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Biomedical subjects

E Lindh

Publications and source records attributed to E Lindh.

At least 37 records · Page 2Linked to original sources

Effects of parathyroid hormone on cyclic AMP-formation and cytoplasmic free Ca2+ in the osteosarcoma cell line UMR 106-01.

The effects of parathyroid hormone (PTH) on cytoplasmic free Ca2+ (Cai2+) and cAMP-formation were investigated in the rat osteosarcoma cell line UMR 106-01. In fura-2 loaded adherent single cells bPTH 1-34 (10 nM - 1 microM) induced a rapid transient increase in Cai2+ in 11% of the studied cells. In fura-2 tracings from UMR 106-01 cells in suspension, bPTH 1-34 (0.1 microM) induced a transient increase in Cai2+ in 20% of the experiments. The transient increase in Cai2+ seen in suspensions of cells was not abolished by addition of EGTA (2.5 mM) prior to challenge with PTH, suggesting that the increase in Cai2+ was derived from intracellular stores. A marked rapid increase in cAMP-formation was observed in all experiments with cells in suspension, also in the experiments where PTH did not affect Cai2+. These data show that PTH causes a release of Ca2+ from intracellular stores in a small percentage of osteosarcoma UMR 106-01 cells, and that PTH is capable of inducing an increase in cAMP-formation without affecting Cai2+ in osteoblasts.

Animals↗

Low plasma levels of insulin-like growth factor 1 (IGF-1) in male patients with idiopathic osteoporosis.

Experimental studies in vitro indicate that insulin-like growth factor 1 (IGF-1) could be of importance for normal bone growth and remodelling, but the clinical relevance of these observations is unknown. In 12 consecutive young to middle-aged male patients (mean age (+/- SD) 46 +/- 8 years, range 30-57 years) with symptomatic idiopathic osteoporosis, the plasma concentrations of IGF-1 were significantly lower than in healthy subjects (0.51 +/- 0.25 vs. 0.73 +/- 0.23 U ml-1; P less than 0.01). The bone mineral densities in the spine, the femoral neck, and the forearm were significantly different between patients and control subjects. There were positive correlations between the plasma IGF-1 concentrations and the bone densities of the spine and the forearm. Three of the patients received a 5-d course of human recombinant growth hormone (GH). During this short period significant increases in plasma IGF-1 levels and in biochemical indices of bone turnover (serum bone-specific alkaline phosphatase, urinary calcium excretion) were recorded. These observations indicate that circulating IGF-1 could have an important role in maintaining bone mass, and suggest that impairment of IGF-1 production is involved in the pathogenesis of osteoporosis.

Adult↗

Screening for antibodies against gliadin in patients with osteoporosis.

Intestinal disease might contribute to osteopenia. Measurements of IgA antibodies to gliadin have been established as an accepted screening procedure for detection of coeliac disease. When we applied these measurements to 92 patients with verified osteoporosis, 11 subjects (12%) were found to have elevated levels. This is markedly higher than the incidence in healthy subjects (3%). However, the patients with raised levels of IgA antibodies displayed no clinical symptoms and no laboratory evidence of calcium malabsorption. Thus their values for serum calcium, phosphate, parathyroid hormone (PTH), alkaline phosphatase and osteocalcin, as well as the fasting urinary excretion of hydroxyproline and calcium, were similar to those found in other patients with osteoporosis. Intestinal biopsy verified coeliac disease in three patients and was normal in another three. This gives an incidence of verified coeliac disease in this patient group that is approximately tenfold higher than that in the healthy population. Subclinical coeliac disease appears to be unusually over-represented among patients with idiopathic osteoporosis, and screening for gliadin antibodies might therefore be a valuable addition to the routine assessment of the osteopenic patient. The mechanisms underlying the relationship are not clear, but calcium malabsorption is not evident.

Aged↗

Detection of human papillomavirus (HPV) using dot blot and Southern blot, hybridizing with a mixture of seven probes.

