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Biomedical subjects

L Grimelius

Publications and source records attributed to L Grimelius.

At least 163 records · Page 9Linked to original sources

Neuroendocrine background of the pathology of the islets of Langerhans. A minireview with particular reference to synaptophysin and chromogranin A as neuroendocrine markers and to the ontogeny of argyrophil insulin immunoreactive cells in the rabbit.

As in diseases of other (neuro)endocrine glands, the pathology of the islets of Langerhans comprises both states of hypofunction, notably hypoinsulinism,--diabetes mellitus--and those of hyperfunction, such as hyperinsulinism from either nesidiodysplasia ("nesidioblastosis") or genuine islet-cell neoplasms. The pathogenesis of some characteristic structural lesions of these diseases of the islet parenchymal cells is reviewed against their neuroendocrine background, both phylogenetically and ontogenetically. A preliminary report is given of the appearance of argyrophil insulin cells during the normal foetal development of the islet parenchyma of the rabbit. In addition, the distribution of the newly discovered neuroendocrine markers synaptophysin and chromogranin A has been reviewed immunohistochemically in normal and neoplastic islet parenchyma cells; the insulin cells do not seem to contain chromogranin A.

Animals↗

Synaptophysin. A new marker for pancreatic neuroendocrine tumors.

Synaptophysin (SYP) is a glycoprotein recently isolated from presynaptic vesicles of bovine neurons. Initial studies have demonstrated its presence in neurons in the brain, spinal cord and retina, and in adrenal medullary cells. A subsequent study demonstrated it in pancreatic islet cells and certain neuroendocrine (NE) neoplasms, including several pancreatic islet cell tumors. Based on these preliminary observations, we examined, by immunohistochemistry, conventionally fixed, paraffin sections of 57 pancreatic endocrine tumors with a monoclonal antibody to SYP. Furthermore, we compared the SYP immunoreactivity of 30 of these same tumors with that of neuron-specific enolase (NSE) and of chromogranin (CG). SYP was demonstrated in all but one of the 57 tumors. In the comparative study, for which material was available in only 30 cases, SYP and NSE were present in 29 of the tumors, whereas CG was seen in only 15 cases. We conclude that SYP is a highly sensitive and useful marker for pancreatic NE neoplasms. Moreover, in view of the increasingly evident limited specificity of NSE, SYP should be considered the marker of choice for pancreatic NE neoplasms.

Adenoma, Islet Cell↗

Histologic parathyroid abnormalities in an autopsy series.

The parathyroid glands from 422 subjects without clinical, biochemical, or advanced histologic signs of renal disease were dissected at autopsy. The glands were evaluated histologically in relation to the subjects' age, sex, histologic renal features, other diseases, and medical therapy. Normal parathyroid glands generally had diffuse cellular arrangements, with variable fat cell content. Increased nodularity was observed, especially in enlarged parathyroid glands. Hyperplasia was present in 7 per cent and adenomas in 2.4 per cent. Hyperplastic glands were often nodular and asymmetric, and numbers of oxyphil cells were frequently increased. Some large nodules were histologically indistinguishable from adenomas. Serum calcium levels were elevated in subjects with adenomas or with hyperplastic glands containing large nodules. The findings seem to indicate that nodularity of the parathyroid tissue is a sign of abnormality and that adenomas may arise from such nodular hyperplasia. Hyperplasia and adenomas were more common in elderly subjects and in those with slight or moderate nephrosclerosis. Other diseases or medical therapy were not found to be correlated with parathyroid weight or histologic features.

Adolescent↗

Identification and characterization of enterochromaffin cells with different staining techniques.

The staining characteristics of the enterochromaffin cell system in the human and rat gastrointestinal tract were studied with 3 histochemical procedures--the Masson method, formaldehyde-induced fluorescence (FIF), and immunocytochemical techniques using both monoclonal and polyclonal serotonin antisera. A simple modification of the Masson technique is described and compared with several other modifications of the same technique. The specificities of the 2 antisera were examined with regard to serotonin and other monoamines and their albumin conjugates, monoamine precursors and metabolites, and also to serotonin-related substances. In the intestine, with very few exceptions the same cells reacted positively with the 3 staining methods, but often serotonin immunoreactivity was observed in larger cytoplasmic areas than the other 2 staining reactions. In the antral mucosa, a cell population with the same staining characteristics as mentioned above was seen, but 2 further cell populations were identified--one displaying FIF-argentaffin reactions but no serotonin immunoreactivity, and the other showing the opposite characteristics. At immunostaining, a discrepancy in the staining results between the 2 antisera was noted--a larger number of antral serotonin immunoreactive cells being demonstrated with the polyclonal than with the monoclonal antiserum; this discrepancy disappeared when the polyclonal antiserum was pretreated with C-terminal tetragastrin. A minor discrepancy in the number of stained cells was still observed between the use of immunostaining with monoclonal or with tetragastrin-pretreated polyclonal antiserum, and the use of the FIF-argentaffin reactions. The reason for this discrepancy is unclear.

