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Biomedical subjects

L Samuelsson

Publications and source records attributed to L Samuelsson.

At least 19 recordsLinked to original sources

Characterization of the human lipoprotein lipase (LPL) promoter: evidence of two cis-regulatory regions, LP-alpha and LP-beta, of importance for the differentiation-linked induction of the LPL gene during adipogenesis.

When preadipocytes differentiate into adipocytes, several differentiation-linked genes are activated. Lipoprotein lipase (LPL) is one of the first genes induced during this process. To investigate early events in adipocyte development, we have focused on the transcriptional activation of the LPL gene. For this purpose, we have cloned and fused different parts of intragenic and flanking sequences with a chloramphenicol acetyltransferase reporter gene. Transient transfection experiments and DNase I hypersensitivity assays indicate that several positive as well as negative elements contribute to transcriptional regulation of the LPL gene. When reporter gene constructs were stably introduced into preadipocytes, we were able to monitor and compare the activation patterns of different promoter deletion mutants at selected time points representing the process of adipocyte development. We could delimit two cis-regulatory elements important for gradual activation of the LPL gene during adipocyte development in vitro. These elements, LP-alpha (-702 to -666) and LP-beta (-468 to -430), contain a striking similarity to a consensus sequence known to bind the transcription factors HNF-3 and fork head. Results of gel mobility shift assays and DNase I and exonuclease III in vitro protection assays indicate that factors with DNA-binding properties similar to those of the HNF-3/fork head family of transcription factors are present in adipocytes and interact with LP-alpha and LP-beta. We also demonstrate that LP-alpha and LP-beta were both capable of conferring a differentiation-linked expression pattern to a heterolog promoter, thus mimicking the expression of the endogenous LPL gene during adipocyte differentiation. These findings indicate that interactions with LP-alpha and LP-beta could be a part of a differentiation switch governing induction of the LPL gene during adipocyte differentiation.

3T3 Cells

The CCAAT/enhancer binding protein and its role in adipocyte differentiation: evidence for direct involvement in terminal adipocyte development.

During the course of differentiation of preadipocytes into adipocytes, several differentiation-linked genes are activated synchronously with morphological changes. To follow this process we have used 3T3-F442A cells, known to undergo adipocyte conversion with high frequency. Accumulation of lipid droplets in the cytoplasm constitutes an easily visualized sign of the terminally differentiated phenotype. In this report we demonstrate that expression of the CCAAT/enhancer binding protein (C/EBP) is an important factor in determining the ability to accumulate lipid droplets in terminally differentiated adipocytes. In one experiment we can suppress C/EBP expression through administration of hydrocortisone to differentiating 3T3-F442A cells, which is accompanied by an inability of the cells to accumulate lipid. In another experiment a C/EBP antisense expression vector has been stably introduced into 3T3-F442A cells and as compared with control cells, a 62% decrease of C/EBP mRNA (p less than 0.01) is demonstrated. This decrease of C/EBP mRNA is accompanied by a change in cellular morphology characterized by a reduced ability to form lipid droplets. We can also demonstrate a correlation between the degree of reduction of C/EBP mRNA and the amount of lipid present in the cells. These findings strongly support the view that C/EBP is a necessary component of terminal adipocyte differentiation.

3T3 Cells

Cisplatin and 5-FU combined with radiotherapy and surgery in the treatment of squamous cell carcinoma of the esophagus. Palliative effects and tumor response.

The combination of cisplatin (90-120 mg/m2) and 5-fluorouracil (5-FU) (1,000 mg/m2/day in continuous infusion for five days) was given for 2-3 cycles, prior to combined radiotherapy and surgery, to 73 patients with esophageal squamous cell carcinoma, 60 with limited disease (LD), and 13 with extensive disease (ED) (i.e. with metastasis) of whom 3 had recurrent disease. Before preoperative radiotherapy among 60 LD patients, 12 (20%) had complete response, 21 (35%) partial response, 25 (42%) had stable disease, and 2 (3%) progressive disease. Swallowing was improved in 35/73 (48%) of the cases. In the resected specimens, no tumor was found in 8/53 (15%) of the cases, microscopic tumor in 18/53 (34%) and macroscopic tumor in 27/53 (51%). In the ED group, complete response of distant metastases was obtained in 6/13 (48%) of the patients, one of whom is still alive with no evidence of disease 62 months after the start of treatment.

Aged

Spinal cord and brain stem anomalies in scoliosis. MR screening of 26 cases.

The spinal cord and brain were examined with magnetic resonance (MR) in 26 patients with idiopathic scoliosis to study the prevalence of spinal cord and brainstem anomalies. Two patients had small centrally located spinal cord syrinxes, one at C6-C8 and the other at T6-T8, without association with any brainstem or cerebellar deformity. The lowest position of the cerebellar tonsils was 0.5 cm below the foramen magnum, which was also seen in 2 other patients. Scoliosis associated with syringomyelia may be more common than previously thought, and may be wrongly classified as idiopathic. A neurogenic cause of scoliosis should always be considered, and at least in atypical cases be excluded by MR imaging of the spinal cord. MR should be mandatory before bracing or operative correction of scoliosis.

