Temperature-sensitive mutants of influenza A virus. XIV. Production and evaluation of influenza A/Georgia/74-ts-1[E] recombinant viruses in human adults

The two temperature-sensitive (ts) lesions present in influenza A/Hong Kong/68-ts-1[E] (H3N2 68) virus were transferred via genetic reassortment to influenza A/Georgia/74 (H3N2 74) wild-type virus. A recombinant clone possessing both ts lesions and the shutoff temperature of 38 C of the Hong Kong/68 ts donor and the two surface antigens of the Georgia/74 wild-type virus was administered to 32 seronegative adult volunteers. Thirty-one volunteers were infected, of whom only five experienced mild afebrile upper respiratory tract illness. The wild-type recipient virus was a cloned population that induced illness in five of six infected volunteers. Therfore, the attenuation exhibited by the Georgia/74-ts-1[E] virus could reasonably be assumed to be due to the acquisition of the two ts-1[E] lesions by the Georgia/74 wild-type virus. The serum and nasal wash antibody responses of the ts-1[E] vaccinees were equivalent to those of the volunteers who received wild-type virus. The two ts lesions present in the Hong Kong/68-ts-1[E] virus have now been transferred three times to a wild-type virus bearing a new hemagglutinin, and in each instance the new ts recombination exhibited a similar, satisfactory level of attenuation and antigenicity for adults. It seems likely that the transfer of the ts-1[E] lesions to any new influenza virus will regularly result in attenuation of a recombinat virus possessing the new surface antigens.     

Biomedical instrumentation in the Soviet Union

A modified technique for vaso-vasostomy is described with the aim to achieve better results in operative recanalization and restoration of fertility after vasectomy. Vaso-vasostomy is a success when the man is able to produce fertile semen. Criteria for a fertile semen are mentioned. Fertile semen was obtained in all 5 patients treated by this modified technique.     

Effect of age and sex on the prevalence of intestinal parasitism in dogs

The effects of age, sex, and neutering on the prevalence of canine intestinal parasitism were evaluated by fecal examination of 1,468 pet dogs admitted to the University of Missouri Veterinary Teaching Hospital during 1975. Evidence of hookworm infection was encountered in 35.8% of the dogs examined, whipworms in 18.5%, ascarids in 17.9%, tapeworms in 5.2%, and coccidia in 4.5%. Evidence of intestinal parasitism was not detected in 653 (44.4%) dogs. Whipworm infections were detected less often in young dogs than in older ones, whereas ascarid and coccidial infections were more prevalent in pups that in mature dogs. In dogs more than 6 months old, hookworm infections were the most common parasitism. Tapeworm infections were diagnosed sporadically in all age groups. For most of these parasites, castrated males and spayed females had decreased prevalence of infection, compared with their respective intact counterparts. There were significant (P less than 0.05) differences in the prevalence of both ascarid and hookworm infections between intact and spayed female dogs. Also, there were significant (P less than 0.001) differences between age categories for all parasites observed. Overall, parasitism tended to decrease with age.     

Glucose tolerance tests and their insulin and growth hormone responses in hemodialysis patients: are they reproducible?

The concept that carbohydrate intolerance improves after hemodialysis has been challenged. Critical to this issue is the reproducibility of GTT in a dialysis population. Thirty-nine oral or i.v. GTT were performed on ten stable hemodialysis patients at weekly intervals for three weeks. Blood glucose was determined by both oxygen consumption rate during glucose oxidation and the ferricyanide method. The coefficient of variation of blood glucose ratios (Glucose at time X/Fasting glucose) by glucose oxidase varied considerably. With the i.v. GTT the coefficients of variation at 90 and 120 minutes were 27.9 and 36.8 percent in one patient but below 15 percent at 60, 90, and 120 minutes in the other four patients. Three of the five patients who received oral GTT displayed coefficients of variation greater than 20 percent at one or more sampling times. The coefficients of variation of the growth hormone ratio (Growth hormone at time X/Fasting growth hormone) during i.v. and oral GTT ranged from 2.1 to 83.6 percent. Coefficients of variation of insulinogenic indexes ranged from 16.3 to 59.3 percent. In summary, large variations in glucose, growth hormone and insulin occur during both oral and i.v. GTT when repeated on a weekly basis in stable hemodialysis patients.     

Antimicrobial prophylaxis for catheter-associated bacteriuria

We evaluated short-term systemic antimicrobial prophylaxis for catheter-associated bacteriuria in women undergoing elective gynecological operations in a prospective, controlled, double-masked study. Nine of 100 placebo-treated patients acquired bacteriuria during catheterization compared with 3 of 96 of the drug-treated group. However, at the time of hospital discharge, clean-voided urine specimens were positive as frequently in the drug-treated group (8 of 82 patients cultured) as in the placebo group (8 of 75 patients cultured). No difference in febrile morbidity due to bacteriuria was noted between the prophylaxis and placebo groups. The incidence of catheter-associated bacteriuria may be reduced by antimicrobial prophylaxis. However, because the protective effect is transient and is associated with the selection of resistant organisms, prophylaxis is not indicated for patients at low risk for acquired bacteriuria and in whom the sequelae of catheter-associated infections are infrequent.     

Solution structure of acidic fibroblast growth factor bound to 1,3, 6-naphthalenetrisulfonate: a minimal model for the anti-tumoral action of suramins and suradistas

Recent data show that anti-angiogenesis may provide a promising route to treat cancer. Fibroblast growth factors (FGFs) are powerful angiogenic polypeptides, whose mitogenic activity requires the presence of heparin-like compounds. It has been shown that angiogenesis promoted by FGFs on inhibition by monoclonal antibodies and antisense targeting can also inhibit tumour growth. Derivatives of suramin, a polysulfonated binaphthyl urea and binaphthylsulfonated derivatives of distamycin, suradistas, constitute an important group of potential anti-cancer agents. These compounds compete with heparin in forming tight complexes with FGFs. This inhibits the recognition of these growth factors by their tyrosine kinase membrane receptors thereby suppressing their angiogenic activity. Here we show that 1,3,6-naphthalenetrisulfonate, a common chemical function of the suramins and suradistas with the highest anti-angiogenic activity inhibits the mitogenic activity of acidic fibroblast growth factor, and that this inhibition is relieved by increasing concentrations of heparin in the assay. We have also solved the three-dimensional structure in solution of the protein complexed to this compound. The structural data provide clues that may help in understanding the inhibitory effect of suramins and suradistas, and could contribute to the development of new anti-tumoral drugs.