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Biomedical subjects

R Holm

Publications and source records attributed to R Holm.

At least 109 records · Page 6Linked to original sources

Carcinoembryonic antigen in medullary thyroid carcinoma: an immunohistochemical study applying six novel monoclonal antibodies.

Six novel mouse monoclonal antibodies raised against carcinoembryonic antigen (CEA) were used to study 22 medullary, ten papillary, ten follicular, and eight anaplastic thyroid carcinomas. The antibodies CEA 12-140-5, -7, and -10 reacted with the same epitope group (GOLD 4), whereas antibodies CEA 12-140-1, -2, and -4 recognized different epitopes (GOLD 5, 2 and 1, respectively) on the CEA molecule. All medullary carcinomas of the thyroid (MCTs) were stained when the antibodies CEA 12-140-5, -7, and -10 were applied, whereas CEA 12-140-1 stained all but five MCTs; CEA 12-140-2 and CEA-12-140 -4 each stained all but two. The CEA immunoreactivity was predominantly located diffusely in the cytoplasm but occasionally was also concentrated along the cell membrane. CEA immunoreactivity was also observed in normal C-cells and C-cell nodules. The follicular, papillary, and anaplastic carcinomas were all CEA-negative with the monoclonal antibodies applied in this study. The differences in staining pattern of MCTs found with the various antibodies may be explained as a lack of expression of some epitopes in some tumors, or they may be due to a varying degree of masking of the epitopes by the extensive glycosylation of CEA and CEA-like substances.

Adolescent↗

Acute psychotic disorders treated with 5% zuclopenthixol acetate in 'Viscoleo' ('Cisordinol-Acutard'), a global assessment of the clinical effect: an open multi-centre study.

In an open clinical multi-centre trial carried out in five Danish psychiatric departments, patients suffering from acute psychosis including mania or exacerbation of chronic psychosis were given injections of 5% zuclopenthixol acetate in 'Viscoleo'. The object of the trial was to evaluate the treatment by means of a global assessment of the severity of the psychosis, the therapeutic effect and the side-effects. The results showed that the treatment was rapidly effective in reducing the severity of psychotic symptoms combined with an advantageous unspecific sedation. The side-effect profile was similar to that after other neuroleptics. Special attention should be paid, however, to a possible occurrence of acute dystonia which was observed particularly in young men with acute psychosis.

Acute Disease↗

Mixed growth hormone- and prolactin cell adenomas of the pituitary gland. An immunoelectron microscopic study.

The morphological features of seven pituitary adenomas producing both growth hormone (GH) and prolactin (PRL) are reported. Up to five different cell types within the same tumour were observed by applying single and double immunoelectron microscopical staining methods. Despite the occurrence of some mammosomatotropic cells in three of the seven cases all fit into the group of mixed GH- and PRL cell adenomas. The mammosomatotropic cells in two cases were found to express GH and PRL in the same and different granules whereas in the third case the hormones were packed only in different granules.

Adenoma↗

Neuroendocrine differentiation in breast lesions.

A review of neuroendocrine features in breast carcinomas is presented and markers for neuroendocrine cells are discussed. Immunostaining for neuron specific enolase is the best screening marker for neuroendocrine cells in breast carcinomas, but immunoreactivity for hormones is not present in all neuron specific enolase (NSE) positive cases. Normal myoepithelial cells are also NSE positive. Thirty per cent of breast carcinomas are NSE positive. Biochemical demonstration of ACTH, PTH and calcitonin, and immunohistochemical demonstration of ACTH, bombesin, serotonin, prolactin, gastrin, VIP, leu-enkephalin, pancreatic polypeptide, beta-endorphin and sub P has been reported in breast carcinomas. Neuroendocrine cells have not been convincingly demonstrated in the normal breast or in benign breast lesions.

Breast↗

Neuroendocrine activity in metastatic breast carcinomas.

