Myelin changes in leprous neuropathy

Summary Myelin changes were observed in fibres of nerves from cases of leprosy. The myelin had a loosened appearance caused by increased and irregular separation of the intraperiod line. Loosening might affect all, or only some, of the lamellae forming a myelin sheath. There was a pathcy distribution of fibres with abnormal myelin, and they were seen only in nerves showing other marked pathological changes including the presence of oedema. The appearances are suggestive of intramyelinic oedema which may be related to the presence of endoneurial oedema.Supported by the Brain Research Trust and the British Council, who funded an exchange arrangement between the Institute of Neurology, London and the Foundation for Medical Research (FMR), Bombay     

Hydroxyurea and periodicity in myeloproliferative disease

Three patients, one with polycythaemia vera (PV) and two with chronic myeloid leukaemia (CML), are described who had cycling of blood counts which became apparent whilst receiving hydroxyurea therapy. Significant periodicity was confirmed with the use of the Lomb periodogram. This is Fourier power spectral analysis tailored for unevenly sampled data. The patient with PV had marked oscillations of platelet counts with a periodicity of 29 d and an amplitude of (202-588)x10(9)/L. Smaller oscillations of neutrophil, monocyte and lymphocyte numbers and Hb levels occurred with a similar periodicity. Anticipatory changes in hydroxyurea dosage or the maintenance of a constant dose did not abolish periodicity, but a change in therapy to the non-cycle-specific drug anagrelide dampened and abolished the cycling. One of the patients with CML had tremendous and clear oscillations in white cell, platelet and Hb levels, with a mean periodicity of 74 d. The other had erratic counts which were confirmed to be significantly periodic (64 d), on spectral analysis. A change in therapy to busulphan in both these patients again dampened and abolished the cycling. Hydroxyurea, which is a cell-cycle-specific agent, probably exacerbates the periodicity which may be present in some patients with myeloproliferative disease. A change in therapy to non-cycle-acting compounds such as busulphan or anagrelide results in much more stable counts in such patients.     

Molecular and epidemiological features of gastroenteritis outbreaks involving genogroup I norovirus in Victoria, Australia, 2002-2010

GI noroviruses are relatively rare and systematic studies of the molecular epidemiology of GI norovirus outbreaks are lacking. The current study examined the molecular virology of GI norovirus outbreaks in Victoria, Australia (2002–2010). Of 1,617 norovirus outbreaks identified, 69 (4.3%) were associated with GI norovirus alone, 1,540 (95.2%) with GII norovirus alone and 8 (0.5%) with GI + GII. Some differences between GI and GII outbreak epidemiology were found. GI outbreaks peaked in the 2‐month period November/December whereas GII outbreaks peaked in the 2‐month period September/October and GI norovirus outbreaks were significantly more common in non‐healthcare settings (37.7%) than GII outbreaks (9.5%). ORF 1/ORF 2 genotypes found in the 69 outbreaks involving GI norovirus alone were: GI.2/GI.2, 7 outbreaks; GI.2/GI.6, 18 outbreaks; GI.3b/GI.3, 14 outbreaks; GI.4/GI.4, 21 outbreaks; GI.8/GI.8, one outbreak; GI.d/GI.3, four outbreaks; and GI.e/GI.13, one outbreak. The current study appears to be the first to have identified the recombinant form, GI.2/GI.6. Whereas GI.2/GI.6 and GI.3b/GI.3 outbreaks occurred with equal frequency in both healthcare and non‐healthcare settings, GI.4/GI.4 occurred predominantly in healthcare settings. GI ORF 1/ORF 2 genotypes found in the eight outbreaks involving GI + GII norovirus were GI.2/GI.6, GI.3b/GI.3, and GI.4/GI.4, indicating GI genotypes in GI + GII outbreaks were similar to those found in outbreaks involving GI alone. Apparent differences in the evolution of different GI genotypes were noted. GI.2/GI.2, GI.2/GI.6, and GI.4/GI.4 strains tended to undergo periodic shifts in nucleotide sequence whereas various GI.3b/GI.3 strains tended to circulate simultaneously. J. Med. Virol. 84:1437–1448, 2012. © 2012 Wiley Periodicals, Inc.     

