two antisera raised against chromogranin (Cg) A and CgA/B and the biotin-avidin technique, the phylogenetic distribution of Pst-immunoreactive (-IR) and Cg-IR cells was studied in the gastroentero-pancreatic (GEP) neuroendocrine system. The investigation was carried out with representatives of all vertebrate classes as well as with the protochordates Branchiostoma lanceolatum and Ciona intestinalis. The study revealed the presence of Pst-IR and Cg-IR cells in the gastro-intestinal mucosal epithelium as well as in the islet parenchyma of all vertebrates studied with the only exception found in rat. In the rat GEP system unequivocal immunoreactions were obtained only by the use of antiserum CgA/B. In the gastro-intestinal tract of the deuterostomian invertebrates no Pst-IR or Cg-IR cells could be observed with any of our antisera. Whether this might indicate that Pst-like or Cg-like peptides are characteristic for vertebrates or, more likely, whether similar proteins/peptides might be present in the alimentary tract of protochordates which do not react with the antisera at hand, remains to be clarified. Thouh pronounced interspecies and some intraspecies differences were found, several general conclusions can be drawn. In all vertebrate species, the Pst-IR and Cg-IR cells observed in the mucosal epithelium of the gastro-intestinal tract showed an endocrine structure and were of the so-called open type. The Pst and the Cg antisera which gave immunoreactions with parenchymal cells in the islets of Langerhans also reacted with cells in the epithelium of the pancreatic ducts. Comparative analysis of the reaction properties of the region-specific antisera used indicated that the Pst-like material in the islet cells of the cartilaginous fish species studied seems to be "mammalian-like," whereas it appears to be different in the other (phylogenetically younger) submammalian vertebrates. In addition, the Pst-like peptides in the gastro-intestinal mucosal epithelium and in those in the islets seem to differ in most submammalians. Finally, in the pyloric-duodenal junction of the quail (Coturnix c. japonica) the presence of a so far unknown peptide of the Cg family is presumed. In general, our results seem to indicate that the phylogeny of Pst-like and Cg-like peptides is not as "straight" as those which have been demonstrated for several other neurohormonal peptides.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1991

Chromogranins or chromogranin-like proteins are present in lamellar bodies and pulmonary surfactant of rat alveolar type II cells.

Rat alveolar Type II cells were immunostained with antibodies directed against chromogranin A (monoclonal, LK2H10) and chromogranins A and B (polyclonal, LKZM1U). The chromogranins or chromogranin-like proteins were identified in cells in lung tissue sections and isolated Type II cells at the light and electron microscopic levels. We used post-embedding immunoelectron microscopy, with immunogold, to detect the proteins' immunoreactivity in osmicated tissues. Gold particles were distributed over the phospholipid lamellae within the lamellar bodies of alveolar Type II cells and over the lattice structure of tubular myelin. Quantitative analysis of gold labeling densities in the various cell compartments indicated that only the latter two structures were specifically labeled. Controls, which included pre-absorption of both anti-chromogranin antibodies with excess chromogranin A or with native surfactant, resulted in a greater than 60% decrease in gold labeling. A possible role of chromogranins or chromogranin-like proteins as Ca2+ binding proteins in alveolar Type II cells is discussed.

Animals↗
PubMed1991

Prevention of relapse of reflux esophagitis after endoscopic healing: the efficacy and safety of omeprazole compared with ranitidine.

