Asymmetries in core-collapse supernovae from maps of radioactive 44Ti in Cassiopeia A.

Asymmetry is required by most numerical simulations of stellar core-collapse explosions, but the form it takes differs significantly among models. The spatial distribution of radioactive (44)Ti, synthesized in an exploding star near the boundary between material falling back onto the collapsing core and that ejected into the surrounding medium, directly probes the explosion asymmetries. Cassiopeia A is a young, nearby, core-collapse remnant from which (44)Ti emission has previously been detected but not imaged. Asymmetries in the explosion have been indirectly inferred from a high ratio of observed (44)Ti emission to estimated (56)Ni emission, from optical light echoes, and from jet-like features seen in the X-ray and optical ejecta. Here we report spatial maps and spectral properties of the (44)Ti in Cassiopeia A. This may explain the unexpected lack of correlation between the (44)Ti and iron X-ray emission, the latter being visible only in shock-heated material. The observed spatial distribution rules out symmetric explosions even with a high level of convective mixing, as well as highly asymmetric bipolar explosions resulting from a fast-rotating progenitor. Instead, these observations provide strong evidence for the development of low-mode convective instabilities in core-collapse supernovae.

Hardening and termination of long-duration γ rays detected prior to lightning.

We report the first observation of 3-30 MeV prolonged gamma-ray emission that was abruptly terminated by lightning. The gamma-ray detection was made during winter thunderstorms on December 30, 2010, by the Gamma-Ray Observation of Winter Thunderclouds experiment carried out in a coastal area along the Sea of Japan. The gamma-ray flux lasted for less than 3 min, continuously hardening closer to the lightning occurrence. The hardening at energies of 3-10 MeV energies was most prominent. The gamma-ray flux abruptly ceased less than 800 ms before the lightning flash that occurred over 5 km away from the experimental site. In addition, we observed a clear difference in the duration of the 3-10 MeV gamma rays and those >10 MeV, suggesting that the area of >10 MeV gamma-ray emission is considerably smaller than that of the lower-energy gamma rays. This work may give a manifestation that a local region emitting prolonged gamma rays connects with a distant region to initiate lightning.

Long-term outcomes of hemostatic therapy for variceal bleeding and the challenge pending in the post-direct-acting antivirals era.

Background and study aims: This study evaluated the longterm outcomes of mainly endoscopic hemostatic therapy for gastrointestinal variceal bleeding and of the transition of hemostatic therapy. Patients and methods: Among 1,163 patients treated for gastrointestinal varices between April 2006 and June 2020, a total of 125 patients who underwent emergency hemostatic therapy were enrolled. Survival rates and secondary evaluation points were analyzed. Additionally, patients were classified into two groups: the previous and latter term. Patients' background, therapeutic method, and treatment results were compared between the groups. Results: 94.4% had cirrhosis. The average Child-Pugh score was 8.90. Successful primary hemostasis rate was 98.4%, and 5.6% died within 2 weeks, all with a Child-Pugh score ≥9. The respective 1- and 5-year survival rates for Child-Pugh grade A/B were 81.3% and 55.4%, while those for Child-Pugh grade C were 58.1% and 17.8%. Child-Pugh grade C or hepatocellular carcinoma was significantly associated with poor prognosis. In total, 21.6% experienced variceal re-bleeding; 62.9% of these cases were triggered by continued alcohol consumption. There was no significant difference in survival between patients with and without variceal re-bleeding and in post-treatment survival between the previous and latter terms. In the latter term, the number of cases caused by continued alcohol consumption significantly increased. Conclusions: Multidisciplinary treatment and continuation of proper management after hemostatic therapy for variceal bleeding are crucial. Continued alcohol consumption leads to variceal bleeding and re-bleeding; its proper management, including alcohol abstinence, is one of the major challenges left in the post-directacting antivirals era.

On-ground detection of an electron-positron annihilation line from thunderclouds.

