Crystal structure and molecular conformation of achatin-I (H-Gly-d-Phe-Ala-Asp-OH), an endogenous neuropeptide containing a d-amino acid residue

In order to investigate the active conformation of achatin-I (H-Gly-d -Phe-Ala-Asp-OH), an endogenous neuropeptide from the Achatina fulica ganglia, its crystal structure and molecular conformation were analysed by the X-ray diffraction method. Crystals from methanol/dioxane are monoclinic, space group P2₁ with a=5.083(1), b= 9.125(1), c= 20.939(3) Å, β=94.73(1)° The structure was solved by direct methods and refined to R = 0.051 for 1714 independent reflections with Fo > σ(Fo). The molecule exists as a zwitterion with the Gly N-terminal end protonated and Asp β-carboxyl deprotonated; the C-terminal of Asp is in a neutral state. The molecule takes a kind of β turn structure with the d -Phe-Ala residues at the corner of the bend. This turn conformation is primarily formed by the strong intramolecular hydrogen bonds of NH(Gly)—O^δ1 (Asp) and NH(Asp)- O^δ1(Asp) pairs, thus forming a 15-membered ring structure. Judging from the published data concerning the structure-activity relationship, this turn conformation may reflect an important feature related to the neuroexcitatory activity of achatin-I.     

Alloimmune Neonatal Neutropenia in Monozygous Twins: High-dose Intravenous Gammaglobulin Therapy

ABSTRACT. An indirect immunofluorescence test using a flow cytometer (FACS420) was useful for detection of antineutrophil antibodies (anti-NA2 antibodies) in a case of monozygous twins with alloimmune neonatal neutropenia. When high-dose intravenous gammaglobulin (300 mg/kg for five consecutive days) was given to one twin, the increase in neutrophils was not obvious. Although neutropenia persisted for about three months, no infections were observed in either of the twins.     

Elimination of Ventricular Arrhythmia in Catecholaminergic Polymorphic Ventricular Tachycardia by Targeting “Catecholamine‐Sensitive Area”: A Dominant‐Subordinate Relationship between Origin Sites of Bidirectional Ventricular Premature Contractions

We report on a patient diagnosed with catechoaminergic polymorphic ventricular tachycardia (CPVT) who underwent catheter ablation of ventricular premature contractions (VPCs) induced by epinephrine. VPCs were classified roughly into three types. Type 1 and Type 2 VPCs (right bundle branch block [RBBB] configuration and inferior axis) were eliminated by radiofrequency applications at the left aortic sinus of Valsalva and the anterolateral papillary muscle (APM), respectively. Although no spontaneous VPCs were seen after the elimination of Type 1 and 2 VPCs, pacing resulting in capture at the APM induced Type 3 VPC (RBBB configuration and superior axis) reproducibly. The electrophysiological findings observed in our representative case have important implications both for understanding the pathophysiology of CPVT and for considering therapeutic strategies.     

Herpetiform pemphigus showing reactivity with pemphigus vulgaris antigen (desmoglein 3)

We report a patient with herpetiform pemphigus(HP)who showed reactivity only with pemphigus vulgaris(PV)antigen but not with pemphigus foliaceus(PF)antigen. Direct and indirect immuno- fluorescence revealed keratinocyte cell surface staining in the lower layers of the epidermis, where desmoglein 3 (Dsg3) is expressed. Immunoblot analysis, using ethylenediamine tetra-acetic acid- separated human epidermal extracts, revealed that the patient's serum recognized only a 130-kDa polypeptide which co-migrated with Dsg3. By antigen-specific immunoadsorption studies, using desmoglein 1 (Dsg1) and Dsg3 recombinant protein produced by baculovirus expression system, immunoreactivity of the patient's serum was completely adsorbed by Dsg3 alone, but not by Dsg1. These results indicate that this HP patient produced only anti-Dsg3 autoantibodies and no other autoantibodies against components of the keratinocyte cell surface. HP could be a variant of PV.in addition to PF, with unique clinical and histological features.     