Ninety-eight patients with erosive and/or ulcerative esophagitis unhealed after at least 3 months' treatment with standard doses of cimetidine (greater than or equal to 1200 mg daily) or ranitidine (greater than or equal to 300 mg daily) were primarily included in an acute healing phase study, and 51 were allocated to 40 mg omeprazole once daily and 47 to 300 mg ranitidine twice daily. After 12 weeks of treatment, 46 (90%) patients given omeprazole were healed, compared with 22 (47%) allocated to ranitidine. Healed patients were then given maintenance treatment with either 20 mg omeprazole once daily or 150 mg ranitidine twice daily for 12 months. Plasma gastrin was determined and gastric mucosal biopsy specimens were obtained during the entire study to assess the structure of the exocrine and endocrine cell populations of the oxyntic mucosa. Sixty-seven per cent of the total number of patients randomized to omeprazole were maintained in clinical and endoscopic remission throughout the 12-month study period as compared with only 10% among those given ranitidine (p less than 0.0001). After 4 weeks of omeprazole treatment basal gastrin levels were slightly increased, with a 95% confidence interval for the change of from 8.6 to 16.9 pmol/l. No further increase in basal gastrin levels was observed during the ensuing study months. No significant histopathologic lesion was found in the oxyntic gland mucosa. In conclusion, omeprazole was far superior to ranitidine in preventing recurrence, a goal achieved without adverse events and significant abnormalities in the oxyntic mucosal exocrine or endocrine cells but with a moderate increase in basal gastrin levels.

Adult↗
PubMed1991

Basal and ACTH-stimulated cortisol and aldosterone release from adrenocortical adenomas in vitro.

Basal and ACTH-stimulated release of aldosterone and cortisol was studied in slices of adrenocortical adenomas and adrenal cortex from 16 consecutive patients with Conn's syndrome (n = 7), Cushing's syndrome (n = 5) or no signs of steroid hypersecretion (n = 4). Clinical data were reviewed and histologic examination was repeated. The adrenal cortex and all tumours but one (non-hyperfunctioning) secreted cortisol. Cortisol release increased after addition of ACTH in 13/15 tumours and all cortex slices. Aldosterone was secreted from the adrenal cortex in all patients and was increased by ACTH in 75% of the tissue specimens. Adenomas from patients with hyperaldosteronism showed the highest basal aldosterone secretion. This secretion was further increased by ACTH. Tumours from patients without signs of corticosteroid excess also released steroids and responded to ACTH. It is concluded that in vitro studies of steroids released from adrenocortical tumours contribute to their diagnostic and functional evaluation.

Adenoma↗
PubMed1991

Hypertension in primary hyperparathyroidism in relation to histopathology.

Hypertension in primary hyperparathyroidism (HPT) was previously attributed to hypercalcemia per se or to impaired kidney function. Of 441 consecutive patients operated on for HPT over 24 years, 57% were hypertensive. Preoperative blood pressure remained fairly constant during the study period, despite otherwise markedly changing clinical picture with, latterly, more asymptomatic patients. The preoperative systolic blood pressure (SBP) was significantly correlated to both serum calcium (p less than 0.001) and serum creatinine (p less than 0.05), but not when the influence of age was taken into account in a multiple regression analysis. Other pathogenetic factors in hypertension were therefore probable. When the statistical analysis was adjusted for differences in age and serum calcium, blood pressure was lower in the HPT patients with parathyroid hyperplasia than in those with adenoma (153 +/- 31/90 +/- 14 vs. 163 +/- 29/91 +/- 14 mmHg, p less than 0.01 for SBP). The concept that parathyroid hyperplasia represents a mild (early) form of HPT that may precede adenoma formation is corroborated by our observations, which also indicate that there is no simple cause-and-effect relationship accounting for hypertension in primary HPT.

Adult↗
PubMed1991

DNA ploidy pattern of parathyroid parenchymal cells in renal secondary hyperparathyroidism with relapse.

The nuclei of parathyroid parenchymal cells, analyzed using image cytometry (ICM), in relapsing and non-relapsing secondary hyperparathyroidism due to uremia, showed a DNA-distribution pattern of diploid type. Nevertheless, some differences were observed within the groups, as regards the concept of 'scattered cells' in ICM DNA histograms. The relative incidence of 'scattered cells' was particularly high in the histograms from parathyroid glands with nodular hyperplasia and in those from parathyroid parenchyma grafted into the skeletal musculature. In these two kinds of parathyroid specimens, the 'scattered cells' were both of chief-cell and oxyphil-cell types. In contrast, 'scattered cells' were not so conspicuous when parenchymal cells of glands with diffuse hyperplasia were analyzed. As there is some clinical and histopathological evidence that the cells in both nodular-hyperplastic and autografted parathyroid parenchyma have increased growth potential, it is hypothesized that the relative incidence of the 'scattered cells' in the ICM DNA histograms indicates an increased proliferative activity.

