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Biomedical subjects

K Sandelin

Publications and source records attributed to K Sandelin.

At least 55 records · Page 3Linked to original sources
PubMed1995

Immediate breast reconstruction: short-term experience in 75 consecutive cases.

Immediate breast reconstructions are being done more often nowadays to avoid the stress that the patient experiences while living without a breast. In this paper, the procedure and short term outcome of 75 patients who underwent immediate breast reconstructions at the Karolinska Hospital are reported. The median age of the patients was 48 years, and most of the tumours were stage O to 2 at the time of the operation, though reconstructions were also done for patients with more advanced cancer, for psychological reasons. The approach was multidisciplinary with oncologists, general surgeons, and plastic surgeons involved. Different reconstructive methods were used, and the operations were tailor-made for each patient. Twenty one permanent prostheses, 11 expanders, 33 expander prostheses, and eight pedicled and two free transverse rectus abdominis musculocutaneous (TRAM) flaps were used for reconstruction. The opposite breast was adjusted in 43 (57%) of the patients. There were 11 postoperative complications (15%), and in only one patient (1%), could the reconstruction not be completed. There was a tendency towards more complicated reconstructive procedures over time. The demand for immediate breast reconstruction is steadily increasing from both patients and doctors.

Adult↗
PubMed1994

Primary hyperparathyroidism. Low surgical morbidity supports liberal attitude to operation.

OBJECTIVE: To evaluate the results of a modern surgical approach in patients with primary hyperparathyroidism. DESIGN: Retrospective analysis. SETTING: University hospital, tertiary care center. PATIENTS: One hundred patients consecutively operated on for suspected primary hyperparathyroidism. Patients were available for follow-up 1 month (n = 100) and 1 year (n = 96) after surgery. INTERVENTION: Cervical exploration. Surgical strategy was to remove enlarged parathyroid glands only and perform a biopsy on no more than one normal gland. MAIN OUTCOME MEASURES: Surgical morbidity and normocalcemia. RESULTS: No operative mortality or wound infection occurred in any patient. Postoperative vocal cord paralysis was recorded in two patients; both recovered fully. Two patients underwent a second operation. (One patient experienced subcutaneous bleeding and the second patient, previously operated on for toxic goiter, experienced persistent hypercalcemia and was operated on 5 days after the initial operation. A second abnormal gland was then found on the contralateral side, not initially surgically explored.) At follow-up, 97 patients were normocalcemic; three patients had hypoparathyroidism: two of these patients, with multiglandular disease, were normocalcemic and received a low dose of vitamin D (1 alpha [OH]D3), and one patient, who had had a single adenoma removed, was slightly hypocalcemic, however, asymptomatic. CONCLUSIONS: More than 90% of patients with primary hyperparathyroidism can be operated on without complications occurring. This supports a liberal attitude to operation.

Aged↗
PubMed1994

The phospholipase C beta 3 gene located in the MEN1 region shows loss of expression in endocrine tumours.

Oncogenesis of tumours related to multiple endocrine neoplasia type 1 (MEN1) is associated with somatic deletions involving the MEN1 locus, suggesting inactivation of a tumour suppressor gene in this region. Identification of meiotic cross-overs in MEN1 families has placed the MEN1 locus centromeric of D11S807. An extended deletion mapping was performed in 27 primary parathyroid tumours, and identified D11S427 as the closest centromeric flanking marker. Through physical mapping using newly isolated cDNA clones, we estimated the distance between the flanking markers D11S807 and D11S427 to be less than 900 kb. One of these cDNA clones showed expression of a 4.4 kb message in multiple tissues, including those affected in MEN1, while in five endocrine tumours no transcript was detected. Sequence characterization showed that this gene encodes for the phospholipase C beta 3, a key enzyme in signal transduction.

Blotting, Northern↗
PubMed1994

Genetic aspects of multiple endocrine neoplasia types 1 and 2.

Multiple endocrine neoplasia (MEN) type 1 is an autosomal, dominantly inherited predisposition to develop neoplastic lesions of the parathyroid glands, the neuroendocrine pancreas-duodenum, and the anterior pituitary. The genetic defect was mapped to the centromeric part of the long arm of chromosome 11 based on studies of somatic deletions in MEN-1-associated tumors and linkage analysis in families in whom the disease is segregated. Combined family and tumor analysis has shown that tumorigenesis in MEN-1 involves loss of the wild-type chromosome, indicating that the putative MEN-1 gene is a tumor suppressor gene. Similar deletions are also seen in a proportion of sporadic parathyroid and pancreatic tumors, suggesting that tumorigenesis involves related mechanisms in both sporadic and familial cases. Based on results from linkage analysis in more than 40 MEN-1 families, predictive testing for MEN-1 using DNA polymorphisms can now be performed with high accuracy. Hence, biochemical screening programs can focus on individuals at risk to identify early signs of tumor development. MEN-2, an autosomal dominant cancer syndrome of variable expressivity, has previously been localized to chromosome 10q11.2 by positional cloning tactics. The RET protooncogene mapping to the MEN2 susceptibility locus has recently emerged as a candidate gene for MEN-2A. RET, a transmembrane receptor protein, has a large glycosylated extracellular domain containing clustered cysteine residues and calcium-binding motifs, a single hydrophobic transmembrane domain, and a cytoplasmic domain with tyrosine kinase catalytic activity. Several germline missense mutations in a codon specifying one of these highly conserved cysteine residues have been detected in patients affected with MEN-2A.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Transformation, Neoplastic↗
PubMed1994

