Surgical pearl: punch excision and grafting for removal of mole.
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Humans↗
Biomedical subjects
S Handa
Publications and source records attributed to S Handa.
Glycolipids in acoustic neurinoma.
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Autoantibodies↗
Functional compensation of the low platelet count by increased individual platelet size in a patient with May-Hegglin anomaly presenting with acute myocardial infarction.
Platelets are known to play a crucial role in normal hemostasis as well as in thrombus formation at sites exposed to blood flow, as in coronary thrombosis. Thus, low platelet count is a strong negative risk factor for the occurrence of arterial thrombosis, such as occurs in acute myocardial infarction. We encountered a patient with May-Hegglin anomaly, presenting with acute myocardial infarction in his sixth decade, even though his platelet counts had always been less than 50 x 10(3)/microl. We investigated the characteristics of his platelets under the effect of shearing and found that shear-induced platelet aggregation and binding of soluble von Willebrand factor (vWF) to platelets could be induced, even when the patient's platelet count was less than 10 x 10(3)/microl, but that virtually no aggregation or vWF binding by normal platelets could be induced by shearing when platelet counts were less than 50 x 10(3)/microl. We conclude that the low platelet counts in a patient with May-Hegglin anomaly can be functionally compensated for by larger individual platelets, in view of the vWF-dependent platelet thrombus formation occurring under the effect of blood flow and that that is why most patients with May-Hegglin anomaly do not have a bleeding tendency, even though their platelet counts are very low.
Blood Platelets↗
3-Amino-5-hydroxybenzoic acid synthase, the terminal enzyme in the formation of the precursor of mC7N units in rifamycin and related antibiotics.
The biosynthesis of ansamycin antibiotics, like rifamycin B, involves formation of 3-amino-5-hydroxybenzoic acid (AHBA) by a novel variant of the shikimate pathway. AHBA then serves as the starter unit for the assembly of a polyketide which eventually links back to the amino group of AHBA to form the macrolactam ring. The terminal enzyme of AHBA formation, which catalyzes the aromatization of 5-deoxy-5-amino-3-dehydroshikimic acid, has been purified to homogeneity from Amycolatopsis mediterranei, the encoding gene has been cloned, sequenced, and overexpressed in Escherichia coli. The recombinant enzyme, a (His)6 fusion protein, as well as the native one, are dimers containing one molecule of pyridoxal phosphate per subunit. Mechanistic studies showed that the enzyme-bound pyridoxal phosphate forms a Schiff's base with the amino group of 5-deoxy-5-amino-3-dehydroshikimic acid and catalyzes both an alpha, beta-dehydration and a stereospecific 1,4-enolization of the substrate. Inactivation of the gene encoding AHBA synthase in the A. mediterranei genome results in loss of rifamycin formation; production of the antibiotic is restored when the mutant is supplemented with AHBA.
Actinobacteria↗
Antibodies to GT1a ganglioside in patients with Guillain-Barré syndrome.
Serum antibodies from 8 (13%) of 62 patients with the acute Guillain-Barré syndrome (GBS) and 1 of 3 patients with the Miller Fisher syndrome (MFS) recognized a minor ganglioside in bovine and human brain trisialoganglioside fractions. The ganglioside antigen migrated between GD1a and GD1b on thin-layer chromatograms. The structure of this ganglioside was established to be GT1a by thin-layer chromatography blotting and mass spectrometry. GT1a a ganglioside was also detected in human and bovine peripheral nerves by thin-layer chromatogram immunostaining. Serum from the GBS patients had IgM, IgG, or IgA antibodies against GT1a detectable by enzyme-linked immunosorbent assay (ELISA). Serum from the MFS patient also had elevated levels of IG against GT1a. None of the sera from 43 patients with other neurological diseases or from 24 healthy controls reacted with GT1a. Sera from 6 of 8 GBS patients with anti-Gt1a antibodies also reacted with GQ1b. There was no difference in the incidence of anti-GT1a immunoglobulins in acute GBS patients with or without oculomotor abnormalities. Levels of anti-GT1a antibodies correlated temporally wit clinical symptoms in GBS patients. Although the incidence of dysphagia was slightly higher in GBS patients with anti-GT1a antibodies than in those without, the number of patients studied may have been too small to detect an association between anti-GT1a antibodies and an a specific clinical variant of GBS. Our data demonstrate that a proportion of GBS patients have antibodies against GT1a ganglioside and suggest that these antibodies may play a role in the pathogenesis of neuropathy in GBS.
