Cortical asymmetry--a preliminary study: neurons-glia, female-male

Previous studies on human cortical area 39 suggested that neuron:glial ratios differed between the sexes. These findings were the inspiration for the present investigation which dealt with neuronal and glial counts in area 39 in the male and female rat cerebral cortex. Transverse, celloidin or frozen sections, were cut from male and female brains (respectively) from 90-day-old Long-Evans rats. Neurons and glia were counted on enlarged photographs of stained sections, including area 39, with 35-mm Kodak Panatomic-X film using a Zeiss photomicroscope (X400). Five-by-three-inch prints were taped together in sequence to yield a 640X enlarged "montage" of area 39. Five cell types were differentiated with reference to a standard: neurons, astrocytes, oligodendrocytes, "dark astrocytes," and unidentified glia. The data were analyzed with a two-way analysis of variance (ANOVA: five cell types by two hemispheres). Student's t test and a paired t test were used when appropriate. The neuron:glial ratios in the male rats were consistently higher than those in the females in both hemispheres. The male right side had 12% (P less than 0.05) more neurons than the left; the female had 13% (P less than 0.05) more neurons on the left than the right. Similar, but not identical, asymmetrical patterns were seen with the glial cells.     

Pygmaeoherin: A Novel Coumarin from Pygmaeopremna herbacea

A new 6-oxygenated coumarin, pygmaeoherin, was isolated from roots of PYGMAEOPREMNA HERBACEA. Its structure was determined by spectroscopic methods. An NOE experiment played an important role in confirming the structure.     

GALC transduction leads to morphological improvement of the twitcher oligodendrocytes in vivo

Globoid cell leukodystrophy (GLD, Krabbe disease) is a severe demyelinating disease caused by a genetic defect of beta-galactocerebrosidase (GALC). To date treatment to GLD is limited to hematopoietic stem cell transplantation. Experimental approaches by means of gene therapy in twitcher mouse, an authentic murine model of human GLD, showed significant but only marginal improvements of the disease. To clarify whether the introduction of GALC could provide beneficial effects on the oligodendrocytes in GLD, we transduced twitcher oligodendrocytes by stereotactically injecting recombinant retrovirus encoding GALC-myc-tag fusion gene into the forebrain subventricular zone of neonatal twitcher mouse. In vivo effects of exogenous GALC on twitcher oligodendrocytes were studied histologically by combined immunostaining for the myc-epitope and the oligodendroglial specific marker, pi form of glutathione-S-transferase, at around 40 days of age. We show here that GALC transduction led to dramatic morphological improvement of the twitcher oligodendrocytes comparing with those in untreated twitcher controls. This study provided direct in vivo evidence that GALC transduction could prevent or correct aberrant morphology of oligodendrocytes in GLD which may be closely related to the dysfunction and/or degeneration of oligodendrocytes and the demyelination in this disease.     

Causal relationship between conformational change and inhibition of domain functions of glycoxidative fibronectin

Glycoxidative modification of various body proteins, including fibronectin (FN), has been shown to change their structural and functional properties, and be implicated in pathogenesis of diabetic complications. Little is known about the role of secondary structure of glycoxidative FN (gFN) in its domain functions. gFN was prepared by incubation with 25 and 200 mM glucose in 0.2 M sodium phosphate buffer at 37 degrees C on a shaking plate under aerobic and sterile conditions for various time intervals up to 49 days, being defined as gFN25 and gFN200, respectively. Unmodified FN (uFN) was prepared by incubation in 0.2 M sodium phosphate buffer without any glucose at 4 degrees C for 49 days. The extent of glycoxidative modification was examined using a noncompetitive enzyme-linked immunosorbent assay with an antibody against N(epsilon) -(carboxymethyl)lysine (CML), one of the major glycoxidation products. The binding activities of uFN and gFN to collagen, gelatin and heparin were determined by a solid phase enzyme immunoassay or heparin-affinity HPLC. Cell attachment was estimated by the extent of adhesion of FITC-labeled smooth muscle cells to uFN or gFN. Conformational change in gFN was detected by SDS-polyacrylamide gel electrophoresis and spectroscopy (circular dichroism). CML was detected in gFN25 and gFN200 after 49 and 21 days of incubation, respectively. Levels of CML were about six-fold higher in gFN200 than in gFN25 after 49 days. Both gFN25 and gFN200 showed a significant decrease in the ability of binding to collagen and gelatin after 7 days of incubation. The binding activity for heparin was significantly decreased in both gFN25 and gFN200 after one day. Cell attachment activity was reduced to 89% and 76% of the unmodified form in both gFN25 and gFN200 after 49 days, respectively. High molecular weight materials were found in gFN25 and gFN200 after 21 and 7 days, respectively. CD spectrum showed that gFN25 had lost its native conformation after 3 days of incubation, depending upon the concentration and incubation interval of the applied glucose. These in vitro results suggest that the loss of native conformation may reduce the domain functions of gFN, including binding activity to macromolecular ligands and cell attachment, and may play a major role in the pathogenesis of diabetic complications.     