A previously presented method for the detection and typing of human papillomavirus (HPV) DNA has been modified for the simultaneous analysis of HPV types 6, 11, 16, 18, 31, 33 and 35. The method has two steps, where a dot blot test is used to exclude cases that do not hybridize with HPV-DNA. The remaining cases are then analysed by a Southern blot procedure, using a mixture of subgenomic probes for the simple and accurate analysis of HPV types. When the procedure was used for the analysis of clinical samples, patient groups at varying risk were found to differ with regard to the prevalence of HPV infections. Thus, the virus was detected in only 8.8% of otherwise healthy young women - i.e. women without clinical signs of HPV-related disease - as compared to 48% of women who also had cervical intraepithelial neoplasia (CIN). A similarly high prevalence was found in patients in whom CIN persisted (42%) as compared to those in whom the morphological lesion regressed to normal (8%).

Blotting, Southern↗

Detection of human papillomavirus (HPV) infections in Japanese women with and without abnormal cervical cytology by dot blot and Southern blot hybridization.

The frequency of human papillomavirus (HPV) was investigated in 245 Japanese women (100 showing normal cytology and 145 showing abnormal cytology). A previously presented method for the detection and typing of HPV DNA was used, where a dot blot test excluded samples that did not hybridize with HPV DNA. Positive samples were further analyzed by a southern blot procedure, to give the HPV type. A mixture of subgenomic probes of the types 6, 11, 16, 18, 31, 33 and 35 was used. HPV DNA was detected in only 2% (2/100) of patients without abnormal cytology. In patients with abnormal cytology, the frequency was 30% (43/145). HPV was detected in 100% (2/2) of the patients with condyloma acuminatum, 39% (26/66) of those with mild to moderate dysplasia, 44% (7/16) of those with severe dysplasia to carcinoma in situ, and 70% (7/10) of those with invasive carcinoma. Young women (20-29 yr.) had the highest HPV frequency (71%). HPV types 16 and 18 were found in 39% of the patients with mild to moderate dysplasia, in 71% of those with severe dysplasia to carcinoma in situ and in 86% of those with invasive carcinoma. These may be considered as high risk types for development to cancer. HPV type 31 may be considered as a moderate risk, as it was detected in 37% (16/43) of the patients. HPV types 6 and 11 were found in 100% of patients with condyloma acuminatum (2/2). To clarify the natural history of the HPV infection in the uterine cervix, it is necessary to conduct further studies.

Blotting, Southern↗

Human papillomavirus infection of the male diagnosed by Southern-blot hybridization and polymerase chain reaction: comparison between urethra samples and penile biopsy samples.

A group of 108 healthy men aged 18 to 23 years underwent penoscopy after application of acetic acid. In 39 (37%) aceto-white lesions were found and a biopsy was taken. From 105 patients a urethra sample was collected with a brush. The prevalence of HPV-DNA by dot-blot and Southern-blot hybridizations (DBH/SBH) and polymerase chain reaction (PCR) as well as the correlation between results from urethra samples and penile aceto-white epithelium were examined. In urethra, HPV-DNA was detected in four of the 66 patients (6%) with normal epithelium and in three of the 39 (8%) with aceto-white epithelium by using DBH/SBH. By PCR the corresponding findings were eight (12%) and 10 (26%) HPV-DNA-positive patients, respectively. Out of the 39 biopsy samples HPV-DNA was detected in six (15%) by DBH/SBH and in 17 (44%) by PCR. Twenty-two (56%) of the patients with aceto-white lesions were by PCR positive in either the urethra sample or biopsy. All samples positive by DBH/SBH were also positive by PCR except for one biopsy with HPV 35, a type not tested for by PCR. HPV 11 was the most common finding in urethra and HPV 6 and 16 in aceto-white epithelium.

Adolescent↗

Synthetic human calcitonin in postmenopausal osteoporosis: a placebo-controlled, double-blind study.