The expression of NSE and hormone immunoreactivity were examined in lymph node metastases from 15 primary breast carcinomas (6 NSE-positive and 9 NSE-negative). NSE immunoreactivity was expressed in metastases in 7 cases. Both the primary tumour and lymph node metastasis(es) were NSE-positive in 3 cases. In 4 cases NSE-negative primary tumours were associated with NSE-positive lymph node metastases. In 2 of the 7 cases with NSE-positive metastases, the metastatic lesions did not express uniform NSE immunoreactivity. Immunoreactivity for hormones (gastrin (1 case), prealbumin (2 cases), ACTH and beta-endorphin (1 case) and somatostatin (1 case] was present in 5 of the 7 NSE-positive lymph node metastatic lesions. In one case only the same hormone (gastrin) was expressed in both the primary tumour and its lymph node metastasis. The present study shows that no relationship exists between primary tumours and the corresponding lymph node metastases with regard to NSE and hormone immunoreactivity.

Adrenocorticotropic Hormone↗

Transgenic mouse model: a new approach for the investigation of endocrine pancreatic B-cell growth.

The transformation and adaptation of pancreatic insulin-producing (B) cells has been studied in a transgenic mouse model using a panel of antisera recognising peptides and general neuroendocrine markers at both light and electron microscopical levels. Stages of tumour genesis in the transgenic mouse model from hyperplasia to neoplasia, have been compared with human B-cell tumours. A normal complement of peptide containing cells was seen in the transgenic mouse pancreas, but cells containing pro-insulin-derived peptides became more numerous as hyperplasia commenced. The transgenic mouse tumours were composed of B cells, although 30-35% of the tumours were also found to contain PP cells--a finding which is directly comparable with that in human insulin-producing tumours. NSE, 7B2 and chromogranin immunoreactivities were found in most cells from all the tumours examined. Antisera to PGP 9.5, a novel marker for elements of the neuroendocrine system, were found to stain hyperplastic and neoplastic B-cells intensely. In contrast, normal mouse B-cells did not show PGP 9.5 immunoreactivity thus it appears that PGP 9.5 is differentially expressed in transformed and/or growing mouse B-cells and hence may be used as an indicator in studies of early tumour growth.

Adenoma, Islet Cell↗

Diagnostic problems in breast pathology: the benefit of ultrastructural and immunocytochemical analysis.

This report deals with the diagnostic importance of intracytoplasmic lumina. The separation between tubular carcinoma and sclerosing adenosis, and the ultrastructural features of variants of lobular carcinoma are discussed. The role of electron dense granules as well as other markers for neuroendocrine cells are evaluated, and finally, the difficult separation of both small-cell and spindle cell tumors is considered.

Adenocarcinoma↗

Breast carcinomas with protein S-100 immunoreactivity. An immunocytochemical and ultrastructural study.

Protein S-100 immunoreactivity was observed in 5 of 50 breast carcinomas (3 infiltrating lobular and 2 infiltrating ductal carcinomas). A diffuse cytoplasmic staining was present in single cells and groups of cells. The majority of normal myoepithelial cells in ducts of unremarkable appearance next to tumor areas were stained in all 50 breast carcinomas. The 5 protein S-100 positive tumors all stained for prekeratin and 4 of them were vimentin-positive. No immunoreactivity for actin or NSE was observed in the 5 tumors. Electron microscopy did not distinguish the protein S-100 positive carcinomas from the 45 protein S-100 negative tumors. The significance of protein S-100 immunostaining in breast carcinomas is discussed.

Adult↗

Electron microscopy and immunostaining of the normal breast and its benign lesions. A search for neuroendocrine cells.

Specimens from 7 patients with normal breast tissue 26 patients with benign breast lesions (6 fibroadenomas, and 4 intraductal papillomas, 2 mammae lactantes, 10 cases of cystic disease and 4 fibrotic lesions) were studied by immunocytochemistry and electron microscopy. Excretory epithelial cells in 2 of the 4 papillomas were immunostained for NSE. Myoepithelial cells were frequently stained as well. All the breast specimens were nonreactive to the antichromogranin antibody we used. The 2 NSE positive intraductal papillomas were tested for presence of hormone immunoreactivity, but no positively stained cells were observed. No cells with neuroendocrine features were observed by electron microscopy. The present study did not reveal neuroendocrine cells in the normal breast specimens and undisputed proof of neuroendocrine differentiation in benign breast lesions was not established. We conclude that if neuroendocrine cells are present in the normal breast, they are very rare, and probably not the cellular origin of all breast carcinomas with neuroendocrine features.

