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Biomedical subjects

M Jensen

Publications and source records attributed to M Jensen.

At least 91 records · Page 5Linked to original sources

Reduced rate of uptake of zinc ions in a calf affected with the lethal syndrome A46 relative to clinically normal calves using whole body radio-isotope scanning of 62Zn.

Four clinically healthy control calves were scanned and blood clearance was determined from blood samples taken during the first hour after intravenous injection of 62Zn. Furthermore, one clinically healthy control calf and one calf suffering from the lethal hereditary syndrome A46 were scanned and blood samples taken from five min after intravenous and abomasal injection of 62Zn and onwards for a period of up to 26th. The results show a very fast liver uptake of 62Zn. The estimated rate of plasma/blood clearance and liver uptake for the control calves agrees with values derived from studies on other animals. In contrast, the A46 calf had a decreased rate of plasma/blood clearance and liver uptake relative to the control calves.

Animals↗

Megestrol acetate for anorexia and cachexia.

Based on promising preliminary information obtained from uncontrolled pilot studies, several randomized, placebo-controlled, double-blind clinical trials have been launched to evaluate the effectiveness of megestrol acetate for the treatment of patients with anorexia and/or cachexia. The results of these studies have demonstrated that megestrol acetate can improve patients' appetites and promote nonfluid weight gain in some. They also suggest that megestrol acetate has antiemetic properties. Ongoing clinical trials are evaluating the dose-response relationship of megestrol acetate for these clinical problems and whether megestrol acetate will improve the survival of patients at risk for developing cancer anorexia/cachexia.

Anorexia↗

Localized in vivo proton spectroscopy in the brain of patients with multiple sclerosis.

Localized proton spectroscopy was performed in 15 patients with acute or chronic multiple sclerosis (MS). Some of the patients were investigated serially, being given a total of 22 spectroscopic investigations. Resonances corresponding to free lipids were observed in six plaques. This was distinctly seen in two plaques at Days 70 and 85 after the occurrence of the plaques. A lesser content of lipids in plaques was observed as early as Day 10 and as late as nearly 1 year after occurrence. The relative concentration of N-acetyl asparate (NAA) was significantly lower in patients than in controls, and the relative concentration of choline (Cho) was significantly higher in patients than in controls. These differences were most pronounced in older plaques. MR spectroscopic demonstration of lipids in a MS plaque probably reflects disintegration of myelin, and a decreased NAA/Cho ratio may be related either to gliosis or to axonal degeneration, which sometimes occurs in longstanding MS.

Acute Disease↗

Multiple antigens in the rat visceral yolk sac induce teratogenic antisera.

Preparative isoelectric focusing was used to fractionate the supernatant from a homogenate of day 19 rat visceral yolk sac. Three fractions, of pI ranges 3.5-5.0, 5.0-7.0, and 7.0-9.0, were isolated and used to immunize rabbits, by four or six weekly injections, each containing 5 mg protein. The resulting antisera were all teratogenic when injected into rats on day 9 of gestation, but widely differing potencies were observed. The most potent antiserum was that against yolk sac components focusing in the pI 7.0-9.0 range: An optimum teratogenic dose of 50 mg protein per kg body weight was observed, and a dose of 100 mg/kg was shown to cause 100% embryonic resorption. Antiserum against the fraction focusing in the pI 3.5-5.0 range was the least teratogenic: A significant incidence of embryonic malformation and death was seen only at doses of 600 mg/kg and above. The two fractions that yielded the more teratogenic antisera were refocused over narrower pH ranges, yielding four subfractions in the pI 5.0-7.0 range and eight subfractions in the pI 7.0-9.0 range. Antisera against each of these 12 fractions were raised in rabbits; most of these antisera were shown to be teratogenic, although of differing potencies. It is concluded that the yolk sac contains many antigens that can elicit antibodies with teratogenic and yolk sac-localizing properties.

Animals↗

Ultrastructure and function of the rat yolk sac: damage caused by teratogenic anti-VYS serum and recovery.

