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Biomedical subjects

J Nilsson

Publications and source records attributed to J Nilsson.

At least 199 records · Page 11Linked to original sources

A disease monitoring system for dairy herds.

A system for recording and evaluating disease, intended for both dairy herd health monitoring and research purposes, is described. The system was initiated in 1960 with the objective of providing a research database and it has been developed to respond to the herd health management needs of modern farmers and veterinarians. The system is probably one of the oldest disease recording systems in existence and has contributed to the expansion of epidemiological knowledge of dairy cattle diseases and has helped to improve the health management of dairy herds. The history of the system, the herd reporting form and various analyses and reports generated with the system are presented.

Animals↗

Median nerve sensory responses evoked by tactile stimulation of the finger proximal and distal phalanx in normal subjects.

We compared the characteristics of near-nerve recorded sensory potentials elicited in response to electrical stimulation of digital nerves versus tactile stimulation of the digital skin in 17 healthy subjects with a mean age of 26 years. We also calculated the density of Meissner's corpuscles in the distal and proximal phalanx of digit III of 6 males who had suffered a violent death, but were free from diseases of the peripheral nerve system. Responses to tactile stimulation had a longer latency and lower amplitude than responses to electrical stimulation. Unlike electrically elicited responses, responses to tactile stimulation, which consisted of six or seven main spike components plus several minor components, were similar in recordings from the wrist and elbow. However, with proximal stimulation the electrically evoked responses were more compact and had a higher amplitude and area, whereas the tactile evoked potential became significantly reduced in maximum amplitude and cumulative area. The differences in sensory conduction between distal and proximal could reflect activation of a larger number of nerve fibers when electrical stimuli are used and a smaller amount of mechanoreceptors when tactile stimuli are used.

Action Potentials↗

Cyclic AMP, early response gene expression, and DNA synthesis in rat smooth muscle cells.

Smooth muscle cells (SMC) isolated from neonatal and adult rats differ markedly in their growth characteristics. The growth of neonatal cells is mainly due to autocrine stimulation, whereas the growth of adult SMC is dependent upon addition of exogenous mitogens. Increasing intracellular cyclic AMP (cAMP) levels effectively inhibits DNA synthesis in adult cells, but is essentially without effect on the rate of DNA synthesis in neonatal cells. In the present study we investigated whether this difference in cAMP sensitivity is due to an effect of cAMP on early response genes. The results show that increasing intracellular levels of cAMP by exposing the cells to the synthetic adenosine analogue N-ethyl-carboxamido adenosine (NECA) results in an accumulation of c-jun and c-fos mRNA in both cell types. NECA also lowered c-myc mRNA levels in neonatal cells, whereas it marginally increased the presence of c-myc mRNA in adult cells. Exposure to NECA also resulted in a limited increase in alpha-actin mRNA levels. NECA did not inhibit DNA synthesis or growth of adult SMC actively proliferating in the presence of 10% serum, suggesting that cAMP interferes with processes taking place during the early G1 phase or in the entry of growth-arrested cells into the G1 phase of the SMC cell cycle. It is concluded that the growth-inhibitory effect of NECA is unlikely to be due to actions of cAMP on early response genes. However, it cannot be completely excluded that an increased synthesis of jun/fos transcription factors may induce the transcription of other, growth-suppressing genes in the cells.

Adenosine↗

Abnormalities in T-lymphocyte populations in blood from patients with demyelinating polyneuropathy associated with monoclonal gammopathy.

Patients with monoclonal gammopathy secrete monoclonal antibodies (M-component), that in some patients are associated with polyneuropathy. The M-component has been shown to react with peripheral nerve myelin in some of these patients. However, it is not known whether the M-component secreting B-cells are autonomous or subject to regulation by T-cells or if other cellular abnormalities may occur. In order to define circulating lymphocyte subpopulations, flow cytometry was done on blood samples from patients with monoclonal gammopathy and demyelinating polyneuropathy (n = 13) and patients with monoclonal gammopathy without polyneuropathy (n = 11), and were compared to healthy controls. Significantly increased proportions of primed T-helper (CD4+) cells, i.e. those expressing helper/inducer function (CD29+ CD4+), providing help for antibody secretion, as well as decreased proportions of naive, unprimed suppressor/inducer (CD45RA+ CD4+) T-helper cells were found in patients with M-component associated polyneuropathy. Within the T-cytotoxic/suppressor population (CD8+) we found an increased proportion of killer/effector (S6F1+ CD8+) cells and a decreased proportion of suppressor/effector (S6F1- CD8+) cells in patients with monoclonal gammopathy and polyneuropathy. Similar findings were found in monoclonal gammopathy patients without polyneuropathy, although the deviations in general were less pronounced and did not reach statistical significance compared to the controls. The proportion of natural killer (NK) cells (CD56+) was markedly decreased in all patients with monoclonal gammopathy. In the whole group of patients with monoclonal gammopathy, we found clear proportions of interleukin-2 receptor (CD25+) expressing lymphocytes, indicating the presence of activated T-cells. No clear correlation between abberations in T-cell subtypes and clinical severity of the demyelinating polyneuropathy or titres of anti-PNM antibodies was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The time constants of motor and sensory peripheral nerve fibers measured with the method of latent addition.

