Head region of unconventional myosin I family members is responsible for the organ‐specificity of their roles in left–right polarity in Drosophila

In Drosophila, Myosin31DF (Myo31DF), encoding a Myosin ID protein, has crucial roles in left–right (LR) asymmetric development. Loss of Myo31DF function leads to laterality inversion for many organs, including the embryonic gut. Here, we found that Myo31DF was required before LR asymmetric morphogenesis in the hindgut, suggesting it functions in LR patterning instead of directly in hindgut morphological changes. Myosin61F (Myo61F) encodes another Myosin I, and Myo31DF or Myo61F overexpression reverses the laterality of different organs. Myo31DF and Myo61F have domains conserved in Myosin proteins, particularly in the proteins' head regions. We studied the roles of these domains in LR patterning using overexpression analysis. The Actin‐binding and ATP‐binding domains were essential for both proteins, but the IQ domains, binding sites for Myosin light chains, were required only by Myo31DF. Our results also suggest that the organ specificities of the Myo31DF and Myo61F activities depended on their head regions. Developmental Dynamics 237:3528–3537, 2008. © 2008 Wiley‐Liss, Inc.     

Inhibition of hypersensitivity reactions by a new drug, N(3',4'-dimethoxycinnamoyl) anthranilic acid (N-5').

N (3', 4'-dimethoxycinnamoyl) anthranilic acid (N-5'), a new antiallergic drug, can be taken orally, has low toxicity, and is a potent inhibitor of homologous passive cutaneous anaphylaxis (PCA) both in rats and in guinea pigs. Anaphylactic mediator release from guinea pig lung was decreased by the drug in vitro. Although reversed cutaneous anaphylaxis and Arthus type reactivity were moderately inhibited with N-5', this agent did not inhibit the Forssman systemic reaction or contact dermatitis. N-5' is considered to be clinically applicable to certain allergic-related diseases, in particular asthma caused by reaginic antibody.     

Inhibition of antigen-induced contraction of guinea pig isolated tracheal muscle with 2-n-butyl-3-dimethylamino-5,6-methylenedioxy indene (MDI-A), indane (MDI-B) and 8-(diethylamino)octyl-3,4,5-trimethoxy benzoate hydrochloride (TMB-8)

The effects of three intracellular calcium antagonists on antigen-induced contraction of sensitized guinea pig tracheal muscle were investigated. The agents employed were: 2-n-butyl-3-dimethylamino-5,6-methylenedioxy indene hydrochloride (MDI-A), 2-n-butyl-3-dimethylamino-5,6-methylenedioxy indane hydrochloride (MDI-B) and 8-(diethylamino)octyl-3,4,5-trimethoxy benzoate hydrochloride (TMB-8). Each of these agents caused a concentration-dependent inhibition of the antigen-induced contraction of sensitized tracheal smooth muscle. Moreover, in histamine and leukotriene D4 (LTD4) incited contractions of guinea pig tracheal muscle, they showed antagonistic action. The induced tracheal muscle contraction, achieved through the addition of compound 48/80 to a solution of ethylene glycol bis (beta-aminoethylether)-N,N,N1, N1-tetraacetic acid (EGTA) in a contained Ca-free medium, was completely inhibited by individual pretreatment with MDI-A, MDI-B and TMB-8. In the case of tracheal muscle contraction induced by CaCl2 in a high potassium, Ca-free medium, only TMB-8 inhibited contraction. Lastly, none of these three intracellular calcium antagonists affected the antigen-induced release of histamine and slow reacting substance of anaphylaxis (SRS-A). These results suggest that MDI-A and MDI-B inhibit the antigen-induced contraction of sensitized guinea pig tracheal muscle by interfering with the contractile responses caused by histamine and LTD4.     

Mean platelet volume in diabetics]

Platelet size is a determinant of platelet function. As platelet size in diabetics has been reported to be larger than normals, we have measured mean platelet volume (MPV) in diabetics simultaneously with fasting plasma glucose, fructosamine, and hemoglobin A1. MPV was positively correlated with fasting plasma glucose and fructosamine. In a sequential observations for a few months of 22 patients, all of whom showed decreasing fasting plasma glucose, MPV decreased in 10 patients, however, increased in only 2 patients. These findings suggest that MPV would be affected with diabetic control.     

Hemocompatibility of a hydrodynamic levitation centrifugal blood pump

A noncontact type centrifugal pump without any complicated control or sensing modules has been developed as a long-term implantable artificial heart. Centrifugal pumps with impellers levitated by original hydrodynamic bearings were designed and have been modified through numerical analyses and in vitro tests. The hemolysis level was reduced by changing the pressure distribution around the impeller and subsequently expanding the bearing gap. Thrombus formation in the bearing was examined with in vitro thrombogenesis tests and was reduced by changing the groove shapes to increase the bearing-gap flow to 3% of the external flow. Unnecessary vortices around the vanes were also eliminated by changing the number of vanes from four to six.     