Hemolytic uremic syndrome after bone marrow transplantation: clinical characteristics and outcome in children.

Hemolytic uremic syndrome (HUS) is an uncommon but potentially life-threatening complication of hematopoietic stem cell transplantation. We retrospectively studied the medical records of 293 children who underwent allogeneic bone marrow transplantation at St. Jude Children's Research Hospital between 1992 and 1999 to describe the clinical course of and to identify risk factors for transplant-associated HUS. Conditioning regimens included cyclophosphamide, cytarabine, and total body irradiation for patients with hematologic malignancies (n = 244); patients with nonmalignant diseases (n = 49) received disease-specific regimens. Grafts from unrelated or mismatched related donors were depleted of T lymphocytes, whereas matched sibling grafts were unmanipulated. All patients received cyclosporine as prophylaxis for graft-versus-host disease. Recipients of grafts from matched siblings also received pentoxifylline or short-course methotrexate. HUS developed in 28 (9.6%) patients at a median of 171 days after transplantation. We identified older donor age (P = .029), use of antithymocyte globulin in the conditioning regimen (P = .008), and recipient CMV seronegativity (P = .011) as being associated with an increased risk of HUS. With a multiple regression analysis, the use of antithymocyte globulin (beta = .86; P = .04) and recipient cytomegalovirus seronegativity (beta = .93; P = .035) remained significant risk factors for the development of HUS.     

多脏器恶性肿瘤术后肝黏膜相关淋巴组织淋巴瘤

目的 探讨肝黏膜相关淋巴组织淋巴瘤的临床病理特征。方法 对1例罕见多脏器恶性肿瘤术后肝黏膜相关淋巴瘤病例结合文献进行临床、病理和免疫组化分析。结果 患者于8年和3年前先后发生胃恶性间质瘤、阴囊阴茎皮肤湿疹样癌，有长期化疗史。肿瘤组织学以单核样B细胞为主，并有淋巴滤泡和淋巴上皮病变形成。免疫表型示瘤细胞CD45、CD79α、CD20阳性，CD5、CD10、ALK、TdT阴性，bcl—2、Ki—67少数肿瘤细胞阳性。结论 肝黏膜相关淋巴瘤可以发生于多脏器恶性肿瘤术后，其发病可能与长期使用免疫抑制剂有关，诊断本病时需与肝继发性淋巴瘤及肝的炎性假瘤鉴别。     

A multi-channel hearing prosthesis for profound-to-total hearing loss

A multi-channel cochlear implant hearing prosthesis providing 22 separate channels of stimulation has been developed. The electronics for the implantable receiver-stimulator have been incorporated on a single chip, using digital circuits and employing CMOS technology. The chip is enclosed in a titanium capsule with platinum/ceramic electrode feed-throughs. A pocket-sized speech processor and directional microphone extract the following speech parameters: signal amplitude, fundamental frequency and formant frequency. The fundamental frequency is coded as electric pulse rate, and formant frequency by electrode position. The speech processor has been realized using hybrid circuits and CMOS gate arrays. The multi-channel prosthesis has undergone a clinical trial on four postlingually deaf patients with profound-total hearing losses. The speech perception results indicate that they were able to obtain open-set speech recognition scores for phonetically balanced words, CID sentences and spondees. In all cases the tests showed significant improvements when using the cochlear prosthesis combined with lipreading compared to lipreading alone.     

Safety and efficacy of oral nemonoxacin versus levofloxacin in treatment of community-acquired pneumonia: A phase 3, multicenter,randomized, double-blind,double-dummy,active-controlled,non-inferiority trial

Background/Purpose

Nemonoxacin is a novel nonfluorinated quinolone with excellent in vitro activity against most pathogens in community-acquired pneumonia (CAP), especially Gram-positive isolates. The purpose of this study was to assess the efficacy and safety of nemonoxacin compared with levofloxacin in patients with CAP.