A placebo-controlled, double-blind study was carried out over 4 months to evaluate two doses of synthetic human calcitonin (0.25 and 0.125 mg) given s.c. three times per week. Enrolled were 60 women, aged 56-82 years, who had experienced a vertebral fracture due to low-energy trauma within the preceding year. During active treatment there was within the first month a dose-dependent decrease of the indices of bone resorption (fasting urinary calcium and hydroxyproline excretions), whereas only the higher dose and a treatment period of 4 months produced a reduction of bone formation (serum osteocalcin). The bone mineral content (BMC) of the nondominant forearm was unchanged. Treatment with calcitonin also had significant, dose-dependent, analgetic effects. The amelioration of pain was, in multivariate analyses, related to a reduction in parameters felt to be markers for bone resorption. In the placebo group there was a significant reduction of the BMC of the forearm but no changes of any of the biochemical markers for bone turnover and no improvement of pain. In conclusion, treatment with two low doses of calcitonin induced changes of the biochemical markers of bone turnover in a dose-dependent manner. The analgetic properties of calcitonin were also of salient clinical importance. The knowledge derived from this study could be adapted to the dosage schedule in long-term trials in osteoporosis.

Aged↗

Skeletal responsiveness to parathyroid hormone in healthy females: relationship to menopause and oestrogen replacement.

In order to directly evaluate the role of parathyroid hormone (PTH) and its interaction with oestrogens for postmenopausal bone loss, studies were performed where synthetic human (1-38) PTH was infused s.c. over 24 h in 15 healthy females. Measurements were made of serum electrolytes, PTH and biochemical indices of bone turnover: serum osteocalcin and alkaline phosphatase and fasting urinary hydroxyproline and calcium. During the infusion of PTH there were significant increases of serum calcium (15%), fasting urinary calcium (55%) and hydroxyproline (80%) but a reduction of the serum osteocalcin concentrations (15%). There were significant relations between the calcaemic response and the increases of urinary calcium and hydroxyproline and the two latter were also closely related. There was, however, no correlation between the responses to PTH for the formative vs the resorptive indices. Postmenopausal women displayed greater increases of serum calcium and fasting urinary hydroxyproline indicating greater skeletal sensitivity to exogenous PTH. Following treatment with oestrogens the indices of skeletal responsiveness were reversed towards the premenopausal values. The findings demonstrate that during short-term infusion of PTH there is a dissociation between bone resorption and formation and, furthermore, that the menopause is associated with an enhanced skeletal sensitivity for PTH.

Adult↗

Phenotypical properties of Enterobacter agglomerans (Pantoea agglomerans) from human, animal and plant sources.

Clinical, animal and plant isolates, representing different geographical areas, were identified as Enterobacter agglomerans (Pantoea agglomerans) using a quantitative bacterial dot method for DNA-DNA hybridization. The phenotypical properties of the 65 strains were investigated by conventional test methods. No strain decarboxylated ornithine. Twenty-two strains, mainly plant isolates, showed delayed acid production from alpha-methyl-glycoside, a trait which may have ecological significance. With regard to these two properties, our results differed from the description of Pantoea agglomerans given by Gavini et al. (6); further investigations will clarify these differences. Three non-pigmented, maltose-negative and salicin-negative variants were derived from yellow pigmented, maltose-positive, salicin-positive strains.

Animals↗

Genomic groups and biochemical profiles of clinical isolates of Enterobacter cloacae.

A collection of 123 clinical strains presumptively identified as Enterobacter cloacae and 12 type and reference strains of Enterobacter spp. were genotypically investigated by a quantitative bacterial dot method for DNA-DNA hybridization, giving an estimate of delta Tm (difference in thermal denaturation midpoint between homologous and heterologous duplexes). The API 20E system was used for phenotypic characterization. Using discontinuities in the values of delta Tm as criterion, five genomic groups of E. cloacae could be demonstrated, eleven ungrouped strains representing at least one additional group. Nine API profiles were found, the ideal phenotype of E. cloacae (i.e. the phenotype showing the most common reaction for the species in all tests studied) being the most frequently found. The type strain of E. cloacae and the reference strain CDC 1347-71 represented rather small genomic groups of three and eight strains respectively, most of them inositol positive. A majority of 98 isolates formed one single genomic group, biochemically dominated by the ideal phenotype. The genomic groups could not be differentiated phenotypically. At present there seems to be no reason for an attempt to split E. cloacae into two or more species. The type strain of E. dissolvens showed itself to be closely related to the type strain of E. cloacae (delta Tm 2.3 degrees C), indicating that the two species may be regarded as subjective synonyms.

