The probability with which EMS-initiated mutagenic lesions generate mutations in CHO cells

In this note we distinguish between multiple mutations affecting a given locus which are generated at separate error-prone lesions and multiple independent mutations generated at a single error-prone lesion. We describe a basis for determining the probability with which the latter class of mutations occurs based on the mutant fraction in the progeny and determine an average probability of 0.6 mutations/replication/mutagenic site for those EMS-modified sites which are mutagenic for G6PDH activity in CHO cells.     

Endocrine function of the heart. Structure and biological properties of peptides secreted by the heart atrium

Apart from the generally known functions, the heart has also an endocrine function. Atrial cardiocytes, being typical secretory cells, release peptide hormones into the blood stream: atrial natriuretic peptide containing 28 amino acids and cardiodilatin. The structure of atrial peptides was determined. It was shown that both peptides were derived from their common precursor, a protein containing 151 amino acids. The presence of specific receptors is demonstrated on plasmatic membranes of cells of kidney epithelium, arterial smooth muscle, arterial endothelium, kidney cortex and hypophysis. The interaction of atrial peptides with these receptors activates the guanylate cyclase system. The biological action of atrial peptides manifests itself in the quick, massive and instantaneous increase of diuresis and electrolyte excretion, elevated clearance of creatinine, decrease of kidney vascular resistance, intensification of glomerular filtration, inhibition of stimulated secretion of aldosterone, relaxation of blood vessels, elimination of arterial and intestinal spasm induced by various endogenous and exogenous vasoconstrictors and in correction of kidney hypertension. Various radioimmunoassays for the presence of atrial peptides in human plasma were developed; it was shown that in patients with congestive heart failure the content of atrial peptides is increased.     

Methods for detecting non-randomness in species co-occurrences: a contribution

Summary Comparison of co-occurrences between species on a group of islands with those expected from a randombased null model could provide evidence on community structure. However, it is difficult to decide on the appropriate null model. Gilpin and Diamond proposed a model and a test for departure from it, but this test is shown to indicate significant structure even when applied to a matrix of random numbers. An alternative method is suggested, using the distribution of Gilpin and Diamond's deviation as test statistic, but determining the expected distribution by Monto Carlo simulation, and using many such simulations as a randomisation test of significance. The null model used accepts the observed totals of occurrences for islands and species; it therefore offers a somewhat conservative test. Applied to the Vanuatu bird data that Gilpin and Diamond used, significant departure from a null model is seen, but with an excess of extreme negative associations, the opposite result from that given by Gilpin and Diamond's method. It is not possible to tell whether the negative associations are due to autecology, biogeography, or to interactions between species.     

Natal philopatry and recruitment of willow ptarmigan in north central and northwestern Canada

Summary Natal philopatry and recruitment were measured in two populations of willow ptarmigan; one near Churchill, Manitoba and the other in northwestern British Columbia. We examined the return of tagged offspring in subsequent years with respect to geographical area, annual variation, their age when tagged, their sex, their body weight, age and number of their parents, and time of hatch (first nest or renest). Most chicks were tagged before they fledged, but chicks tagged after that had the highest rate of return. We also observed a strong positive relationship between fledging success of broods and offspring return in following years.Patterns of offspring return were similar in both populations except that male offspring in Manitoba settled closer to their natal sites than those in British Columbia and more yearling captured in Manitoba had been tagged as chicks. Return of offspring did not vary with year, their body weights shortly after hatch, or with the age or number of parents raising them. However, a significantly higher proportion of offspring hatched from first nests (first-initiated clutches) returned compared to those hatched from renests (replacement clutches). The low return of chicks hatched from renests may due to low survival, low philopatry, or both. We observed no differences in the mating status (recruitment) of returning offspring with respect to the time they hatched or the number of parents that raised them.     

A homologous radioimmunoassay for guinea pig corticosteroid-binding globulin

A rapid, specific, and sensitive (requiring only 20 fmole of antigen equivalent to 0.007 microliter of serum) radioimmunoassay (RIA) was developed for the measurement of guinea pig corticosteroid-binding globulin (CBG). CBG was purified to homogeneity from guinea pig serum by affinity chromatography and used for immunization, as the standard and as the radiolabeled trace in the RIA. The antiserum to CBG was raised in rabbits. It was judged specific by immunoelectrophoresis and by comparison of RIA values with steroid-binding assay profiles obtained on serum separated on the basis of size and ion-exchange properties. The results of the radioimmunoassays agree with those of a steroid-binding assay run on identical samples. The sensitivity of the assay allows detection of CBG in serial serum samples, other biologic fluids such as milk, and cell culture supernatants.     

Genetic and biological analyses of a herpes simplex virus intertypic recombinant reduced specifically for neurovirulence.