Thunderclouds can produce bremsstrahlung gamma-ray emission, and sometimes even positrons. At 00:27:00 (UT) on 13 January 2012, an intense burst of gamma rays from a thundercloud was detected by the GROWTH experiment, located in Japan, facing the Sea of Japan. The event started with a sharp gamma-ray flash with a duration of <300 ms coincident with an intracloud discharge, followed by a decaying longer gamma-ray emission lasting for ∼60 s. The spectrum of this prolonged emission reached ∼10 MeV, and contained a distinct line emission at 508±3(stat.)±5(sys.) keV, to be identified with an electron-positron annihilation line. The line was narrow within the instrumental energy resolution (∼80keV), and contained 520±50 photons which amounted to ∼10% of the total signal photons of 5340±190 detected over 0.1-10 MeV. As a result, the line equivalent width reached 280±40 keV, which implies a nontrivial result. The result suggests that a downward positron beam produced both the continuum and the line photons.

Supernovae. 44Ti gamma-ray emission lines from SN1987A reveal an asymmetric explosion.

In core-collapse supernovae, titanium-44 ((44)Ti) is produced in the innermost ejecta, in the layer of material directly on top of the newly formed compact object. As such, it provides a direct probe of the supernova engine. Observations of supernova 1987A (SN1987A) have resolved the 67.87- and 78.32-kilo-electron volt emission lines from decay of (44)Ti produced in the supernova explosion. These lines are narrow and redshifted with a Doppler velocity of ~700 kilometers per second, direct evidence of large-scale asymmetry in the explosion.

Nonfamilial prealbumin-type amyloid polyneuropathy.

A 53-year-old man with nonfamilial prealbumin-type amyloid polyneuropathy had severe motor, sensory, and autonomic polyneuropathy, beginning at age 48 years. These clinical features closely resembled familial amyloid polyneuropathy (FAP), but abnormal serum prealbumin levels, specific to FAP (Japanese type), were not detected by radioimmunoassay; DNA sequence for prealbumin was normal. Thus, the diagnosis of FAP was excluded. A possible diagnosis of systemic senile amyloidosis was also considered.

A missense mutation in the exon 8 of lamin A/C gene in a Japanese case of autosomal dominant limb-girdle muscular dystrophy and cardiac conduction block.

A case of autosomal dominant limb-girdle muscular dystrophy with atrioventricular conduction block (LGMD1B) has been documented. In this family, 13 members, nine males and four females, had cardiac arrhythmia requiring pacemakers. The proband, a 67-year-old male, had longstanding proximal muscle weakness later associated with cardiac arrhythmia but showed neither rigid spine nor joint contracture. His muscle enzymes were within normal range and muscle biopsy showed myopathic changes. Gene analysis of the proband revealed Tyr481His mutation in the exon 8 of lamin A/C (LMNA) gene which is adjacent to the codon mutated in reported cases of familial partial lipodystrophy. This is the first report of muscular dystrophy shown to have a mutation of LMNA in a Japanese family as well as the first case of missense mutation in the exon 8 with LGMD1B phenotype.

Fukuyama-type congenital muscular dystrophy: close relation between changes in the muscle basal lamina and plasma membrane.

Despite the recent advance in genetic study of Fukuyama-type congenital muscular dystrophy (FCMD), the mechanism of muscle degeneration in the disease remains unclear. To clarify it, muscle biopsies from six cases of FCMD were subjected to immunohistochemical and ultrastructural studies. On the muscle cell surface, decreased expression of laminin alpha2 subunit was seen along with aberrant expression of laminin alpha5 and neural cell adhesion molecule. Electron microscopy revealed breach of muscle basal lamina. The electron density of plasma membrane was significantly lower at the places without identifiable basal lamina. Thus in FCMD changes of laminin and other proteins on the cell surface involve a process common to developing muscles, and loss of normal structure of the basal lamina is closely associated with changes of the plasma membrane. This suggests that the primary cause of FCMD is related to formation and maintenance of the basal lamina.

Experimental allergic myositis in SJL/J mouse. Reappraisal of immune reaction based on changes after single immunization.