Animals↗

Peptide-hormone- and serotonin-immunoreactive cells in normal and hyperplastic prostate glands.

Peptide-hormone- and serotonin-immunoreactive cells of endocrine type are present both in the normal prostatic gland and in the nodules of benign prostatic hyperplasia of man. They are located in the epithelium of the acini and the ducts of all the different parts of the gland, as well as in the urothelium of the prostatic part of the mucosa of the urethra. The endocrine cells are usually argyrophil, sometimes even argentaffin, and immunoreactive with neuron-specific enolase; they can be either of open or of closed type and usually occur widely scattered as single cells. Three kinds of endocrine cells were observed both in the normal gland and in the hyperplastic parenchyma. In the by far most prevalent type serotonin was found to co-exist with a peptide immunohistochemically related to the thyroid stimulating hormone (TSH). In a more rare type serotonin co-existed immunohistochemically with calcitonin. The third kind of endocrine cells was somatostatin-immunoreactive cells; they were also rather rare. The only difference observed between the normal and hyperplastic parenchyma was an increase in the number of all the three kinds of endocrine cells in the hyperplastic nodules. The endocrine cells could easily be visualized by means of silver-staining techniques, even using conventionally formalin-fixed, paraffin-embedded specimens.

Adult↗

Alteration in density, morphology and parathyroid hormone release of dispersed parathyroid cells from patients with hyperparathyroidism.

Dispersed parathyroid cells from normal human and bovine glands and from 10 patients with primary (7 adenomas, 3 hyperplasias) and 4 patients with uraemic hyperparathyroidism (HPT) have been investigated with respect to density, morphology and parathyroid hormone (PTH) release. Percoll density gradients enabled an efficient isolation of viable parathyroid cells which generally banded between 1.035-1.090 g/ml. The average density was significantly higher in cells from the normal than the abnormal glands. The pathological glands contained large chief cells, oxyphil and transitional oxyphil cells and, in one case, water-clear cells which were enriched in fractions with densities below 1.055 g/ml. Measurements of cell diameters revealed an increased proportion of enlarged cells in the preparation of abnormal glands. Nuclear diameters were similar in the normal human glands, adenomas and hyperplasias, but the variability was greater among the adenomas. In comparison to normal bovine parathyroid cells, PTH release of cells from the pathological human glands was reduced and abnormally insensitive to extracellular calcium. The oxyphil and water-clear cells secreted similar amounts of PTH as the chief cells of the abnormal glands. The disturbed PTH release in secondary HPT seemed to be confined mainly to cells within nodules of the hyperplastic glands. The results show that the disturbed hormone regulation in HPT is related to morphological changes of the cells and that buoyant density gradients can be used to accumulate the abnormal cells.

Adenoma↗

Fine needle biopsy and scintigram in the preoperative diagnosis of thyroid lesions.

Fine needle biopsies (FNB) of the thyroid were examined from 860 patients. In 703 cases follicular cells without atypia were found and in this group of patients the clinical diagnosis was nodular goitre. Operations were performed in 138 patients and in 97 cases the cytological finding could be correlated to the histopathological diagnosis. In 33 of these patients thyroid carcinoma was histologically verified. In 26 of the carcinoma cases cytologic examination showed grave atypia or changes indicating carcinoma. The cases in which the cytological diagnoses were falsely negative are discussed. Moderate cellular atypia occurred in one case with papillary carcinoma. In two cases the cytological examination gave a false positive diagnosis of cancer, both representing thyroiditis of the lymphoid type. The scintigrams in patients with thyroid carcinoma are also presented. Cold nodules were found in 10/19 patients and a hot nodule in .1 patient. In 3 patients the scintigrams were normal and in another 5 inconclusive. The results indicate that thyroid scintigrams can only be used as a supplement to the physical examination and a guidance for FNB. The contribution of FNB in the decision to operate is discussed and it is concluded that FNB is a valuable adjunct in preoperative diagnosis of thyroid lesions. The best diagnostic results are obtained when there is a close cooperation between clinician, radiologist, cytologist and pathologist.

