Centronuclear Myopathy with Abundant Nemaline Rods in a Japanese Black and Hereford Crossbred Calf.

Histopathological examination was performed on skeletal and diaphragmatic muscles from an 8-month-old male crossbred calf showing abnormal gait and tremor of the hindlimbs. There were numerous round fibres with centrally placed nuclei forming nuclear chains in longitudinal sections, associated with interstitial fibrosis or adipose tissue infiltration. On nicotinamide adenine dinucleotide tetrazolium reductase (NADH-TR) staining, some muscle fibres in severe lesions showed a spoke-like appearance due to a radial arrangement of sarcoplasmic strands. Additionally, increased NADH-TR activity in the subsarcolemmal structures, appearingas ring-like or necklace-like forms, were observed. Transmission electron microscopy revealed dilated sarcoplasmic reticulum and variably shaped electron-dense inclusions consisting of myofibrillar streams. Another prominent feature was the existence of numerous nemaline rods within muscle fibres; these were stained red by Gomori's trichrome stain. Immunohistochemistry revealed that the nemaline rods showed strong immunoreactivity with α-actinin and desmin antibodies. Electron microscopically, these structures were composed of dense-homogeneous material and continuous with the Z disk. The case was diagnosed as centronuclear myopathy with increased nemaline rods.

Compound heterozygotes for filaggrin gene mutations do not always show severe atopic dermatitis.

BACKGROUND: Mutations in FLG, which encodes profilaggrin, cause ichthyosis vulgaris (IV) and are an important predisposing factor for atopic dermatitis (AD). IV shows autosomal hemidominant (semidominant) inheritance, and patients with bi-allelic FLG mutations tend to have severe IV phenotypes. However, the effect of bi-allelic FLG mutations on AD incidence and severity remains a subject of controversy. OBJECTIVE: In this study, we studied individuals with bi-allelic null FLG mutations to elucidate the effect of bi-allelic FLG mutations on AD incidence and severity. METHODS: Six individuals with bi-allelic FLG null mutations from three families of IV/AD were investigated. We report the detailed clinical features of the individuals. The phenotype was confirmed by the clinical examinations and the severity of IV and AD was scored using ichthyosis score and Eczema Area and Severity Index (EASI). RESULT: It was found that five of the six patients had severe IV, and the remaining patient showed moderate IV. Two of the six had moderate AD and three of the six had mild AD. The remaining patient had no AD. CONCLUSION: Our results suggest that individuals with bi-allelic FLG mutations do not always have severe AD and confirm that not all individuals with bi-allelic FLG mutations have AD.

A case of lichen planus pemphigoides with autoantibodies to the NC16a and C-terminal domains of BP180 and to desmoglein-1.

Lichen planus pemphigoides (LPP) is a rare autoimmune blistering disease that occurs in association with lichen planus (LP). This report describes a 59-year-old Japanese female patient with LPP. The patient first showed LP lesions on her hands, and subsequently developed bullae on her extremities and erosions of the oral mucosa. The patient's serum was positive for IgG autoantibodies against the BP180 NC16a domain, the BP180 C-terminal domain and desmoglein-1. However, a serum sampled one and a half years before the diagnosis of LPP was negative for autoantibodies against BP180 NC16a and BP180 C-terminal domains. These findings strongly suggest that the damage to the basal cells in the LP lesions exposed a sequestered antigen or formed neoantigens, leading to the production of pathogenic autoantibodies for LPP. Most of the previous cases of LPP have produced autoantibodies to the NC16a domain of BP180. This is the first case in which autoantibodies to the C-terminal domain of BP180 were detected. The oral mucosal symptoms in this case may have been caused by autoantibodies to the BP180 C-terminal domain.

Kinetics and mechanisms of CF3CHFOCH3, CF3CHFOC(O)H, and FC(O)OCH3 reactions with OH radicals.

