Expression of Lewis Y (Ley) Antigen in Human Anagen Hair Follicles

Lewis Y (Le^y) antigen, a difucosylated tetrasaccharide found on type 2 blood group oligosaccharides of glycolipids and glycoproteins, is thought to be a phenotypic marker predictive of cell differentiation. The distribution of this antigen in human anagen hair follicles was examined by immunohistochemical staining using a monoclonal antibody (AH-6) to Le^y. In the bulbar and suprabulbar portion of anagen hair follicles, Le^y antigen was detected in the three layers of the inner root sheath. Subsequently, the positive staining became translocated to the innermost layer of the outer root sheath in the middle part of the hair follicles. In the upper portion of the hair follicles, Le^y antigen was found in the outer cells of the outer root sheath. These findings suggested that the expression of Le^y antigen in the anagen hair follicles was correlated with the processes of keratinization or terminal differentiation.     

Effects of naftidrofuryl oxalate, a 5HT2 antagonist, on neurotransmission and transduction systems in the gerbil hippocampus

We investigated the effects of age and naftidrofuryl oxalate (Naftidrofuryl), a 5-HT₂ antagonist, on neurotransmission and transduction systems in the gerbil hippocampus using quantitative autoradiography. [³H]Quinuclidinyl benzilate (QNB), [³H]cyclohexyl-adenosine (CHA), [³H]MK-801, and [³H]muscimol were used to label muscarinic acetylcholine, adenosine A1, N-methyl-d-aspartate (NMDA), and γ-aminobutyric acid-A (GABA_A) receptors, respectively. [³H]PN200-110 labeled L-type Ca²⁺ channels. [³H]Forskolin, [³H]cyclic adenosine monophosphate (cAMP), [³H]phorbol 12,13-dibutyrate (PDBu), and [³H]inositol 1,4,5-triphosphate (IP₃) were used to label adenylate cyclase, cAMP-dependent protein kinase, protein kinase C (PKC), and IP₃ receptors, respectively. Approximately 20% reductions in [³H]QNB, [³H]forskolin, and [³H]PDBu binding were observed in the hippocampus of 9-month-old gerbils in comparison with 5-week-old gerbils. Treatment with Naftidrofuryl (10 mg/kg, i.p., once a day for 7 days) ameliorated these reductions. No changes were found in [³H]CHA, [³H]MK-801, [³H]muscimol, [³H]PN200-110, [³H]cAMP, and [³H]IP₃ binding. The results suggest that Naftidrofuryl may have beneficial effects on the age-related alterations in signal transmission and transduction systems in the brain. Because the acetylcholine system, adenylate cyclase, and PKC are considered to be involved in learning and memory processes, the result may have clinical implications.     

Development and Initial Testing of a Permanently Implantable Centrifugal Pump

Abstract: To be able to salvage heart failure patients, the need for an economical permanent ventricular assist device is increasing. To meet this increasing demand, a miniaturized centrifugal blood pump has been developed as a permanently implantable device. The Gyro permanently implantable model (PI-601) incorporates a sealless design with a blood stagnation free structure. The pump impeller is magnetically coupled to the driver magnet in a sealless manner. This pump is atraumatic and antithrombogenic and incorporates a double pivot bearing system. A miniaturized actuator was utilized in this system in collaboration with the University of Vienna. The priming volume of this pump is 20 ml. The overall size of the pump actuator package is 53 mm in height and 65 mm in diameter, 145 ml of displacement volume, and 305 g in weight. Testing to date has included in vitro hydraulic performance and hemolysis. This pump can provide 5 L/min against a 110 mm Hg total pressure head at 2,000 rpm and 8 Limin against 150 mm Hg at 2,500 rpm. The normalized index of hemo-lysis (NIH) value of this pump was 0.0028 g/100 L at 5 Limin against 100 mm Hg. A preliminary anatomical study revealed the possibility of the implantability of 2 such systems in biventricular bypass at a preperitoneal location. This system is feasible for use as a permanently implantable biventricular assist device.     

Reversal of multidrug resistance by new dihydropyridines with lower calcium antagonistic activity

Summary BS compounds, a series of new dihydropyridines, successfully overcame multidrug resistance in P388/ADR cells in vitro. These agents synergistically potentiated the cytotoxicity of Adriamycin to P388/ADR cells at a concentration of 1–2 M, whereas they showed hardly any synergistic effect in the parental cell line (P388/S) at the same concentration. They inhibited the active drug efflux in P388/ADR cells as well as the binding of [G-³H]-vinblastine to membrane vesicles from P388/ADR, which was increased in resistant P388 cells as compared with parental cells. Besides, unlike the activity of clinically used calcium antagonists, the calcium antagonistic activity associated with BS compounds was very weak: their arterial relaxation activity was <21% of that of verapamil. These data suggest that BS compounds specifically overcome multidrug resistance without the serious hypotensive side effects that accompany the use of verapamil orother calcium antagonists.     