SJL/J mice have been subjected to immunization with wide varieties of antigens to produce models of autoimmune disorders including experimental myositis. They also have a defect in dysferlin gene and spontaneously develop muscle fiber degeneration, a condition akin to limb-girdle type muscular dystrophy and Miyoshi myopathy. To know whether muscle inflammation of SJL mice after immunization with muscle fractions really represents immune-mediated myositis or no more than an epiphenomenon of muscle degeneration due to dysferlin defect, we studied immunological parameters after immunization with rabbit myosin B fraction. Initial infiltration of macrophages and CD4+ lymphocytes on day 11 was followed by increase in number of CD8+ cells. Such increase was not observed in the nontreated and adjuvant controls. Some infiltrating cells were interferon gamma (IFN-gamma) positive. Furthermore, increased expression of the signal transducers and activator of transcription 1 (STAT-1) and interferon regulatory factor 1 (IRF-1) mRNA was shown in the first 2 weeks. These results indicate Th1 system activity in the muscle, rather than simple dysferlin deficiency, particularly 1-3 weeks after immunization. Thus it is concluded that an immune-mediated myositis is taking place at this stage. This model can be helpful in understanding pathomechanisms involved in the early stage of human myositides. It has also important implications concerning immune reactions associated with transplantation or gene therapy for muscular dystrophies.

Congenital myopathy with myasthenic features and congenital cataract in two siblings.

Two siblings with congenital myopathy showing myasthenic manifestations together with congenital cataract are reported. Their muscle weakness fluctuated and was alleviated by edrophonium chloride. Their serum creatine kinase activity was elevated, and the waning phenomenon was observed on repetitive nerve stimulation. Biopsied muscle showed degenerative changes with type 1 fibre predominance and abnormal morphology of neuromuscular junctions.

Beta-protein immunoreactivity in brains of patients with neuronal ceroid lipofuscinosis: ultrastructural and biochemical demonstration.

The storage pigment in neuronal ceroid lipofuscinoses (NCL) has a close similarity to age pigment lipofuscin. We studied immunoreactivity of isolated neuronal pigments from the juvenile form of NCL and aging control, using monoclonal antibodies (mAbs) against amyloid beta-protein. Ultrastructural localization of the immunoreactivity demonstrated that in NCL the epitopes are distributed mainly in curvilinear multilamellar arrays of the storage pigments and less in fingerprint profiles, while in aging control they are more homogeneously distributed on age pigment lipofuscin. The different distribution of the epitopes may reflect some catabolic as well as morphologic differences in lysosomes. A unique 31-kDa polypeptide detected on Western blots in NCL possibly derives from the same precursor, amyloid beta-protein precursor (ABPP). ABPP processing may be aberrant in NCL brains, and this can be detected as a 31-kDa polypeptide reactive with the mAbs.

Characterization of the gene encoding mouse platelet glycoprotien Ib beta.

Platelet glycoprotein (GP) Ib/IX/V complex is a major receptor for von Willebrand factor (vWF), which mediates platelet adhesion and aggregation under high shear stress conditions. It is composed of GPIb alpha, GPIb beta, GPIX, and GPV. All subunits for the human receptor have been cloned and characterized. However, the function of GPIb beta is still elusive. To obtain further information of GPIb beta, we have determined the genomic sequence of mouse GPIb beta (1466 bp). The deduced amino acid sequence (206aa) was 88% identical to the human GPIb beta protein. All cysteine residues, putative N-linked glycosylation site (Asn41), and putative phosphorylation site (Ser166) were conserved. The promoter region contained putative GATA and ets binding motif implicated in megakaryocytic expression. Mouse GPIb beta also contained a leucine-rich glycoprotein (LRG) sequence of 24 amino acids same as human GPIb beta.

Formalin fixed brains are useful for magnetic resonance imaging (MRI) study.

We carried out magnetic resonance imaging (MRI) studies on human brains which had been fixed in formalin solution for over 2 years and had been proven neuropathologically to be cases of multiple sclerosis (MS), progressive multifocal leukoencephalopathy (PML), and Balo's concentric sclerosis (Balo). Using spin echo (SE) and inversion recovery (IR) pulse sequences to detect demyelinated lesions in a living person with MS, the demyelinated lesions of the fixed brains in cases of MS, PML and Balo definitely re-appeared, although T1 and T2 in the gray and white matter were reduced following fixation. High signal areas on the SE images corresponded not only to the characteristic distribution of demyelinated lesions in the white matter but also to sparse myelin, gliosis and mild perivascular cuffing in the white matter around the demyelinated foci in cases of the fixed MS, PML and Balo brains. On the IR images, only MS plaques were evident. This MRI study of fixed brains proved useful to elucidate clinicopathological correlations.