Untersuchungen zur circadianen Periodik bei der genuinen Epilepsie vom Aufwachtyp

Zusammenfassung Untersucht wurden an 3 Kontrollpersonen und an 6 Patienten mit genuiner Epilepsie vom Aufwachtyp über einen Zeitraum von 72 h die Herzfrequenz, die Körpertemperatur sowie die Ausscheidung der Elektrolyte Calcium, Kalium und Natrium im Urin. Für alle Patienten, Aufwachepileptiker und Kontrollpersonen, bestanden auf der Station konstante Bedingungen, sie erhielten eine Standarddiät mit konstanten Werten für Calcium, Kalium und Natrium, mit der 2 Tage vor Beginn der eigentlichen Meßreihe begonnen wurde. Während der Untersuchungszeit wurden keinerlei Medikamente eingenommen.Bestimmt wurden anhand der Originaldaten die Zeiten der Kurvenwendepunkte und durch die Power-Spektralanalyse die Periodendauern der einzelnen gemessenen Parameter.Bei den Aufwachepileptikern ergaben sich inkonstantere Befunde hinsichtlich der Lage der Maxima und Minima und auch der 24 h-Periodik, ohne daß jedoch eine konstante Abweichung in eine Richtung, d. h. entweder eine Vorverschiebung oder eine Verspätung in der Phasenlage, vorlag und auch ohne konstante Veränderung in den Periodendauern aller gemessenen Größen bei ein und demselben Aufwachepileptiker.Zumindest hinsichtlich der hier unter den genannten Bedingungen gemessenen Parameter fand sich kein sicherer Unterschied zwischen den Aufwachepileptikern und den Kontrollpersonen, der als spezifisches, allen Aufwachepileptikern gemeinsames Merkmal einer gestörten circadianen Rhythmik gelten könnte.

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Studies on the circadian periodicity in patients with the awakening type of idiopathic epilepsy

Summary In 6 patients with idiopathic epilepsy of the awakening type and 3 control subjects, the heart rate, body temperature and urinary excretion of sodium, potassium and calcium were measured over 72 h. The patients and the control subjects stayed in the hospital under constant environmental conditions including a standard diet with a constant content of sodium, potassium and calcium. The diet began 2 days before the onset of data collection. No drugs were given during the whole period.The data obtained during the 72-hour period were scored visually concerning the position of the maxima and minima, whereas the period duration was calculated by means of power spectral analysis.The epileptic patients showed more inconstant results concerning the time of maxima and minima as well as the 24-hour periodicity.However, a constant deviation i.e. a constant phase shift or a constant change in period duration into the same direction could not be observed. The different parameters showed different behavior even in the same patient. Thus a constant difference in the circadian periodicity between normal subjects and patients with epilepsy of the awakening type could not be found in the data recorded in the present study.

     

室性早搏自发变异周期性的分析

用圆形分布方法对８１例室性早搏（ＶＰＣ）患者无服药期连续２４ｈ的ＶＰＣ发生次数的周期性作了分析，发现大部分患者ＶＰＣ发生次数的高峰在日间，ＶＰＣ发生次数的昼夜变化符合含两个谐量的余弦曲线模型。     

Cell that are O4 antigen-positive and O1 antigen-negative differentiate into O1 antigen-positive oligodendrocytes

In freshly dissociated viable cells of early postnatal mouse cerebellum, O1 antigen-positive oligodendrocytes have been eliminated by complement dependent immunocytolysis. Before seeding residual cells in culture, O4 antigen-positive cells were immunolabeled by O4 antibody which had been directly conjugated with rhodamine. After various periods of time in culture, cells were treated with fluorescein conjugated O1 antibody, in order to assay for the appearance of O1-positive oligodendrocytes. After 6.5 h in vitro, the first cells carrying both the previously applied rhodamine label and the freshly applied fluorescein label were seen. The simultaneous appearance of both labels indicates tha O4-positive and O1-negative cells are direct precursors of O1 antigen-positive oligodendrocytes.     

Zebrafish GADD45beta genes are involved in somite segmentation

Somites in vertebrates are periodic segmented structures that give rise to the vertebrae and muscles of body. Somites are generated from presomitic mesoderm (PSM), but it is not fully understood how cellular differentiation and segment formation are achieved in the anterior PSM. We report here that zebrafish gadd45beta1 and gadd45beta2 genes are periodically expressed as paired stripes adjacent to the neural tube in the anterior PSM region where presomitic cells mature. In mammals, it is known that GADD45 (growth arrest and DNA damage) family proteins play a role in cell-cycle control. We found that both knockdown and overexpression of gadd45beta genes caused somite defects with different consequences for marker gene expression. Knockdown of gadd45beta genes with antisense morpholino oligonucleotides caused a broad expansion of mesp-a in the PSM, and both cyclic expression of her1 and segmented expression of MyoD were disorganized. On the other hand, injection of gadd45beta1 or gadd45beta2 suppressed expression of mesp-a and her1 in anterior PSM and MyoD in paraxial mesoderm. These results indicate that regulated expression of gadd45beta genes in the anterior PSM is required for somite segmentation.     