Predisposition for breast cancer in carriers of constitutional translocation 11q;22q.

A translocation between the long arms of chromosomes 11 and 22, t(11;22)(q23;q11), is the most frequent constitutional reciprocal translocation in man. This chromosome abnormality has not previously been reported to be associated with an increased risk for neoplasia. The observation of one patient with a constitutional translocation t(11q;22q) and breast cancer prompted us to study the relationship between these two conditions. The incidence of breast cancer was determined in carriers of t(11q;22q). The karyotypes were determined by QFQ-banding, and the breakpoints were then further characterized by fluorescent in situ hybridization. Eight families with a total of 22 balanced carriers were found. In five of these families there was one case of breast cancer each. In another family a case of an unknown malignancy was reported in one member. No other malignancies were found among these patients. The number of breast cancer cases was significantly higher than expected among the translocation carriers (P < .001). The chromosomal breakpoints showed the same localization with the markers used, in the seven families studied. The association of constitutional translocation t(11q;22q) and breast cancer identifies a subset of patients with a highly increased risk for breast cancer who would benefit from counseling and screening. It also suggests the involvement of genes on 11q and/or 22q, in the tumorigenesis of breast cancer.

Breast Neoplasms↗
PubMed1993

Exclusion of FAU as the multiple endocrine neoplasia type 1 (MEN1) gene.

The FAU gene (FBR-MuSV associated ubiquitously expressed gene) encodes the ribosomal protein S30 fused with a Ubiquitin-like molecule. The FAU gene is expressed in a wide range of tissues, is evolutionarily conserved, and has putative tumour suppressor activity in vitro. The human FAU gene maps to the long arm of chromosome 11 band q13, close to the PYGM locus. This locus is tightly linked to the Multiple Endocrine Neoplasia type 1 (MEN1) locus. The FAU gene properties, together with its chromosomal localisation on 11q13, make it a candidate gene for MEN1. To test this hypothesis we screened 33 unrelated patients with MEN1 for constitutional genetic alterations in the FAU gene by Southern blot analysis, denaturing gradient gel electrophoresis (DGGE) and in two cases complemented by DNA sequencing to confirm the DGGE data. Furthermore, 10 parathyroid and pancreatic tumours from MEN1 patients and 15 each of sporadic parathyroid and pituitary tumours were similarly examined. In addition, we studied the expression of the FAU gene at the RNA level in 9 MEN1-associated tumours by Northern blot analysis. No FAU gene anomalies could be demonstrated by any of these techniques. We conclude that FAU is not likely to be the MEN1 tumour suppressor gene.

Base Sequence↗
PubMed1993

Histopathological variables and DNA cytometry in parathyroid carcinoma.

To undertake an evaluation of histopathological variables in parathyroid carcinoma, 95 cases with this diagnosis were collected from 37 hospitals. Two tumor categories emerged from a review of tissue sections and follow-up information: 56 cases demonstrating extraglandular invasiveness or tumor recurrence were classified as definitive carcinomas, whereas 39 tumors lacking these criteria were classified as equivocal cases. Several morphological variables other than invasiveness differed between the two groups: Fibrosis, necrosis, nuclear atypia (especially macronucleoli), and mitotic figures were significantly more frequent in the carcinoma group. These variables also showed a positive correlation with an aberrant DNA pattern demonstrated by image cytometry. The triad macronucleoli, more than five mitoses per 50 high-power fields, and necrosis were associated with an aggressive behavior in terms of recurrent disease. A minority of the carcinomas had a bland cytologic appearance and differed from benign lesions only by their invasiveness. Certain patterns of fibrosis and necrosis were common but neither pathognomonic nor constant features of malignancy. Mitotic activity constituted a prognostic risk factor but was of limited diagnostic significance. In half of the carcinomas, the frequency of mitoses did not exceed values recorded in benign parathyroid lesions.

Adenoma↗
PubMed1992

Morphology, DNA ploidy and allele losses on chromosome 11 in sporadic hyperparathyroidism and that associated with multiple neoplasia, type 1.