Adult↗
N-glycolylneuraminic acid-containing GM1 is a new molecule for serum antibody in Guillain-Barré syndrome.
To clarify the pathogenesis of Guillain-Barré syndrome (GBS) after parenteral injections of bovine brain gangliosides, we searched for new molecules in bovine brain gangliosides recognized by sera from GBS patients. Gangliosides fractionated in a Q-Sepharose column were used as the antigens, and the binding of serum IgG or IgM was examined by thin-layer chromatography/immunostaining. Fourteen of 175 serum samples from the patients reacted with the monosialoganglioside fraction 2. In the neutral solvent system, a band in this fraction migrated with N-acetylneuraminic acid-containing GM1 [GM1(NeuAc)], whereas in the alkaline solvent system it migrated slower. This suggested that the band was N-glycolylneuraminic acid-containing GM1 [GM1(NeuGc)]. In both solvent systems, its mobility was almost the same as that of authentic GM1(NeuGc) from mouse liver. Secondary ion mass spectrometry showed that the ganglioside's structure was consistent with that of GM1(NeuGc). IgG anti-GM1(NeuGc) antibodies in sera from the GBS patients were significantly absorbed by GM1(NeuAc), indicative that the anti-GM1(NeuGc) antibodies cross-react with GM1(NeuAc). N-Glycolylneuraminic acid-containing gangliosides are so highly immunogenic in humans that the injection of GM1(NeuGc) could induce the production of IgG anti-GM1(NeuGc) antibody, which cross-reacts with GM1(NeuAc).
Animals↗
Evaluating precursor-directed biosynthesis towards novel erythromycins through in vitro studies on a bimodular polyketide synthase.
BACKGROUND: Modular polyketide synthases (PKSs) catalyse the biosynthesis of complex polyketides using a different set of enzymes for each successive cycle of chain extension. Directed biosynthesis starting from synthetic diketides is a potentially valuable route to novel polyketides. We have used a purified bimodular derivative of the erythromycin-producing polyketide synthase (DEBS 1-TE) to study chain extension starting from a variety of diketide analogues and, in some cases, from the alternative acyl-CoA thioester substrates. RESULTS: Chain initiation in vitro by DEBS 1-TE module 2 using a synthetic diketide analogue as a substrate was tolerant of significant structural variation in the starter unit of the synthetic diketide, but other changes completely abolished activity. Interestingly, a racemic beta-keto diketide was found to be reduced in situ on the PKS and utilised in place of its more complex hydroxy analogue as a substrate for chain extension. The presence of a diketide analogue strongly inhibited chain initiation via the loading module. Significantly higher concentrations of diketide N-acetylcysteamine analogues than their corresponding acyl-CoA thioesters are required to achieve comparable yields of triketide lactones. CONCLUSIONS: Although a broad range of variation in the starter residue is acceptable, the substrate specificity of module 2 of a typical modular PKS in vitro is relatively intolerant of changes at C-2 and C-3. This will restrict the usefulness of approaches to synthesise novel erythromycins using synthetic diketides in vivo. The use of synthetic beta-keto diketides in vivo deserves to be explored.
Catalysis↗
Disproportional response between refractory period and blood flow to alpha 1- and beta-adrenoceptor blockade in canine ischemic myocardium.