The Molecular Mechanism of Human Resistance to HIV-1 Infectionin Persistently Infected Individuals—A Review,Hypothesis and Implications

Resistance to HIV-1 infection in Europeans is associated with a mutation in the gene that codes for the CCR5 protein that is present in Th2 cells and serves as a coreceptor for HIV-1 R5 strain. A deletion of 32 amino acids from the cytokine receptor prevents infection. This mutation prevails in Europeans and is absent in Africans. However, duplication of a gene that codes for a chemokine that binds to the CCR5 was discovered in Africans (mean gene copy 6 while in non-Africans the mean gene copy is 3). Higher expression of these genes protects T cells against HIV-1 infection in vitro. It should be noted that resistance to HIV-1 R5 variant does not protect against HIV-1 R4 variant. It was reported that a minority of highly HIV-1 exposed African professional sex workers (APSW) were resistant to the virus infection during a 10 years period. Recently, the analysis of the cytokines in the serum of the persistently infected seronegative women revealed that the latter hypo-expresses the cytokine IL-4. Since the molecular events during HIV-1 infection are associated with a marked increase in the levels of IL-4 and IgE in the sera of the infected individuals, it suggests that AIDS is an allergy. Thus, a very low level of IL-4 production may abrogate the virus infection. Studies on the human IL-4 gene revealed that together with the IL-4 mRNA a spliced variant with a deletion of exon 2 is synthesized. The latter is a natural antagonist of IL-4 and when expressed in an individual at a level higher than IL-4, the person will resist a microbial infection (e.g. Mycobacterium tuberculosis) or asthma. The present hypothesis suggests that the HIV-1 resistant APSWs produce more IL-4 delta 2 molecules than IL-4 molecules. The binding of IL–4 delta 2 to IL-4 receptors on T and B cells prevents their functions and the infection by HIV-1. The implications of these studies are that treatment of HIV-1 infected people with drugs that will block the IL-4 receptors will stop HIV-1 infections and the determination of the levels of IL-4 and IL-4 delta 2 in the sera of HIV-1+ patients will enable to identify the individuals that have a natural resistance to HIV-l/AIDS and those who need treatments.     

Lack of association between the 3092 T-->C Clock gene polymorphism and cluster headache

Recent studies suggested that genetic factors play a role in cluster headache (CH). However, the type and the number of genes involved in the disease are still unclear. We performed an association study in a cohort of Italian CH patients to evaluate whether a particular allele or genotype of the Clock gene would modify the occurrence and the clinical features of the disease. One hundred and seven CH patients, diagnosed according to the International Classification of Headache Disorders, 2nd Edition, (ICHD-II) criteria, and 210 healthy age, sex and ethnicity-matched controls were genotyped for the 3092 T-->C Clock gene polymorphism (also known as 3111 T-->C). Phenotype and allele frequencies were similarly distributed in CH patients and controls. The clinical features of the disease were not significantly influenced by different genotypes. In conclusion, our study suggests that the 3092 T-->C polymorphism of the Clock gene is unlikely to play an important role in cluster headache.     

A follow-up study of 60 patients after an assumed first period of cluster headache

During 1981-96 a series of 60 consecutive out-patients was examined in relation to an assumed first period of cluster headache (CH). On follow up in 1998 we found that six were deceased at a mean age of 56.5 years (range 45-74 years), of whom one had a definitive CH diagnosis and five had one documented headache period only. Six patients were lost to follow up because they could not be reached. In the final group for evaluation (n = 49) it was found that 13 (26.5%) patients had had one cluster period only during a mean observation time of 8.9 years. Out of 36 patients with a definitive CH diagnosis according to International Headache Society (IHS) criteria, 31 patients had episodic CH, four patients had primary chronic CH and one patient had secondary chronic CH. Of the patients with a definitive CH diagnosis, 83% on follow up had had a recurrence of a second period of CH within 3 years or continuous attacks (chronic/semichronic CH) from the onset. Evidently some patients may suffer from one cluster period only. In our patient material only 17% had a second cluster period after 3 years.