Passive immunization of newborn rhesus macaques prevents oral simian immunodeficiency virus infection

To determine if passively acquired antiviral antibodies modulate virus transmission and disease progression in human pediatric AIDS, the potential of pre- and postexposure passive immunization with hyperimmune serum to prevent oral simian immunodeficiency virus (SIV) infection or disease progression in newborn rhesus macaques was tested. Untreated neonates became infected after oral SIV inoculation and had high viremia, and most animals developed fatal AIDS within 3 months. In contrast, SIV hyperimmune serum given subcutaneously prior to oral SIV inoculation protected 6 newborns against infection. When this SIV hyperimmune serum was given to 3 newborns 3 weeks after oral SIV inoculation, viremia was not reduced, and all 3 infants died within 3 months of age due to AIDS and immune-complex disease. These results suggest that passively acquired antihuman immunodeficiency virus (HIV) IgG may decrease perinatal HIV transmission. However, anti-HIV IgG may not impart therapeutic benefit to infants with established HIV infection.     

Stenting of symptomatic stenosis of the intracranial internal carotid artery

Sarcoidosis presenting solely as a granulomatous colitis is rare and appears identical to Crohn's disease. A 56-yr-old woman developed a Crohn's-like illness, which remitted after 5-ASA therapy. Two months later, she developed fever, adenopathy, muscle weakness, and peripheral neuropathy. A diagnosis of sarcoidosis was made after an extensive search for an infectious or rheumatological cause. This case illustrates the utility of serum angiotensin converting enzyme level in differentiating sarcoidosis from Crohn's disease.     

Measuring quality of life in oncology: is it worthwhile? II. Experiences from the treatment of cancer

This is the second part of the paper on quality of life in cancer patients which appeared in this journal (Montazeri et al., 1996a). In this part experiences from the treatment of cancer are given and relevant literature is reviewed. Several topics have been covered, including new directions and methods in assessing quality of life. It is argued that in a chronic condition, adding life to years instead of years to life is an important task. Adding years to life may prolong survival, but whether this is to the benefit of patients is debatable. Considering patients' views, their values and preferences may improve the quality of care and at the same time, reduce the psychological distress and physical discomfort in patients with cancer. It is concluded that quality of life measures have considerable potential in this challenging issue.     

Mutational analysis of Escherichia coli elongation factor Tu in search of a role for the N-terminal region

We have mutated lysine 2 and arginine 7 in elongation factor Tu from Escherichia coli separately either to alanine or glutamic acid. The aim of the work was to reveal the possible interactions between the conserved N-terminal part of the molecule, which is rich in basic residues and aminoacyl-tRNA. The enzymatic characterization, comprising GDP and GTP temperature stability assays and measurement of nucleotide dissociation and association rate constants, GTPase activity and aminoacyl-tRNA binding, shows that position 2 is not involved in aminoacyl-tRNA binding, while position 7 is necessary to accomplish this activity. Furthermore, arginine 7 seems to play a role in regulating the binding of GTP. The three-dimensional structure of the ternary complex, EF-Tu:GTP:Phe-tRNAPhe, involving Thermus aquaticus EF- Tu and yeast Phe-tRNA(Phe), shows that Arg7 is in a position which permits salt bridge formation with Asp284, thus binding the N-terminus tightly to domain 2. We propose that this interaction is needed for aminoacyl-tRNA binding, and also for completing the structural rearrangement, which takes place when the factor switches from its GDP to its GTP form.      

Design and construction of a hybrid immunoglobulin domain with properties of both heavy and light chain variable regions

The complementarity-determining regions (CDRs) of a human kappa light chain were replaced with CDRs from a murine gamma-1 heavy chain and, by use of molecular modeling, key heavy chain framework residues were identified and thus included to preserve the native conformation of the heavy chain CDRs. Co-expression of this hybrid human kappa chain (V[HB]C[L]) with a human kappa chain counterpart (V[L]C[L], engineered to contain murine light chain CDRs) resulted in the secretion of high levels of a heterodimeric protein (V[HB]C[L]::V[L]C[L]) termed 'kappabody'. This protein also had equivalent affinity for antigen as the Fab' of the parent murine IgG1. High-level secretion was also observed for the hybrid chain as homodimers (V[HB]C[L]::V[HB]C[L]), which is not observed for chimeric chains consisting of a heavy chain variable region and light chain constant region, i.e. V[H]C[L] homodimers or single chains are not secreted. This indicates that regions within the variable domain, required for secretion of light chains, reside outside of the hypervariable regions (CDRs) and that the heavy chain CDRs and supporting residues do not prevent secretion. These results demonstrate the possibility of designing small, single- domain molecules possessing a given binding activity which may be secreted at high levels from mammalian cells.      

Ovarian follicular populations in lactating dairy cows treated with recombinant bovine somatotropin (sometribove) or saline and fed diets differing in fat content and energy

Interactions of dietary energy and fat with recombinant bST (sometribove) injections were tested for their effects on ovarian function. Lactating dairy cows were fed one of three diets differing in energy concentration (NEL) and percentage of DM of calcium salts of long-chain fatty acids: diet 1, 1.68 Mcal/kg and 0%; diet 2, 1.68 Mcal/kg and 2.2%; and diet 3, 1.78 Mcal/kg and 2.2%. Cows were injected daily with bST or saline during one of two 19-d interestrous periods (crossover design) in which ovarian follicles were measured by ultrasonography. The bST-treated cows produced more FCM and were in lower energy balance than saline-treated cows. Before d 12 (first follicular wave, estrus = d 0), bST-treated cows had more ovarian follicles in classes 1 (3 to 5 mm; cows on diet 3) or 2 (6 to 9 mm; cows on diets 1 and 2) than saline-treated cows. After d 12 (preovulatory follicular wave), numbers of follicles in different size classes were similar for bST-treated and saline-treated cows, but cows fed diet 2 had larger preovulatory follicles. Lower dietary energy and bST treatment were both associated with larger subordinate follicles. Ovarian follicles less than 10 mm were stimulated by bST, and calcium salts of long-chain fatty acids increased diameters of preovulatory follicles.