Erythropoietin structure-function relationships: high degree of sequence homology among mammals

To investigate structure-function relationships of erythropoietin (Epo), we have obtained cDNA sequences that encode the mature Epo protein of a variety of mammals. A first set of primers, corresponding to conserved nucleotide sequences between mouse and human DNAs, allowed us to amplify by polymerase chain reaction (PCR) intron 1/exon 2 fragments from genomic DNA of the hamster, cat, lion, dog, horse, sheep, dolphin, and pig. Sequencing of these fragments permitted the design of a second generation of species-specific primers. RNA was prepared from anemic kidneys and reverse-transcribed. Using our battery of species-specific 5' primers, we were able to successfully PCR- amplify Epo cDNA from Rhesus monkey, rat, sheep, dog, cat, and pig. Deduced amino acid sequences of mature Epo proteins from these animals, in combination with known sequences for human, Cynomolgus monkey, and mouse, showed a high degree of homology, which explains the biologic and immunological cross-reactivity that has been observed in a number of species. Human Epo is 91% identical to monkey Epo, 85% to cat and dog Epo, and 80% to 82% to pig, sheep, mouse, and rat Epos. There was full conservation of (1) the disulfide bridge linking the NH2 and COOH termini; (2) N-glycosylation sites; and (3) predicted amphipathic alpha- helices. In contrast, the short disulfide bridge (C29/C33 in humans) is not invariant. Cys33 was replaced by a Pro in rodents. Most of the amino acid replacements were conservative. The C-terminal part of the loop between the C and D helices showed the most variation, with several amino acid substitutions, deletions, and/or insertions. Calculations of maximum parsimony for intron 1/exon 2 sequences as well as coding sequences enabled the construction of cladograms that are in good agreement with known phylogenetic relationships.     

Bone marrow disorders: characterization with quantitative MR imaging

Thirty patients with various hematologic disorders and 15 healthy control subjects underwent quantitative magnetic resonance (MR) imaging of the lumbar spine with spin-echo techniques. Images of patients with infiltrative bone marrow disorders showed significantly more prolonged T1 times than those of control subjects (P less than .001). It was not possible to distinguish different diffuse infiltrative bone marrow disorders on the basis of T1 values. Aplastic anemia could be distinguished from normality because of significantly shortened T1 (P less than .001). A significant correlation was seen between T1 and bone marrow cellularity (r = .74, P less than .001). T2 was of no value in the characterization of bone marrow disorders. Quantitative MR imaging dose not improve the diagnostic potential of bone marrow imaging in the detection of diffuse marrow infiltrates.     

Olfaction and human neonatal behaviour: clinical implications

About 1-2% of the human genome is allocated to production of receptors for the olfactory epithelium-a hint as to the possible importance of this chemical sense, which includes two anatomically distinct systems: the main olfactory system with sensory cells located in the upper part of the nasal cavity, and the vomero-nasal organ with sensory cells on the nasal septum. In adults, individual odours may influence mate preferences and a growing body of evidence indicates that naturally occurring odours play an important role in the mediation of the infant's behaviour. Even foetal olfactory learning seems to occur and breast odours from the mother exert a pheromone-like effect at the newborn's first attempt to locate the nipple. Newborns are generally responsive to breast odours produced by lactating women. Olfactory recognition may be implicated in the early stages of the mother-infant attachment process, when the newborns learn to recognize the own mother's unique odour signature-a process possibly facilitated by the high norepinephrine release and the arousal of the locus coeruleus at birth. New knowledge about human odour physiology may have diagnostic and therapeutic implications-the initiation and stabilization of breastfeeding and termination of apnoeic spells are mentioned as examples.     

Autoradiographic localization of 2[125I]iodomelatonin binding sites in the gastrointestinal tract of mammals including humans and birds

ABSTRACT: In-vitro autoradiography was utilized to compare the distribution of 2[¹²⁵I]iodomelatonin binding sites or putative melatonin receptors in the gastrointestinal tracts of humans, guinea pigs, mice, rats, hamsters, rabbits, ducks, chickens, pigeons, and quail. In humans, binding was detected in the mucosa of the colon, caecum, appendix, and on their blood vessels but not in the ileum. In the other mammals, significant binding was only demonstrated in the mucosa of the rabbit rectum, mouse colon, mouse rectum, and guinea pig ileum. The distribution of 2[¹²⁵I]iodomelatonin binding in the avian gut varied with species. In the esophagus, binding was present in the lamina propria and blood vessels of all four birds. However, only the lamina propria of the chicken and quail proventriculus and ventriculus showed positive binding. For the duodenum and ileum, binding was very strong in the duck lamina propria, weak in the chicken lamina propria, and absent in the quail. In contrast, the pigeon muscle layer was weakly positive. The most striking species difference was found in the caecum where the duck lamina propria showed very strong binding, while the chicken lamina propria was only weakly positive. Conversely, the caecal muscle layer was strongly positive in chicken and quail but negative in duck and pigeon. In the rectum, a similar but less intense pattern of distribution was observed. The tremendous diversity in the distribution of 2[¹²⁵I]iodomelatonin binding sites in the gastrointestinal tract is in accord with the hypothesis that melatonin may serve different functions in the gut of different species.     

The clinical features of immunoglobulin light-chain (AL) amyloidosis with heart involvement

We reviewed clinical presentation, investigations, therapy, prognosis and outcome of 232 patients with primary (AL) cardiac amyloidosis. There were 142 men and 90 women. Median age at presentation was 59 years (range 29-85). AL heart disease was unusual both in patients under the age of 40 (3.0%) and in non-Caucasians (6.5%). Fatigue and weakness were the commonest presenting symptoms. Hallmark features of periorbital ecchymoses and macroglossia were present in 12.5% and 27.2%, respectively. AL cardiac amyloidosis was unusual in isolation (3.9%), and most frequently patients had features of multiorgan dysfunction; heavy proteinuria and features of malabsorption predominating in this respect. Heart involvement represents the worst prognostic indicator, with a median survival from diagnosis of 1.08 years, falling to 0.75 years with the onset of heart failure. Current therapeutic procedures appear to prolong survival, with left ventricular wall thickness, mass and ejection fraction on echocardiography and late potentials on signal averaged electrocardiography of use in prognostic stratification. Cardiac involvement from AL amyloidosis is rapidly fatal. It should be suspected in all patients with heart failure who have wall thickening on echo, normal chamber sizes, low EKG voltages and evidence suggesting a multisystem disease.      

Studies on fastidious adenoviruses in Ontario: a distinct strain associated with gastroenteritis.

From 100 cases of gastroenteritis among children caused by adenovirus infection in Ontario, 33 virus isolates were divided into three categories according to their biological behavior in tissue cultures. So far, the results of neutralization tests, structural protein analysis, and DNA restriction patterns showed that the virus of category 1 was similar to adenovirus type 40. However, the adenovirus of category 2 was a distinct adenovirus which shared some similarities with adenovirus type 5. Viruses of category 3 are still under investigation.