Adenofibroma↗

Medullary thyroid carcinoma with thyroglobulin immunoreactivity. A special entity?

Fourteen medullary carcinomas of the thyroid (MCT) immunoreactive for both thyroglobulin and calcitonin were studied by light microscopy and immunohistochemistry. Thyroglobulin immunoreactivity was seen in neoplastic follicles and/or in solid foci in the lymph node metastases of two cases. Colocalization of thyroglobulin and calcitonin was found in the same neoplastic cells of eight cases using a double immunostaining method; in three of these (including one with metastases), thyroglobulin was found to be colocalized with calcitonin gene related peptide as well. Our histological and immunohistochemical results support the assumption that MCT with thyroglobulin immunoreactivity is an unusual variant of the multihormone producing MCT and strengthen the hypothesis that a common stem cell is the origin of these tumors. The available clinical data suggest that thyroglobulin-positive MCT carry a better prognosis than thyroglobulin-negative MCT.

Adult↗

Neurone specific enolase immunostaining in the diagnosis of breast carcinomas with neuroendocrine differentiation. Its usefulness and limitations.

Thirty-eight infiltrating ductal carcinomas, nine infiltrating lobular carcinomas, two tubular carcinomas and one papillary carcinoma were studied by light microscopy, immunocytochemistry and electron microscopy. Seventeen cases showed immunoreactivity for NSE. Immunostaining for different peptide-hormones was observed in 12 of these 17 cases and in none of the 10 NSE-negative cases used for controls. Scattered cells were positive for gastrin in five cases, pancreatic polypeptide in five, leu-enkephalin in three, sub-P in two, ACTH in one, bombesin in one and beta-endorphin in one case. Four cases revealed immunoreactivity for more than one peptide-hormone. Typical neuroendocrine granules were seen in five cases (all positively stained for NSE). Small, electron dense granules of possible neuroendocrine nature were not found in any of the 33 NSE-negative tumours. Our results confirm that immunoreactivity for NSE is present in a high proportion of breast carcinomas, but that neuroendocrine differentiation cannot be proved to be present in all these cases.

Breast Neoplasms↗

Multicystic peritoneal mesothelioma.

A multicystic peritoneal mesothelioma in a 55-year-old man is reported. The large multicystic tumor was only partially removed. 36 months after the first presentation he is still working and his only complaint is abdominal swelling. The light microscopical, immunocytochemical and ultrastructural features are described and differential diagnoses discussed.

Histocytochemistry↗

A mucinous carcinoma of the thyroid.

A primary mucinous carcinoma of the thyroid is reported. The tumour cells, arranged in small nests and trabecules, were surrounded by abundant intercellular substance which was positively stained for mucicarmine, alcian blue and PAS before and after diastase treatment. Diastase-resistant, PAS-positive material was also present in the tumour cells. Electron microscopy revealed neoplastic cells linked by desmosomes and not surrounded by basal lamina; the nuclei had irregular contours, prominent nucleoli and numerous pseudoinclusions; mucin granules and rough endoplasmic reticulum were the prominent organelles in the cytoplasm. Follicles and follicle-like structures were not found, either by light or by electron microscopy. A definite diagnosis could only be established after the disclosure of intense immunostaining for thyroglobulin in several groups of tumour cells. Criteria for the diagnosis are discussed and the question of histogenesis raised.

Adenocarcinoma, Mucinous↗

A study of different markers for neuroendocrine differentiation in breast carcinomas.