The kinetics and mechanism of oxidation of CF3CHFOCH3 was studied using an 11.5-dm3 environmental reaction chamber. OH radicals were produced by UV photolysis of an O3-H2O-He mixture at an initial pressure of 200 Torr in the chamber. The rate constant of the reaction of CF3CHFOCH3 with OH radicals (k1) was determined to be (1.77 +/- 0.69) x 10(-12) exp[(-720 +/- 110)/T] cm3 molecule(-1)(s-1) by means of a relative rate method at 253-328 K. The mechanism of the reaction was investigated by FT-IR spectroscopy at 298 K. CF3CHFOC(O)H, FC(O)OCH3, and COF2 were determined to be the major products. The branching ratio (k1a/k1b) for the reactions CF3CHFOCH3 + OH --> CF3CHFOCH2* + H2O (k1a) and CF3CHFOCH3 + OH --> CF3CF*OCH3 + H2O (k1b) was estimated to be 4.2:1 at 298 K from the yields of CF3CHFOC(O)H, FC(O)OCH3, and COF2. The rate constants of the reactions of CF3CHFOC(O)H (k2) and FC(O)OCH3 (k3) with OH radicals were determined to be (9.14 +/- 2.78) x 10(-13) exp[(-1190 +/- 90)/T] and (2.10 +/- 0.65) x 10(-13) exp[(-630 +/- 90)/T] cm3 molecule(-1)(s-1), respectively, by means of a relative rate method at 253-328 K. The rate constants at 298 K were as follows: k1 = (1.56 +/- 0.06) x 10-13, k2 = (1.67 +/- 0.05) x 10-14, and k3 = (2.53 +/- 0.07) x 10-14 cm3 molecule(-1)(s-1). The tropospheric lifetimes of CF3CHFOCH3, CF3CHFOC(O)H, and FC(O)OCH3 with respect to reaction with OH radicals were estimated to be 0.29, 3.2, and 1.8 years, respectively.

Kinetics and mechanism of (CF3)2CHOCH3 reaction with OH radicals in an environmental reaction chamber.

The atmospheric chemistry of (CF3)2CHOCH3, a possible HCFC/HFC alternative, was studied using a smog chamber/FT-IR technique. OH radicals were prepared by the photolysis of ozone in a 200-Torr H2O/O3/O2 gas mixture held in an 11.5-dm3 temperature-controlled chamber. The rate constant, k1, for the reaction of (CF3)2CHOCH3 with OH radicals was determined to be (1.40 +/- 0.28) x 10(-12) exp[(-550 +/- 60)/T] cm3 molecule(-1) s(-1) by means of a relative rate method at 253-328 K. The value of k1 at 298 K was (2.25 +/- 0.04) x 10(-13) cm3 molecule(-1) s(-1). The random errors are reported with +/-2 standard deviations, and potential systematic errors of 15% could increase k(1). In considering OH-radical reactions, we estimated the tropospheric lifetime of (CF3)2CHOCH3 to be 2.0 months using the rate constant at 288 K. The degradation mechanism of (CF3)2CHOCH3 initiated by OH radicals was also investigated using FT-IR spectroscopy at 298 K. Products (CF3)2CHOC(O)H, CF3C(OH)2CF3, CF3C(O)OCH3, and COF(2) were identified and quantified. The branching ratio, k1a/k1b, was estimated to be 2.1:1 for reactions (CF3)2CHOCH3 + OH --> (CF3)2CHOCH2*+ H2O (k1a) and (CF3)2CHOCH3 + OH --> (CF3)2C*OCH3 + H2O (k1b).

Stable operation of a 300-m laser interferometer with sufficient sensitivity to detect gravitational-wave events within our galaxy.

TAMA300, an interferometric gravitational-wave detector with 300-m baseline length, has been developed and operated with sufficient sensitivity to detect gravitational-wave events within our galaxy and sufficient stability for observations; the interferometer was operated for over 10 hours stably and continuously. With a strain-equivalent noise level of h approximately 5x10(-21)/sqrt[Hz], a signal-to-noise ratio of 30 is expected for gravitational waves generated by a coalescence of 1.4M-1.4M binary neutron stars at 10 kpc distance. We evaluated the stability of the detector sensitivity with a 2-week data-taking run, collecting 160 hours of data to be analyzed in the search for gravitational waves.

Studies on the activation mechanisms of guanylyl cyclase by serotonin, probably through a novel subtype of serotonin receptor (5-HTGC).

Characterization of the serotonin-induced increase in guanosine 3',5'-cyclic monophosphate (cyclic GMP) was investigated and compared with that induced by atrial natriuretic peptide (ANP) in NG108-15 cells. The cyclic GMP formed by serotonin or ANP was transported in a similar manner to the extracellular medium, although the cyclic GMP formed by bradykinin was not. Serotonin and ANP raised cyclic GMP additively. Serotonin-induced cyclic GMP formation was completely inhibited by pretreatment with 100 nM 12-o-tetradecanoylphorbol 13-acetate (TPA), although that induced by ANP was only partially inhibited and the effects were blocked by pretreatment with staurosporin. In membrane preparations, ANP stimulated cyclic GMP formation in the presence of ATP, but serotonin did not. Serotonin-stimulated cyclic GMP formation was found to occur in neuroblastoma N18TG-2, but not in glioma C6Bu-1. These results suggest that a novel subtype of serotonin receptors (5-HTGC) which stimulates membrane-bound guanylyl cyclase, different from that stimulated by natriuretic peptide, may exist especially in neurons.

