Type 4b Research Articles

Axonal Charcot-Marie-Tooth Disease and the Neurofilament Light Gene ( NF-L)

Axonal Charcot-Marie-Tooth Disease and the Neurofilament Light Gene ( NF-L)

Charcot-Marie-Tooth type 4B is caused by mutations in the gene encoding myotubularin-related protein-2.

A gene mutated in Charcot-Marie-Tooth disease type 4B (CMT4B), an autosomal recessive demyelinating neuropathy with myelin outfoldings, has been mapped on chromosome 11q22. Using a positional-cloning strategy, we identified in unrelated CMT4B patients mutations occurring in the gene MTMR2, encoding myotubularin-related protein-2, a dual specificity phosphatase (DSP).

Classification of paraglacial barrier systems: coastal New England, USA

The New England coast harbours a wide variety of barrier forms, which we organize into six barrier‐coastline types. The barriers develop in response to the relative importance of several spatially and temporally variable parameters, particularly antecedent topography and geology, sediment abundance and size, exposure to wave and tidal energy and sea‐level history. The six coastline types can also be identified in other paraglacial regions. Existing barrier‐coastline classification schemes do not allow consistent subdivision of paraglacial barrier coasts. This paper presents a new scheme that is applicable to paraglacial and non‐paraglacial barrier coasts alike. Aside from hydrodynamic regime, which forms the basis of the barrier classification most commonly used to date, it includes a compartmentalization factor. Sediment‐starved ‘isolated’ (‘type 1’) barrier coastlines are characterized by short, widely spaced barriers. Small, localized updrift and offshore sources have provided sediment for short barriers along ‘clustered headland‐separated’ (‘type 2’) barrier coastlines. Various amounts of sediment from larger updrift and offshore glaciofluvial deposits or directly from rivers have formed the longer barriers along ‘wave‐dominated mainland‐segmented’ (‘type 3a’), ‘mixed‐energy mainland‐segmented’ (‘type 3b’), ‘wave‐dominated inlet‐segmented’ (‘type 4a’) and ‘mixed‐energy inlet‐segmented’ (‘type 4b’) barrier coastlines. Geomorphic form, grain size and stratigraphy can be used to characterize individual barriers along barrier coastlines. Most paraglacial barriers form as spits, but many are transformed subsequently. Welded barriers are common along ‘type 1’ and ‘type 2’ coasts. Baymouth barriers are characteristic of ‘type 3’ coasts, and barrier islands occur exclusively along ‘type 4’ coasts. The coarsest grained barriers are located along ‘type 1’ and ‘type 2’ coasts. Progradational barrier sections are concentrated along ‘type 3’ and ‘type 4’ coasts with abundant sediment supply, but are also present along ‘type 2’ coasts. Temporary increases in sediment supply, common in paraglacial regions, result in transitions between retrogradational and progradational barrier behaviour, which may be recognized on shore‐perpendicular stratigraphic cross‐sections.

Anatomical study of the valves of the superficial veins of the forearm

The valves of the cephalic, basilic and median cubital veins were investigated in the superficial veins of the left forearm in 9 cadavers, aged 25-95. The radial forearm flaps involving these veins are of special clinicoanatomical importance. The following results were obtained: (1) Valves were most frequently evident at Site G of the cephalic vein. No valves were present in Section A-B, (2) type B valves were located at confluences, junctions and branches and were more frequent (54.7%) than Type A (45.3%) located in the straight trunks of superficial forearm veins, (3) Type 2 valves accounted for most (82.3%), and these were followed by Type 1 and Type 4b (5.9%), Type 4a (4.4%) and Type 3 (1.5%).

Sequencing analyses and comparison of parainfluenza virus type 4a and 4b np protein genes

The nucleotide sequences of the cDNA copies of the mRNA coding for the nucleocapsid proteins (NPs) of human parainfluenza viruses type 4A (PIV-4A) and type 4B (PIV-4B) were determined. The copy of PIV-4A N P mRNA contained 1885 nucleotides encoding a protein with a calculated molecular weight of 62,561. The same number of amino acids with a similar molecular weight (62,425) were predicted for the PIV-4B NP protein. Comparisons on the nucleotide sequence and the amino acid sequence of NP protein between these two subtypes revealed extensive homologies in the nucleotide sequence (87%) and in the amino acid sequence (93%). Furthermore, a conserved region with about 100 amino acids was observed between PIV-4s and other paramyxoviruses, Newcastle disease virus (NDV), Sendai virus, mumps virus (MuV), PIV-3, BPIV-3, measles virus (MV), and canine distemper virus (CDV), indicating a common ancestor for these nine viruses. Our data also indicated that the PIV-4 NP proteins were more closely related to MuV and NDV than to other parainfluenza viruses, PIV-3, BPIV-3, and Sendai virus. Interestingly, the NP protein homology between PIV-4s and the morbillivirus group, MV and CDV, was slightly higher than that between PIV-4s and the parainfluenza viruses, PIV-3, BPIV-3, and Sendai virus.

