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Biomedical subjects

L Grimelius

Publications and source records attributed to L Grimelius.

At least 127 records · Page 7Linked to original sources
PubMed1990

Adrenocortical carcinoma. A retrospective study of a rare tumor with a poor prognosis.

A retrospective study was performed on 54 patients diagnosed as having adrenocortical carcinoma during 1974-1983. The initial symptoms were often diffuse: abdominal pain, weight loss, or fever, and more than 60% of the patients showed no evidence of overproduction of hormone. The median tumor diameter was 13 cm and almost half of the tumors had metastasized at diagnosis. A radical tumor resection could be performed in less than 50% of the patients, and at histopathological re-examination some tumors were not conclusively verified as malignant. Capsular invasion, nuclear pleomorphism and mitoses were found more commonly in patients who succumbed to the disease. Seven of 29 patients treated with chemotherapy showed an objective response and two of them are still alive and free of disease. The overall 5-year-survival rate was 19%, compared with 45% for patients with radically resected tumors. Patients with no biochemical signs of overproduction of adrenocortical hormone appeared to have a better prognosis than those with hormone excess. Together with increased use of ultrasound and computed tomography, a urinary steroid profile might hopefully contribute to earlier discovery of these often clinically silent tumors. However, it remains to be determined whether these diagnostic improvements, together with more aggressive surgery and adrenolytic chemotherapy, can improve the poor prognosis.

Adolescent↗
PubMed1989

Chromosome studies in thyroid neoplasia.

Cytogenetic studies in thyroid neoplasia were performed by G-banding of chromosome preparations obtained from the in vitro cultures of nine adenomas, one follicular carcinoma, five papillary carcinomas, and two medullary carcinomas. Complex structural chromosome aberrations were found in one adenoma. Two more adenomas, both composed of Hürthle cells, showed multiple numerical chromosome deviations with trisomy 4 and tetrasomy 7 in common. Six metastasizing carcinomas were characterized by normal stemlines, which indicates that malignancy in thyroid neoplasia cannot be excluded by cytogenetic techniques used currently. Comparisons between cytogenetic findings and cytophotometric DNA measurements in the material studied illustrate that euploid tumors represent a heterogenous group including cases with various gross structural chromosome aberrations of yet unknown clinical significance. Further studies of additional material with long-term follow-up are called for by our findings of structural and numerical chromosome aberrations in follicular neoplasms that are benign according to histologic criteria.

Adenoma↗
PubMed1989

Histopathologic characteristics and nuclear DNA content as prognostic factors in medullary thyroid carcinoma. A nationwide study in Sweden. The Swedish MTC Study Group.

Complete follow-up for 4 to 27 years was achieved for virtually all 249 patients with medullary thyroid carcinoma (MTC) diagnosed in Sweden in a 23-year period. Tumor specimens from 241 patients were re-examined with regard to calcitonin immunoreactivity, amyloid content, argyrophil reaction, tumor capsule condition, and nuclear DNA content. In univariate analyses, these factors, with the exception of the argyrophil reaction, were strong predictors of survival. There were twofold-to-threefold differences in hazard rate between patients with a high (greater than 50%) and low (less than 10%) frequency of calcitonin-immunoreactive tumor cells, between those with amyloid-containing and amyloid-free tumors, and between those with an intact and a nonintact tumor capsule. Calcitonin immunoreactivity and the amyloid content also provided prognostic information in multivariate analyses that adjusted for all the other factors mentioned above and in the full multivariate model, which in addition considered age, sex, heredity, stage of the disease, tumor size, and treatment. The strong prognostic capacity of the nuclear DNA content found in univariate analyses became considerably weaker when other morphologic characteristics were considered.

Adult↗
PubMed1989

Expression of tachykinins by ileal and lung carcinoid tumors assessed by combined in situ hybridization, immunocytochemistry, and radioimmunoassay.

