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Biomedical subjects

B Lund

Publications and source records attributed to B Lund.

At least 181 records · Page 10Linked to original sources

The structure of the human tissue-type plasminogen activator gene: correlation of intron and exon structures to functional and structural domains.

A genomic clone carrying the human tissue-type plasminogen activator (t-PA) gene was isolated from a cosmid library, and the gene structure was elucidated by restriction mapping, Southern blotting, and DNA sequencing. The cosmid contained all the coding parts of the mRNA, except for the first 58 bases in the 5' end of the mRNA, and had a total length of greater than 20 kilobases. It was separated into at least 14 exons by at least 13 introns, and the exons seemed to code for structural or functional domains. Thus, the signal peptide, the propeptide, and the domains of the heavy chain, including the regions homologous to growth factors, and to the "finger" structure of fibronectin, are all encoded by separate exons. In addition, the two kringle regions of t-PA were both coded for by two exons and were cleaved by introns at identical positions. The region coding for the light chain, comprising the serine protease part of the molecule was split by four introns, revealing a gene organization similar to other serine proteases.

Amino Acid Sequence↗

Novel cluster of alpha-interferon gene sequences in a placental cosmid DNA library.

A human cosmid library was constructed and probed with a human alpha interferon (IFN-alpha) cDNA clone. One clone giving a strong hybridizing signal was isolated and characterized. The cosmid DNA insert represents a section of the human genome containing three regions of IFN-alpha-like sequences. The DNA was characterized with restriction endonuclease mapping, thereby allowing comparison to similar linkage groups reported recently and determination of homologous regions on the known physical map. The three IFN-alpha-like sequences were analyzed by a partial sequence analysis. Mapping and sequence data establish this section as a not-yet-described cluster of IFN-alpha sequences in the human genome; however, a part of the section matches to some degree to a previously described genomic region. The region described here could represent genetic polymorphism or a duplicated segment.

Base Sequence↗

Effect of propranolol treatment on bone mass, bone mineral content, bone remodelling, parathyroid function and vitamin D metabolism in hyperthyroidism.

The effect of propranolol 160-640 mg/day for 3 months on the accelerated loss of bone matrix and mineral in hyperthyroidism was studied in seventeen patients. A rise in serum thyroxine (P less than 0.01) during the first 3 weeks was followed by a fall (P less than 0.02). Serum triiodothyronine declined during the study (P less than 0.02). The enhanced bone mineral mobilization and collagen turnover continued during treatment and the bone mineral content decreased 3.2% (P less than 0.01). The secondary adaptive changes in serum parathyroid hormone and vitamin-D metabolites and in renal phosphate handling stayed unchanged. Iliac crest bone biopsies after tetracycline double-labelling showed initially a high bone turnover (P less than 0.01) with a reduced amount of cortical and trabecular bone (P less than 0.05). Following treatment bone formation rate decreased at both cellular and tissue level (P less than 0.01). No significant changes were observed in the amount of cortical and trabecular bone. The investigation shows that propranolol, in contrast to antithyroid medication, lacks any curative effect on the accelerated bone loss in hyperthyroidism.

Adult↗

Bone histology and calcium metabolism in patients with nephrotic syndrome and normal or reduced renal function.

Bone histology and its relationship with calcium metabolism was evaluated in adult patients with nephrotic syndrome: 29 had normal renal function (GFR 103 +/- 4 ml/min/1.73 m2) (group 1) and 20 had renal insufficiency (GFR 31 +/- 4 ml/min/1.73 m2) (group 2). In group 1, serum PTH, 1.25-HCC and 24.25-HCC levels were normal, while 25-HCC values were reduced. Bone histology was normal in 76% of the patients, while 17% had isolated osteomalacia and 7% an associated bone resorption. Group 2 showed a higher incidence of bone resorption when compared with a matched group of patients with renal failure and no proteinuria (40% vs. 13%) and a comparable frequency of isolated mineralization defect (25% vs. 34%). PTH levels were definitely increased and serum total calcium and all the vitamin D metabolites were reduced. A significant correlation between the apparent duration of the disease and the severity of osteodystrophy was found only in group 2. In conclusion, no constant derangement of calcium metabolism and bone histology is evident in patients with nephrotic syndrome and normal renal function, while patients with persistent proteinuria are at high risk of osteodystrophy even in the early phases of renal failure.