The time constants of motor and sensory fibers in the human ulnar, median and tibial nerves were determined using the method of latent addition. Two square-wave stimuli were applied: the first one was subthreshold and the second, at various delays relative to the first, was adjusted to achieve threshold activation. Strength-delay curves were obtained, from which the time constant was determined using a mathematical model. Sensory fibers had time constants that were about 3 times the time constant for motor fibers. The strength-delay curves gave similar time constants as those obtained from strength-duration curves.

Adolescent↗

Expression of HLA-DR antigen and smooth muscle cell differentiation markers by valvular fibroblasts in degenerative aortic stenosis.

OBJECTIVES: This study was designed to analyze the functional characteristics of fibroblasts present in aortic valves with degenerative stenosis. BACKGROUND: Morphologic analysis of degenerative stenosis of tricuspid aortic valves has revealed an extensive interstitial fibrosis. METHODS: Stenotic aortic valves collected during aortic valve replacement and control valves collected at autopsy were fixed in formaldehyde, cryosectioned and stained with antibodies against leukocyte markers, HLA-DR and intracellular filaments. Fibroblasts isolated from stenotic valve and skin explants were grown in cell culture, and their proliferative activity was analyzed by cell counting and uptake of tritiated thymidine. RESULTS: In the stenotic valves nearly all interstitial cells expressed vimentin, and approximately 60% of the cells also expressed alpha-actin and desmin. HLA-DR was present on inflammatory cells as well as on one-third of the fibroblast-like cells in the interstitium. Macrophages were found in the interstitium and T lymphocytes close to calcium deposits and in subendothelial areas. In control valves, fibroblasts expressed vimentin but not alpha-actin or desmin. Few inflammatory cells were present in these valves, and HLA-DR expression was restricted to the endothelial surface. In culture, stenotic valve fibroblasts had a reduced ability to proliferate in serum and to activate DNA synthesis in response to growth factors compared with skin fibroblasts from the same patient. CONCLUSIONS: The observation that fibroblasts present in aortic valves with degenerative stenosis express smooth muscle cell characteristics and HLA-DR antigen and show signs of cellular senescence in vitro suggests that they are in a state of chronic activation similar to that observed in fibromatosis and scleroderma lesions.

Actins↗

Accumulation of T lymphocytes and expression of interleukin-2 receptors in nonrheumatic stenotic aortic valves.

OBJECTIVES: Cell-specific antibodies were used to identify immunocompetent cells in a comparison of valves from patients who had symptomatic tricuspid aortic stenosis with subjects who had no evidence of valvular heart disease. BACKGROUND: Nonrheumatic valvular aortic stenosis is the most common valvular heart disease among adults. The biologic processes involved in the development of this disease are poorly understood. METHODS: Tricuspid stenotic aortic valves were obtained from 19 patients undergoing surgery for nonrheumatic valvular aortic stenosis, and 10 control valves were collected at autopsy. The valves were fixed in formaldehyde, cryosectioned and stained with antibodies against fibroblasts, endothelial cells, macrophages, T lymphocytes and interleukin-2 receptors. A subset of valves were also analyzed with antibodies against T-helper cells and cytotoxic T cells. RESULTS: Stenotic valves were characterized by a basal accumulation of calcium deposits and a cell-rich subendothelial thickening. The immunohistologic analysis indicated that the cells in the subendothelial connective tissue were fibroblasts. T lymphocytes appeared to be the most common cell type in the vicinity of the calcium deposits and were also found close to the endothelial lining of the valves. T-helper cells were more frequent than cytotoxic T cells. Expression of interleukin-2 receptors occurred at the same location as T lymphocytes. Control valves lacked subendothelial thickening and contained only few cells reacting with antibodies against lymphocytes and macrophages. CONCLUSIONS: The presence of activated T lymphocytes in tricuspid stenotic valves suggests that immunologic mechanisms may be involved in the etiology of nonrheumatic aortic stenosis.