We investigated the response of refractory periods and blood flow to blockade of alpha 1- and beta-adrenoceptors alone, or in combination on endocardium and epicardium, during myocardial ischemia. Dogs were anesthetized with alpha-chloralose and divided into bunazosin (an alpha 1-blocking agent)-treated (0.1-0.2 mg/kg, i.v., n = 14), propranolol-treated (0.2 mg/kg, i.v., n = 12), and vehicle-control (n = 10) groups. The diagonal branches of the left anterior descending artery were ligated. The refractory period (ERP) and blood flow (RMBF) were determined by an S1-S2 extrastimulus method and a nonradioactive microsphere technique, respectively. The duration of regional electrograms (DRE) was measured in the endocardial and epicardial sites. Bunazosin alone reversed the ischemia-related shortening of ERPs at both the endocardial and epicardial sites, with a greater effect seen epicardially (P < .05). Subsequent administration of propranolol further prolonged ERPs in both sites, although the effect was greater in the epicardial surface (P < .05). Bunazosin reduced RMBF to a greater degree at the endocardial site than at the epicardial site in the ischemic zone (P < .01 and P < .05, respectively), but the magnitude of the reduction in RMBF and the difference in RMBF between sites were similar to the control group (P < .01). Propranolol alone and subsequent administration of bunazosin prolonged the ERP more at the epicardial site (P < .01) than at the endocardial sites in the ischemic zone. Propranolol produced no significant difference in RMBF between both sites. DREs in animals treated with bunazosin and propranolol alone, or in combination, were similar to those in animals treated with vehicle. These results suggest that differences in ERPs between endocardium and epicardium with blockade of alpha 1- and/or beta-adrenoceptor are not due to concomitant alterations in RMBF, but to differences in electrophysiological properties of the endocardial and epicardial cells during the acute phase of myocardial ischemia.
Adrenergic alpha-1 Receptor Antagonists↗
Analysis of glycosphingolipids of human head and neck carcinomas with comparison to normal tissue.
Glycosphingolipids of head and neck carcinomas from six tumor-bearing patients were analyzed and compared to those of normal tissue from similar areas. The total glycosphingolipid content and the lipid-bound sialic acid were much higher in carcinomas than in normal tissue. Major neutral glycolipids were glucosylceramide, lactosylceramide, trihexosylceramide and paragloboside. Sulfatides were seen only in extracts from normal tissue which also showed a rather simple ganglioside pattern with #GM3 and GD3 as major species, whereas tumors showed additional species such as GM2 and GD2, along with a strong increase in LM1, GM1, GD1a and GT1b.
Biomarkers, Tumor↗
Coronary thrombosis. Effects of blood flow on the mechanism of thrombus formation.
The mechanism of arterial thrombosis, including coronary thrombosis, is different from that of thrombosis which occurs at sites of blood stasis such as deep venous thrombosis. Considering the onset of arterial thrombus formation, soluble coagulant factors may not play important roles for its onset since they are diluted by the effect of blood flow and cannot reach high enough concentrations to form insoluble fibrin. Platelets, which can stick to damaged vascular lumen even in the presence of shearing effects of blood flow, may play a crucial role in the onset of arterial thrombus formation. Thus, the mechanism of platelet thrombus formation should be assessed in the presence of blood flow. However, current dogma that fibrinogen binding to activated GP IIb/IIIa is the final common pathway for platelet thrombus formation was developed by using the function assay system of aggregometer, in which the effects of blood flow were not seriously considered. We are proposing in this review that plasma ligand protein of von Willebrand factor (vWF) and its interactions with platelet GP lb and GP IIb/IIa, which become apparent only in assays systems under influence of high shear rates of flow condition such as flowchambers or coneplate viscometers, are the key events leading to the onset of arterial thrombosis. A better understanding of the vWF-mediated mechanism of platelet thrombus formation is important for the development of better clinical tools to prevent ischemic heart disease as well as for a complete understanding of the mechanism of coronary thrombosis.
Blood Circulation↗
Primary cutaneous cryptococcosis in an immune competent patient.
A 50-year-old female developed a swelling in the epigastrium which later ruptured to form a sinus. A diagnosis of primary cutaneous cryptococcosis was made with the help of histopathology and microbiological studies. Treatment with amphotericin-B and 5-flucytosine gave a good therapeutic response and the sinus healed within 2 months.
Antifungal Agents↗
[Significance of the early maximal negative T wave in acute anterior myocardial infarction].