Adolescent↗

Vitamin D levels and trabecular bone remodelling before and after surgery for medullary thyroid carcinoma.

We previously reported increased mean serum 1,25-dihydroxyvitamin D (1,25-(OH)2D) and increased trabecular bone remodelling in patients with medullary thyroid carcinoma (MCT) and hypercalcitoninaemia. In the present paper we report that serum 1,25-(OH)2D and trabecular bone remodelling decreased following surgical cure for MCT and hypercalcitoninaemia in 4 patients despite no detectable post-surgical hypoparathyroidism or hypothyroidism. The results obtained in the present small number of patients suggest that the altered vitamin D metabolism and trabecular bone remodelling in patients with MCT is caused by the hypercalcitoninaemia.

24,25-Dihydroxyvitamin D 3↗

Hip joint distension in osteoarthrosis. A triple-blind controlled study comparing the effect of intra-articular indoprofen with placebo.

In a triple-blind controlled study, significant pain alleviation (p less than 0.01) was registered in patients with osteoarthrosis (OA) of the hip in the first 24 h after hip joint distension. There was no significant difference between treatment with indoprofen (a new non-steroidal anti-inflammatory drug for intra-articular use) and placebo. Pain relief lasted for at least 12 weeks in approximately half of the patients, in whom a significant increase in joint mobility was registered. Intra-articular indoprofen was not superior to placebo as regards pain relief or increased joint mobility. These findings indicate that the effect of a single hip joint distension in OA is due to a mechanical distension of the joint capsule, perhaps involving disruption of local agglutinations, and not due to suppression of inflammation.

Adult↗

Osteopenia with normal vitamin D metabolites after small-bowel resection for Crohn's disease.

Thirty-six unselected patients were investigated 3-24 years (mean, 7.8 years) after small-bowel resection for Crohn's disease (mean small intestinal resection, 105 cm). Iliac crest bone biopsies after in vivo tetracycline double-labelling showed a markedly reduced trabecular bone mass (controls, 0.25 +/- 0.06; patients, 0.15 +/- 0.05; p less than 0.01). The average bone remodeling and osteoid mineralization was normal, and only two patients demonstrated signs of frank but slight osteomalacia. The mean serum levels of the three vitamin D metabolites 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D were normal. The observed reduction in trabecular bone mass may theoretically be followed by an increased risk of spontaneous fractures.

24,25-Dihydroxyvitamin D 3↗

Effects of hypovolemia on local metabolic changes in skeletal muscle following high velocity missile injury.

The effect of blood loss and reinfusion after 6 h on the tissue damage around a high-velocity missile tract in skeletal muscle has been studied in pigs (n = 13). Hemodynamic variables and blood chemistry were monitored and the levels of ATP, creatine phosphate (CP), glucose, glucose-6-phosphate ( G6 -P), and lactate were repeatedly analyzed in muscle samples from the wound area and from control tissue. In vitro amino acid incorporation into proteins by isolated ribosomes was also studied. The missile injury induced pronounced local metabolic disturbances in the muscle tissue surrounding the missile tract. After 6 h these disturbances were more pronounced and extended further out from the wound channel in bled than in unbled animals. One hour after reinfusion of the shed blood, no remaining difference in the size of the metabolically disturbed tissue area between the two groups of animals could be demonstrated. It is thus concluded that a moderate hypovolemia markedly increases the metabolic deterioration around a high-velocity missile tract in skeletal muscle but that volume restitution, even if given as late as 6 h after the missile injury and the blood loss, will almost completely within 1 h reverse the effects caused by the hypovolemia.