Adult↗
PubMed1991

Distribution of sodium, magnesium, phosphorus, sulphur, chlorine, potassium, calcium and iodine in mammalian thyroid gland.

Anhydrous specimen preparation techniques and X-ray microanalysis were used to study the elemental composition of the rat thyroid follicular cells and colloid in the follicular lumen. Analysis were performed in morphologically defined follicular cells and adjacent colloid. Use of semithin cryosections allowed us to selectively analyze cell nucleus and dense vesicles in the cytoplasm of follicular cells. The analytical results indicate that the basolateral and apical cell membrane of follicular cells act differently in the transport of iodine and other ions, thus creating ionic gradient in the follicular lumen as compared to that found in the follicular cells. High potassium levels were found in the colloid. This finding indicates an active secretion of potassium from the apical plasma membrane into the follicular lumen. High sulphur and calcium levels were also found in the colloid. Dense vesicles found in the cytoplasm of follicular cells varied in size and had different elemental composition.

Animals↗
PubMed1990

Nuclear DNA content and survival in medullary thyroid carcinoma. Swedish Medullary Thyroid Cancer Study Group.

In a nationwide study of medullary thyroid carcinoma, the relation between nuclear DNA content and survival was studied in 211 patients with complete follow-up of up to 27 years. Morphologically identified tumor cells were analyzed by an image cytometric method. The DNA histograms were classified (1) by an objective method in which the degree of aneuploidy was defined as the percentage number of tumor cells with DNA values exceeding the 90th percentile of diploid control cells (P90), and (2) according to a subjective evaluation of whether the DNA profiles represented a euploid or an aneuploid DNA pattern. Both classifications separated groups with marked differences (P less than 0.001) in survival. A multivariate proportional hazards analysis indicated that each method provided additional information when the other one was taken into account. In patients whose tumors were classified according to the objective P90 method 1, the relative hazards (with 95% confidence interval) in the groups with P90 values of 36% to 69% and greater than or equal to 70% were 1.6 (0.9-2.8) and 2.1 (1.1-4.0) respectively, compared with the reference group. With the subjective method 2 the corresponding figure for the group with aneuploid tumors was 1.7 (1.0-2.0) compared with the group with euploid tumors.

Adolescent↗
PubMed1990

Substance P-like immunoreactive neurons in the nervous system of Drosophila.

With an antiserum against substance P a small number of neurons could be resolved in great detail in the nervous system of the fruitfly Drosophila melanogaster. In the brain, 10 substance P-like immunoreactive (SPLI) neurons were individually identified. Two of these form extensive bilateral connections with dorsal and ventral protocerebral neuropil. Another two neurons have cell bodies located ventrally in the subesophageal ganglion and processes throughout subesophageal neuropil. In the thoracico-abdominal ganglia 10 SPLI neurons could be identified. Eight of these have large cell bodies located ventrally in thoracic ganglia and two have small cell bodies located posteriorly in the abdominal ganglia. Six of the 8 thoracic SPLI neurons could be resolved in detail and were found to form: (1) processes in dorsal thoracic and abdominal neuropil as well as processes running through the cervical connective into the subesophageal ganglia; and (2) processes running into the dorsal neural sheath of the thoracic ganglia. The latter processes form an extensive network of varicose terminals over the thoracic ganglia. Our results indicate that a substance P-like neuropeptide can act as a neurohormone released into the circulation from terminals in the neural sheath as well as a neurotransmitter/neuromodulator released by interneurons in the brain.

Animals↗
PubMed1990

Somatostatin analogue and tissue cultures in the study of a human malignant glucagonoma.

