Comparative analyses of multi-species sequences from targeted genomic regions.

The systematic comparison of genomic sequences from different organisms represents a central focus of contemporary genome analysis. Comparative analyses of vertebrate sequences can identify coding and conserved non-coding regions, including regulatory elements, and provide insight into the forces that have rendered modern-day genomes. As a complement to whole-genome sequencing efforts, we are sequencing and comparing targeted genomic regions in multiple, evolutionarily diverse vertebrates. Here we report the generation and analysis of over 12 megabases (Mb) of sequence from 12 species, all derived from the genomic region orthologous to a segment of about 1.8 Mb on human chromosome 7 containing ten genes, including the gene mutated in cystic fibrosis. These sequences show conservation reflecting both functional constraints and the neutral mutational events that shaped this genomic region. In particular, we identify substantial numbers of conserved non-coding segments beyond those previously identified experimentally, most of which are not detectable by pair-wise sequence comparisons alone. Analysis of transposable element insertions highlights the variation in genome dynamics among these species and confirms the placement of rodents as a sister group to the primates.

Serratia marcescens meningitis associated with a contaminated benzalkonium chloride solution.

Serratia marcescens is recognized as an important and potentially hazardous nosocomial pathogen. The organism has been implicated here as the first reported case of S. marcescens meningitis associated with skin disinfection. A quaternary ammonium compound ( QAC --Benzalkonium Chloride), was used to sterilize the skin prior to injection in a physician's office. Epidemiological studies were initiated. Six spray bottles containing disinfectant, the opened stock bottle of QAC , and an unopened bottle of disinfectant were all cultured. S. marcescens was noted growing in the spray bottles as well as in the opened stock bottle. Antibiograms of the patient and epidemiological isolates are essentially the same. It is our contention as well as that of the Centers for Disease Control that an appropriate skin disinfectant such as Tincture of Chlorhexidine, Iodophors , or Tincture of Iodine should be used, and that physicians performing surgical techniques in the office be aware of the potential hazard of contamination. The consequences of nosocomial infection with resistant organisms warrant every precaution by health care professionals.

Interferon in biopsy and autopsy specimens of brain. Its presence in herpes simplex virus encephalitis.

Quantitative virus and interferon titers were assayed in temporal lobe brain biopsy specimens (six patients); in various regions of the brain at autopsy (five of the six patients); and in serums and CSF during courses of herpes simplex virus, type 1 (HSV-1) encephalitis. Until the tenth day of neurologic disease, interferon (geometric mean titer, 25 units/mL) was present in each virus-positive brain biopsy specimen. The geometric mean HSV-1 titer at brain biopsy was 328 tissue culture dose (TCD)50/g. On the sixth day of disease, CSF from the sole survivor contained 160 units/mL, but five other samples of CSF contained no detectable interferon. No serums from any of the six patients contained interferon. At autopsies performed on the sixth to 19th day of neurologic disease, 13 of 35 of the regional areas of the brain retained HSV, but only a single specimen from a temporal lobe had measurable interferon. Early in the course of HSV-1 encephalitis, substantial interferon titers are present in areas of virus multiplication. This local brain interferon is insufficient alone to inhibit progression of a disease but could possibly be important in combination with antiviral chemotherapy.

Modified polyriboinosinic-polyribocytidylic acid complex: induction of serum interferon, fever, and hypotension in rabbits.

The purposes of this study were to determine whether the febrile and hypotensive reactions to the administration of polyriboinosinic-polyribocytidylic acid [poly (I)-poly (C)] complexed with poly-L-lysine and carboxymethylcellulose (poly ICLC) (9S) encountered in humans could be duplicated in rabbits, and when such duplication was demonstrated, to ascertain whether these untoward reactions could be avoided by (i) administration of hydrocortisone (HC), (ii) alteration of the route of delivery, or (iii) administration of poly ICLC (4S) an interferon inducer of lower molecular weight. Responses to intravenous poly ICLC (9S) in rabbits reproduced adverse reactions in humans, namely fever and hypotension, and were accompanied by high titers of serum interferon. Continuing investigations showed that (i) intravenous pretreatment of rabbits with HC ameliorated hypotensive responses but markedly diminished interferon induction. When HC was given after poly ICLC (9S), both interferon and hypotension induction were likewise depressed. (ii) Intramuscular or subcutaneous poly ICLC (9S) produced neither high titers of serum interferon nor toxic effects. (iii) Poly ICLC (4S) induced high titers of serum interferon and fever, but no hypotension. Poly ICLC (4S) warrants further study.

[8-year experience in 40 patients with an axillary-femoral graft]. / Ocho años de experiencia en 40 enfermos con injerto axilo-femoral.

The 8 years (1967-1975) experience with axillary-femoral and femoro-femoral grafts in 40 patients is presented; 6 females and 34 males, between 50 and 90 years of age, with arteriosclerosis, all complicated by chronic illnesses. The results have been satisfactory, as the grafts are functioning from 2 months to 80 months (6 years, 8 months), most of them being more than 12 months old. Twenty eight of the 40 patients operated are alive. Four patients (10%) had infection of their grafts. In 6 (15%) the graft closed because of severe progresive distal obstruction. Three patients (7.5%) died in the first 32 post-operative days. In 9 (22.5%) the deaths were not related to surgery. The indications for placement of axillary-femoral and femoro-femoral grafts is established.

[Morphological study of the myocardium in children and adults under normal conditions and in hypoxia]. / Estudio morfológico de miocardio de niños y adultos en condiciones normales y en la hipoxia

At the light and electronic microscopes, 32 myocardial biopsies from 16 patients were studied. The study was carried out in 8 children under 5 years of age and in 8 adults over 20 years during open-sky surgery of the chest done to correct some congenital or acquired heart anomaly. Control biopsies were taken before the application of extracorporeal circulation and a second biopsy, after an average of 30 minutes of hypoxia, which was the time taken to perform the surgical correction of the anomaly. Following extracorporeal circulation, all cases showed mitochondrial mutuations, such as disorganization of their crests, marked distension, from edema to emptiness due to hypoxia. The lack of glycogen, the disorganization of the myofibrillae, decreased neatness of the sarcoplasm and nuclei with marginated chromation, were all preceded by mitochondrial mutations due to oxidative phosphorylation deficiency.

An estimate of the course of herpes simplex virus encephalitis.

Serologic responses, physical findings, and survival were studied in 51 cases of proved (14 patients) or presumptive (37 patients) herpes simplex encephalitis occurring in North America between 1965 and 1972. On the basis of a statistical analysis of 16 serological parameters tested in both groups, presumptive cases are likely similar to definitive cases. Using this assumption, the following tentatives conclusions are possible. Complement-fixing antibodies may be more sensitive measures of rises in anti-herpes simplex virus antibodies than are conventional or complement-requiring neutralizing or passive hemagglutinating antibodies. Mortality in herpes simplex virus encephalitis may vary from 0 to 80% and may be predictable depending upon the occurrence of seizures, paralysis and coma. Coma seems to dictate the dour prognosis. When 51 cases of herpes simplex virus encephalitis reported in the literature by others between 1944 and 1972 were analyzed by this method, a comparably varied mortality was obtained. It did not appear that treatment with idoxuridine increased the likelihood of survival.