Crystal structure of a complex of alpha-cyclodextrin with 2-fluoro-4-nitrophenol.3H2O.

The crystal structure of a complex of alpha-cyclodextrin (alpha-CD) with 2-fluoro-4-nitrophenol.3H2O has been determined by the X-ray diffraction technique. The complex crystallizes in space group P2(1)2(1)2(1) with cell dimensions: a = 13.431(3), b = 15.299(4), c = 24.780(5) A. The structure was solved by direct methods and refined to R = 6.7% for 4483 reflections. The crystal structure is isomorphous to the alpha-CD-4-nitrophenol.3H2O complex. The phenyl group is inside the cavity, so that the O-4 hexagon of the alpha-CD is distorted in a systematic manner: the longest diagonal [O-4(G2)...O-4(G5)] is in the direction of the benzene ring. The phenolic OH group protrudes from the secondary OH side of the cavity and the NO2 group is situated on the primary OH side. The hydrophobic F atom is statistically disordered over two sites and is located in the hydrophilic space, just beyond the rim of the secondary OH side of the cavity.

[Action of propranolol on the perfusion pressure into the peripheral vasculature of rat hindquarters].

Several investigators have confirmed that beta-adrenergic blocking agents produced a sustained pressor action in anesthetized rats. In this experiment, rat hindquarters were perfused with the rat's own blood under a constant perfusion rate. The effect of propranolol administered intraarterially to the hindquarters was studied. Propranolol (0.001--0.1 mg/ml, 5 microliter intraarterial injection) produced a sustained rise in the perfusion pressure dose-dependently. In contrast, propranolol did not produce any sustained rise in the perfusion pressure of guinea pigs and rabbits. These results support that the beta-adrenoceptive vasodilation in skeletal muscle is stronger in rats than in guinea pigs and rabbits.

[Absorption, distribution and excretion of 14C-putrescine in mice (author's transl)].

In order to know in detail the distribution, absorption and excretion of putrescine (1,4-diaminobutane), after a single subcutaneous injection of 14C-putrescine (carrier free) in mice, localization of radioactivity in various tissues was followed by whole-body autoradiography and changes in radioactivity levels in blood, various tissues, expiration, urine and feces were examined. During 6 hours after injection, 22.5 +/- 3.2% of radioactivity was excreted in the urine, and after that the percentage excretion increased only slightly. The percentage of fecal excretion was small, being 2.7 +/- 0.2% during 5 days after injection. A considerable amount of putrescine was rapidly degraded to 14CO2; during 2 hours 34.4 +/- 4.9% of radioactivity was expired as 14CO2. In the studies on distribution in the tissues, at 10 minutes after injection, the highest radioactivity per g wet tissue was found in the kidney, but the radioactivity decreased rapidly. At 10 minutes after injection, the next highest distribution was found in the intestine. The high radioactivity in the intestine was detected also at 1 hour and 24 hours. The radioactivity in the pancreas was highest at 1 hour and 24 hours. A high radioactivity was also detected in the bone marrow by autoradiography. Therefore, the present study suggest that the accumulation of putrescine in mice take place mainly in the pancreas, bone marrow, intestine and liver.

Increase of urinary putrescine in 3,4-benzopyrene carcinogenesis and its inhibition by putrescine.

A significant increase in putrescine was noted in the urine of mice with experimental s.c. tumors induced by a single injection of 3,4-benzopyrene solution (2.52 mg of 3,4-benzopyrene in 0.5 ml of tricaprylin). When 10 mg of putrescine were added to the 3,4-benzopyrene solution, the development of tumors was completely inhibited and the increase of urinary putrescine in mice was suppressed simultaneously. Animal weight data of a control group receiving only putrescine indicated that the inhibitory effect of putrescine is not due to its toxicity.

Cardiovascular actions of optical isomers of propranolol.

Effects of the optical isomers of propranolol on blood pressure in the rat, and in the spinal rat during adrenaline infusion were studied to investigate the mechanism of the pressor action of propranolol. Both isomers of propranolol produced a sustained pressor action in the rat and in the spinal rat infused with adrenaline. The magnitude of the pressor action produced by the d- and 1-propranolol was proportional to their beta-adrenoceptor blocking activities in the heart as was reported by several investigators. It is concluded that the pressor action of propranolol is due to the blockade of the beta-adrenoceptors mediating vasodilation in the skeletal muscle vascular beds.