The significance of the early maximal negative T wave on electrocardiography was evaluated in 74 patients with initial acute anterior myocardial infarction (MI) admitted within 6 hours of onset. The relationship between the negative T wave and the severity of MI, as assessed by MI size and left ventricular dysfunction, was investigated. Serial electrocardiography, maximal creatine phosphokinase (CKmax), total myocardial perfusion index by thallium-201 single photon emission computed tomography myocardial scintigraphy, and left ventricular ejection fraction (LVEF) by technetium-99m scintigraphy were obtained. The amplitude of maximal negative T wave (NTmax) was observed between 4 and 96 hours after the onset (mean 46.3 +/- 19.3 hours). NTmax was significantly correlated with CKmax-1 (r = 0.613, p < 0.001) and with LVEF (r = 0.542, p < 0.002). Patients were divided into 3 groups based on NTmax: the deep negative T (DNT: NTmax > or = 10 mm) group, intermediate negative T (INT: 4 mm < or = NTmax < 10 mm) group and shallow negative T (SNT: NTmax < 4 mm) group. Compared with the SNT group, the DNT group revealed smaller CKmax (p < 0.05), more reduced LVEF and myocardial perfusion index (p < 0.05, respectively). The INT group had intermediate values. Serial electrocardiography of the DNT group showed the reappearance of R waves in leads V1-V4, normalization of the ST segment, and relatively early appearance of terminal T wave inversion (p < 0.05, respectively). NTmax reflects the infarct size, and is a clinically simple and useful parameter to estimate the severity of acute anterior myocardial infarction.
Adult↗
[Assessment of global and regional LV function obtained by quantitative gated SPECT using 99mTc-tetrofosmin: comparison with left ventricular cineangiography and echocardiography].
The quantitative gated SPECT (QGS) software that has automatic edge detection algorithm of the left ventricle, is able to calculate LV volumes and visualize LV wall motion with perfusion throughout the cardiac cycle. We evaluated the reliability of global and regional LV function derived from QGS using 99mTc-tetrofosmin by comparing with left ventricular cineangiography (LVG) and echocardiography (ECHO). In 22 cardiac patients, end-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (LVEF) were calculated. Using cinematic display, regional LV wall motion were scored on a 3-point scale (1 = normal, 2 = hypokinesis, 3 = akinesis; WMS). EDV, ESV and LVEF correlated well with those by LVG (p < 0.001 for each). Correlation between WMS derived from QGS and ECHO was high (r = 0.85, p < 0.001). There was an inverse correlation between WMS and LVEF (r = 0.77, p < 0.001). In conclusion, QGS is useful to evaluate global LV function. Regional wall motion evaluated by QGS is good enough for clinical application.
Cineangiography↗
Preparation of peptides which mimic glycosphingolipids by using phage peptide library and their modulation on beta-galactosidase activity.
We describe the use of a phage-displayed random pentadecamer peptide library for searching glycosphingolipid mimicking peptides. Two phage clones (AD-1 and AD-2) were selected by biopanning using monoclonal antibody AD117m, directed to lactotetraosylceramide (Lc4Cer). The amino acid sequences of the selected clones showed high homology (VPPXFXXXY) in 9-mer. Three phage clones were selected by using monoclonal antibody H11, directed to neolactotetraosylceramide (nLc4Cer), the linkage isomer of Lc4Cer, and the displayed amino acid sequences were compared. One of these peptides showed the same amino acid sequence as that of AD-2 except for one amino acid substitution. Pentadecamer, 9-mer and point mutated 9-mer peptides were synthesized on the basis of the displayed amino acid sequences. Binding activity of the peptides to the monoclonal antibodies or Ricinus communis lectin showed that 9-mer peptides are enough to mimic the epitope carbohydrate structure. Furthermore, six of the synthesized peptides inhibited Jack bean beta-galactosidase activity towards nLc4Cer at a high concentration of the enzyme, whereas at lower enzyme concentrations some peptides showed potent activation of the enzyme activity. This is the first report of carbohydrate mimicking peptides which modulate glycosidase activity.
Amino Acid Sequence↗
Structure of a novel phosphocholine-containing aminoglycoglycerolipid of Mycoplasma fermentans.
Mycoplasma fermentans is thought to be a pathogen of rheumatoid arthritis or a cofactor of AIDS (acquired immunodeficiency syndrome). To elucidate the possible involvement of membrane constituents in the pathogenesis of these diseases, we studied its lipid components. Several alkali labile glycophospholipids were detected and named glycoglycerophospholipids (GGPLs). Previously, we purified and determined the structure of one of them as 6'-O-phosphocholine-alpha-glucopyranosyl-(1'-3)-1,2-diacyl-sn-glycerol (GGPL-I). The present paper describes the purification and structural characterization of GGPL-III, the major GGPL of M. fermentans using 1H-, 13C- and 31P-nuclear magnetic resonance spectroscopy, and mass-spectroscopy as 1"-phosphocholine,2"-amino dihydroxypropane-3"-phospho-6'-alpha-glucopyranosyl-(1'-3)-1,2-dia cyl-glycerol.
