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Biomedical subjects

B Johansson

Publications and source records attributed to B Johansson.

At least 613 records · Page 34Linked to original sources

Does successful interferon treatment of tumor patients require life-long treatment?

Case histories of 5 tumor patients treated with natural leukocyte interferon-alpha (IFN-alpha) are presented. One patient with juvenile laryngeal papillomatosis responded well to interferon treatment, but the disease recurred when therapy was withdrawn. Upon reinstitution of treatment, the patient once again responded well. Another patient with myelomatosis also responded well to interferon therapy and in this case, too, the tumor recurred when interferon treatment was withdrawn. Reinstitution of interferon therapy was, however, unsuccessful. One patient with generalized giant cell tumor of bone responded with regression after more than 5 years of interferon treatment. Another patient with pulmonary osteosarcoma metastases, having received irradiation and interferon combination therapy followed by sole interferon treatment, responded well with a lasting stationary radiogram after 6 years of interferon treatment. One patient with malignant glioma, showing signs of tumor growth during the first few months of interferon therapy, eventually responded, and became disease-free after 6 years. The latter 3 patients are continuously receiving interferon therapy although more than 5 years have elapsed since their interferon therapy was initiated. It is suggested that interferon therapy for malignant tumors be given for life (or to progression of disease) in responding patients. Such a concept entails biological implications for interferon therapy in general and for antitumor action of interferons in particular. Other possible clinical schedules should only be constructed within the framework of controlled clinical trials.

Adult↗

Effect of syngeneic anti-idiotypic antibody on influenza virus neuraminidase antibody response.

Influenza viruses possess two major surface glycoproteins - hemagglutinin (HA) and neuraminidase (NA). Py203, a monoclonal antibody (Ab) specific for the neuraminidase of the PR8 (H1N1) influenza virus, was used to prepare syngeneic monoclonal anti-idiotypic (anti-Id) Abs. From a BALB/c mouse immunized with Py203 (anti-N1), we obtained RM1, a monoclonal anti-Id Ab. The Py203-Id was detected in a significant fraction of immunoglobulins (Igs) in the primary and secondary responses elicited by PR8 (H1N1) and X31 (H3N2) viruses. In animals injected with minute amounts of RM1 and subsequently boosted with an identical dose of RM1, no detectable anti-NA activity was noted, but a significant increase in Py203-Id-bearing Igs was observed. In the sera of animals injected with minute amounts of RM1 and subsequently boosted with PR8 (H1N1) or X31 (H3N2) viruses, an increase in anti-NA activity and in the level of Py203-Id was noted. Animals injected with large amounts of RM1 and boosted with PR8 and X31 showed a marked suppression of the Py203-Id but no alteration in the anti-NA response. The anti-Id recognizes an idiotope (the Py203 idiotope) shared by antibodies specific for the N1 and N2 neuraminidase variants.

Animals↗

Calcium and regulation of contraction: a short review.

The purpose of this paper is to review very briefly how our understanding of the control of muscle contraction by calcium has developed, and to give an overview of the different regulatory systems that have been shown so far. It should provide a background for some of the more specific presentations that appear later in the symposium. Three different molecular mechanisms for calcium regulation of actin-activated myosin Mg-ATPase activity have been identified. Control of contraction and relaxation in different types of muscle is dominated by one or the other of these regulatory mechanisms. The troponin-tropomyosin system associated with the actin filaments is the best known of the calcium control systems. It operates, for instance, in vertebrate skeletal and cardiac muscles. Direct binding of Ca2+ to myosin controls contraction in muscles of certain invertebrates such as the scallop. This calcium binding is dependent on the presence of the regulatory light chains on the myosin molecules. In vertebrate smooth muscle, calcium in conjunction with calmodulin activates an enzyme, myosin light chain kinase, which phosphorylates the regulatory light chains of the myosin, and this phosphorylation triggers contraction. Relaxation is brought about by dephosphorylation of the light chains through the action of phosphatase(s). Additional regulatory mechanisms, not yet fully identified, appear to operate in smooth muscles.

Actomyosin↗

Contractures induced by reversed Na+/Ca2+ exchange in rat portal vein: effects of calcium antagonists.

Spontaneous electrical and mechanical activity was abolished in isolated preparations of rat portal vein by exposure to K+-free Krebs solution. This procedure probably also increased the intracellular [Na+] owing to interference with the active transmembrane Na+-K+ transport. Contractures could be induced under these conditions by lowering extracellular [Na+] from the control level of 144 to 17 mM using sucrose, TrisCl, or LiCl as NaCl substitutes. Contractile force depended on the type of substitute: sucrose greater than TrisCl greater than LiCl. These contractures are thought to be caused by influx of extracellular Ca2+ through the Na+/Ca2+ exchanger, which otherwise transports Ca2+ in the opposite direction at normal transmembrane Na+ gradient. The contractile response to low Na+ was rapidly and completely abolished in nominally Ca2+-free medium; it was strongly inhibited by 0.4 mM MnCl2 but was not affected by high concentrations of the organic calcium antagonists, felodipine (10(-6) M), verapamil (10(-5) M), or diltiazem (10(-5) M). We conclude that the Na+/Ca2+-exchanger is an effective pathway for Ca2+ transport over vascular smooth muscle cell membrane; this pathway is not blocked by calcium antagonists.