Mid-gut carcinoid tumors have been shown to produce substance P, a tachykinin. A recent addition to this family of peptides is neurokinin A which is cleaved from the same precursor as substance P; beta-pre-pro-tachykinin. The authors have examined mid-gut and pulmonary carcinoid tumors for the presence of the two tachykinins, using immunocytochemical study and radioimmunoassay, and have applied the techniques of in situ hybridization and Northern blot analysis to investigate the expression of mRNA for beta-pre-pro-tachykinin. All gut tumors (n = 8) and three of the six lung tumors examined were found by immunocytochemical study to contain both tachykinins or neurokinin A alone. Chromatographic analysis of tumor extracts suggests that this peptide is being detected as a separate molecule and/or as the C-terminal portion of a larger, uncleaved form. Three of the cases positive for tachykinins showed no detectable serotonin immunoreactivity. Strong hybridization signals for beta-pre-pro-tachykinin mRNA were seen in all but one of the cases studied which contained tachykinin immunoreactivity. Intact mRNA and positive hybridization was found by Northern blot analysis in two mid-gut tumors. Concentrations of tachykinins were found by radioimmunoassay to be higher in mid-gut tumors (substance P 27.2 +/- 19.7 pmol/g; neurokinin A 31.8 +/- 24.2 pmol/g; mean +/- SEM, n = 5) than in lung cases (substance P mean 0.8, range 0.5-1.0 pmol/g; neurokinin A mean 11.0, range 10.0-12.0 pmol/g; n = 3). These results show that mid-gut and pulmonary carcinoid tumors produce tachykinins, which are detected, in some cases, where no serotonin immunoreactivity can be found, possibly because of a high rate of amine secretion. Screening for tachykinins may prove to be a useful diagnostic adjunct for these tumors.

Blotting, Northern↗
PubMed1989

Insulin and C-peptide co-localization in the beta granules of normal human pancreas and insulinomas. A quantitative immunocytochemical approach.

It has been shown, by using the immunogold technique, that C-peptide and insulin are co-localized in the mature granules of human pancreatic beta cells and insulinomas with typical granules. The mean gold bead densities of both C-peptide and insulin were at least twice as high in the normal pancreas when compared with the insulinomas. The mean granule diameter of the insulinoma cells (D = 0.30 +/- 0.12 micron) was smaller than that of human pancreatic cells (D = 0.45 +/- 0.15 micron). The morphometric data indicate that each of the antigens (C-peptide and insulin) is distributed similarly in the halos and the dense cores of the beta granules. Thus, no topological segregation of these two antigens occurs within the beta granules of either normal human pancreas or insulinomas.

Adenoma, Islet Cell↗
PubMed1989

The course of neuroendocrine differentiation in prostatic carcinomas. An immunohistochemical study testing chromogranin A as an "endocrine marker".

To gain further insight into the pathogenetic aspects of neuroendocrine (NE) differentiation in prostatic carcinoma, the incidence of NE manifestations was studied during tumour progression in the course of the disease. This follow-up took the form of semiquantitative assessment of the NE cells in carcinomas by means of repeat biopsies at intervals of a few years, correlating the findings with those of conventional histopathological grading of the prostatic tumours. Immunoreactivity to chromogranin A (ChrA) and the Grimelius silver-staining technique were used to detect NE cells. A strong correlation was observed in all the 25 carcinomas studied between the results obtained with the Gimelius silver-staining and those obtained on the basis of immunoreactivity to ChrA. In addition, cells immunoreactive to an antiserum against ChrA found in virtually all sections from 24 cases of hyperplastic prostatic glands were found to be almost invariably argyrophil. Most of the 25 carcinomas underwent marked tumour progression, while the number of NE cells concomitantly increased. An unequivocal relationship can be stated between the degree of NE differentiation and tumour progression in our series of prostatic carcinomas treated with steroids-i.e., the more anaplastic the prostatic carcinoma, the more numerous are its NE cells. ChrA may be considered to be a sensitive marker for NE cells both in hyperplasia and in prostatic carcinomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Oral E2 prostaglandins affect endocrine cell populations in the gastric antrum of the rat.