Glycolipids↗
Ganglioside GD1alpha functions in the adhesion of metastatic tumor cells to endothelial cells of the target tissue.
We studied the role of glycosphingolipids expressed on the cell surfaces of a metastatic tumor cell line. Glycosphingolipid compositions of the low-metastatic murine lymphosarcoma cell line RAW117-P and its sub-line, RAW117-H10, which shows higher metastatic potential for the liver than P cells, were compared. Both types of cells had LacCer, Gg3Cer, and Gg4Cer as the major neutral glycosphingolipids and GM1b and GD1alpha as the gangliosides. There are differences in glycosphingolipid contents, the neutral glycosphingolipid contents in the parental cells being 1.5-fold higher than that in the variant ones. In contrast, the level of GD1alpha in H10 cells was twice as much as that in the P cells; however, the expression of other gangliosides was down-regulated. On the basis of the results of glycosphingolipid analysis, we investigated the functional role of GD1alpha in H10 cells in the adhesion of the tumor cells to the target tissue by using hepatic sinusoidal endothelial (HSE) cells. GD1alpha and GM1b inhibited the adhesion when HSE cells were incubated prior to coculture with the tumor cells. This inhibitory effect by GD1alpha and GM1b was observed within 30 min after addition of H10 cells to HSE cells and was dose dependent. GD1alpha showed a higher inhibitory effect on the adhesion than GM1b, whereas other glycosphingolipids showed no inhibitory effect. Anti-GD1alpha monoclonal antibody also inhibited the adhesion between the H10 and HSE cells. When cultured without fetal bovine serum for 30 min in a various glycosphingolipids-coated dish for bacterial culture, HSE cells adhered to the area coated with GD1alpha but not to areas coated with other glycosphingolipids. HSE cell adhesion depended on the amount of GD1alpha coated on the plate. These data indicate that GD1alpha functions as an adhesion molecule in the process of metastasis of H10 cells.
Animals↗
Acute myocardial infarction plasma augments platelet thrombus growth in high shear rates.
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Blood Platelets↗
Effects of methylprednisolone on hemodynamics and beta-adrenergic receptor signaling in rabbits with acute left ventricular failure.
Studies suggest that corticosteroids may restore the responsiveness to catecholamines in hypotensive patients. Since the significance of this promising intervention in congestive heart failure remains to be explored, we determined the effects of methylprednisolone, a potent activator of beta-adrenergic receptor signaling, on hemodynamics and beta-adrenergic receptor regulation in an animal model of heart failure. Acute left ventricular overloading was produced by aortic regurgitation (AR) in 22 Japanese white rabbits. Eleven animals received an intravenous administration of methylprednisolone (AR + PSL), while 11 received saline (AR + C) for 1 week. A sham operation was performed on 10 other rabbits (S). There was no difference between the AR + C and AR + PSL groups in the decrease in aortic diastolic pressure immediately after the production of AR. The aortic diastolic pressure and regurgitant fractions were also similar in the two groups. The left ventricular end-diastolic and end-systolic dimensions were both larger, and the left ventricular end-diastolic pressure was higher in AR + C or AR + PSL than in S rabbits. Between the AR + C and AR + PSL, there were no differences in any of these variables. Cardiac output was lower in AR + C, but not in AR + PSL, than in S. Cardiac output in AR + PSL was significantly higher than in AR + C. The myocardial concentration of norepinephrine and the number of beta-adrenergic receptors were both lower in the AR + C and AR + PSL than in the S groups. The number of receptors in AR + PSL was higher than in AR + C. Maximal isoproterenol-stimulated adenylyl cyclase activity was similar in the AR + C and AR + PSL groups. Results suggest methylprednisolone yielded some benefits, including an increase in cardiac output and in total beta-adrenergic receptor number, in this animal model of heart failure.
Animals↗