Animals↗

Felodipine sensitivity in vivo and in vitro of activation pathways in vascular smooth muscles.

Felodipine is a dihydropyridine calcium antagonist that exerts a markedly selective inhibition of the smooth muscle of arterial resistance vessels. In this paper, we report on the effects of felodipine on vascular smooth muscle in vivo and in vitro. Contractions in these effector cells are categorized according to means of activation, membrane events, and sensitivity to felodipine and are discussed in terms of four schematic "activation pathways." Stimulation of aortic smooth muscle by K+ or noradrenaline may be accounted for by separate pathways (I and IV) that might involve potential-operated and receptor-operated Ca2+ channels with high and low sensitivity to calcium antagonists. In the spike-generating vascular smooth muscle of the portal vein, both spontaneous myogenic activity and responses to adrenergic stimuli of physiological intensity are more adequately described in terms of an action potential-mediated pathway (II). This pathway is sensitive to felodipine in nanomolar concentrations irrespective of the primary means of stimulation. Basal tone and adrenergic responses of resistance vessels in vivo show similar sensitivity to felodipine, suggesting that they are also mediated by II or by a closely related pathway (III) involving graded changes in membrane potential rather than in action potentials. The latter activation pathways (II and III) are the ones relevant to the pharmacodynamic effects of felodipine for therapeutic purposes.

Action Potentials↗

Blood clonal B cell excess at diagnosis in multiple myeloma: relation to prognosis.

112 patients with multiple myeloma have been studied at diagnosis for the presence of blood clonal B-cell excess (CBE), defined as a ratio between kappa+ and lambda+ lymphocytes outside the normal range (0.9-3.5). 48 patients (43%) had CBE. The increase in light chain-bearing lymphocytes was always that of the M component light chain isotype. The proportions of patients exhibiting CBE were the same in different stages. The response frequency was not influenced by the presence of CBE. However, patients with CBE had a shorter remission duration time (p less than 0.001) and total survival (p less than 0.05) than those without CBE. This was also noticed when each clinical stage was analyzed separately. Moreover, survival was shorter in patients with a large fraction of CBE than in those with a small one. Cox regression analysis revealed that CBE was a much stronger predictor of remission duration than age, clinical stage and renal dysfunction. CBE and response to initial treatment independently were the best factors to indicate survival. It is suggested that analysis of CBE should be included in the clinical characterization of untreated patients with multiple myeloma.

Adult↗

Lack of effects of polychlorinated biphenyls on testosterone synthesis in mice.

Male mice were exposed to two different preparations of PCBs. The pure congener 2,2',4,4',5,5'-hexachlorobiphenyl (6-CB) was given at daily doses of 4, 20, and 40 mg/kg b.wt. during the perinatal or pubertal period. A technical mixture of PCB (Clophen A50) was administered during puberty at daily doses of 8, 40, 80, 120, and 160 mg/kg b.wt. Treatments were, in the different experiments, carried out every second or third day for three to five weeks. Treatment during puberty was started when the mice were 5 weeks old. The perinatal exposure was started on day 13 of gestation and ended on day 24 post partum. There were no significant differences in the plasma levels of testosterone between the treated mice and the controls after any of the treatments, but there was an increase in the relative testes weights for the animals treated perinatally. No influence on the biosynthesis of testosterone in the testicular interstitial cells in vitro could be demonstrated.

Animals↗

Prealbumin: its association with amyloid.

In recent years prealbumin has been shown to be a major component of two forms of systemic amyloid, senile systemic amyloid (SSA), and familial amyloidotic polyneuropathy (FAP). Despite the fact that the amyloid fibril proteins associated with these two forms of amyloid, designated ASc1 and AF, respectively, share many similarities the clinical features of the two diseases are remarkably different. To understand better this paradox the clinical, histochemical, immunological and biochemical features of SSA and FAP were reviewed.

Adult↗

Plasma testosterone concentrations in male rats during short and long-term stress stimulation.

Plasma testosterone concentrations were analysed in 14 male rats submitted to short-term and prolonged stress stimulation, and the results were compared with those obtained from a control group of seven rats not submitted to the corresponding experimental stress stimuli. Increased levels of circulating testosterone were recorded during the short term stress stimulus. As compared with the control group, plasma testosterone concentrations were reduced after prolonged stress stimulation for 10 days. The increased stress stimulation, that the animals subjected to short- and long-term standardized stress stimuli were subjected to, compared to the corresponding stress of the animals in the control group, was reflected in an increased concentration of catecholamines in arterial blood.

Animals↗

Prosthetic rehabilitation in bilateral high above elbow amputation.

Rehabilitation in patients with bilateral high above elbow amputation presents a considerable prosthetic problem. A patient with high upper arm amputations after a high-voltage injury is presented. He was successfully fitted with multifunctional myoelectric hand prostheses. The problems in rehabilitation of adult bilateral arm amputees are discussed and the value of fitting these patients with electrically powered prostheses is assessed. The balance between technical and clinical aspects is discussed in relation to patient acceptance. In our case good acceptance and functional benefit was noted. The fact is stressed that the bilateral upper extremity amputee can regain considerable physical function with the fitting of suitable prostheses, even if the limb remnants are short and provide little or no function. An extensive team approach at specialized centres will favour the results.