DNA, Bacterial↗

Short-term effects of pamidronate on biochemical markers of bone metabolism in osteoporosis--a placebo-controlled dose-finding study.

The bisphosphonates are potent inhibitors of osteoclastic bone resorption that mainly have been used for treatment of hypercalcaemia secondary to malignancy. We have performed a controlled dose-finding study of oral pamidronate that was given to 60 patients with a history of fracture of the distal forearm, an enhanced bone turnover and a lowered bone mineral density. Different doses of pamidronate, 75 mg and 150 mg daily, or placebo were given to parallel groups. Fasting specimens of blood and urine were collected before the treatment period and at regular intervals. Oral pamidronate caused a dose-related reduction on the biochemical markers of bone resorption, i.e. fasting urinary calcium, hydroxyproline, pyridinoline and deoxypyridinoline that was seen already after the first week. The inhibition was evident during the treatment period and 4 weeks thereafter but not 12 weeks after cessation of therapy. Also the levels of serum osteocalcin, a marker of bone formation, were lowered during treatment with the higher dose.

Administration, Oral↗

Disturbance of basal and stimulated serum levels of intact parathyroid hormone in primary hyperparathyroidism.

In patients with primary hyperparathyroidism, measurements were made of basal and stimulated levels of intact parathyroid hormone (PTH). The basal PTH values were elevated in all but six of 89 patients and provided clear separation towards normal individuals (n = 75) and patients with hypercalcemia of other origin (n = 34). The PTH value correlated with the serum calcium concentration in hyperparathyroidism and with the weight of excised parathyroid adenomas but not with that of chief cell hyperplasias. A constant ethylenediaminetetraacetic acid infusion during 60 minutes of induced essentially linear reductions of plasma-ionized calcium concentrations, averaging 0.02 mmol/L/10 minutes, which were associated with swift, curvilinear, elevations of PTH levels that reached a plateau after 10 to 20 minutes. The increment in serum PTH level correlated with the basal PTH value both in patients with hyperparathyroidism and controls. However, in proportion to the much greater glandular mass in the patients with hyperparathyroidism, the secretion of PTH was relatively reduced. The findings support the value of the intact PTH assay in the differential diagnosis of hypercalcemia and show that PTH secretion in vivo is extremely sensitive to hypocalcemic stimulation, that the pathological parathyroid tissue in hyperparathyroidism is characterized by a reduction of hormone release per unit weight, and that the hormone secretion in hyperparathyroidism operates closer to its maximal capacity than under normal circumstances.

Adult↗

Antibiotic susceptibility and beta-lactamase production in clinical isolates of Enterobacter spp.

The in vitro susceptibility of 237 clinical isolates of Enterobacter spp. (E. aerogenes, E. agglomerans and E. cloacae; 41, 64 and 132 respectively) to 16 different antibiotics is described. Four quinolones (ciprofloxacin, lomefloxacin, norfloxacin and ofloxacin), two new cephalosporins (cefpirome and cefepime) and imipenem, all showed high activity against the three Enterobacter species tested (MIC50 less than or equal to 0.125 mg/l, MIC90 less than or equal to 0.5 mg/l). Also the aminoglycosides gentamicin and tobramycin were highly active antibiotics (MIC50 less than or equal to 0.5 mg/l, MIC90 less than or equal to 1.0 mg/l). The susceptibility of beta-lactam-antibiotics to beta-lactamase produced by Enterobacter spp. was evaluated, and imipenem and cefepime were found to be most stable. Different methods for detection of inducible beta-lactamases were used, the agar dilution method being more sensitive than the double-disc diffusion test. Elevated beta-lactamase production was detected, via induction, in 83% of E. aerogenes strains and 70% of E. cloacae strains, with cefamandole used as the substrate and cefoxitin as the inducer. Constitutive, high level enzyme production was detected in 7 and 13% respectively of the E. aerogenes and the E. cloacae strains. In all the strains of E. agglomerans, 10% of E. aerogenes and 13% of E. cloacae, no beta-lactamases could be detected with the methods studied.

