Hierarchy of effects of the MHC and T cell receptor beta-chain genes in susceptibility to Theiler's murine encephalomyelitis virus-induced demyelinating disease.

Intracerebral inoculation of susceptible mice with Theiler's murine encephalomyelitis virus induces a demyelinating disease that is similar to human multiple sclerosis. This murine model for human multiple sclerosis is apparently immune-mediated and the genes involved in the immune response influence the outcome of disease susceptibility as observed with human multiple sclerosis. These genes include the MHC and TCR genes. However, the functional relationships among these genes on the disease susceptibility has not yet been studied. In this study, we demonstrate that the effect of the H-2s genotype from susceptible SJL/J mice overrides the resistant effect of the BALB/c TCR beta-chain gene in CXJ recombinant-inbred and BALB.S congenic mice. These results strongly suggest the presence of a hierarchy of genes involved in the immune response in Theiler's murine encephalomyelitis virus-induced demyelinating disease.     

Role of kallikrein-kininogen system in insulin-stimulated glucose transport after muscle contractions.

Serum proteins [molecular weight (MW) > 10,000] are essential for increased insulin-stimulated glucose transport after in vitro muscle contractions. We investigated the role of the kallikrein-kininogen system, including bradykinin, which is derived from kallikrein (MW > 10,000)-catalyzed degradation of serum protein kininogen (MW > 10,000), on this contraction effect. In vitro electrical stimulation of rat epitrochlearis muscles was performed in 1) rat serum +/- kallikrein inhibitors; 2) human plasma (normal or kallikrein-deficient); 3) rat serum +/- bradykinin receptor-2 inhibitors; or 4) serum-free buffer +/- bradykinin. 3-O-methylglucose transport (3-MGT) was measured 3.5 h later. Serum +/- kallikrein inhibitors tended (P = 0.08) to diminish postcontraction insulin-stimulated 3-MGT. Contractions in normal plasma enhanced insulin-stimulated 3-MGT vs. controls, but contractions in kallikrein-deficient plasma did not. Supplementing rat serum with bradykinin receptor antagonist HOE-140 during contraction did not alter insulin-stimulated 3-MGT. Muscles stimulated to contract in serum-free buffer plus bradykinin did not have enhanced insulin-stimulated 3-MGT. Bradykinin was insufficient for postcontraction-enhanced insulin sensitivity. However, results with kallikrein inhibitors and kallikrein-deficient plasma suggest kallikrein plays a role in this improved insulin action.     

How to become comfortable talking about sex to your patients.

Dealing with patients'' sex-related complaints is uncomfortable for many physicians. It can become more comfortable if the physician learns to apply his or her clinical knowledge of sexuality in combination with specific interpersonal interviewing skills. The level of comfort can be increased if the physician accepts his or her professional limitations in providing therapy and knows what other sources of care are available.     

Determination of the biological activity of Clostridium difficile toxins in in vivo and in vitro experiments

The biological activity of the filtrates of 29 C. difficile strains was studied in vivo (suckling white mice) and in vitro (cell cultures of different species and origin). The action of the filtrates on the experimental models in vivo was evaluated from the cytotoxic effect index, while in vitro the intensity of the cytotoxic effect was evaluated from the percentage of dead cells in the monolayer. The results of the comparative determination of toxicity characteristics in vivo and in vitro demonstrated that cell cultures were more sensitive experimental models than suckling white mice. The use of cell cultures permitted the quantitative evaluation of the cytotoxic activity of the filtrates under study, as well as the detection of their cell-directed action at minimal concentrations.     

Effect of alpha-fetoprotein on isolated mouse oocytes

Data are presented which indicate a possible action of alpha-fetoprotein (AFP) on female germinal cells. The in vitro maturation of mature mice oocytes was significantly inhibited when mouse AFP replaced albumin in the culture medium. In addition, the degenerative aspect of oocytes cultured with AFP seemed to indicate that this me?otic inhibition was caused by a premature degeneration of oocytes rather than by a blockage at a specific stage of maturation. Thus AFP, perhaps through its ligands, may play a role in the reduction of germinal cells during fetal and immediate post-natal life rather than in the arrest of me?osis at the diplotene stage.     

Care of the diabetic child in the community.

Brief admission of the new diabetic child and of a parent to an enlightened hospital for stabilisation, preliminary education, and familiarisation with hospital and community staff is well worth while. The greater the demand for constant control of the highest quality, the greater the need for a close understanding of the psychosocial factors concerned and for clinical skill. The nature of the home and the family relationships should in theory be available from the child''s general practitioner at the time of the first referral since he has so much information about the whole family. With the virtual disappearance, however, of mutual consultation in the patient''s home in many places, the opportunity for oral communication has declined, and availability on the telephone is not always easy. The busy general practitioner (far less an unknown physician from a deputising service without access to the records) has little time to write a comprehensive letter. In practice a relatively small hospital-based mobile team of specially experienced sisters who are keen to communicate in the home, the GP''s surgery, and the school makes a major contribution to the diabetic care of a young population vulnerable to major handicap in what should be the prime of life. Their cost effectiveness may be difficult to prove but it is not at all in doubt--especially when the sisters as in this area deal in the community with a wider range of chronic illnesses and handicaps in children.