Forty-two breast carcinomas were studied with different markers for detecting neuroendocrine differentiation. The Bodian and Grimelius silver stains were applied, as well as immunostaining for neurone specific enolase (NSE), chromogranin, prealbumin and a battery of hormones. All cases were studied by electron microscopy as well. The material included 29 infiltrating ductal carcinomas, 10 infiltrating lobular carcinomas and 3 tubular carcinomas. Immunostaining for hormones was obtained in 11 cases (gastrin and PP (4 cases each), leu-enkephalin (3 cases), substance P (2 cases), beta-endorphin (2 cases), ACTH (1 case) and bombesin (1 case). Three cases revealed immunostaining for more than one hormone. Sixteen cases were positively stained with rabbit anti-NSE (Dako Corporation) and included all the 11 cases with proven immunoreactivity for hormones. 20 cases were positively stained with sheep anti-NSE and only 8 of the 11 cases with immunoreactivity for hormones were included. Immunostaining for prealbumin was observed in only 1 case and chromogranin in only 5 cases. All cases were unstained with the Bodian stain, whereas 3 cases showed a positive argyrophilic reaction with the Grimelius technique. Ultrastructural studies revealed typical small membrane-bound electron dense granules in cytoplasm in 4 cases, all among the 11 cases with immunoreactivity for hormones. We conclude that immunostaining with rabbit anti-NSE is the best screening method for detecting breast carcinomas with neuroendocrine differentiation.

Adenocarcinoma↗

Electrophysiological properties of calcitonin-secreting cells derived from human medullary thyroid carcinoma.

Primary cultures of human medullary thyroid carcinoma tissue were prepared from lymph node metastases in two patients. The parenchymal, cultured cells displayed positive immunocytochemical staining for CT, and the cells also released the hormone into the culture medium. The membrane potential and resistance of the CT-producing cells were 50.1 +/- 8.9 mV and 634 +/- 154 M omega (mean +/- SD, n = 46). TTX sensitive action potentials with maximum rate of rise up to 51 V s-1 were evoked by current injection in Na+-containing solution, whereas TTX insensitive action potentials with maximum rate of rise up to 9 V s-1 were generated in Na+-free solution. These action potentials were reversibly blocked by D-600. We conclude that the action potentials of the human MTC cells have both a Na+ and a Ca2+ component. Ejection of CA2+-free solution close to the cells caused membrane hyperpolarization associated with decreased membrane resistance. The reversal potential of this response was -66.2 +/- 10.9 mV (n = 10), indicating that a permeability increase to Cl- and/or K+ may be involved. We suggest that elevated plasma Ca2+ concentration in vivo may cause increased excitability due to membrane depolarization and resistance increase, thus leading to enhanced Ca2+ influx and hormone secretion.

Action Potentials↗

Crystalluria and ciprofloxacin, influence of urinary pH and hydration.

Ciprofloxacin is one of the newer 4-quinolones. It combines a high antibacterial activity and a broad spectrum with favourable pharmacokinetic properties. The present study was designed to detect the influence of urinary pH and fluid consumption on crystalluria. Six healthy volunteers aged 25-41 years, 3 of each sex, participated in the study. Single doses of 1,000 and 500 mg of ciprofloxacin were given orally. The urinary pH was varied by giving each subject three different diets: a regular diet, a diet supplemented by ammonium chloride to acidify urine, and a diet supplemented by sodium bicarbonate to obtain alkaline urine. The urine volume and pH were measured and microscopically examined at 37 degrees C immediately after voiding. After the very high dose of 1,000 mg ciprofloxacin the regular diet regimen led to crystalluria in only one subject. Even with this high dose, but with the acidifying regimen, no crystals were observed in any one of the volunteers. When bicarbonate was supplemented 5 to 6 volunteers presented crystals in 22 of the 36 urine samples. 21 of the crystalluric urine samples showed a pH greater than or equal to 7.3. After the usual 500-mg dose and regular diet no crystals were observed at all; only in 3 subjects who received bicarbonate supplement crystals have been seen. In the urine of two subjects crystals emerged 'ex vivo' after some hours of storage at both 37 degrees C and room temperature; these results show the importance of sediment observation at 37 degrees C immediately after voiding to differentiate between real and 'ex vivo' crystalluria. Results of different examinations permit the conclusion that the crystals contain mostly unchanged ciprofloxacin as major component and magnesium as characteristic element. Participation of the metabolite 2 in the crystal formation cannot be excluded. No significant change was observed in blood counts and blood chemistry of any subject. Urinalysis showed no modifications except the eventual presence of the typical drug-related crystals. Hematuria never occurred.

Adult↗