Molecular characterization of a high A2 beta thalassemia by direct sequencing of single strand enriched amplified genomic DNA

Two families, one of Anglo-Saxon-Dutch descent, and the other, West Indian black, have an atypical beta thalassemia characterized by an unusually high level of Hb A2 in the heterozygous state. Restriction endonuclease mapping showed a deletion of about 1.35 kilobase (kb) in the 5' region of the beta globin gene. Direct sequencing of a specific region of genomic DNA amplified by a new modification of the polymerase chain reaction defined the deletion to be 1,393 base pairs (bp) and to be the same in both families. The deletion extends from 485 bp 5' to the mRNA CAP site to the middle of the second intervening sequence. This deletion, together with three others previously described that remove the 5' end of the beta gene but leave the delta gene intact, are all associated with unusually high levels of Hb A2 in the heterozygous state.     

The role of metallothionein II in neuronal differentiation and survival

Metallothionein I and II (MT-I+II) are antioxidant and tissue protective factors. We have previously shown that MT-I+II prevent oxidative stress and apoptotic cell death and are of therapeutic value in brain inflammation. However, MT-I+II are expressed in glia and it remains to be elucidated if MT-I+II can affect neurons directly. It is likely that MT isoforms could be beneficial also during neurodegenerative disorders. In this study, we have examined if MT-II affects survival and neurite extension of dopaminergic and hippocampal neurons. We show for the first time that MT-II treatment can significantly stimulate neurite extension from both dopaminergic and hippocampal neurons. Moreover, MT-II treatment significantly increases survival of dopaminergic neurons exposed to 6-hydroxydopamine (6-OHDA) and protects significantly hippocampal neurons from amyloid beta-peptide-induced neurotoxicity. Accordingly, treatment with MT-II may be of therapeutic value in neurodegenerative disorders.     

An assessment of emergency medical technicians' performance as related to seasonal population influx

The periodic influx of large numbers of people into resort areas substantially increases the use of emergency medical services. This investigation assesses the effects of such a threefold increase in the summer population of the Cape Cod area upon the accuracy of emergency medical technicians' diagnoses and treatments. The technicians' diagnoses for ambulance patients were evaluated against those given by the emergency room physicians during the months of August 1975 and February 1976. The distribution of conditions was similar for both months and the observed frequency of correct diagnoses for common conditions was more than 90% in both months. The overdiagnosis rate of 25% to 50% for common conditions and the correct treatment rate for suspected myocardial infarction of 65% did not vary significantly between summer and winter.Thus, a large influx in population does not seem to affect adversely EMT diagnosis rates. Although misdiagnoses were uncommon, a high frequency of overdiagnosis was found, as well as a 41% rate of failure to follow through with a correct treatment for patients with suspected myocardial infarctions, thus indicating the need for better quality control on EMT performance.The authors are with the Department of Medicine, Boston University School of Medicine, and Boston City Hospital, Thorndike Memorial Laboratories, Boston, Massachusetts. Requests for reprints should be addressed to Dr. Pozen, Cardiology Department, Sears 108, Boston City Hospital, 818 Harrison Avenue, Boston, Massachusetts 02118. This work was supported by research grants from the Massachusetts Regional Medical Program, the Emergency Medicine Foundation, and The Medical Foundation, Inc., Boston, Massachusetts.     

Ultrastructural localization of VIP-immunoreactivity in canine distal oesophagus

Summary The localization of vasoactive intestinal polypeptide (VIP) immunoreactivity in canine distal oesophagus was studied using different fixation and embedding procedures and labelling with protein A-gold. The retention of immunoreactivity and the preservation of ultrastructure was best after fixation with a mixture of 0.1% glutaraldehyde and 4% paraformaldehyde, and embedding in LR White resin using the cold-cured method. VIP immunoreactivity was localized exclusively over large granular vesicles in the myenteric plexus and in nerves of the circular muscle. Most varicose profiles in circular muscle were labelled, but some large granular vesicles in the same profiles which contained labelled vesicles as well as some varicose profiles with large granular vesicles were unlabelled. From these data it was uncertain whether unlabelled large granular vesicles contained VIP or other neuropeptides. A striking finding was the dense and close innervation of the interstitial cells of Cajal with nerve containing VIP-labelled large granular vesicles. This finding is consistent with earlier suggestions that VIP-immunoreactive nerves may innervate these cells which are in gap junction contact with smooth muscle and that this arrangement may be involved in the transmission of non-adrenergic, non-cholinergic nerve activity in distal oesophagus.     

Effect of fosinopril on the rate of neurohumoral and proinflammatory activation in patients with heart failure

The purpose of the study was to examine the effect of fosinopril on the magnitude of neurohumoral and proinflammatory activation in patients with severe heart failure (HF). Twenty-eight patients aged 52-68 years who had Functional Class (FC) III-IV HF that had developed due to coronary heart disease were examined. All the patients were divided into 2 groups (with 14 patients in each group) and they received routine therapy including an angiotensin-converting enzyme inhibitor (ACEI) and a beta-adrenoblocker. Group 1 patients were given the ACEI fosinopril in a dose of 10-20 mg/day, Group 2 patients took captopril in a dose of 50-75 mg/day. The course of therapy was 12 weeks. All the patients underwent echocardiography by the routine procedure. The plasma levels of angiotensin-II, aldosterone, and brain natriuretic peptide (BNUP) were determined by radioimmunoassay. The plasma contents of tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein (C-RP) were verified by enzyme immunoassay. An analysis of the findings indicated that during therapy the FC of HF decreased on the average by 10.9% in Group 1 and by 11. 7% in Group 2 (p = 0.14). With this, fosinopril was superior to captopril not only in its capacity of improving overall left ventricular contractile function, but it was characterized by a more pronounced effect on regression of the plasma pool of C-RP and TNF-alpha. The marked depressive action of the ACEI fosinopril on the plasma pool of products of the renin-angiotensin system, BNUP, and proinflammatory cytokines may be considered to be as a basis for preferably prescribing the agent to patients with severe HF.