It was hypothesized that heterologous anti-rat visceral yolk sac serum (AVYS) exerts its teratogenic effect by reducing the endocytosis of serum proteins by the visceral yolk sac (VYS), thus reducing the supply of amino acids to the embryo and VYS. To evaluate this hypothesis, we studied the effect of teratogenic AVYS on the endocytic function of the VYS and the ultrastructure of the VYS and parietal yolk sac (PYS). Rat conceptuses were exposed to a teratogenic dose of AVYS on the 10th day of gestation in vivo or in vitro. Control and AVYS-exposed specimens were collected 24-192 hr later and prepared for scanning and transmission electron microscopy (SEM and TEM, respectively) utilizing standard procedures. The Endocytic Index was calculated for the VYS utilizing standard procedures. Approximately 97% of the in vivo exposed and 94% of the in vitro exposed embryos were morphologically abnormal. Ultrastructural observations showed that exposure to AVYS in vivo or in vitro caused severe damage to the VYS endodermal epithelial cells with loss of cellular borders, reduction in the number and length of microvilli, and increased cellular inclusions; and some damage to PYS endodermal cells with increased blebbling and decreased cell number. Recovery was evident at 72 hr and complete by 96 hr. The Endocytic Index was significantly reduced in the VYS 24 and 48 hr after injecting AVYS into the pregnant rat but was not significantly different at 96 and 192 hr. Our results show that the AVYS antiserum damaged visceral endodermal epithelium experienced ultrastructural recovery with parallel functional recovery. These studies suggest that transient yolk sac placental ultrastructural damage and dysfunction was probably sufficient to cause irreversible damage to the developing embryo during early organogenesis. We conclude that the proximate effect of the AVYS was on the plasma membrane of the visceral endoderm and that decreased pinocytosis is a consequence of this effect.

Animals↗

Effects of chronic systemic insulin delivery on insulin action in dogs.

The metabolic consequences of the prolonged systemic insulin delivery associated with human pancreas transplantation have not been precisely defined. To determine if systemic insulin delivery in the absence of immunosuppressive agents results in alterations in hepatic or extrahepatic insulin action, three groups of dogs were studied 2 months after either a sham operation or after their pancreatic venous drainage was severed and anastomosed to the inferior vena cava or portal vein (sham, peripheral and portal groups, respectively). The pattern of venous drainage was documented by measuring vena cava and portal insulin concentrations before and after glucose injection. Systemic insulin concentrations were higher (p less than 0.05) in the peripheral group than in the portal group both following a 14-h fast and after intravenous glucose. During a hyperinsulinaemic euglycaemic clamp (1 mU.kg-1.min-1), glucose utilization (measured using [6(3)H]glucose) was slightly lower (p = 0.07) in the peripheral than in the portal group. Hepatic glucose release was equal in all groups. Carbon dioxide incorporation into glucose (an estimate of gluconeogenesis) was higher in the portal than peripheral group in the fasted state but not during insulin infusion. Plasma concentrations and flux rates of fatty acids and amino acids did not differ between groups. We conclude that chronic systemic insulin delivery results in a) systemic but not portal hyperinsulinaemia, b) a minimal impairment in insulin-stimulated glucose uptake, without altering insulin-induced suppression of hepatic glucose release, and c) no effect on fatty acid or amino acid turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Insulin-like growth factor 1 (IGF-1) in burn patients.

Variations in growth factor IGF-1 levels during wound healing were assessed in 23 patients with burns of varying extent and severity. The patients were followed during the postburn period and the IGF-1 levels were regularly measured by radioimmunoassay. All patients with large burns had reduced IGF-1 levels which correlated with the surface area of burn. The most plausible reason for the suppressed IGF-1 level in these patients may be diffusion from the burned skin as we have found a strong correlation between IGF-1 and serum albumin. The reduced IGF-1 levels may contribute to impaired wound healing in these patients.

Adult↗

Substitution of proline 82 by threonine induces autophosphorylating activity in GTP-binding domain of elongation factor Tu.