Adult↗

Late results of operation for primary hyperparathyroidism in 441 patients.

The late results of operation for primary hyperparathyroidism (HPT) were analyzed in 441 patients operated on 4 to 27 years earlier (mean follow-up time, 7.7 years). A conservative surgical approach was mainly used, attempting if possible to visualize all four parathyroid glands and extirpate only the enlarged glands. Subtotal resection was performed in patients with hyperplasia. The histopathologic diagnosis was adenoma in 77% and hyperplasia in 18%. In 5% of the patients, the histopathologic classification was uncertain. Hypercalcemia persisted after operation in 8% of all patients. This generally occurred because of an incomplete neck exploration or too limited a resection in the patients with hyperplasia. Recurrent hypercalcemia occurred in 16% of the patients operated on for hyperplasia and was noted 1 to 19 years after surgery. Recurrences were also seen in 3% of the patients with adenomas but not earlier than 9 years after the operation. These findings suggest that primary HPT may even in patients with adenomatous disease, sometimes affect all parathyroid glands. Nevertheless, it was obvious that most of the patients with adenomas would not have benefited from a more radical procedure. On the other hand, it was evidently important to obtain a correct histopathologic diagnosis intraoperatively so that patients with hyperplasia could be identified and adequatley treated.

Adenoma↗

The immunogold-silver staining method. A powerful tool in histopathology.

Immunostaining of routinely fixed, wax embedded tissues may present problems to the pathologist since destruction of antigens can lead to false negative results. In an attempt to overcome this problem, we have compared the results of the standard peroxidase anti-peroxidase (PAP) method with those obtained using the newly developed and very sensitive immunogold-silver staining (IGSS) method. Sections from routine histopathological material as well as from normal tissue specimens were used in the comparison. Antisera to a variety of antigens commonly employed in pathology were used, including regulatory peptides and a range of other markers. In all cases the IGSS method was found to give superior or at least equal results to those obtained with the PAP technique. In some cases staining was obtained with IGSS method when the PAP technique gave no result. The intense black reaction product allowed much easier and more rapid screening of immunostained preparations as well as permitting sections to be counterstained with routine histological stains such as haematoxylin and eosin. It is therefore suggested that immunogold-silver staining is a valuable technique for the pathologist, particularly when examining overfixed or badly processed tissues.

Animals↗

The effect of truncal vagotomy on serotonin distribution in the rat gastrointestinal tract.

The 5-HT levels in biopsies from the rat gastrointestinal tract were measured by a sensitive liquid chromatography method with electrochemical detection. The highest levels were found in the gastroduodenal and cecal regions. Sham-operated controls were compared with rats subjected to combined truncal vagotomy and pyloroplasty or pyloroplasty alone 5 weeks after surgery. Significantly decreased 5-HT levels were demonstrated in animals subjected to vagotomy + pyloroplasty or to pyloroplasty alone, compared with sham-operated controls. In the upper gastrointestinal tract of vagotomized animals significantly decreased 5-HT levels were found when compared with animals subjected to pyloroplasty alone. However, anesthesia and surgery (sham operation) per se markedly increased 5-HT levels of the gut even 5 weeks postoperatively, when compared with acutely killed rats. The underlying mechanism is still obscure. However, vagotomy largely prevented this increase. Therefore, the importance of correct controls is emphasized, since previous investigations claim to have demonstrated increased 5-HT levels in vagotomized animals, when compared with nonoperated controls.

Animals↗

Phylogenetical aspects on islet hormone families: a minireview with particular reference to insulin as a growth factor and to the phylogeny of PYY and NPY immunoreactive cells and nerves in the endocrine and exocrine pancreas.