OBJECTIVE: To analyse different forms of hyperparathyroidism (for example, sporadic and multiple endocrine neoplasia type 1 (MEN 1)) by histopathology, DNA cytometry and by the presence of allele losses on chromosome 11, thereby identifying common characteristics. MATERIAL: Enlarged glands from 26 patients with hyperparathyroidism (23 sporadic and 3 MEN 1). Cytometric assessment was made of 28 glands. RESULTS: Nine patients had multiple gland disease and 15 had single gland disease (14 sporadic and 1 MEN 1). DNA cytometry showed that 18 (15 sporadic and all 3 MEN 1) were diploid, seven tetraploid, and two aneuploid. Two glands from one sporadic case showed different ploidy patterns. Seven patients with sporadic and all three with MEN 1 hyperparathyroidism had allele losses for chromosome 11 in the analysed glands. CONCLUSION: There were no significant differences in histopathological appearances, ploidy, or allele losses among abnormal glands from a variety of forms of hyperparathyroidism.

Adult↗
PubMed1992

Oestrogen, progesterone, and glucocorticoid receptors in normal and neoplastic parathyroid glands.

OBJECTIVE: To verify the presence or absence of steroid receptors in the parathyroid glands of patients undergoing operations on the parathyroid and thyroid glands. DESIGN: Open experimental study. SETTING: Karolinska Hospital, Stockholm, Sweden. MATERIAL: 165 parathyroid glands from 137 patients, 108 of whom underwent operations on the parathyroid glands and 29 on the thyroid gland. INTERVENTIONS: Normal and neoplastic parathyroid tissue was analysed for its content of oestrogen and progesterone and glucocorticoid receptors using either ligand binding or antibodies raised against oestrogen and progesterone receptors. RESULTS: Positive reactions to female sex steroid receptors (defined as > 0.05 fmol/microgram DNA) were uncommon (9%) regardless of the morphological classification of the glands or the age, sex, and menopausal status of the patients. Glucocorticoid receptors were detected in 107/163 (66%) of all glands analysed (mean value 0.43 fmol/micrograms DNA, range 0-44). Seventy of the 96 diseased glands (73%) contained receptors, as did 27/67 normal glands from patients with primary hyperparathyroidism or those undergoing thyroid operations. The difference was again not associated with age, sex, and menopausal status. CONCLUSIONS: It seems unlikely that sex steroid hormones play a physiological part in the secretion of parathyroid hormone, but our finding of glucocorticoid receptors in normal as well as diseased parathyroid tissue suggests that they may have a role in the regulation of parathyroid function.

Adult↗
PubMed1991

Metastatic parathyroid carcinoma: dilemmas in management.

The incidence of parathyroid carcinoma in patients surgically treated for primary hyperparathyroidism at the University of Michigan Hospital was 0.4% during an 18-year period. The courses of the five patients with metastatic disease are described. Histologic reevaluation and assessment of the DNA ploidy pattern were performed in each case. Localization studies preceded all reexplorations. The number of operative procedures in each patient ranged from two to 10. Two patients are living with recurrent disease and one has been disease free for 42 months. Two patients died after 2 and 12 years, respectively. Three patients had aneuploid tumors; one had a diploid tumor. One patient had both aneuploid and diploid cell populations. Dilemmas in diagnosis, localization, and medical and surgical management were encountered in patients with metastatic carcinoma. The chosen treatment should be evaluated individually in each case because of the variability in aggressiveness of this malignancy. Surgical resection proved most effective in some of these patients for both local and distant recurrences. Bisphosphonates and gallium nitrate have been reported to be effective in controlling hypercalcemia. Only the former had some effect in one of our patients.

Adult↗
PubMed1990

Genotoxicity of p-aminophenol in somatic and germ line cells of Drosophila melanogaster.

p-Aminophenol (PAP; as a component of, e.g., hair dyes, photographic developers, as adsorbent in gas filters, as a metabolite of various fungicides, pesticides and drugs) has been tested for genotoxicity in Drosophila by means of the sex-linked recessive lethal test (SLRLT) and the somatic mutation and recombination test (SMART) of the wing. While the SLRLT was not significant, the SMART clearly indicated that the compound has genotoxic properties in this in vivo test in agreement with a majority of mammalian short-term tests in vitro and in vivo. The reducing agent dithiothreitol enhanced the genotoxic effects of PAP in the SMART; the reasons for this interaction remain to be elucidated.

Aminophenols↗
PubMed1990

Localization of the MEN1 gene to a small region within chromosome 11q13 by deletion mapping in tumors.

