Chronic myelogenous leukemia with a complex Ph1 translocation in an XYY male

We encountered a 38-year-old Japanese male patient with chronic myelogenous leukemia (CML), whose bone marrow and peripheral blood cells during the chronic and blastic phases contained a complex Ph¹ translocation and an extra Y chromosome [i.e., 47,XYY,t(9;22;13)(q34;q11;q14)]. A karyotypic analysis of PHA-stimulated lymphocytes showed the constitutional karyotype to be 47,XYY. Thus, it was considered that CML with a complex Ph¹ translocation developed in an XYY male; such a case has not been reported, so far. A B-lymphocyte cell line with the complex Ph¹ translocation was established by the procedure of Epstein-Barr virus transformation. The presence of the complex Ph¹ translocation in the B-lymphocyte cell line suggests that some of the B lymphocytes in this patient originated from the CML clone.     

Antikörperbildung gegen Poliovirus-N- und -H-Antigen bei Immunisierung von Meerschweinchen

Zusammenfassung Sieben Gruppen von Meerschweinchen zu je 15 Tieren wurden mit virulenten und attenuierten StÄmmen von Poliomyelitis immunisiert und die Antikörperbildung gegen N- und H-Antigen beobachtet. In allen Gruppen wurden zuerst H-Antikörper und spÄter N-Antikörper gebildet. Im weiteren Verlauf der Immunisierung nimmt bei Typ I und Typ II die Bildung von N-Antikörpern wesentlich schneller zu, so da\ die N-Titer bald höher sind als die H-Titer. Gleichzeitig reagieren zuerst mehr Versuchstiere mit H-Antikörper-Bildung, wÄhrend spÄter mehr Tiere N-Antikörper bilden.Bei der Immunisierung mit Typ III reagieren mehr Tiere mit Antikörperbildung gegen H als gegen N, gleichzeitig sind die H-Titer wÄhrend des ganzen Verlaufs höher oder ebenso hoch wie die N-Titer. Die Antikörperbildung gegen die ImpfstÄmme entsprach weitgehend dem Verlauf bei den virulenten StÄmmen. Die Reaktion des Organismus auf die Zufuhr von N- und H-Antigen Ändert sich im Laufe der Immunisierung. Die zu einem spÄteren Zeitpunkt vorgenommenen Booster-Injektionen vermögen das initiale übergewicht der H-Antikörper nicht wiederherzustellen, selbst wenn mehr H- als N-Antigen zugeführt wird.

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Antibody production versus poliovirus N and H antigen after immunisation of guinea pigs

Summary Seven groups of guinea pigs consisting of 15 animals each were immunized with virulent and attenuated strains of poliomyelitis virus. Subsequently the antibody production versus N and H antigen was studied. The animals of all groups responded primarily by production of H antibodies and later by N antibodies. During the further course of immunization the production of N antibodies was much faster for type I and II, thus anti N titers soon were higher than anti H titers. In addition, more animals responded initially by production of H antibodies, while later on more animals produce N antibodies. During the immunization with type III more animals produced H than N antibodies and H titers were always higher than N titers or equal. Antibody production to vaccination strains corresponded to a far extent to that of virulent strains. Response of the organism changes during the course of immunization. Booster injections given at a later time do not recall the initial peak of H antibodies, even if a greater dose H antigen is given than N.

     

Spectrum of CLN6 mutations in variant late infantile neuronal ceroid lipofuscinosis

