Comparison of receptors for insulin-like growth factor II from various rat tissues

Receptors for insulin-like growth factor II (IGF-II) have been compared in solubilized microsomal membranes from rat lung, brain, kidney, heart, epididymal and subcutaneous fat, ovary, testis and adrenals. Highest binding/microgram protein was seen with testicular membranes. Receptors from all tissues showed high affinity for human IGF-II (mean association constant = 65 litres/nmol) and a high degree of specificity (mean IGF-I cross-reactivity 0.3%; no cross-reactivity with insulin). Affinity labelling followed by sodium dodecyl sulphate polyacrylamide gel electrophoresis showed binding was only to a type-II IGF receptor, with a major band seen at a molecular weight of about 230,000 in lung, brain, kidney and testis, and 240,000 in heart, fat and adrenal gland. All tissues showed broad or bimodal pH dependence of binding, with optima seen at about pH 6 and pH 9. Mild stimulation of IGF-II binding by low calcium concentrations (1-2 mmol/l) was seen in all tissues, although higher concentrations were inhibitory in the brain. It was concluded that IGF-II receptors from different rat tissues, when studied under uniform conditions, show similar binding affinities but differences in size and regulation which might be missed if receptors are examined in separate studies.     

Parkinson's and motoneuron disease morbidity in the Twin Cities metropolitan area: 1979-1984

To better characterize the morbidity from Parkinson's disease and motoneuron disease, we examined hospital discharge diagnosis data for all acute care facilities (except for the Veterans Administration Medical Center) in the Minneapolis-St. Paul area in each year from 1979 to 1984 for persons aged 30-74 years. For each person in whom the discharge diagnosis included either Parkinson's disease or motoneuron disease, the age, gender, and year of admission were recorded. Annual age-gender-specific and age-adjusted gender-specific hospital discharge diagnosis rates were calculated. For Parkinson's disease, for both, men and women, the age-adjusted hospital discharge diagnosis rate declined by 26-27%. Component age-specific data for Parkinson's disease showed more variable temporal changes. For motoneuron disease, no temporal changes were observed, although the number of observations was small. These data suggest that Parkinson's disease is declining in prevalence in the hospitalized population. The implications for motoneuron disease are less clear. Further studies in this area are needed.     

AUR Memorial Award 1991. Immunogenicity of gadolinium-based contrast agents for magnetic resonance imaging. Induction and characterization of antibodies in animals.

To evaluate the immunogenic potential of gadolinium-based magnetic resonance imaging (MRI) contrast agents, Sprague-Dawley rats were sensitized with gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) dimeglumine and with Gd-DTPA covalently linked to either human serum albumin, dextran, or polylysine. IgG antibodies directed against Gd-DTPA were detected in immune sera by an enzyme-linked immunosorbent assay (ELISA), and were confirmed by competitive inhibition of antibody binding using free Gd-DTPA dimeglumine. Antiserum induced by immunization with human serum albumin-(Gd-DTPA) was characterized by a monophasic competition curve with 50% inhibition (IC50) = 5.5 x 10(-4) M when Gd-DTPA dimeglumine was used as both the well-coating and the displacing agent in a competition ELISA. Antiserum induced by Gd-DTPA dimeglumine alone was characterized by a biphasic competition curve with IC50 = 6.5 x 10(-7) M and 7.9 x 10(-4) M. Antisera obtained after exposure to either dextran-(Gd-DTPA) or polylysine-(Gd-DTPA) were of insufficient titer for characterization. The detection of antibodies specific for Gd-DTPA suggests in vivo protein binding with formation of hapten-carrier conjugates. This hypothesis is supported by increased relaxivity values observed when Gd-DTPA dimeglumine is incubated in serum rather than in water. Gd-DTPA dimeglumine and albumin-(Gd-DTPA) are immunogenic in rats under idealized experimental conditions. Additional studies will be necessary to determine the potential for immunologic response in humans to gadolinium chelates under conditions of exposure inherent in clinical use.     

Veterans Helping Veterans: a NSW Example

World War II veterans are now in their seventies and eighties. Health problems that were experienced during the years of conflict have a lasting effect on this unique section of the community. Through VWAWC, a nucleus of veterans and the widows of veterans on the Central Coast of New South Wales have developed successful strategies of support for the wider veteran community, to help them accomplish healthier, happier ageing.     

Modulatory effects of serotonin, FMRFamide, and myomodulin on the duration of action potentials, excitability, and membrane currents in tail sensory neurons of Aplysia.