The gene for multiple endocrine neoplasia type 1 (MEN1), an inherited predisposition to neuroendocrine neoplasm of the parathyroid glands, the pancreatic islet parenchyma, and the anterior pituitary gland, was recently mapped to chromosome 11q13 based on genetic linkage in families. We now show that the pathogenesis of MEN1-associated parathyroid lesions involves unmasking of a recessive mutation at the disease locus and that sporadic primary hyperparathyroidism shares the same mechanisms. By examination of allele losses in MEN1-associated lesions, we could define deletions of chromosome 11 and map the MEN1 locus to a small region within chromosome band 11q13, telomeric to the PYGM locus. In contrast, a low incidence of deletions involving the MEN1 gene was found in sporadic pituitary adenomas.

Adenoma↗
PubMed1986

Rapid diagnosis of respiratory adenovirus infections in young adult men.

Rapid viral diagnosis was attempted in 106 military conscripts with pneumonia and in 101 military conscripts with other types of respiratory infections. Nasopharyngeal suction specimens (NPS) were assayed for viral antigens by immunofluorescence and enzyme immunoassay (EIA). Sputum specimens from 97 pneumonia patients were assayed for viral antigens by EIA. Also, 71 NPS and 13 sputum specimens were examined for the presence of adenovirus DNA by a sandwich hybridization (HYB) method. The reference test was adenovirus isolation in cell culture from the NPS. Adenoviruses were isolated from 6 pneumonia patients and from 20 patients with other respiratory infections. Of these 26 NPS, rapid diagnosis was successful in 13, 16, and 14 cases by EIA, immunofluorescence, and HYB, respectively. Four antigen-positive specimens were found among the 181 specimens which were negative by virus isolation. Sputum was found to contain adenovirus antigen by EIA in 5 of 97 tested specimens. Of these 97 specimens, 13 were selectively tested in HYB, and a positive signal was observed in 4 cases. Serological testing of paired sera revealed 23 adenovirus infections in the pneumonia group and 42 in the group with other respiratory infections. Other viral infections were found only sporadically. All rapid virus detection methods showed excellent specificity but had a lower sensitivity (60%) than virus isolation. Our results show that rapid methods for diagnosing respiratory adenovirus infections can be successfully used in selected groups of adults.

Adenoviridae Infections↗
PubMed1982

A simple, fully enzymic bioluminescent assay for triglycerides in serum.

In this fully enzymic bioluminescent assay, triglycerides are cleaved by lipase (EC 3.1.1.3) and carboxylesterase (EC 3.1.1.1), and the glycerol obtained is phosphorylated with ATP and glycerol kinase (EC 2.7.1.30). The ATP consumed in the latter reaction is determined by the firefly luciferin-luciferase reaction, and corresponds to the concentration of triglycerides. All the enzymic reactions and the bioluminescent reading can be performed in the same test tube. The precision (CV) of the assay varied between 1 and 7% at different concentrations with a fully enzymic method based on spectrophotometry (r = 0.98).

Enzymes↗
PubMed1977

Echovirus type 7 isolated from conjunctival scrapings.

Echovirus type 7 was isolated from 7 conjunctival scrapings obtained during an epidemic of meningoencephalitis caused by the same virus. The patients suffered from conjunctivitis or keratoconjunctivitis, and also had gastrointestinal symptoms, fever, headache and lymphadenopathy early in their illness. Two characteristics of the isolated strains were not in agreement with those of the standard echovirus type 7: they adapted only slowly to cell cultures, and no viral hemagglutinin for human red blood cells could be demonstrated. Our data suggest an etiologic association of echovirus 7 with eye disease.

Adult↗
PubMed1977

Experimentally caused proliferation of lysosomes in cultured BHK cells involving an increase of biphosphatidic acids and triglycerides.

When cultured hamster fibroblasts (BHK 21 cells) were incubated in a synthetic serum-free medium up to 4 days, they developed signs of a progressive proliferation of lysosomes. The cells became filled with vacuoles that contained polymorphic debris and showed acid phosphatase activity. The specific activities of acid protease and acid phosphatase in the cell cultures increased three- to fourfold. The process was accompanied by a marked decrease in the contents of protein, deoxyribonucleic acid, and total phospholipids of the cultures. The concentration of lysobisphosphatidic acid increased during the incubation from about 1.5% to 3-6% of the cellular phospholipids. The concentrations of two related lipids, bisphosphatidic acid and semilysobisphosphatidic acid also increased substantially. The triglyceride content of the cells increased several fold, whereas the concentration of phosphatidylcholine decreased markedly. Lysobisphosphatidic acid did not increase upon induction of vacuolization by exogenous sucrose, nor when there was an accumulation of triglyceride due to addition of oleic acid to the growth medium. These findings suggest that the formation of the bisphosphatidic acids may be specifically linked to the autolysis of the phospholipids of the cellular membranes and the formation of triglycerides associated with this process.

Acid Phosphatase↗