Aminoglycosides↗

Use of cervical Cytobrush samples for dot-blot detection and Southern blot typing of human papillomaviruses using subgenomic probes.

The use of Cytobrush samples for the detection and typing of cervical human papillomavirus (HPV) infections was analyzed. The average yield of squamous cells from Cytobrush samples was on the order of 10(6) cells when the sample was collected in a lytic collection buffer, which was approximately double the content of (1) samples collected in ethanol and (2) an average biopsy specimen. The material obtained could be used for sensitive detection and typing of HPV infections using, respectively, a nonradioactive dot-blot method and the Southern blot procedure performed with subgenomic probes, which permitted a simple interpretation even in cases of mixed infections. A sample containing at least 500,000 viral copies was required for the detection and typing. At this level of sensitivity, the frequencies of HPV obtained in different risk groups varied from 6% (in "healthy" young women) to 53% (in women with abnormal cytologic findings in simultaneous smears). The noninvasive nature of the sampling procedure and the relative simplicity of the test should allow this method to be applied in large-scale studies.

Blotting, Southern↗

Ornithine decarboxylating strains of Klebsiella pneumoniae demonstrated by DNA-DNA hybridization.

Genotypic relatedness was assessed to clarify the taxonomic position of strains phenotypically behaving like K. pneumoniae, but for the ornithine reaction. Using DNA-DNA hybridization it could be shown that 25 non-motile ornithine decarboxylating strains showed high genotypic relatedness to the type strain of K. pneumoniae. Thus, it is proposed that they be considered as ornithine decarboxylating strains of the species K. pneumoniae. The API 20E system was used for phenotypic characterization, but the API code obtained by these strains was not registered in the API Profile Index. However, except for the ornithine reaction the isolates behaved as typical K. pneumoniae. Three ornithine negative strains of E. aerogenes were identified as K. pneumoniae by the API 20E System, but they showed high genotypic relatedness to the type strain of E. aerogenes.

DNA, Bacterial↗

Relative proton density and relaxation times in liver metastases during interferon treatment.

Relaxation times and relative proton densities were calculated from magnetic resonance examinations of the liver in eight patients with liver metastases from neuroendocrine tumours. Single, spin-echo sequences with eight different repetition times and a four-echo sequence were used to calculate T1 and T2 in tumour and normal liver, and the proton density tumour-liver quotient, before and during treatment with interferon. Changes over time of these parameters were compared with variations in tumour marker levels and changes in size and number of the metastases. During therapy, six out of eight cases showed a decrease in tumour T1, five responding to therapy and one with stationary disease, while the two patients with progressive disease showed unchanged tumour T1. The proton density quotient also decreased in a corresponding way, indicating a change in water content in tumours responding to interferon therapy. No significant change in liver T1, tumour T2 or liver T2 occurred in any patient. It is thus possible to perform reliable measurements of relaxation parameters over time, which may be valuable in follow-up of tumour treatment.

Adult↗

Increased fracture risk in hypercalcemia. Bone mineral content measured in hyperparathyroidism.

In the present study, 39 women with mild hypercalcemia, which had been detected 18 years earlier during a health survey, and presumably caused by primary hyperparathyroidism (HPT), were investigated together with 34 age-matched controls. The bone mineral content (BMC) of the nondominant distal forearm was measured by single-photon absorptiometry, and the occurrence of fractures was recorded. Among women up to the age of 70 years, those with hypercalcemia had lower BMC than the controls (P less than 0.05), whereas among the older women, there was no difference. Twelve of the women with probable primary HPT had suffered a distal radius fracture as compared with 3 of the controls (P less than 0.05). Thus, also mild hypercalcemia is a risk factor for bone loss and distal forearm fractures. The findings constitute arguments in favor of early detection and treatment of primary HPT.

Aged↗