High-resolution analysis of locomotor activity rhythms indisconnected,a visual-system mutant ofDrosophila melanogaster

Free-running locomotor activity and eclosion rhythms ofDrosophila melanogaster, mutant at thedisconnected (disco) locus, are substantially different from the wild-type phenotype. Initial periodogram analysis revealed little or no rhythmicity (Dushayet al., 1989). We have reanalyzed the locomotor activity data using high-resolution signal analysis (maximum-entropy spectral analysis, or MESA). These analyses, corroborated by autocorrelograms, uncovered significant residual circadian rhythmicity and strong ultradian rhythms in most of the animals tested. In this regard thedisco mutants are much like flies expressing mutant alleles of theperiod gene, as well as wild-type flies reared throughout life in constant darkness. We hypothesize that light normally triggers the coupling of multiple ultradian oscillators into a functional circadian clock and that this process is disrupted indisco flies as a result of the neural lesion.This work was supported in part by NIH Grant FM-33205.     

Reproducibility of Immunological Tests Used To Assess Multiple Chemical Sensitivity Syndrome

Whether persons with multiple chemical sensitivity syndrome (MCS) have immunological abnormalities is unknown. To assess the reliability of selected immunological tests that have been hypothesized to be associated with MCS, replicate blood samples from 19 healthy volunteers, 15 persons diagnosed with MCS, and 11 persons diagnosed with autoimmune disease were analyzed in five laboratories for expression of four T-cell surface activation markers (CD25, CD26, CD38, and HLA-DR) and in four laboratories for autoantibodies (to smooth muscle, thyroid antigens, and myelin). For T-cell activation markers, the intralaboratory reproducibility was very good, with 90% of the replicates analyzed in the same laboratory differing by ≤3%. Interlaboratory differences were statistically significant for all T-cell subsets except CD4⁺ cells, ranging from minor to eightfold for CD25⁺ subsets. Within laboratories, the date of analysis was significantly associated with the values for all cellular activation markers. Although reproducibility of autoantibodies could not be precisely assessed due to the rarity of abnormal results, there were inconsistencies across laboratories. The effect of shipping on all measurements, while sometimes statistically significant, was very small. These results support the reliability of fresh and shipped samples for detecting large (but perhaps not small) differences between groups of donors in the T-cell subsets tested. When comparing markers that are not well standardized, it may be important to distribute samples from different study groups evenly over time.     

Merozoite vaccination against Plasmodium knowlesi malaria.

Free malarial merozoites isolated from in vitro cultures of P. knowlesi and emulsified with Freund's complete (FCA) or incomplete (FIA) adjuvant were used to vaccinate twelve Rhesus monkeys against the uniformly lethal infection caused by P. knowlesi. Initial challenge of six monkeys with the same parasite variant as used for vaccination produced no detectable infection in three monkeys, while three others developed low-grade parasitaemia (maximum 1.5 per cent), which terminated after 6-11 days. Vaccination with merozoites in either FCA or FIA induced protection against homologous variant challenge. Six other monkeys were challenged first with a parasite variant different from that used for vaccination. Two animals immunized with merozoites in FIA alone or in FCA on only one occasion developed fatal infections. The other four animals vaccinated at least twice with merozoites in FCA showed low-grade parasitaemia (maximum 1.5 per cent) which terminated after 8-12 days. Eight monkeys rechallenged on eleven occasions at intervals of up to 16 weeks were completely resistant to several variants and a distinct laboratory strain of P. knowlesi, but developed chronic malaria similar to that in unimmunized controls when challenged with a different species of malaria, P. cynomolgi bastianellii. It is concluded that merozoite vaccination of Rhesus monkeys induces immunity against the erythrocyte stages of P. knowlesi far greater in degree and significantly broader in variant specificity than that achieved by previous methods of immunization or by repeated drug-controlled infections.     

Early cellular responses to intradermal injection of Kveim suspension in normal subjects and those with sarcoidosis.