1. The electrophysiological properties of sensory neurons that mediate withdrawal reflexes of Aplysia can be modulated by a variety of neurotransmitters. We compared the known excitatory actions of serotonin (5-HT) with the actions of FMRFamide (Phe-Met-Arg-Phe-NH2) and myomodulin (Pro-Met-Ser-Met-Leu-Arg-Leu-NH2) on the durations of action potentials and excitability. In addition, with the use of voltage-clamp and pharmacological separation techniques, we characterized the membrane currents that were modulated by each of the three agents. 2. Application of 5-HT produced an increase in the duration of action potentials and an enhancement of excitability in somata of the tail sensory neurons. FMRFamide and myomodulin reversed these excitatory effects and decreased the duration of action potentials and excitability. These results indicated that FMRFamide and myomodulin exerted inhibitory effects on the electrophysiological properties of the sensory neurons. properties of the sensory neurons. 3. FMRFamide appeared to modulate three K+ currents. The first current, which was increased by FMRFamide, had properties closely resembling those of the S-K+ current (IK,S). These properties include slow activation, little inactivation, and relative insensitivity to the K+ channel blockers 4-aminopyridine (4-AP) and tetraethylammonium (TEA). The second current, which was reduced by FMRFamide, had kinetic and pharmacological properties similar to those of a component of the Ca(2+)-activated K+ current (IK,Ca). Finally, at large depolarizations, FMRFamide appeared to increase a third current that was attenuated by 4-AP, suggesting that FMRFamide also modulated the delayed or voltage-dependent K+ current (IK,V). 4. Myomodulin appeared to modulate two of the currents modulated by FMRFamide, because it increased both IK,S and IK,V. Unlike FMRFamide, however, myomodulin did not appear to modulate IK,Ca. 5. Arachidonic acid mimicked the modulation of IK,S, IK,Ca, and IK,V by FMRFamide. Because myomodulin did not modulate IK,Ca, it appears that a second messenger other than arachidonic acid or its metabolites mediates the modulatory effects of myomodulin. 6. These results indicate that both FMRFamide and myomodulin can inhibit the tail sensory neurons by increasing IK,S. FMRFamide, but not myomodulin, also reduces IK,Ca, which suggests that under some conditions FMRFamide may also have excitatory actions. Finally, these results suggest that the effects of FMRFamide and myomodulin may be mediated by different second-messenger systems.     

Oral ondansetron decreases vomiting after tonsillectomy in children

Vomiting is a common, unpleasant aftermath of tonsillectomy in children. Intraoperative intravenous ondansetron (OND) reduces vomiting after this operation. Our doubleblind, placebocontrolled, randomized investigation studied the effect of the oral form of OND on vomiting after outpatient tonsillectomy in children. We studied 233 healthy children age 2–14 yr undergoing elective tonsillectomy. Subjects were given placebo (PLAC) or OND 0.1 mg · kg^?1 rounded off to the nearest 2 mg one hr before surgery. Anaesthesia was induced with either propofol or halothane/N₂O. Vecuronium 0.1 mg · kg^?1 was administered at the discretion of the anaesthetist. Anaesthesia was maintained with halothane/N₂O, 50 μg · kg^?1 midazolam iv and 1–1.5 mg · kg^?1 codeine im. At the end of surgery, residual neuromuscular blockade was reversed with neostigmine and atropine. All episodes of inhospital emesis were recorded by nursing staff. Rescue antiemetics in the hospital were 1 mg · kg^?1 dimenhydrinate ivfor vomiting × 2 and 50 μg · kg^?1 droperidol iv for vomiting × 4. Parents kept a diary of emesis after discharge. Postoperative pain was treated with morphine, codeine and/or acetaminophen. The two groups were similar with respect to demographic data, induction technique and anaesthesia time. Oral OND (n = 109) reduced postoperative emesis from 54% to 39%, P < 0.05. This effect was most dramatic inhospital, where 10% of the OND-patients and 30% of the PLAC-group vomited, P < 0.05. The OND-subjects required fewer rescue antiemetics, 7% vs 17%, P < 0.05. In conclusion, oral ondansetron decreased the incidence of vomiting after outpatient tonsillectomy in children.     

The relevance of pulse repetition rate and radiant exposure to the neurophysiological effects of low-intensity laser (820 nm/pulsed wave) irradiation upon skin temperature and antidromic conduction latencies in the human median nerve

The effects of low-intensity near-infra-red laser irradiation (820 nm; 1.5 and 9.0 J cm^–2; pulsed at 12 Hz, 73 Hz and 5 kHz) upon peripheral neurophysiology and skin temperature were investigated using antidromic conduction studies in the human median nerve in vivo. Healthy human volunteers (n = 90) were recruited and allocated randomly to either a control group (n=10) or one of eight experimental groups (two radiant exposures, 1.5 J cm^–2 and 9.0 J cm^–2 at one of three pulse repetition rates, 12 Hz, 73 Hz or 5 kHz, in addition to a placebo group for each radiant exposure;n = 10 all groups). Analysis of variance (ANOVA) demonstrated a significant (p0.05) decrease in skin temperature following irradiation at the lowest radiant exposure (1.5 J cm^–2) combined with pulse repetition rates of 73 Hz and 5 kHz, with the greatest effect at 73 Hz. These changes in skin temperature were coupled with increases in negative peak latency (NPL); ie changes in NPL were inversely related to changes in skin temperature. However, in contrast to the authors' previous findings using continuous wave (CW) laser irradiation, differences in NPL were not found to be significant. These findings, therefore, provide little evidence of the neuro-physiological effects of low-intensity infra-red irradiation at the dosage levels and pulse repetition rates used here.