Aged↗

Recombinant apolipoprotein A-I Milano reduces intimal thickening after balloon injury in hypercholesterolemic rabbits.

BACKGROUND: Several epidemiological studies have shown an inverse relation between high-density lipoprotein (HDL) cholesterol levels and coronary heart disease. Recently, observational studies have suggested a similar inverse relation between HDL and restenosis after coronary balloon angioplasty. Despite these observations, it is unclear whether this inverse relation reflects a direct vascular protective effect of HDL or apolipoprotein (apo) A-I, the major apolipoprotein component of HDL. Therefore, to determine whether HDL directly influences neointima formation, we investigated the effect of recombinant apo A-I Milano (apo A-I M), a mutant of human apo A-I with Arg-173 to Cys substitution, on intimal thickening after balloon injury in cholesterol-fed rabbits. METHODS AND RESULTS: Cholesterol feeding was initiated 18 days before injury and continued until the time of death. Eight rabbits received intravenous injections of 40 mg of apo A-I M linked to a phospholipid carrier on alternate days, beginning 5 days before and continuing for 5 days after balloon injury of femoral and iliac arteries. Eight rabbits received the carrier alone, and four received neither apo A-I M nor the carrier. Three weeks after balloon injury, apo A-I M-treated rabbits had significantly reduced intimal thickness compared with the two control groups (mean +/- SD): 0.49 +/- 0.29 versus 1.14 +/- 0.38 mm2 and 1.69 +/- 0.43 mm2, P < .002 by ANOVA). The intima-to-media ratio was also significantly reduced by apo A-I M (0.7 +/- 0.2 versus 1.5 +/- 0.5 and 2.1 +/- 0.1, P < .002 by ANOVA) compared with the two controls. The fraction of intimal lesion covered by macrophages, as identified by immunohistochemistry using macrophage-specific monoclonal antibody, was significantly less in apo A-I M-treated rabbits compared with carrier-treated animals (25.3 +/- 17% versus 59.4 +/- 12.3%, P < .005). Aortic cholesterol content, measured in an additional 10 rabbits, did not differ significantly between apo A-I M-treated animals (n = 5) and carrier-treated controls (n = 5). CONCLUSIONS: Apo A-I M significantly reduced intimal thickening and macrophage content after balloon injury in cholesterol-fed rabbits without a change in arterial total cholesterol content. Although the precise mechanism of action remains to be defined, these findings are consistent with a direct vascular effect of apo A-I, which could have potential therapeutic implications.

Animals↗

Disproportional bone growth and reduced weight gain in gonadectomized male bovine growth hormone transgenic and normal mice.

Sex steroids have been shown to influence longitudinal bone growth during sexual maturation, partially by increased GH secretion. Mice transgenic for metallothionein promoter bovine GH were developed by pronuclear injection as a model with sex steroid-independent GH secretion. Prepubertal normal and transgenic, male and female mice were either gonadectomized or sham operated. The growth was divided into two segments: peripubertal growth from 30-60 days of age and adult growth from 60-90 days of age. Orchidectomy resulted in a decreased growth rate of the lumbar spine and a decreased weight gain during the peripubertal growth, whereas tibia growth was unaffected. The alteration in proportions between the lumbar spine and the tibia was apparent for both normal and bovine GH transgenic mice, suggesting that the effect was not mediated via decreased GH secretion. Orchidectomy resulted in increased adult tibial growth, whereas weight gain and lumbar growth were unaffected. In female mice, gonadectomy did not influence these parameters during either time period studied. In summary, we present data indicating that the male gonads in a GH secretion-independent manner stimulate pubertal growth of the spine and inhibit the tibial growth of adult animals.

Animals↗

Supramaximal inhibition of cholecystokinin-induced pancreatic amylase release involves desensitization to cytoplasmic Ca2+.