A patient with metastasizing glucagonoma producing multiple molecular forms of glucagon is reported. The patient responded to symptomatic treatment with a somatostatin analogue (SMS 201-995). Glucagonoma tumour cells were studied in two tissue culture systems: intraocular transplants of immunosuppressed rats and long-term cell cultures. In both systems, several region-specific glucagon antisera gave a positive immunoreaction with tumour cells indicating synthesis of multiple molecular species. Intraocular tumour transplants released glucagon into the chamber fluid. In animals with unilateral transplants, glucagon was also detected in the contralateral eye chamber, indicating passage from the transplants via unknown mechanisms. Treatment of tumour cells during culture with SMS 201-995 inhibited rapidly the spontaneous release of glucagon without evident cytotoxic effects. The inhibitory effect decreased with time.

Adenoma, Islet Cell↗
PubMed1990

Silver stains for identification of neuroendocrine cells. A study of the chemical background.

The chemical background of silver stains used for visualization and characterization of peripheral neuroendocrine cells in the gastrointestinal tract and pancreas, and of their corresponding tumours, was studied in tissue sections and by a dot-blot technique. Sequential staining of pancreatic islets with an immunohistochemical procedure and silver staining of the same tissue section revealed that chromogranin A immunostained cells also displayed an argyrophil reaction with the Grimelius method, but no argentaffin reaction with the Masson technique. Accordingly, purified chromogranin A (15 micrograms or less) treated in formalin and applied to nitrocellulose did not show any argentaffin reaction but displayed a dose-related argyrophil reaction. Equal quantities of other polypeptide components did not give rise to any silver reaction. Further dot-blot studies showed that the tryptophan and tyrosine metabolites, dopamine, norepinephrine, 5-hydroxytryptamine and 5-hydroxinodole caused strongly argentaffin and argyrophil reactions while epinephrine, 5-hydroxyindole-3-acetic acid and 5-hydroxytryptophan gave only the former reaction. Among other chemical components studied, only guanine displayed weak silver staining. The results indicate that the reaction products between aldehydes and the granular content of biogenic amines synthesized from tryptophan and tyrosine display an argentaffin reaction and that the granular chromogranin A caused an argyrophil but no argentaffin reaction.

Animals↗
PubMed1990

The enterochromaffin cells in the mouse gastrointestinal tract after streptozotocin treatment.

Effects of 5 weeks streptozotocin treatment on the mouse gastrointestinal tract were studied with special emphasis on enterochromaffin (EC) cells. In the streptozotocin-treated animals the frequency of EC cells was reduced in the antral area and in the small intestine, but increased in the colon. The length of the intestinal tract and the mucosal thickness were increased in these animals. Possible mechanisms underlying these abnormalities of the EC cell system are discussed.

Animals↗
PubMed1990

The influence of a histamine2-receptor antagonist on the healing of an experimentally induced gastric mucosal lesion.

The effect of an H2-receptor antagonist (ranitidine) on the healing of gastric mucosal lesions was studied. Mucosal lesions were induced by a standardized thermo-mechanical technique. The healing process was assessed by macro- and light microscopical examination. It was further evaluated by measurements of the tissue contents of hydroxyproline, a chemical compound reflecting collagen, and of DNA and RNA, reflecting cell frequency and protein synthesis respectively, in the gastric wall from both injured and wound-free areas. The healing process was more rapid in ranitidine-treated animals than in controls. After four weeks, however, the lesion in nine out of ten animals had healed in the ranitidine-treated group and seven of nine rats in the control group. At that time the amounts of hydroxyproline, DNA and RNA did not differ between the two groups. These findings may be taken as an indication that the tissue components of the healed lesions were similar in ranitidine-treated rats and in the saline controls, i.e. the different speeds of the healing process did not seem to influence the components of the scar tissue.

Animals↗
PubMed1990

The role of gastric resection in the management of multicentric argyrophil gastric carcinoids.

A patient with pernicious anemia, atrophic non-antral gastritis, hypergastrinemia, and widespread hyperplasia of enterochromaffin-like cells and manifest enterochromaffin-like cell carcinoma was followed up during 39 months, including 15 months after gastric resection. In this case normalization of gastrin levels did not prevent the development of multiple gastric carcinoids in the fundic mucosa, suggesting that factors other than gastrin are of importance in the pathogenesis.

Anemia, Pernicious↗