A common feature in the phylogeny of the four islet hormones (insulin, somatostatin, glucagon, PP) is that they do not seem to occur in the most primitive metazoan animals investigated so far, namely the coelenterates. However, already in the earliest protostomian invertebrates, such as flatworms and annelids, somatostatin and PP immunoreactive nerve fibres were found. In highly developed forms of protostomian invertebrates, such as insects, all the four islet hormones are represented as immunoreactive nerve cells and nerve fibres in the brain. In deuterostomian invertebrates a brain-gut-axis has evolved as regards somatostatin and PP, whereas insulin and glucagon now seem to occur exclusively as cells of open type in the gut mucosa. This brain-gut-axis for somatostatin and PP persists in all the vertebrates. The insulin cells, however, leave the gut mucosa already in the earliest forms of vertebrates and then appear only as cells in the islet parenchyma and in the mucosa of the bile duct (Agnatha) or in the pancreatic ducts (Gnathostomi). To some extent, glucagon islet cells evolve in a similar manner; here, however, cells immunoreactive with the precursor hormone, glicentin (enteroglucagon), persist in the gastrointestinal tract mucosa. A few PYY immunoreactive cells have been found in the pancreatic islet parenchyma of reptiles and mammals, often as disseminated cells in the acinar tissue. In the pancreas of these phyla NPY only occurs in neurons and nerve fibres. In pilot studies the effects of hagfish insulin as a growth factor have been compared with those of pig insulin on Swiss 3T3 mouse embryonic fibroblasts.

Animals↗

The structure and hormone content of the endocrine pancreas of the one-humped camel (Camelus dromedarius).

Little is known of the blood sugar regulation in the camel and the morphology and function of its endocrine pancreas. The present paper describes the light microscopic structure and hormone content of the endocrine pancreas of the one-humped camel. Staining of pancreatic sections with haematoxylin-eosin or aldehyde-fuchsin showed numerous islets evenly distributed in all parts of the pancreas. Immunocytochemical staining for insulin or glucagon indicated that islets were predominantly composed of centrally located B-cells, surrounded by a peripheral rim of A-cells. Corresponding stainings for somatostatin or pancreatic polypeptide (PP) demonstrated that D-cells comprised only a small part of the islet volume while PP-cells were common both within and outside the islets. There were no obvious differences between the frequency of the various islet cells in different pancreatic regions. The pancreatic hormone concentrations roughly corresponded to the frequency of the different islet cell types. Insulin appeared most abundant followed by glucagon, PP and somatostatin in decreasing order. The concentrations of each of the hormones were similar in different regions of the gland. It is concluded that the endocrine pancreas of the one-humped camel is dispersed into islets of the same size and cellular composition as has been described in many other mammalian species.

Animals↗

The potential of the immunogold-silver staining method for paraffin sections.

The immunogold-silver staining technique is shown to be of great value in the detection of regulatory peptide-containing nerves and endocrine cells in routinely fixed, paraffin-wax-embedded tissues. The method appears to be better for this system than peroxidase anti-peroxidase (PAP) which can yield poor or variable results. Antibodies to regulatory peptides, including calcitonin gene-related peptide (CGRP), substance P, neuropeptide tyrosine (NPY), glucagon, pancratic polypeptide, and somatostatin 14 and 28, as well as to neurofilaments, neuron-specific enolase (NSE) and S-100, were used on sections of a variety of tissues from rat and pig including respiratory tract, skin, gut, pancreas, vagina, uterus, fallopian tube and kidney. In all cases, stronger immunostaining of nerves was obtained with the immunogold-silver technique than with PAP. The inherent density of the staining was also found to improve the visibility of endocrine cells in the section, and to permit the use of routine histological stains for counterstaining. As immunogold-silver staining is sensitive, rapid, cheap and avoids hazardous reagents, we feel it has great potential for the immunostaining of nerves and endocrine cells that contain regulatory peptides in routinely fixed and embedded tissues and may prove useful in pathology.

Animals↗

Histological changes in parathyroid glands in subclinical and clinical renal disease. An autopsy investigation.

In an autopsy material of patients with varying degrees of renal impairment, the parathyroid glands were examined regarding glandular and parenchymal cell weights and cellular types and arrangement. The findings were related to the different stages of renal disease. The study comprised 69 cases--29 females and 40 males. Their mean age was 74 years (range 33-98 years). There was a positive relation between serum creatinine level and total parathyroid parenchymal cell weight (r=0.37, p less than 0.01) and an inverse correlation between kidney weights and parathyroid parenchymal cell weight (r=-0.24, p less than 0.05). The patients with the most advanced renal impairment had significantly higher mean total glandular and mean total parenchymal weights than those with less pronounced renal disease. Nodular arrangement and an increased number of oxyphil and transitional oxyphil cells were noted in cases with advanced histological kidney changes but normal serum creatinine levels. This nodularity as well as the frequency of oxyphil cells increased in parallel with deterioration of renal function. The two most important factors that influenced the proportion of oxyphil cells were the parenchymal cell weights and the age of the patient. It is concluded that signs of stimulation of the parathyroids are present already in early stages of renal disease, in some cases before renal dysfunction is clinically manifested.

Adipose Tissue↗