Adolescent

Mammographic follow-up after breast conserving surgery and postoperative radiotherapy without boost irradiation for mammary carcinoma.

Pre- and postoperative mammograms were reviewed in 103 women undergoing conservation surgery and irradiation for breast cancer stage I. The main reactions to radiotherapy were increased breast parenchymal density and increased skin thickness. Changes reached a peak at 9 months. No new changes were seen at 2 years, and most had regressed at this time. Following surgery, 71 of the patients displayed noticeable scar tissue in the surgical area, sometimes causing diagnostic difficulties. Two of the patients had a local recurrence of carcinoma, while 3 developed cancer in the other breast.

Adult

Digital luminescence mammography. Early clinical experience.

In a pilot study, mammography using digital luminescence was compared to conventional film-screen mammography regarding detectability of micro-calcifications and malignant tumors. The data processing algorithms were designed by the manufacturer to produce an image with characteristics close to conventional mammograms. Three observers reviewed 99 digital and their corresponding conventional mammograms. There was no difference in the detectability of micro-calcifications between digital and conventional mammography. On the digital mammograms, however, artifacts were misjudged as micro-calcifications. In an ROC analysis regarding malignant breast tumors, no significant difference was found between the 2 systems. There was a slight, but not significant, difference between the results of different observers regarding the digital system.

Adult

Electrolysis with different electrode materials and combined with irradiation for treatment of experimental rat tumors.

In order to make electrolytic tumor destruction more effective new electrode materials were tested (Part I) as well as a combination of electrolysis and megavolt therapy (Part II). All tests were performed in experimental tumors implanted subcutaneously in rats. Altogether in 41 rats in 5 series (Part I) electrodes made of rhodium (Rh), copper (Cu), or brass (Zn-Cu alloy) were investigated but the effect was not found to be better than that of the previously tested platinum (Pt). Oxidation and corrosion made Rh and Cu electrodes less suitable for electrolysis compared to Pt, while brass electrodes became isolated through zinc-salt-formation and performed unsatisfactorily. The radiosensitizing properties of electrolysis were tested in 55 rats with experimental tumors (Part II). One control group had only Co-irradiation, while in 2 other groups Cu- or Pt-electrolysis of the tumors was carried out before irradiation. The combined treatment resulted in a significantly better effect on the tumors, registered as inhibition of tumor growth or disappearance of tumor. As the electrolyzed, necrotic tissue remained in the tumor the effect might not be mediated through diminished target volume. An inflammatory reaction around the electrolytic lesion with increased blood flow and higher oxygenation of the tumor could cause a more positive response to megavolt treatment.

Animals

Effect of chemotherapy and radiotherapy on squamous cell carcinoma of the esophagus. A preoperative radiologic evaluation.

In a series of 82 patients with epidermoid carcinoma of the esophagus, 68 were available for review of barium examinations and 44 for review of CT examinations showing the effect of preoperative treatment. After 3 courses of chemotherapy--Cisplatinum and 5-fluorouracil, and 24 Gy of presurgical irradiation--over a total of 10.5 weeks, the patients were ready for surgery. The results of the presurgical radiographic examinations were compared with the findings of histopathologic studies after surgery. Where both the CT and the barium examination showed a complete response, none of the patients had remaining macroscopic cancer. When healing with stenosis was included, CT and barium studies in combination were necessary to exclude a residual macroscopic tumor. Therefore, a combination of barium esophagography and CT is recommended to estimate the preoperative effect of treatment.

Aged

Evaluation of syringomyelia and Chiari malformations using ultra-low magnetic resonance imaging.

The accuracy of ultra-low field magnetic resonance imaging (MRI) compared to medium-field MRI in detecting syringomyelia and associated Chiari malformations is examined. In all cases the size of the syrinxes and the type and extent of the Chiari malformations was clearly shown at low-field MRI. The present spatial solution and high sensitivity allows for low-field imagers to localize even minor morphological changes of the spinal cord, brainstem, and cerebellum.

Adolescent

An angiographic technique for three-dimensional determination of arterial supply patterns in cadaver soft tissue.

A method for arterial tree mapping that can be used in cadaver soft tissue is presented. In situ angiograms and photographs are supplemented with profile angiograms of relatively narrow bands of tissue from the removed specimen. The described method was better suited for mapping the course and supply patterns of a soft-tissue arterial network than either in situ angiograms or dissection. While practical problems were encountered with most of the solutions used for providing radiopacity or structural support to the vessels, pure barium sulfate was found to be suitable because it filled the vascular tree to the capillary level without leakage during excision of the specimen.

Angiography

Neuro-ophthalmological findings in relation to CNS lesions in patients with myelomeningocele.