Rapid serodiagnosis of active pulmonary Mycobacterium tuberculosis by analysis of results from multiple antigen-specific tests

We have prospectively analyzed three antigens for serodiagnosis of tuberculosis (TB). These antigens were tuberculous glycolipid antigen, lypoarabinomannan polysaccharide antigen, and antigen 60 (A60), which was derived from purified protein derivatives. Of the 131 patients with active pulmonary TB, 57 were both smear and culture negative and 14 had chronic active pulmonary TB that remained smear positive for >12 months of chemotherapy. One hundred twenty healthy adults were controls. The percentages of patients positive in all three tests were 58.8% for smear-positive active pulmonary TB and 71.4% for chronic active pulmonary TB. When the results of the three serodiagnostic tests were evaluated in combination, the sensitivity increased to 91.5% in patients with active pulmonary TB and to 86.0% in smear- and culture-negative patients. The false-positive rate of the three-test combination was 12.5% in the healthy control groups. In conclusion, it was not possible to detect all of the antibodies against antigenic substances in the cell walls of the tuberculous bacilli in the sera of all TB patients by using available serodiagnostic tests. However, the combined use of tests with three separate antigens maximizes the effectiveness of serodiagnosis.     

Prospective clinical evaluation of the serologic tuberculous glycolipid test in combination with the nucleic acid amplification test

We have conducted a prospective controlled multicenter study to evaluate differences in the levels of clinical utility of the tuberculous glycolipid (TBGL) serodiagnostic test and the nucleic acid amplification test in patients with smear-negative active pulmonary tuberculosis (TB). The TBGL test and the PCR test were individually not so useful for the rapid diagnosis of smear-negative active pulmonary TB. However, clinical utility was considerably improved by using the TBGL test and the PCR test in combination, especially in patients with smear-negative and culture-negative active pulmonary TB and in patients with minimally advanced lesions.     

Glyceraldehyde 3-phosphate dehydrogenase is a novel autoantigen leading autoimmune responses to proliferating cell nuclear antigen multiprotein complexes in lupus patients

Using 2-dimensional electrophoresis and ion-pair chromatography, we have identified elements of proliferating cell nuclear antigen (PCNA) multiprotein complexes that are reactive to antibodies in sera from patients with systemic lupus erythematosus. Among the various elements of the complexes, a 37 kDa protein (PI 8.5) that specifically reacted with SLE sera, but not with sera from patients with other connective tissue diseases, was identified as glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Immunoblot analysis showed that SLE sera reactive with the 37 kDa protein specifically reacted with GAPDH, as did anti-GAPDH mAbs. The purified autoantibodies to GAPDH from lupus serum showed both nuclear speckled and cytoplasmic staining patterns in immunofluorescence on Hep-2 cells. In addition, enzyme-linked immunosorbent assay (ELISA) revealed the presence of anti-GAPDH autoantibodies in 47% of lupus patients. Longitudinal analysis of the reactivity of lupus sera to PCNA complexes showed the autoimmune response to spread from GAPDH to other elements of PCNA complexes, and the presence of anti-GAPDH antibodies was significantly correlated with increased levels of serum PCNA. Taken together, these findings suggest that GAPDH interacting with PCNA in association with its cellular function is a novel autoantigen recognized by lupus sera, and that GAPDH thus plays an important role in the induction of autoimmune responses against the PCNA complex.     

Architectural remodelling in lungs of rabbits induced by type V collagen immunization: a preliminary morphologic model to study diffuse connective tissue diseases

The pathogenesis of diffuse connective tissue diseases (DCTD) is still unknown and has been extensively studied regarding its autoimmunity aspects related to extracellular matrix (ECM) remodelling, with an emphasis on the collagens at the inflammatory site. The present paper describes the pulmonary architectural and repair/remodelling responses to injury after immunization of rabbits with human type V collagen. The animal model consisted of rabbits immunized with collagen mixed with Freund's adjuvant and sacrificed 7, 15, 30, 75, and 120 days after the first of four doses of antigen. Pulmonary architecture remodelling response was evaluated by histology, morphometry, and the immunofluorescence method, according to compartments of reference (parenchyma and interstitium) and injury: 1 inflammation (polymorphonuclear and mononuclear cells); 2-repair (fibrosis) and 3-ECM remodelling (collagen system). The results showed an intense inflammatory involvement of the pulmonary vascular and bronchiolar parenchyma, characterized by increased wall thickness in small arteries, infiltrations by pseudoeosinophils, and mononuclear cells. Progressive remodelling of the pulmonary ECM was characterized by collagen deposition in the septal and bronchovascular interstitium, especially in rabbits sacrifices at 75 and 120 days. The ECM remodelling process was not reproduced when rabbits were inoculated with collagen types I and III. We conclude that the model reproduces morphologic changes similar to those observed in many DCTD, encouraging realization of other experiments to gain a better understanding of the pathogenesis of these diseases.