Microbes, molecular mimicry and molecules of mood and motivation.

The hypothesis proposed is that functional disorders, such as irritable bowel syndrome, chronic fatigue syndrome and anorexia nervosa are caused by auto-antibodies to neuronal proteins induced by molecular mimicry with microbial antigens. The age incidence of these conditions, the marked female excess, increase with economic and technological advance, precipitation by infection, and the paucity of histological changes are all consistent with the hypothesis. It can be tested directly using human sera to search for cross reaction with brain proteins in model systems such as Drosophila melanogaster. The conditions might be amenable to treatment using pooled immunoglobulin. Identification and elimination from the microbial flora of the bacteria that express the cross reacting antigens should be possible.

Disseminated lymphangiosarcoma in a dog.

This case is unusual due to its extended clinical course. Clinical, histopathological, and immunohistochemical findings are presented.

Transport of CaM kinase along processes elicited by neuronal contact evokes an inhibition of arborization and outgrowth in D. melanogaster cultured neurons.

Transgenic Drosophila strains expressing an inhibitory peptide of Ca2+/calmodulin dependent protein kinase II (CaM kinase), or a constitutively activated CaM kinase, show altered neuronal process morphology compared to wild type in scanning electron microscopy (SEM) of cultured mature neurons from embryonic neuroblasts. We observed significantly enhanced process growth in cells with inhibited enzyme, and reduced process growth in cells with activated enzyme, suggesting that active CaM kinase is involved in the inhibition of neurite growth during development. The subcellular distribution of CaM kinase in wild type neuronal cultures was determined using a gold particle labeling procedure which allowed the mapping of the enzyme directly in the scanning electron microscope (SEM). Before neuronal contact there was little labeling of processes, but after connections had been made the processes were heavily labeled. Our results suggest that the major transport of CaM kinase to the terminals does not occur until after or during the formation of neuronal connections when a functional synapse might be formed. Taken together, these results suggest a target-dependent transport of the enzyme along processes and an inhibitory role for CaM kinase on neurite branching.

Endogenously inhibited protein kinase C in transgenic Drosophila embryonic neuroblasts down regulates the outgrowth of type I and II processes of cultured mature neurons.

Embryonic neurons were cultured from transgenic Drosophila melanogaster expressing a highly specific pseudosubstrate inhibitor of protein kinase C (PKC). Flies homozygous for this transgene, which is under the control of the yeast UAS promoter, were crossed to flies homozygous for the yeast heat shock inducible transcription factor GAL 4. Following heat shock, the progeny express the pseudosubstrate inhibitor at high levels. This strategy, which has the advantage of avoiding the non-specific effects of drugs, was used to study the role of PKC in process growth of cultured, differentiating neuroblasts. An external gold particle labeling procedure using a cell surface antigen expressed by mature neurons and processes was used to visualize neuronal processes directly in the scanning electron microscope. We observed that cell cultures expressing a low concentration of the pseudosubstrate inhibitor showed a significant decrease in the number of type I and II processes as compared to control cultures, while the proportions of neuroblasts, ganglion mother cells (GMCs), and mature neurons in the clusters were little affected.

Haemophilus influenzae type b infections in Victoria, Australia, 1985 to 1987.

Invasive Haemophilus influenzae type b (HIB) infections occurring from 1985 to 1987 in children younger than 16 years of age living in the state of Victoria were reviewed. There were 547 cases which fulfilled the case definition, including 231 cases of meningitis, 219 of epiglottitis and 97 other infections; 14 (2.6%) children died, 8 with meningitis, 5 with epiglottitis and 1 with pneumonia. Ninety-five percent of cases occurred in children younger than 5 years of age, in whom the case attack rate was 58.5/100,000/annum. Nearly two-thirds of cases (46% of meningitis; 91% of epiglottitis; 45% of other infections) occurred in children more than 18 months of age (the age at which vaccine is presently given in the United States). Compared with the United States, the case attack rate for HIB disease in Victoria is lower, the mean age of affected children higher and the proportion with epiglottitis is greater. However, the incidence, age distribution and clinical manifestations of HIB disease in Victoria are similar to those described in Scandinavia before the successful introduction of vaccines. Effective conjugate vaccines against HIB disease are now available and the majority of cases are preventable (depending on the immunization schedule used). These data suggest that immunization of Victorian children against HIB infection should be cost-effective.

A review of Haemophilus influenzae infections in Cambridge 1975-1981.

Invasive Haemophilus influenzae infections diagnosed in Cambridge between January 1975 and December 1981 are reviewed. Altogether, 81 sites in 77 patients were infected. Of these patients, 41 had meningitis, 20 epiglottitis, 8 bone or joint infections (2 with concurrent meningitis), 4 cellulitis, 5 pneumonia (2 with concurrent epiglottitis) and 3 septicaemia in the absence of documented localised infection. Most patients (88%) were children less than 5 years of age. Only 8 adults with such infections were identified. Of these, 6 had an identifiable predisposing condition. The incidence of meningitis was 18 cases per 100 000 children less than 5 years of age. There were 3 deaths. Of the strains of H. influenzae isolated, 16% were ampicillin-resistant. The unusual age-specific incidence of epiglottitis and the incidence of deafness after meningitis are emphasised.