The neuronal ceroid lipofuscinoses (NCLs) are a group of autosomal recessive neurodegenerative diseases of childhood. CLN6, the gene mutated in variant late infantile NCL (vLINCL), was recently cloned. We report the identification of eight further mutations in CLN6 making a total of 18 reported mutations. These mutations include missense, nonsense, small deletions or insertions, and two splice-site mutations. Ten mutations affect single amino acids, all of which are conserved across vertebrate species. Minor differences in the pattern of disease symptom evolution can be identified. One patient with a more protracted disease progression was a compound heterozygote for a missense mutation and an unidentified mutation. Fifteen CLN6 mutations occur in one or two families only, and families from the same country do not all share the same mutation. Unlike NCLs caused by mutations in CLN1, CLN3, CLN5, and CLN8, there is no major founder mutation in CLN6. However, one mutation (E72X) is significantly more common in patients from Costa Rica than two other mutations present in that same population. In addition, a 1-bp insertion (c.316insC) is associated with families from Pakistan and I154del may be common in Portugal. A group of Roma Gypsy families from the Czech Republic share two disease-associated haplotypes, one of which is also present in a Pakistani family, consistent with the proposed migration of the Roma from the Indian subcontinent 1,000 years ago. All mutations are recorded in the NCL Mutation Database together with their country of origin for use in the development of rapid screening assays to confirm diagnosis and to facilitate carrier testing appropriate to a population.     

Constitutive Secretion of Interleukin-6 by Human Decidual Stromal Cells in Culture. Regulatory Effect of Progesterone

PROBLEM : Although several studies have demonstrated that decidual stromal cells (DSC) can secrete cytokines in culture, none of these studies documented the purity of the cultures. Since other cells of the decidua, such as macrophages and epithelial cells, also produce cytokines, it is important to ensure purity of the culture so that cytokine production can be ascribed with confidence to DSC. METHOD : DSC from early human pregnancies were highly purified and maintained in culture. Basal secretion by these cells of IL-6, together with other cytokines considered critical for pregnancy (IL-1β, TNFα and IFNγ), was measured with immunological techniques. RESULTS : We found that DSC in culture produce insignificant quantities of IL-1β, TNFá and IFNΓ, but appreciable amounts of IL-6. The production of this later cytokine was, however, inhibited by the effect of progesterone. CONCLUSIONS : Basal production of IL-6 by DSC may be involved in physiological functions at the maternal-fetal interface. Nevertheless, the secretion of this cytokine is regulated by progesterone, probably to prevent excessive production of this cytokine from triggering an inflammatory response that might compromise pregnancy.     

Axonal and myelin lesions inβ-mannosidosis: Ultrastructural characteristics

Summary Ultrastructural changes in central nervous system (CNS) white matter of three goats affected with-mannosidosis were analyzed to further define characteristics and pathogenesis of axonal and myelin abnormalities. The variations in myelin association and contents of axonal spheroids were delineated. The occurrence of spheroids in a 96/150-day fetus documented the early development of these axonal lesions. In regions of severe myelin deficits, the presence of apparently normal axons and a reduction in the number of oligodendrocytes were confirmed. Many remaining cells in myelin-deficient regions were characterized by dark, vacuolated cytoplasm. The occurrence of internodes with myelin sheaths adjacent to internodes without myelin sheaths suggested that an axonal defect is not primarily responsible for the absence of myelin sheaths. A mild myelin deficit in the spinal cord was indicated by the presence of unmyelinated axons. Except for occasional mild cytoplasmic vacuolation, the spinal cord glial cells appeared relatively normal. The findings presented here are consistent with the hypothesis that an oligodendrocyte defect, expressed by regional differences, is a major factor in the pathogenesis of myelin deficiency in-mannosidosis.Supported by NIH grant NS-16886 to MZJ and BRSG funds from the College of Osteopathic Medicine, Michigan State University, to KLL     

Striatal membrane-bound and soluble catechol-O-methyl-transferase after selective neuronal lesions in the rat