BACKGROUND: Cholecystokinin (CCK) is a major stimulant of pancreatic enzyme secretion. The dose-response relationship for CCK-induced secretion is bell-shaped, with a characteristic supramaximal inhibition. The mechanism for this inhibition has now been studied. METHODS: The kinetics of amylase release and the changes of the cytoplasmic Ca2+ concentration ([Ca2+]i) were recorded during stimulation of guinea-pig pancreatic acinar cells with different concentrations of cholecystokinin octapeptide (CCK-8) and the Ca2+ ionophore ionomycin. RESULTS: Individual cells reacted with [Ca2+]i oscillations at 10(-11)-10(-10) M CCK-8 and with an initial peak followed by a sustained suprabasal level at 10(-9)-10(-8) M of the agonist. The latter response was also seen in suspensions of acinar cells at all tested concentrations of CCK-8 and at 10(-6)-10(-5) M of ionomycin. With increases of extracellular Ca2+ from 0.5 to 5.0 mM there was a rise of [Ca2+]i during exposure to 10(-9)-10(-8) M CCK-8 or 10(-5) M ionomycin but a paradoxical decrease at lower concentrations of CCK-8 or ionomycin. A dose-dependent increase of amylase release was seen at CCK-8 concentrations from 10(-11) to 10(-9) M. At 10(-9)-10(-8) M CCK-8 secretion was characterized by an initial peak followed by a sustained phase. Whereas the initial peak of secretion remained unaffected by increasing CCK-8 from 10(-9) to 10(-8) M, the sustained phase was inhibited (supramaximal inhibition). Increasing extracellular Ca2+ from 0.5 to 5.0 mM transiently enhanced secretion in response to 10(-9) M but lacked effect during supramaximal inhibition of secretion by 10(-8) M CCK-8. CONCLUSIONS: Both initial and sustained CCK-8-stimulated amylase release increase with [Ca2+]i. However, supramaximal inhibition of secretion was not due to a decrease of [Ca2+]i but was characterized by desensitization to the stimulatory effect of [Ca2+]i.

Amylases↗

The role of lipids and antioxidative factors for development of atherosclerosis. The Probucol Quantitative Regression Swedish Trial (PQRST).

The effect of probucol on the development of atherosclerosis is being investigated in the Probucol Quantitative Regression Swedish Trial (PQRST). Hypercholesterolemic patients are randomized to receive either probucol 0.5 g twice daily or placebo in a double-blind manner, in combination with dietary therapy and cholestyramine 8-16 g daily for a 3-year period. The primary endpoint of the trial is the change in atheroma volume, assessed by annual quantitative angiography involving 20-cm segments of the femoral artery. Data from the open diet and prerandomization phase indicate that probucol added to dietary intervention plus cholestyramine produced highly significant reductions in total (-17%), low-density lipoprotein (LDL; -10%), and high-density lipoprotein (-30%) cholesterol. From a subpopulation, LDL levels were isolated during different stages of the prerandomization phase. LDL was exposed to the oxidant Cu2+ and binding to fibroblasts as well as degradation by macrophages was measured. The generation of thiobarbituric acid-reactive substances (TBARS) was also measured. Probucol prevented degradation of copper-exposed LDL by macrophages and also reduced the formation of TBARS, indicating that probucol protected LDL from oxidation. After the trial concludes in December 1992, statistical models will be used to investigate how much of the change in atherosclerosis is explained by changes in lipoprotein concentrations and how much is explained by probucol's antioxidative effects. Thus, other metabolic factors such as dietary intake and circulating levels of lipid soluble vitamins and fatty acids that may modify the possible antioxidative effects of probucol are also measured and will be related to change in atherosclerosis.

Aged↗

The human carboxyl ester lipase-like (CELL) gene is ubiquitously expressed and contains a hypervariable region.

In this paper we characterize the human carboxyl ester lipase-like (CELL) transcript. An analysis of the tissue distribution of the expression of the gene shows that it is expressed in low amounts in all tissues analyzed. This is in contrast to its closely related and functional gene, the carboxyl ester lipase (CEL) gene, which is expressed only in human lactating mammary gland and pancreas. The primary structure of the cDNA encoding the carboxyl ester lipase-like transcript has been determined. The average length of the cDNA is 1214 bases. This sequence includes several termination codons in all three reading frames. The longest open reading frame with the same start of translation as that of the CEL transcript could encode a 59-amino-acid-long peptide, presumably without any function. The CELL gene may have arisen as a result of a gene duplication of the CEL gene followed by deletions and point mutations. However, the mutations are unevenly distributed. In the first three exons no mutations are found compared to the corresponding exons of the CEL gene. On the other hand, in the next exon several point mutations and a 2-base insertion are found and are present in all individuals analyzed. A hypervariable region present in the last exon of the CELL gene is also characterized. Several allelic variants can be resolved by polymerase chain reaction amplification of this region followed by sequencing using an automated laser fluorescent sequencer.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