Alteration in immunoexpression of glucose transporter 2 in liver of tumour-bearing rats

To elucidate interactions between the glucose transport system and hepatic glucose production in the tumour-bearing state, glycogen storage, expression of glucose transporter isoform 2 (Glut 2) and activities of glucose-6-phosphatase (G-6-Pase) and hexokinase were histochemically examined in hepatocytes of tumour-bearing rats. Five male F344 rats, subcutaneously inoculated with methylcholanthrene(MCA)-induced sarcoma cells were compared with five pair-fed animals and four ad libitum fed controls. Glycogen storage was markedly decreased in liver cells of tumour-bearing rats compared to in those of control animals. Glut 2 immunoreactivity was uniformly seen in the cellular membrane of hepatocytes from control animals. In rats bearing sarcoma, the staining intensity was significantly decreased, suggesting that Glut 2 with its bi-directional transport capacity was down-regulated in the tumour-bearing state. Positive staining for hexokinase activity was located in the perivenous area in livers from control animals and was more diffusely located and more intense in livers from tumour-bearing animals. G-6-Pase activity, limited to the peripheral area in livers from controls, extended to the intermediate area and had stronger reactivity in livers from tumour-bearing animals. In the tumour-bearing cachectic condition, glucose may be partially consumed by a futile cycle, hepatic metabolic zonation was disturbed, and the release of glucose from the liver may not be mediated by a facilitative glucose transporter-2.     

Myocardial bridging of the left anterior descending coronary artery without relation to the site of hypertrophy in hypertrophic cardiomyopathy

Myocardial bridging of the left anterior descending coronaryartey producing complete systolic occlusion was demonstratedin a patient with hypertrophic cardiomyopathy. who had lolcalizedmyocardial hypertrophy in the lateral left ventricular walloutside the territory of that artery. Although a case and effectrelationship between systolic compression of the coronary arteryand myocardial hypertrophy has previously been postulated inhypertrophic cardiomyopathy the lack of relation between thesite of the myocardial bridging and the region of the left ventricularhypertrophy in our patient suggests that the myocardial bridginigof the left anterior descending coronary artery may not be relatedto the pathogenesis of asymmetric septal hypertrophy.     

Rearrangement of the BCL6 gene in B-cell lymphoid neoplasms: comparison with lymphomas associated with BCL2 rearrangement

We report a series of B-cell neoplasms with regard to rearrangement of the BCL6 gene on chromosome band 3q27. Southern blot analysis using probes from the major translocation cluster (MTC) region of the BCL6 revealed rearrangement in 21/197 patients (10.7%) with B-cell neoplasms studied at presentation, and 11/25 patients (44%) first studied at relapse. In non-Hodgkin's lymphoma (NHL) studied at diagnosis, rearrangements of the BCL6 gene were not closely associated with a specific histopathologic subtype but distributed in subcategories in the Working Formulation. The incidence in follicular lymphoma was 12.1%, with significantly higher frequency in mixed and large cell subtypes, and that in diffuse aggressive lymphoma was 14.1%. Comigration analysis using probes from the immunoglobulin genes revealed association of the BCL6 gene with one of the three immunoglobulin loci in 9/25 cases analysed. A comparative study between NHL associated either with BCL2 or BCL6 rearrangement showed that advanced disease and bone marrow involvement were more frequent in BCL2(+) NHL. In contrast, extranodal involvement was more frequently observed in the BCL6(+) NHL. The survival curve of BCL6(+) NHL was characterized by a rapid decline followed by a plateau. Of the total of 32 BCL6(+) patients, six carried both BCL2 and BCL6 rearrangements; five of these six showed clinicopathological properties characteristic of follicular lymphoma, suggesting that the presence of the two genetic abnormalities does not necessarily have synergistic effects on malignant phenotypes. The high level of BCL6 expression in follicular lymphoma cell lines carrying a BCL2 rearrangement suggests that the deregulated BCL2 gene may have an effect on the development of genetic abnormalities of the BCL6 gene. The present study suggests that BCL6 gene rearrangement is primarily involved in large cell lymphoma irrespective of growth pattern of neoplastic cells, and that BCL6(+)BCL2(?) NHL could be curable with modern intensive chemotherapy.