[Effects of oral hypoglycemic agents, gliclazide and tolbutamide, on the cardiovascular system (author's transl)].

Recent clinical studies have suggested an association of tolbutamide (TB) therapy with an increased incidence of cardiovascular deaths. In this study, the effects of a newly synthetized hypoglycemic agent, gliclazide (GC), on the cardiovascular system were investigated, and compared with those of TB. Results are as follows: GC was found to be about ten times as active as TB in decreasing blood glucose in rabbits. GC and TB produced a dose-dependent increase in blood pressure and little change in heart rate in rats and rabbits. In driven left rat and rabbit atria, these agents produced a positive inotropic effect. The positive inotropic effects of these drugs were not altered by pretreatment with propranolol, or theophylline. These agents produced little change in the rate in spontaneous beating rat, rabbit and guinea pig atria. Higher doses produced a slightly negative chronotropic response. Neither agent potentiated the intropic effects of isoproterenol on the rabbit and guinea pig left atria. In isolated perfused working rabbit hearts, these compounds produced a slight decrease in coronary flow. It is concluded that GC and TB possess positive inotropic effects on isolated atria, and these effects are not mediated either through adrenergic mechanisms or the cyclic AMP system.

[Pressor action of propranolol; with special reference to relationship between the pressor action and peripheral vascular tone].

We showed in previous studies that pro pranolol produced a pressor action in the rat, and that this action was also observed in the spinal rat infused with adrenaline, noradrenaline and a mixture of isoproterenol and vasopressin, but not with vasopression alone. The action was also observed in the guinea pig infused with adrenergic beta-stimulants. In the present work, conditions in the peripheral vessels in which propranolol observed in the spinal rat infused with a mixture of various doses of isoproterenol and vasopressin. The effect of propranolol on the blood pressure in guinea pigs and rabbits with a reduced vasoconstrictive tone in the peripheral vascular beds with alpha-blockade was studied. Propranolol produced a pressor action in the spinal rat infused with a mixture of isoproterenol and vasopressin, and the magnitude of the rise depended on the mixing rate of the doses of these two drugs. The drug also produced a sustained rise in blood pressure in guinea pigs and rabbits treated with alpha-blockers. Thus, it is concluded that propranolol produces a marked pressor action when peripheral vessels are maintained in conditions with an appropriate constrictive and beta-adrenoceptive vasodilator tone.

Effects of several beta-blockers on blood pressure in the rat.

Effects of practolol, alprenolol and pindolol on blood pressure in the rat were studied. Also effects of these three beta-blocking agents on blood pressure and heart rate in spinal rats during adrenaline infusion were studied and compared with those of propranolol. The beta-blocking agents produced a sustained pressor action in the rat, and in the spinal rat infused with adrenaline. The magnitude of the pressor action induced by the beta-blockers was in the following order: pindolol larger than or equal to propranolol larger than or equal to alprenolol greater than practolol. Minimum doses of these beta-blockers required to cause a pressor action in the spinal rat infused with adrenaline were in the following order; practolol greater than alprenolol larger than or equal to propranolol larger than or equal to pindolol. The magnitude of the pressor action produced by the same dose of these beta-blockers and minimum doses of these beta-blockers required to cause a pressor action in the spinal rat infused with adrenaline seemed to be roughly proportional to their beta-receptor blocking activities. It was concluded that the minimum doses of these beta-blockers required to cause a pressor action and the magnitude of the pressor action induced by the beta-blockers in the spinal rat infused with adrenaline could be used to compare their beta-blocking activities and that practolol, a cardioselective beta-blocker, seems to block not only cardiac beta-receptor but to some extent also peripheral vascular beta-receptors.

Cardiovascular action of propranolol in rats under various anesthetic procedures.

We previously reported that the pressor action of propranolol was observed in the rat anesthetized with urethane. In the present study, rats, anesthetized with pentobarbitone or ether, treated with curare or unanesthetized, were used to investigate the influence of anesthetics on the blood pressure response to propranolol. Propranolol always produced a pressor response under these experimental conditions as well as urethane anesthesia. But under pentobarbitone anesthesia, the magnitude of the pressor action was significantly lower than that obtained under the other experimental conditions. It is concluded that the choice of urethane as the anesthetic does not create a situation irrelevant to that found with other anesthetics and that the cardiovascular responses of rat to propranolol are unique when compared to other species.