乳用牛のリステリア症の発生と給与中のサイレージからのリステリア菌の分離

In May, 1985, a Holstein cow suffered from nervous symptoms and was condemned within a day. Pathological examination revealed local necrosis, degeneration of nerve cells and perivascular infiltration mainly in the brain stem. Listeria monocytogenes type 4b was isolated from the brain stem. Simultaneously, the same bacteria were isolated from the deteriorated silage feeded. This result showed good agreement with the isolated from the cow biochemically and serologically. Consequently, the silage seemed to be responsible for the disease.

Opsonization of Listeria monocytogenes type 4b by human adult and newborn sera.

We studied the requirements for opsonization of Listeria monocytogenes type 4b with chemiluminescence and bactericidal assays and electron microscopy. Preopsonization with 3% adult serum had good opsonic activity (27,300 +/- 11,000 [standard deviation] counts, chemiluminescence assay), while 3% newborn cord serum was not opsonically active (820 +/- 530 counts, P less than 0.001 versus adult serum). In addition, organisms opsonized with cord serum were not killed (0% bacterial killing) and were less frequently visualized intracellularly on electron micrographs (0 to 4 bacteria per cell) than organisms opsonized with adult serum (70% killing and 10 to 20 bacteria per cell). Opsonic requirements for L. monocytogenes type 4b at low concentrations of serum were studied in detail with Sepharose-protein A-treated adult serum to obtain immunoglobulin G (IgG) and IgM fractions and zymosan-absorbed and C4 inactivator-treated serum to obtain alternative and classical complement pathway-deficient sera, respectively. In the presence of complement, IgM was opsonically active (59% of control) while IgG was not (6% of control). In addition, classical complement activity was required for efficient opsonization (greater than 100% of control) while the alternative complement pathway was unnecessary (3% of control). Since IgM is absent and classical complement activity is low in neonatal serum and at the common sites of neonatal Listeria infection, the requirement for IgM and classical complement activity for efficient opsonization of L. monocytogenes type 4b at low serum concentrations may be a factor in the pathogenesis of neonatal disease.

Tetracycline-resistant L-forms isolated from an antibiotic-susceptible strain of Listeria monocytogenes.

A tetracycline-susceptible strain of Listeria monocytogenes type 4b was converted to stable L-forms by penicillin. L-form variants resistant to tetracycline were then selected from a predominantly tetracycline-susceptible L-form population on plates containing penicillin and increasing concentrations of tetracycline. The origin of tetracycline-resistant L-forms from the parent Listeria strain was confirmed biochemically, by immunofluorescence, and by polyacrylamide gel electrophoresis. Scanning and transmission electron microscopy confirmed the typical L-form structure and the complete lack of cell wall in both L-form strains. The level of [3H]tetracycline uptake was lower in tetracycline-resistant than in susceptible cells.

Enamines in the synthesis of 2-(substituted amino)-3,3-dialkylchromanones

Ethanamines with two alkyl groups at position 2 react with derivatives of 2-hydroxybenzaldehyde to give 2-alkylamino-3,3-dialkylchroman-4-ols such as (4a) as mixtures in which one diasteroisomer preponderates. Oxidation supplies the corresponding chromanones of type (4b) as single racemates except for the bischromanone derived from piperazine. The enamines used were derived from morpholine, pyrrolidine, N-methylaniline, and piperazine as bases, and 2-methylpropanal, 2-methylbutanal, and cyclohexanecarbaldehyde as carbonyl components. 2-Hydroxybenzaldehyde itself, and its 3-methoxy-, 4-methoxy3,5-dibromo-, 4,6-dimethyl-, 5-nitro-, and 3-nitro-derivatives, and also 2-hydroxynaphthalene-1-carbaldehyde were employed.