Characterization of cDNA encoding full-length mouse platelet glycoprotein IX.

Glycoprotein (GP) IX is a platelet membrane 20 kD protein, which is associated with GPIbalpha, GPIb beta, and GPV to form GPIb/IX/V complex. GPIb/IX/V complex is a major receptor for von Willebrand factor, which mediates platelet adhesion and aggregation under high shear stress conditions. The relevance of this receptor for hemostasis has been implicated by a congenital bleeding disorder lacking the receptor, Bernard-Soulier syndrome. All subunits for the human receptor have been cloned and characterized. However, the function of GPIX is still elusive. To obtain further information of GPIX, we have determined a cDNA sequence of mouse GPIX (811 bp). The deduced amino-acid sequence (177aa) was 71% identical to the human GPIX protein. All cysteine residues in extracytoplasmic domain and putative N-linked glycosylation site (Asn44) were conserved. Mouse GPIX contained a leucine-rich glycoprotein sequence composed of 24 amino acids, as did human GPIX.

Selection of scientific periodicals to monitor drug safety information using Excerpta Medica and Japicdoc in the post marketing surveillance of drugs.

In order to select important journals to be monitored for efficient collection of literature information on drug safety, a retrospective search was made of the safety information in the Excerpta Medica (EM) database between 1979 and 1981. The search provided 54,005 references to drug safety, which were found in a total of 2,536 journals. Fifty percent of the references appeared in only 148 journals, or 6% of all journals surveyed. A similar search, carried out using the Japicdoc (JD) database, provided 9,268 references in 172 journals. To cover all the necessary information appearing in overseas journals, however, a retrospective search of a bibliographic database is required as a cost-effective means to improve the comprehensiveness of the collection of information. In domestic journals, because JD includes fewer journals than EM, all of the 172 journals can be monitored for the collection of drug safety information.

[A female case of carnitine palmitoyltransferase deficiency].

A 17-year old woman noted myalgia after taking a long distance walk at the age of 10. In adolescence, she had several episodes of myalgia and pigmenturia after athletic activity or infection. At age 17, myoglobinuria and abnormally increased serum creatine kinase were documented after one of these episodes. The neurological examination revealed mild proximal muscle weakness of upper extremities. Electromyography showed myogenic patterns, such as brief, small abundant potentials on them. Venous lactate was raised normally on the ischemic exercise test. During prolonged fasting, plasma ketone bodies increased normally but there were abnormal elevations of plasma creatine kinase and myoglobin. Morphometric analysis of electron microscopy in muscle showed few lipid deposits and that of light microscopy revealed no abnormality. CPT activity in muscle was only 15% of normal value by the isotope-exchange assay. These results were consistent with the diagnosis of CPT deficiency. Although several cases of CPT deficiency with recurrent myoglobinuria have been reported in Western countries, our patients is the first case of Japanese showing recurrent myoglobinuria. CPT deficiency should be considered as a differential diagnosis in cases of recurrent myoglobinuria.

[Postmarketing survey on the clinical use of cefotiam].

We performed a survey of clinical experience of cefotiam (CTM: Pansporin) as postmarketing surveillance (PMS), and evaluated the efficacy and safety of CTM in 10,499 cases of data which were collected during the first 2 years after approval. The following results were obtained. The efficacy rate of CTM in the treatment of various infections was 83.2%, which was equal or superior to the clinical results obtained before approval. A total of 472 adverse drug reactions was reported by 10,499 patients (4.50%). The commonest adverse drug reactions was liver function abnormality (230 cases), followed by dermal symptoms (103 cases), gastrointestinal symptoms (53 cases) and renal function abnormality (20 cases) in the order mentioned. All of these adverse drug reactions had already been known for cephem antibiotics, and no remarkable adverse drug reactions specific to CTM was found. The above PMS results indicate the same efficacy of CTM that obtained from premarketing studies. As regards safety, there was no remarkable unexpected adverse drug reaction and their profile was also the same as that found in premarketing studies. Thus, the utility of CTM was confirmed.