Twenty-eight patients (14 male, 14 female; aged four to 34 years) with myelomeningocele were studied. Magnetic resonance imaging was used to determine the correlation between disturbances of ocular motility and the degree of hydrocephalus, tectal plate deformity and dislocation of the cerebellum and medulla oblongata. All patients had Chiari malformations. Strabismus and spontaneous nystagmus were strongly related mainly to the degree of hydrocephalus and to some extent to the amount of lower brainstem deformities. Ocular motility defects with regard to oblique muscle functions and horizontal and vertical gaze and saccadic control often correlated with lower brainstem lesions. Convergence defects correlated with deformities of the upper brainstem. However, these correlations were not valid in the individual patient; some had no strabismus and normal ocular motility, in spite of advanced hydrocephalus and Chiari malformations.

Adolescent

Hip instability in myelomeningocele. 158 patients followed for 15 years.

In 158 patients with myelomeningocele, the prevalence of hip dislocation at birth and subluxation or dislocation of unoperated on hips at 2 and 15 years of age were assessed. In neonates examined during the first 10 weeks of life, 10 percent of the hips were dislocated. In children with a thoracic or L1-2 neurologic level, the cumulative incidence of dislocated hips increased from 8 to 26 percent and subluxations from 33 to 45 percent. In children with L3 and L4 levels, one fourth of the hips had dislocations and nearly half subluxations. At L5 and the sacral motor level, dislocations did not occur, but one fifth of the hips had subluxations. Children with L3 or L4 neurologic levels had bilateral hip dislocation at an earlier age than those with higher levels of paralysis. There appears to be no risk of developing hip dislocation at neurologic levels below L4, and spasticity promotes hip dislocation above L3.

Age Factors

CT demonstration of fistulae in patients with gynecologic neoplasms.

Ten women treated for gynecologic neoplasms (8 cervical carcinomas, one vaginal and one endometrial carcinoma) were found at computed tomography (CT) to have a fistula although only 5 patients had symptoms that could be related to a fistula. Five women had vesico-vaginal fistulae, 2 recto-vaginal, 2 entero-cervical and one a vulvo-pubical fistula. We regard CT as the radiologic method of choice in diagnosing gynecologic fistulae.

Adult

Influence of "nuclear" estrogen receptor content on prognosis of early stage carcinoma of the uterine body. A short-time follow-up.

Sixty-five patients with Stage I and II endometrial carcinoma were investigated. After a short-time follow-up (17-24 months) significant differences in frequency of relapses were observed between patients with tumors containing low amounts of estrogen receptor (ER less than 60 fmol/mg DNA) in the nuclear pellet, and those with tumors containing greater than 60 fmol ER/mg DNA (p = 0.01). Other prognostic factors showed no differences in frequency of relapses. In this small patient material with a short-time follow-up we therefore suggest that ER in the nuclear pellet may be an important prognostic factor.

Adenocarcinoma

Prognostic factors influencing survival in combined radiotherapy and surgery of squamous cell carcinoma of the esophagus with special reference to a histopathologic grading system.

Sixty-six patients with squamous cell carcinoma of the esophagus were treated with combined surgery and radiotherapy, mostly in a sandwich fashion. Fourteen patients received misonidazole during preoperative radiotherapy. Prospective cumulative survival at 1, 2, and 5 years was 60%, 35%, and 17%, respectively. Original biopsy specimens and operation specimens were evaluated according to a histopathologic grading system based on an evaluation of the tumor cell population in terms of cell differentiation, structure, nuclear polymorphism, and the frequency of mitotic figures. The tumor-host relationship was also estimated by the mode of invasion, stage of invasion, vascular invasion, and degree of lymphocytic infiltration. A multivariate regression analysis according to Cox and actuarial survival were used to determine the relative contributions of the clinical and histopathologic parameters to patient outcome. The major results were as follows: (1) patients who were old (70 to 80 years) fared as well as younger patients (P = 0.9198); (2) tumor site did not influence therapeutic outcome (P = 0.1100); (3) there was an insignificant difference in survival between patients with M0 and M1 disease (P = 0.7130); (4) radical surgery gave better survival; (5) misonidazole administered preoperatively was associated with worse survival (P = 0.0147); and (6) the histopathologic malignancy grading score system was very useful for prognostication--the tumor-host score in the operative specimen was the strongest of all analyzed predictive parameters. Since palliation was excellent in all patients treated in the combined fashion, selection criteria should be wide for such a program, not the least since long-term survival is possible also for patients with very advanced tumors.

Carcinoma, Squamous Cell

Scoliosis in myelomeningocele.

Prevalence, type, and magnitude of scoliosis were studied in 163 patients with myelomeningocele. A scoliosis was diagnosed in 143 of them, congenital in 15 percent of the cases and developmental in the remaining patients. The severity of scoliosis increased with age and was more severe the higher the level of the neurologic deficit. The direction of the curves was correlated with pelvic obliquity, but not with hip dislocation. Although some patients with low level anomalies may develop severe scoliosis, patients with levels above L3 run a considerably higher risk in this respect. The radiographic baseline examination of the spine carried out in the newborn seems to permit a reasonable prognosis in regard to future scoliosis. Gross syringohydromyelia caused or contributed to scoliosis in 5 percent of the cases. However, less extensive syringohydromyelia and Chiari malformations due to abnormal neuromuscular control also promote the development of scoliosis in these patients.

Adolescent