The aim of the present study was to investigate antral endocrine cell populations and tissue and circulating hormone levels following a 4-week oral regimen with prostaglandin E2 (25, 250 and 5000 micrograms/kg-1 b.i.d.) or a stable methyl analogue (5 and 50 micrograms kg-1 b.i.d.). Epithelial hyperplasia of the gastric antrum was observed with the highest dose of prostaglandin E2 and both doses of the analogue, as evaluated by stereological methods and conventional cell count. The treatments significantly affected the endocrine cell population. Somatostatin-immunoreactive cells were increased in proportion to the increased epithelial cellularity and plasma levels of somatostatin were increased in parallel. The tissue content of somatostatin-like immunoreactivity differed according to the extraction procedure used, and was significantly higher than controls in specimens extracted in neutral water. In the neutral extracts an immunoreactive somatostatin of unidentified molecular structure dominated quantitatively over somatostatin 14 and 28, which were the major components in acetic acid extracts. The serotonin-immunoreactive cell population was also significantly increased by natural prostaglandin E2 and the analogue but the gastrin cell population was not significantly affected by treatments. Accordingly, no significant changes were observed in tissue or plasma gastrin levels. It is concluded that the epithelial hyperplasia of the antral epithelia produced by E2 prostaglandins is associated with selective changes of endocrine cell populations. The changes were proportional to the increases of epithelial cellularity and required quantitative determination of the total antral volume to be detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1989

Association of Campylobacter pylori with induced expression of class II transplantation antigens on gastric epithelial cells.

Campylobacter pylori was identified with immunoperoxidase staining and a mouse monoclonal antibody directed against C. pylori in gastric biopsy specimens from 24 patients with gastritis. C. pylori was not found in gastric biopsy specimens from six subjects with histologically normal mucosa. The monoclonal antibody, which was reactive with a surface protein of approximately 20 kilodaltons, was found to be specific for C. pylori, and the immunoperoxidase staining proved to be more sensitive and rapid than culture in detecting the organism. In the tissue specimens where C. pylori was detected with the monoclonal antibody, there was a strong expression of class II transplantation antigens on the epithelial cells and an increased number of T lymphocytes. These findings indicate that C. pylori may initiate local immune responses.

Antibodies, Monoclonal↗
PubMed1989

Transthyretin immunoreactivity in human and porcine liver, choroid plexus, and pancreatic islets.

We examined transthyretin immunoreactivity (TTR-IR) in human and porcine liver, choroid plexus, and pancreatic islets with both polyclonal and monoclonal antibodies to TTR. The specificity of the immunoreactions and the effects of various fixatives were tested in immunohistochemical and dot-blot systems. B-5 fixative (mercuric chloride and sodium acetate in formalin) was the best immunopreservative. In both species, the TTR-IR in choroid plexus epithelial cells was strong and was much greater than that in hepatocytes. Glucagon cells in pancreatic islets were also strongly TTR immunoreactive. Insulin cells were slightly TTR immunoreactive in human but strongly so in porcine pancreas. The finding of TTR-IR in normal islets explains the presence of TTR-IR in human endocrine pancreatic tumors, notably glucagonomas and malignant insulinomas.

Animals↗
PubMed1989

Serum calcitonin levels in anesthetized rats.

In order to determine whether a short period of general anesthesia influences the levels of serum calcitonin (CTs) and whole blood ionized Ca2+ and pH, 10 rats were sequentially anesthetized at 5-day intervals by halothane, ether, or CO2/O2, respectively, and retroorbital blood samples were collected during anesthesia. We noticed significant differences of serum calcitonin but the role of the anesthetics remains unclear, since other factors also could have accounted for the observed variations. Blood pH was strongly decreased by CO2/O2. Whole blood ionized calcium exhibited marked changes, but no correlation was found between whole blood ionized calcium and serum calcitonin.