Adult↗

Simplified quantitative determination of plasma phenytoin: on-line pre-column high-performance liquid immunoaffinity chromatography with sample pre-purification.

A method for on-line high-performance liquid immunoaffinity chromatographic analysis of 5,5-diphenylhydantoin (phenytoin) in human plasma is described. The technique is simple and does not require sample preparation or addition of an internal standard, and the phenytoin is eluted from the columns in 12 min. A phenytoin-specific polyclonal immunoglobulin was attached to an organic silane derivative on silica. The immunosorbent was packed into a short liquid chromatography column and installed in a modified high-performance liquid chromatography system for on-line sample pre-purification. Standard curve linearity of plasma phenytoin was obtained at concentrations up to 160 mumol/l. When compared to conventional high-performance liquid chromatography, plasma phenytoin levels gave a correlation coefficient of 0.993. The phenytoin is highly bound to plasma proteins (ca. 87%). When plasma is injected onto the pre-column, a dissociation and partition of phenytoin from plasma proteins to a complete association with on-column insolubilized antibodies results.

Chromatography, High Pressure Liquid↗

Rapid and sensitive on-line precolumn purification and high-performance liquid chromatographic assay for disulfiram and its metabolites.

The disulfiram (Antabus) metabolites diethyldithiocarbamate, diethyldithiocarbamate methyl ester, carbon disulphide and bis(diethyldithiocarbamato) copper complex were quantitatively analysed from directly injected heparin plasma by reversed-phase high-performance liquid chromatography. The highly volatile metabolite, carbon disulphide, was converted to the methyl ester of dimethyldithiocarbamate before chromatography. The analytical procedure is simple and does not require sample preparation or addition of an internal standard, and the compounds are eluted from the columns in 15 min. After automated on-line precolumn enrichment, the parent compound and biotransformation products could be back-flushed and chromatographed on an ordinary reversed-phase column. The influence of plasma protein binding on the constituents in the precolumn enrichment step was also investigated. Dissociation and partition of constituents from plasma proteins gave a complete retardation on the precolumn. The time courses of diethyldithiocarbamate and its methyl ester were followed in patients receiving therapeutic doses of disulfiram.

Alcoholism↗

Exposure to triarylphosphate and polyneuropathy: a case report.

This report describes a case of polyneuropathy in a 48-year-old mechanic who was heavily exposed to hydraulic fluids containing isopropylated triphenylphosphate (ITP). A cross-sectional examination of eight other men exposed to hydraulic fluids and eight controls showed differences in EMGs but not in nerve conduction velocities or other values measured in a clinical examination. The study indicates a possible association between heavy occupational exposure to hydraulic fluids and ITP and polyneuropathy.

Adult↗

Serum lipoproteins and apolipoproteins in young male survivors of myocardial infarction.

Concentrations of serum lipoprotein lipids and apolipoproteins A-I, A-II and B were determined 3-6 months after myocardial infarction in 116 males below the age of 45 and in 116 age-matched controls. Among single variables the sum of cholesterol concentration in VLDL and LDL divided by the HDL cholesterol level was the best discriminator between patients and controls. The concentrations of serum triglycerides, apolipoprotein B, VLDL triglycerides and cholesterol, serum cholesterol, HDL cholesterol and LDL triglycerides, in that order, were better discriminators than was LDL cholesterol level. Among variables reflecting HDL concentration and composition HDL cholesterol was the best discriminator followed by HDL2 cholesterol, apolipoprotein A-I and the HDL cholesterol/apolipoprotein A-I ratio. Multivariate analysis indicated independent significance of elevated VLDL lipid and LDL cholesterol concentrations, and a decreased HDL cholesterol concentration, in relation to MI. The present data suggest that a disturbed triglyceride metabolism, in addition to elevated LDL and decreased HDL cholesterol levels, has an independent and pathogenetic significance for MI at a young age.

Adult↗

Prognostic influence of early diagnostic splenectomy in Hodgkin's disease. A long-term follow-up.

The influence of early laparotomy with splenectomy on prognosis in patients with Hodgkin's disease who were regarded as having uncertain prognostic indices (all patients except those with lymphocytic predominance and nodular sclerosis stages IA and IIA with right-sided presentation, stage IV disease, splenomegaly or age greater than 65 years) was evaluated in a randomized trial initiated in Jan. 1973. The patients were treated with total nodal irradiation (excluding the splenic and hepatic areas) and 33 of 69 patients were randomized to laparotomy with splenectomy. No significant difference in relapse-free or overall survival was found between the two groups after a median observation time of 85 months. Progressive or recurrent disease was as common in splenectomized as in non-splenectomized patients. Splenectomized patients with splenic tumour involvement fared worse than those without. It is concluded that diagnostic laparotomy with splenectomy is of no benefit in this clinical setting.

Adolescent↗