Mutation of Pro82 into Thr, a residue situated in the second element (D80CPG83) of the consensus sequence proposed to interact with GTP/GDP in GTP-binding proteins was introduced via site-directed mutagenesis in the isolated guanine nucleotide-binding domain (G domain) of elongation factor Tu. G domainPT82 displays virtually no GTPase activity. As a major change, the apparent inhibition of the GTPase reaction is associated with the appearance of autophosphorylating activity, as in ras product p21 in the case of mutation Ala59----Thr, corresponding to 82 in elongation factor Tu. Dependence of this reaction on mono- and divalent cation concentration and on pH is essentially the same as for the GTPase of wild-type G domain. The autokinase reaction follows an apparent first order rate, suggesting an intermolecular mechanism. Analysis of amino acid and peptide composition of the 32P-labeled G domainPT82, as well as Edman degradation of the tryptic peptide containing the covalently bound 32P, shows that Thr82 is the phosphorylated residue. Taken together, these results point out that Thr82 is in close proximity to the gamma-phosphate of GTP, as in the case of Thr59 in p21. These results are in agreement with the observations derived from x-ray diffraction analysis that the tertiary structure of the GTP-binding domain of elongation factor Tu and that of p21 are similar.

Base Sequence↗

Quantitation of blood-brain barrier defect by magnetic resonance imaging and gadolinium-DTPA in patients with multiple sclerosis and brain tumors.

In this study quantitation of the degree of deficiency of the blood-brain barrier (BBB) in patients with multiple sclerosis or brain tumors, by using MRI, is shown to be possible. As a measure of permeability of the BBB to Gadolinium-DTPA (Gd-DTPA) the flux per unit of distribution volume per unit of brain mass was used. This quantity was found by introducing the longitudinal relaxation rate (R1) as a measure of concentration of Gd-DTPA in the brain tissue in the mathematical model for the transcapillary transport over the BBB. High accordance between the observed data points and the model was found, and the results were comparable to results obtained from similar studies using positron emission tomography. The improved possibility of quantitating the defect of the BBB by MRI may give new information about pathogenesis or etiology, and leads to improved methods in monitoring the efficacy of treatments in intracranial diseases.

Blood-Brain Barrier↗

Experimental manipulation of the rodent visceral yolk sac.

The visceral yolk sac (VYS) is an especially important placental organ in the rodent because it is the primary source of exchange between the embryo and mother during early organogenesis before the chorioallantoic placenta circulation is established. The VYS is involved with nutritional, endocrine, metabolic, immunologic, secretory, excretory, and hematopoietic functions. The VYS also plays a role in steroid metabolism and interacts with a variety of blood-borne factors: parathyroid hormone, glucocorticoids, insulin, and vitamin D metabolites. The importance of the VYS during development is emphasized by the embryotoxicity resulting from exposure to agents which cause VYS dysfunction when administered to the pregnant animal during organogenesis. Several experimental procedures have provided useful information concerning a variety of VYS functions from early organogenesis to term: Culture of the Embryo, Fetal Incubation, Culture of the Fetus, Giant Yolk Sac, Short- and Long-Term Culture of the Yolk Sac, Modified Ussing's Chamber, Single or Double Diffusion Chamber, and the use of Heterologous Rodent Visceral Yolk Sac Antibodies. Since human yolk sac pathology has been associated with developmental toxicity and spontaneous abortion, it is important to discover whether there are some common functional roles among different mammalian species and to determine if other experimental animal models can be used to study the possible contribution of human yolk sac dysfunction to some human reproductive problems.

Animals↗

Experimental yolk sac dysfunction as a model for studying nutritional disturbances in the embryo during early organogenesis.