Anesthesia, Inhalation↗
PubMed1989

DNA evaluation in growth hormone producing pituitary adenomas: flow cytometry versus single cell analysis.

DNA patterns were analysed in 26 GH-producing pituitary adenomas by flow cytometry as well as by microspectrophotometry. Twelve tumours (46%) were diploid according to both methods, whereas 5 tumours (19%) showed aneuploid DNA patterns. Nine tumours were classified differently by the two methods: flow cytometry resulted in diploidy in 2 and aneuploidy in 7 patients, whereas microspectrophotometry showed diploidy in 5 tumours, tetraploidy in 3 and aneuploidy in 1. Methodological limitations may explain the discrepancy in the results obtained by the two methods. However, both the flow cytometry and the microspectrophotometry method show the presence of aneuploid DNA patterns in GH-producing pituitary adenomas despite their benign growth characteristics and the clinically benign course of the disease. This comparative study with two methods measuring DNA content, shows that depending on the criteria used for diploidy-aneuploidy, the frequency of aneuploidy will vary. In this material of 26 GH-producing adenomas, 46% were aneuploid according to flow cytometry and 23% according to microspectrophotometric. However, no correlation to tumour size or GH levels was found with either method when patients with aneuploid and diploid tumours were compared. Therefore, no clinical significance can so far be drawn from these results.

Acromegaly↗
PubMed1989

Transthyretin in endocrine pancreatic tumors.

The occurrence of transthyretin (TTR) in 25 endocrine pancreatic tumors was investigated by immunohistochemical methods using both polyclonal and monoclonal antibodies. All malignant insulinomas were strongly TTR immunoreactive, more so than their benign counterparts, which in some cases were TTR negative. All glucagonomas and nonfunctioning tumors were TTR immunoreactive, whereas gastrinomas and VIPomas were TTR negative. TTR, chromogranin A, and the argyrophil reaction (Grimelius' silver technique) had similar distributions among the cells in many, but not all, tumors. Coexistence of TTR with glucagon, insulin, or pancreatic polypeptide in tumor cells was demonstrated. TTR was also quantitated in preoperative serum samples by electroimmuno assay in some cases. Although one patient with a glucagonoma had a markedly increased serum TTR level, five other patients with endocrine tumors, including two patients with glucagonoma, had TTR levels in serum that were within or below the reference range.

Adenoma, Islet Cell↗
PubMed1989

ABO blood group antigens in parathyroid adenoma and hyperplasia.

Immunohistochemical determination of ABO blood group antigens was performed on parathyroid tissue to see if the presence or absence of such antigens could be used as an aid to distinguish adenoma from hyperplasia in primary hyperparathyroidism. Material from nine cases of solitary adenoma and seven cases of hyperplasia fixed in formalin and embedded in paraffin was studied using monoclonal antibodies and avidin-biotin-peroxidase complex technique. The two categories of tissue did not show any consistent differences in the extent or intensity of immunoreactivity, and the method tested did not permit distinction between adenomatous and hyperplastic disease of the parathyroid glands.

ABO Blood-Group System↗
PubMed1989

Nuclear DNA measurements in follicular thyroid adenomas.

The nuclear DNA content was measured retrospectively in histologically confirmed follicular adenomas in 20 patients, and prospectively in 25 patients. In the retrospective group two of the adenomas, and in the prospective group three of the adenomas were classified as atypical due to high cellularity and nuclear atypia, but with no sign of micro-invasive growth. In the group of patients studied retrospectively, the two patients with atypical adenoma had an aneuploid DNA pattern. One of these died 11 years after diagnosis with generalized disease. The other patient in this group with an aneuploid atypical adenoma is alive, as are all the remaining 18 patients with diploid adenomas. In the prospective group there were five aneuploid tumours. The atypical adenomas were aneuploid in two cases and polyploid in one case. No patient in the prospective group has shown any evidence of recurrence so far. Although DNA measurements are of value in distinguishing between low and high malignant potential in invasive tumors, the prognostic information if no invasion is found is uncertain. The importance of examining an adequate number of tissue blocks from the capsular region is emphasized.