Homologous passive cutaneous anaphylaxis in various strains of mice

Passive cutaneous anaphylaxis (PCA) was elicited both in the ear and in the dorsal skin of 13 strains of mice at the same time and assessed quantitatively by measuring the amount of extravasated dye. Body pigments of colored mice such as DBA/2 (chocolate), C3H/He (brown) and C57BL/6 (black) did not interfere with the measurement of dye. In the ear response, ICR was a higher responder, C57BL/6 and BALB/c-nu/nu were lower responder strains. In the dorsal skin response, however, ICR was a lower responder, BALB/c-nu/nu, Hairless and WBB6F1-+/+ were higher responders. WBB6 F1-W/Wv was a nonresponder in both responses. The ear response was highly reproducible and the dorsal skin response of each strain was 1/2-1/10 of its ear response except for BALB/c-nu/nu. The PCA bluing regions on the dorsal skin of BALB/c-nu/nu were clearly delineated and the response was almost comparable to its ear response.     

Protein kinase C in human pheochromocytoma

Subtypes of protein kinase C were analyzed in adrenal and extra-adrenal pheochromocytoma of humans. Almost all protein kinase C of the adrenal tumor was type III, while the enzyme of the extra-adrenal tumor was separated into two major fractions corresponding to type II and type III by hydroxyapatite column chromatography. The extra-adrenal tumor but not the adrenal tumor spontaneously produced neurite-like processes when the cells were cultured in vitro. These results suggest that the high proportion of type II enzyme may reflect neuron-directed differentiation in human pheochromocytoma.     

DNA-damaging potency and genotoxicity of aflation M1 in somatic cells in vivo of Drosophila melanogaster

Aflatoxin M₁ (AFM₁), a metabolic hydroxylation product of aflatoxinB₁ (AFB₁), and the parent compound were comparatively assayedfor DNA-damaging potency and genotoxicity in vivo in Drosophilamelanogaster using, respectively, the mei-9^a mei-41^D5 DNA repairtest and the mwh/flr³ wing spot test. In the repair test, larvalstock, consisting of meiotic recombination-deficient doublemutant mei-9^a mei-41^D5 males and repair-proficient females,was exposed to the test agents, and the preferential killingof the mutant larvae was taken as evidence of the DNA-damagingeffect. In this test, AFM₁ was registered as a DNA-damagingagent with an activity 3-fold lower than that of AFB₁. In thewing spot test, where larval flies, trans-heterozygous for thesomatic cell markers mwh and flr³, were treated and the wingswere inspected at adulthood for spots manifesting the phenotypesof the markers, AFM₁ exerted a genotoxic effect compatible tothat of AFB₁. Based on these results and other data, we predictthat AFM₁ may be genotoxic in mammalian in-vivo systems as well. ⁵To whom correspondence should be addressed     

Influence of histamine on the bradykinin response of canine testicular polymodal receptors in vitro

Effects of histamine on the testicular polymodal receptors were studied in vitro using canine testisspermatic nerve preparations. Histamine induced distinct increase in the discharge rate in 6 out of 17 units tested (high responders), while it only weakly excited the remaining 11 units (low responders). The bradykinin response of low responders tended to be slightly facilitated by pretreatment with histamine, while that of high responders tended to be suppressed. Significant correlation was observed between the magnitude of histamine-induced discharges and the magnitude of change in the bradykinin responses.     

Role of peptide-leukotrienes in liver injury in mice

The role of peptide leukotrienes (p-LTs), especially LTC₄ and LTD₄ in liver disease, was investigated in mice experimental liver injury models. The liver injury was induced by the injection of bacterial lipopolysaccharide (LPS) intoCorynebacterium parvum pretreated mice. Carbon tetrachloride (CCl₄)-induced liver injury in mice was used as a standard model. In both injury models, extensive liver parenchymal cell damage was observed by the elevation of glutamate transaminase (GOT and GPT) activity and confirmed by significant histopathological changes in the liver. Moreover, significant elevation of LTC₄ in the liver was observed in both models 1 and 6 h after the onset of disease. Administration of AA-861, a selective 5-lipoxy-genase inhibitor (0.5, 1, and 2 mg/kg) and LY-171883, a p-LT receptor antagonist (50 and 200 mg/kg) suppressed the elevation of serum GOT and GPT levels and histopathological changes in both experimental liver injury models. In addition, when authentic LTC₄ or LTD₄ was injected into the mouse, clear elevation of serum GOT and GPT and histopathological changes of the liver were observed. These results suggest that p-LTs play a role in the onset of liver diseases in mice.