RS6 is a herpes simplex virus intertypic recombinant derived from type 1 strain 17 syn+ and type 2 strain HG52. With a 50% lethal dose of about 10(5) PFU after intracerebral inoculation of mice, RS6 was approximately 100,000 times less neurovirulent than either of its wild-type parental viruses were. When compared with strains 17 syn+ and HG52, RS6 replicated intermediately in primary mouse embryo fibroblasts in vitro at 38.5 degrees C (mouse temperature) and to wild-type peak titers in mouse feet in vivo. In contrast, following intracranial inoculation of mice, RS6 replicated significantly less well than did either of its parental viruses in brains. The genetic defect(s) responsible for the reduced neurovirulence of RS6 was stable after in vitro and in vivo serial passage, was not manifested as temperature-sensitive plaquing in vitro, and did not affect thymidine kinase expression. These data indicate that RS6 has a genetic defect(s) specifically affecting its ability to replicate in the mouse brain. Using marker rescue technologies, we increased the neurovirulence of RS6 and localized one genetic determinant(s) involved with the reduced neurovirulence of this agent to 0.72 to 0.87 map units (and, tentatively, to 0.79 to 0.83 map units) of the herpes simplex virus genome. When coupled with the work suggesting that thymidine kinase expression is essential for efficient replication in nerve tissues and earlier reports from this laboratory and others, the results presented in this study indicate that more than one herpes simplex virus gene is involved with neurovirulence.     

Hynes pharyngoplasty revisited

The treatment of velopharyngeal incompetence remains unsatisfactory because the causes are many, as are the variations in anatomic and physiologic defects. Therefore, full assessment and investigation are essential in tailoring the surgery to the defect. A modified Hynes pharyngoplasty has been used in 40 patients, aged 4 to 52, over a 4-year period for velopharyngeal incompetence of varying etiologic causes. Speech was assessed before and at least 6 months after pharyngoplasty. At the same time, radiologic and, when possible, nasendoscopic investigations were undertaken. Thirty-eight patients had no or variable nasal escape (variable defined as achieving intermittent closure), whereas 33 had normal or slight hyponasal resonance. There was only one complication, an asymptomatic dehiscence of the "bucket handle" flap from the posterior wall. Thirteen patients had an assortment of side effects, none requiring surgical treatment. We believe that patients who are suitable for the described sphincter pharyngoplasty are those with slight or moderate nasal escape having a mobile palate with an anteroposterior gap of 5 mm or less.     

Further refinements on the triangular flap closure of the cleft lip

Refinements in the triangular flap closure of the unilateral cleft lip are presented. Randall's mathematical interpretation of the Tennison repair has been extended by using a series of arcs to determine the crucial points which form the triangular flap. Using this easily taught method, an isosceles triangular flap can be plotted which will interdigitate into the noncleft side of the lip. Two symmetrical vertical distances on either side of the cleft are thus formed. This allows for a standardized repair which may be more readily taught than the rotation-advancement technique. In addition, flaps are created which are turned medically toward the cleft and are used to accentuate the philtral pout, close the nostril floor, and reinforce the lip repair, allowing closure of even extremely wide clefts in one stage. These refinements in using the triangular flap closure for the repair of the unilateral cleft lip are diagrammatically presented. We believe that these refinements enhance the results of this closure.     

The effects of ionizing radiation on the pulmonary vasculature of intact rats and isolated pulmonary endothelium

We studied the effects of ionizing radiation on the morphology of the pulmonary circulation using an in vivo rat model and an in vitro pulmonary artery endothelial cell model. Gamma radiation was given as either an acute (30 Gy) or fractionated (5 X 6 Gy) dose to one hemithorax of rats. An acute 30-Gy dose delivered resulted in a 70% decrease in pulmonary arterial perfusion, using technetium-99m microaggregated albumin (99mTc-MAA), in the irradiated lung by 2-3 weeks after irradiation. Pulmonary microradiographs, using a barium sulfate perfusion method, obtained 2-3 weeks after irradiation demonstrated widespread loss of capillary filling and segmentation of the vessels. Histologic examination demonstrated intact capillaries, suggesting that the alterations in pulmonary perfusion were at the precapillary level. Similar abnormalities in lung perfusion and morphology were found after delivery of fractionated doses of radiation, but the onset of the changes was delayed, occurring 4-6 weeks postirradiation. Using cultured pulmonary endothelial cell monolayers, cell sloughing and retraction from the surface substrate were observed within 24 h after in vitro delivery of 30 Gy. Similar findings occurred in monolayers given fractionated doses (5 X 6 Gy) of radiation 2-3 days after the final dose. The in vivo animal and in vitro endothelial cell models offer a useful means of examining the morphologic alterations involved in radiation lung vascular damage.