Adenoma↗
PubMed1989

Parathyroid histology and cytology with monoclonal antibodies recognizing a calcium sensor of parathyroid cells.

Two monoclonal antibodies reacting with surface structures on exclusively parathyroid cells and proximal kidney tubule cells were evaluated in the microscopic diagnosis of parathyroid disease. Immunostained cryosections of adenomatous and hyperplastic parathyroid glands from 30 hypercalcemic patients with primary or uremic hyperparathroidism (HPT) showed a reduced and heterogeneous staining with the antibodies. This contrasted with the intense and even staining of normal and suppressed human parathyroid glands, as well as lymph node metastases of parathyroid carcinoma. Fine-needle aspiration biopsies and imprints of the parathyroid glands showed a conspicuous antibody staining that enabled the identification of parathyroid cells. The antibodies seem to provide new means for histologic and cytologic identification of normal and pathologic parathyroid tissue, in conjunction with their highly restricted tissue reactivity. Because one of the antibodies interacts with a surface receptor mechanism of the parathyroid cells that is involved in the sensing and gating of calcium and, thereby, also with the regulation of parathyroid hormone release, the unequivocal demonstration of reduced staining of the adenomatous and hyperplastic parathyroid tissue suggests that HPT is associated with reduced expression of the calcium sensoring mechanism of the pathologic parathyroid tissue.

Adenoma↗
PubMed1988

Structural characterization of a high-molecular-mass form of calcitonin [procalcitonin-(60-116)-peptide] and its corresponding N-terminal flanking peptide [procalcitonin-(1-57)-peptide] in a human medullary thyroid carcinoma.

Four peptides derived from procalcitonin were isolated in high yield from an extract of a human medullary thyroid carcinoma. The peptides were identified as procalcitonin-(1-57)-peptide, procalcitonin-(60-91)-peptide (calcitonin), procalcitonin-(60-116)-peptide and procalcitonin-(96-116)-peptide (katacalcin). Determination of the amino acid sequence of procalcitonin-(1-57)-peptide has demonstrated that the Ala25-Ala26 bond in preprocalcitonin is the site of cleavage of the signal peptide. Procalcitonin-(60-116)-peptide represents calcitonin extended from its C-terminus by the sequence Gly-Lys-Lys-Arg-katacalcin, and its formation is indicative of an aberrant pathway of procalcitonin processing in the tumour cells.

Amino Acids↗
PubMed1988

Molecular forms of katacalcin, calcitonin gene-related peptide and gastrin-releasing peptide, in a human medullary thyroid carcinoma.

Peptides synthesized by a human medullary thyroid carcinoma were purified to homogeneity by reverse-phase high performance liquid chromatography and structurally characterized by determination of amino acid composition, amino acid sequence, and fast atom bombardment mass spectra. The katacalcin-related material in the tumor extract was heterogeneous. Katacalcin (1-21) represented the predominant molecular form but metabolites, identified as katacalcin (1-20), (1-19), (1-15) and (1-13), were also identified in high concentration. Calcitonin gene-related peptide-I was isolated from the tumor but calcitonin gene-related peptide-II was absent. A minor component of calcitonin gene-related peptide-like immunoreactivity was of higher molecular weight and may represent an incompletely processed form of the prohormone. Gastrin-releasing peptide (1-27) and gastrin-releasing peptide (18-27) (neuromedin C) were isolated from the tumor but gastrin-releasing peptide (14-27) and bombesin were absent.

Adult↗