Our investigations concerning the importance of cell surface macromolecules during embryonic development led us to the discovery in 1961 that heterologous anti-rat kidney serum produced teratogenesis, growth retardation and embryonic death when injected into the pregnant rat during early organogenesis. It was established that IgG was the teratogenic agent, primarily directed against the visceral yolk sac (VYS) but not the embryo. Heterologous anti-rat VYS serum was prepared which was teratogenic localized in the VYS and served as a model for producing VYS dysfunction and embryonic malnutrition. The role of the yolk sac placenta in histiotrophic nutrition is now recognized to be critical for normal embryonic development during early organogenesis in the rodent. VYS antiserum affects embryonic development primarily by inhibiting endocytosis of proteins by the VYS endoderm, resulting in a reduction in the amino acids supplied to the embryo. Our laboratory has recently developed teratogenic monoclonal yolk sac antibodies (MCA) which can be utilized; to study VYS plasma membrane synthesis and recycling, to compare yolk sac function among different species, and to identify components of the plasma membrane involved in pinocytosis. MCA prepared against certain VYS antigens provide an opportunity to study embryonic nutrition with minimal interference with the nutritional state of the mother. Recent developments in the study of the human yolk sac along with our laboratory's ability to isolate a spectrum of yolk sac antigens, prepare monoclonal antibodies, and perform functional studies, should provide information that will increase our understanding of yolk sac function and dysfunction in the human and determine the relative importance of various amino acids to normal development during mammalian organogenesis.

Animals↗

Localized in vivo proton spectroscopy of the bone marrow in patients with leukemia.

Volume selective magnetic resonance (MR) proton spectroscopy was used to investigate the haemopoietic (iliac bone) and fatty bone marrow (tibia) in patients with leukemia and polycythaemia vera. Selective measurements of the relaxation times T1 and T2 for the "water" and "fat" resonances in the bone marrow spectra were performed. Nine patients with acute leukemia and three patients with chronic leukemia were examined at diagnosis. Three patients with acute leukemia in remission were also examined. Five of the leukemic patients had follow-up examinations performed in relation to chemotherapeutic treatment. Nine patients with polycythaemia vera and 21 normal control subjects were examined with identical methods for comparison. All patients had bone marrow biopsies performed prior to every MR examination. Significant differences could be detected in the spectral patterns from iliac bone marrow in patients with leukemia at diagnosis compared to the healthy normal controls. The "relative water content" was increased in the iliac bone marrow spectra of the leukemic patients compared to the normal subjects, which indicates an increase in the amount of haemopoietic tissue and a corresponding decrease in marrow fat content. The T1 relaxation times of the "water" resonance in the spectra from the iliac bone marrow of the leukemic patients were significantly prolonged at diagnosis, compared to the normal controls and the patients with polycythaemia vera. After chemotherapeutic induction of remission, the spectra from the iliac bone marrow in the patients with leukemia resembled normal spectra. Four leukemic patients had abnormal spectra from the tibial bone marrow and one patient showed early changes in tibial marrow during chemotherapeutic treatment, before any major changes could be detected in the iliac bone marrow.

Bone Marrow↗

Effects of recombinant human erythropoietin on the haemopoietic bone marrow monitored by magnetic resonance spectroscopy in patients with end-stage renal disease.

Volume selective magnetic resonance (MR) proton spectroscopy was used to investigate changes in the haemopoietic bone marrow in patients with end-stage renal disease undergoing treatment with recombinant human erythropoietin (rHuEPO). Significant changes could be detected in the spectra 14 days after the beginning of treatment, before any response was seen in the haemoglobin concentration of peripheral blood. The spectral changes indicate an alteration in cellular composition of haemopoietic bone marrow with an increase in the amount of haemopoietic active tissue. One patient showed a major change in the spectrum four days after treatment began, indicating that MR spectroscopy may detect early changes in the cellular composition of the bone marrow. This noninvasive method may be useful in evaluating treatment effects of recombinant human haemopoietic growth factors in the bone marrow, as well as investigating bone marrow response from different modes of rHuEPO administration.

Adult↗

MR pulse sequences for selective relaxation time measurements: a phantom study.

The accuracy of relaxation time measurements of spectroscopic inversion recovery and CPMG multi-echo pulse sequences together with ISIS and stimulated echo-pulse methods have been tested on a reference phantom (test object no. 5, of the EEC Concerted Research Project). For the measurements a Siemens Magnetom wholebody magnetic resonance scanner operating at 1.5 Tesla was used. For comparison six imaging pulse sequences for relaxation time measurements were tested on the same phantom. The spectroscopic pulse sequences all had an accuracy better than 10% of the reference values.

Humans↗