Amino Acids↗

Phase-I study of alpha-1,3,5-triglycidyl-s-triazinetrione (NSC 296934).

alpha-1,3,5-Triglycidyl-s-triazinetrione (TGT) is a triepoxide derivative with alkylating properties discovered by random screening. TGT has been found to be active against a wide variety of murine tumors, including a P388 subline resistant to cyclophosphamide. The starting dose in this phase-I study was 30 mg/m2 as a single dose IV, repeated every 3-4 weeks, increasing up to 2,700 mg/m2. Severe dose-limiting toxicity took the form of phlebitis becoming apparent a few days after treatment. This was initially seen at the 480 mg/m2 dose level, and was observed with increasing frequency and intensity at higher dose levels. Leukopenia occurred regularly at dose levels above 1,800 mg/m2 and resulted in life-threatening leukopenia in one patient, and in a toxic death at 2,700 mg/m2 in another patient. Other toxic side-effects included moderate reversible thrombocytopenia, nausea, and vomiting. It is recommended that further trials with TGT await the development of more water-soluble formulations or of other triepoxide derivatives.

Adult↗

Properties of white trunk muscle from saithe Pollachius virens, rainbow trout Salmo gairdneri and herring Clupea harengus: protein synthesis in vitro, electrophoretic study of proteins.

1. Ribosomes were isolated from white trunk muscle of saithe (Pollachius virens), rainbow trout (Salmo gairdneri) and herring (Clupea harengus). 2. Incorporation of amino acids into protein by the ribosomes was determined in systems containing liver cell sap from rainbow trout. 3. Incorporation of phenylalanine into protein was as follows: saithe 163.19 +/- 7.64 pmol, rainbow trout 126.99 +/- 3.07 pmol, herring 29.34 +/- 1.28 pmol per g wet weight of tissue and 4 min of incubation at 28 degrees C. 4. Proteins associated with the ribosome fractions showed minor differences between the species as analysed by polyacrylamide gel electrophoresis in sodium dodecylsulfate. Proteins of myofibrillar origin were predominant in those fractions.

Animals↗

Depressive effects of acrylic cement components on bone metabolism. Isotope release and phosphatase production studied in vitro.

In vitro methyl methacrylate bone cement components were found to depress the release of radioactive calcium and proline as well as the activity of both alkaline and acid phosphatases. These effects were dose dependent and reached levels observed for dead bone. These observations may reflect part of the pathogenesis of loosening of joint replacements involving the use of bone cement.

Acid Phosphatase↗

Long-term treatment of rheumatoid arthritis with fenclofenac or gold: a controlled, single blind trial comparing clinical and biochemical parameters.

A randomized parallel group study to compare the effects of fenclofenac and gold was carried out in 35 patients with active rheumatoid arthritis. Patients were treated with either 1200 mg fenclofenac per day or gold in standard doses in addition to their non-steroidal anti-inflammatory therapy and monitored for up to twelve months. The two treatments produced similar improvements in erythrocyte sedimentation rate, orosomucoid and haptoglobin. In addition, gold produced improvements in haemoglobin, IgG and alpha 1-antitrypsin, but there were no statistically significant differences between the clinical responses. Fenclofenac caused significantly fewer and less serious unwanted effects.

Anti-Inflammatory Agents↗

Regional muscle tension and pain ("fibrositis"). Effect of massage on myoglobin in plasma.

In thirteen patients, all women, with regional muscle tension and pain ("fibrositis") plasma myoglobin concentration was measured before and after massage. A significant increase was observed in the plasma myoglobin concentration reaching a maximum three hours after the start of massage treatment (median 133 micrograms/l). A positive correlation was found between the degree of muscle tension and the increase in plasma myoglobin concentration. After repeated massage treatment a gradual decline could be demonstrated in the increase of the plasma myoglobin concentration in coincidence with the efficacy of the treatment. Opposed to this only normal levels of myoglobin were found in plasma when muscles without tenderness and pain were treated with massage. The observed increase of myoglobin in plasma after massage indicates a leak of myoglobin from the muscle fibres, which suggests that regional muscle tension and pain is associated with disorders in the muscle fibres.

Adult↗