2, 3‐Disubstituted γ‐Butyrolactams from the Michael‐Additions of Doubly Deprotonated, Optically Active β‐Hydroxycarboxylates to Nitroolefins. Preliminary Communication

AbstractThe conjugate addition of the chiral, non‐racemic alkoxy‐enolates 5 and 6 to nitroolefins furnishes the hydroxynitroesters 7–13, which are catalytically hydrogenated to give the lactams 14–18. The configuration of adduct 7 from nitroethylene was elucidated by NMR. analysis of the acetal 20 derived from 7. The assignment establishes that the reaction follows the stereochemical rule of attack depicted in 21 and previously deduced for other electrophiles, i.e. formation of erythro‐products of type 3b and 4b. No stereocontrol was found at the newly formed chiral centers in α‐ and β‐position to the NO2 group of 8–12.

Isolation, characterization, and biological properties of an endotoxin-like material from the gram-positive organism Listeria monocytogenes.

The bacterial component responsible for the induction of transient cold agglutinin syndrome in rabbits after intravenous injection of heat-killed Listeria monocytogenes type 4B has been purified and biologically and chemically characterized. A purified immunoglobulin M cold agglutinin was prepared from high-titer sera resulting from the immunization of rabbits with heat-killed L. monocytogenes type 4B and was subsequently used to monitor the purification of the bacterial component responsible for its induction. The bacterial component was isolated from a hot phenol-water extract of lyophilized L. monocytogenes type 4B by multiple molecular sieve chromatography. Upon chemical analysis the purified material was found to be strikingly similar in chemical composition to gram-negative lipopolysaccharide endotoxins. The material contained 15% total fatty acid (of which 50% was beta-hydroxymyristic acid), 40 to 45% neutral sugar (glucose, galactose, and rhamnose), 11.5% amino sugar, 12% uronic acid, 2.5% 2-keto-3-deoxyoctonic acid, 2% heptose, 0.87% phosphorus, and 1.6% amino acid, thereby accounting for 85 to 90% of the weight of the component. Electron micrographs of the purified material were similar to those of lipopolysaccharide preparations from gram-negative organisms. The purified material exist in aqueous solutions as large aggregates, but can be dissociated into a single smaller subunit (3.1S) by dialysis against sodium dodecyl sulfate buffer. The listerial component was toxic and pyrogenic to rabbits, producing symptoms typical of gram-negative endotoxins. Activity in the limulus lysate gelation assay and in the carbocyanine dye assay provides a further link of this material with classical gram-negative endotoxins.

リステリア菌4d型による髄膜炎の一症例

All strains of Listeria monocytogenes isolated from human listeriosis in Japan so far have been identified as type 1 or type 4b.A strain was isolated from the cerebrospinal fluid of a meningitis baby (1 year and 4 months old, male) in Ishikawa Prefecture, December of 1971, and this strain was named as “Tsuchiyama strain”. Its morphological findings and biochemical properties are identical with those of Listeria monocytogenes.By serological tests, i.e. by cross agglutination test and absorption test using immune serum of standard strains (type 4a, 4b, 4c, 4d, 4e) and Tsuchiyama strain, it was identified as Listeria monoc ytogenes type 4d.It is the first case of listeriosis due to type 4d strain in Japan.

Antibody Heterogeneity in Experimental Listeriosis

Summary In uninoculated sheep and cattle, IgM antibodies to Listeria monocytogenes types 1, 2 and 4b were uniformly demonstrable. The 7S antibodies were divided into subclasses designated “slow IgG” and “fast IgG.” It was noteworthy that only one sheep in a group of 12 ruminants had 7S antibodies (slow IgG) to Listeria serotype 4b prior to immunization. Thus the basis for antibody activity in the serum of apparently normal animals is largely a function of the IgM class of immunoglobulins. All immunized animals synthesized both subclasses of 7S antibodies. Results were less distinctive on studies with Listeria types 1 and 2, Staphylococcus aureus and Streptococcus faecalis. Among four sheep studied in detail all contained IgM agglutinins prior to immunization, in addition to variable distribution of 7S antibody populations reacting with the four microorganisms. Whole serum titers to Listeria types 1 and 2 were not markedly increased by immunization of the animals with the Streptococcus or Staphylococcus. However, titers did increase following the inoculation of live Listeria cells into the same animals. The detection of IgG agglutinins to Listeria type 4b in serum after reduction of IgM globulins with 2-mercaptoethanol would appear to have diagnostic significance.

Isolation of Listeria monocytogenes from oat silage.

A culture of Listeria monocytogenes isolated from the brain of an infected sheep from a flock fed contaminated silage and cultures isolated from this silage were all serological type 4b, establishing a definite epidemiological relationship.