In a detailed controlled study of the cellular response to Kveim suspension in vivo we used immunohistological and histochemical methods to examine cryostat sections of immature Kveim biopsy specimens in subjects with sarcoidosis and normal controls. Changes seen at 48 hours, at which time papular reactions have sometimes been reported, are described. Eight cases of sarcoidosis previously confirmed by a positive Kveim test were studied, in five of whom the test remained positive; plus two subjects with sarcoidosis studied prospectively; and four healthy controls. There were two main features of the 48 hour response: collagen disruption with associated histiocytes, which showed increased acid phosphatase activity; and perivascular infiltrates of lymphocytes and small groups of dendritic cells. The T4:T8 ratios in the infiltrates were similar to those found in the peripheral blood of the subjects, and few lymphocytes showed evidence of activation. T lymphocytes were also seen free in the dermis and migrating to the epidermis. Small juxtacapillary clumps of dendritic cells, identified by NA1/34 (= OKT6; Langerhans' cells) and RFD1 (interdigitating cell) monoclonal antibodies, were found. The Langerhans' cells in the epidermis were, however, normal in number and distribution. These features, which were found in all groups, are not consistent with pre-existing hypersensitivity to Kveim suspension in sarcoidosis. Subsequent differences between sarcoid and normal subjects in the development of granulomas in the Kveim response may therefore relate to the different handling of the foreign material by the cells affected, rather than to differences in the early non-specific recruitment of the cells to the test site.     

Treatment of bipolar affective illness with zimeldine, a 5-HT uptake inhibitor

A small group of patients who had been successfully treated with lithium for a number of years were treated with zimeldine in order to determine whether this antidepressant could be substituted for lithium in patients with a bipolar affective illness. The proposed treatment period of 6 months was not reached by any patient due to depression, hypomania, mania or unusual adverse symptoms. The results of this pilot study suggest that bipolar patients being treated with lithium should not then be treated by antidepressants including those which are potent and selective inhibitors of 5-HT uptake.     

Congenital diaphragmatic hernia with probable autosomal recessive inheritance in an extended consanguineous Pakistani pedigree.

We report four cases of congenital diaphragmatic hernia occurring in two generations of a consanguineous Pakistani family. The affected subjects resembled no recognised genetic syndrome. This family provides further evidence for possible autosomal recessive inheritance of congenital diaphragmatic hernia in some cases.     

HIV/AIDS surveillance in Japan, 1984-2000

The HIV/AIDS surveillance system in Japan, which began collecting data on the number of AIDS patients in 1984 and the number of HIV-infected persons in 1987, has played an important role in monitoring the trend and magnitude of Japan's HIV/AIDS epidemic and its distribution across various population subgroups. However, the system lacks any personal identifiers, making it impossible to eliminate duplication or to track cases for disease progression. It also does not permit the identification of the residence of HIV-infected persons because the residence of only the reporting physician is documented under the New Infectious Diseases Control Law, effective since April 1, 1999. The number of people with HIV/AIDS in Japan continues to grow. Among youth, sexually transmitted diseases, induced abortion, and sexual activities have shown a marked increase since the mid-1990s. Behavioral risk of infection for both injection drug users (IDUs) and men who have sex with men (MSM) remains alarmingly high. Accurate monitoring of infection rates is critical to the planning and evaluation of treatment, care and prevention programs. Japan should restructure its HIV/AIDS surveillance system to more accurately monitor the HIV/AIDS epidemic and related risk behaviors.     

Diagnostic issues in a family with late onset type 2 neurofibromatosis.

We report a family with type 2 neurofibromatosis and late onset tumours. Five members of this family have developed hearing loss late in life, two of whom have only been shown to have the diagnosis in their seventies, and three other obligate gene carriers died undiagnosed at 64, 72, and 78 years of age. A missense mutation at the C-terminal end of the NF2 protein has been identified in this family and segregates with disease. The use of highly polymorphic markers for predictive testing is also shown. There appears to be an autosomal dominant form of spinocerebellar degeneration which is segregating separately to NF2 in this family, which created a diagnostic dilemma.