Summary Activities of the two forms of catechol-O-methyltransferase (COMT), viz. the soluble (S-COMT) and the membrane-bound (MB-COMT), have been studied in the rat striatum to characterize their localization in relation to the nigrostriatal dopaminergic neurons. Selective unilateral nigrostriatal dopaminergic lesions were produced by an intranigral injection of 6-hydroxydopamine (6-OHDA; 8g/site). 6-OHDA caused an extensive lesion of the dopaminergic neurons as revealed by non-detectable concentrations of dopamine in the striata of the lesioned sites. In spite of that neither S-COMT nor MB-COMT activities were altered in comparison with the intact control striata. The intrastriatal injection of kainic acid significantly increased S-COMT activity but to some extent decreased MB-COMT activity. Kainic acid did not alter the striatal concentration of dopamine.These results suggest that both S-COMT and MB-COMT reside postsynaptically the nigrostriatal dopaminergic neurons. S-COMT seems to be found mainly in striatal glial cells, whereas striatal MB-COMT might be located both in postsynaptic neuronal and extraneuronal cells.     

Aqueductal lesions in 6-aminonicotinamide-treated suckling mice

Summary Suckling mice which received a single intraperitoneal injection of 6-aminonicotinamide on the 5th postnatal day, consistently developed hydrocephalus. During the early stages of hydrocephalus (7–9 days after injection), aqueductal lesions were characterized by edematous ependymal and subependymal cells, and spongy changes in the periaqueductal area, which resulted in aqueduct stenosis. Later stages (after 20 days post-injection) showed that these edematous changes totally subsided, leaving an obliterated aqueduct which was similar to that of human congenital hydrocephalus. At the completely obliterated area, ultrastructural investigation disclosed a normal-looking neuropil but no aqueductal lumen. In the remaining ependymal cell, increased intermediate filaments and lipid droplets occurred. These data suggest that acute ependymal cell degeneration during the perinatal period may result in the profile of aqueduct agenesis in human congenital hydrocephalus.Supported in part by research grants NS-03356, NS-10803 from NINCDS, USPHS     

The interaction of 1-alkyl-4, 4-diphenylpiperidines with the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine receptor binding site

Summary 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) is a selective neurotoxin which produces degeneration of the nigrostriatal bundles in the central nervous system of man and animals. In these areas of the brain are concentrated the receptor binding sites for [³H]MPTP. 1-Alkyl-4, 4-diphenylpiperidines displace [³H]MPTP from these binding sites with K₁ values in the micromolar range. The t-butyl analogue in this class of substances, budipine, is a novel therapeutic agent for Parkinsonism whose mechanism has not yet been fully clarified. The affinity of budipine for the MPTP receptor binding site was determined as a K₁ value of 2.2M. Other 4, 4-diphenylpiperidine derivatives such as 1-methyl-4, 4-diphenylpiperidine and 1-i-propyl-4, 4-diphenylpiperidine have substantially lower affinities. Monoamine oxidase inhibitors such as deprenyl, pargyline and harmaline have affinities to the MPTP receptors which parallel their affinity for the B type of monoamine oxidase (MAO B). This supports the theory that the MPTP receptor binding sites is identical with membrane bound MAO B.     

Effect of vibration on red cell metabolism

Summary In investigating the influence of vibrational energy on the metabolism of the erythrocyte, it was hypothesized that under conditions of normal PaO₂ and SaO₂ in arterial blood, vibration induced vasoconstriction would decrease local blood flow and induce hypokinetic hypoxia. This decreased blood flow and therefore decreased delivery of oxygen to the tissue would markedly lower tissue PO₂ (hypokinetic hypoxia), which would influence the energetics and metabolism of the erythrocyte. The metabolism of the red blood cell (RBC) was evaluated by measuring the enzymatic activities of PFK (2.7.1.11), PGI (5.3.1.9), PK (2.7.1.40), and aldolase (4.1.3.13) from the anaerobic glycolytic cycle and D-G-6-P (1.1.1.49) from the pentose cycle. Also measured were the levels of ATP and 2,3 DPG and the in-vitro production of lactic acid. In the group of workers showing early changes (vibration angioneurosis) associated with the vibration syndrome, changes in RBC metabolism were demonstrated. Statistically significant were increases of PFK, PK and the production of lactic acid, indicating the activation of anaerobic glycolysis. Furthermore statistically significant were the increased 2,3 DPG and decreased ATP levels.