Use of Glycopeptidolipid Core Antigen for Serodiagnosis of Mycobacterium avium Complex Pulmonary Disease in Immunocompetent Patients

We report the development of a serodiagnostic method for Mycobacterium avium complex (MAC) disease with an enzyme immunoassay (EIA) with the MAC-specific glycopeptidolipid (GPL) core as the antigen. In this study, we confirmed by EIA that the GPL core antibody was in the sera of immunocompetent patients with MAC disease. The EIA for quantifying the GPL core antibody was evaluated as a clinical tool for serodiagnosis of pulmonary MAC disease. A significant increase in GPL core antibodies (immunoglobulins G, A, and M) was detected in sera of patients with MAC pulmonary diseases when they were compared to patients who were colonized with MAC, patients with Mycobacterium kansasii disease or tuberculosis, and healthy subjects. The sensitivities and specificities of the GPL core-based EIA for diagnosis of MAC pulmonary disease were 72.6% and 92.2%, respectively, for IgG, 92.5% and 95.1%, respectively, for IgA, and 78.3% and 91.0%, respectively, for IgM. The best sensitivity and specificity were obtained by measuring immunoglobulin A antibodies against GPL core antigen. The level of GPL core antibodies reflected disease activity, since it decreased in cured MAC patients who had responded to chemotherapy. Measurement of serum antibodies against GPL core is useful for both diagnosis and assessment of disease activity in MAC disease of the lung.     

Extracellular matrix remodeling in oral submucous fibrosis: its stage-specific modes revealed by immunohistochemistry and in situ hybridization

BACKGROUND: Oral submucous fibrosis (OSF) is a chewing habit-related pre-cancerous condition of the oral mucosa affecting predominantly south Asians. It is histopathologically characterized by epithelial atrophy and fibrosis of the subepithelial connective tissue. Fibrosis extends all the way into the muscle layer, leading to difficulty in mouth opening. However, the dynamics of extracellular matrix (ECM) remodeling with OSF progression is largely unknown. METHODS: Forty biopsy specimens of OSF and 10 of normal buccal mucosa were examined for expression/deposition modes of eight ECM molecules by histochemistry, immunohistochemistry, and in situ hybridization. RESULTS: In the early stage of OSF, tenascin, perlecan, fibronectin, collagen type III were characteristically enhanced in the lamina propria and the submucosal layer. In the intermediate stage, the ECM molecules mentioned above and elastin were extensively and irregularly deposited around muscle fibers. In the advanced stage, such ECM depositions decreased and were entirely replaced with collagen type I only. Their gene expression levels varied with progression of fibrosis, but the mRNA signals were confirmed in fibroblasts in the submucosal fibrotic areas. CONCLUSIONS: The results indicate that the ECM remodeling steps in OSF are similar to each phase of usual granulation tissue formation. Restricted mouth opening may be a result of loss of variety of ECM molecules including elastin into the homogeneity of collagen type I replacing muscle fibers.     

Scintigraphic detection of recurrence of medullary thyroid cancer

A case of recurrent medullary thyroid cancer (MTC) was evaluated with¹²³I-MIBG,^99mTc(V)-dimercaptosuccinic acid (DMSA), and²⁰¹Tl scintigraphy. This patient had been operated on for MTC in the right thyroid. Recently a left neck mass was noticed, and was suspected of being a. recurrence of MTC based on increased plasma calcitonin (CT) and carcinoembryonic antigen (CEA). He was operated on for the neck mass which revealed MTC, and papillary thyroid cancer was incidentally found in the left thyroid, but the CT and CEA levels remained high, and remaining MTC tumor was suspected. But the location of the tumor was unknown. Although^99mTc(V)-DMSA scintigraphy is generally believed to be superior in sensitivity to¹²³I-MIBG scintigraphy, it did not demonstrate the tumor site but²⁰¹Tl and¹²³I-MIBG did. Furthermore,¹²³I-MEBG scintigraphy has greater specificity for tumors which arise in the neural crest. Judging from the results of this case and cases reported in the literatures, both¹²³I-MIBG and^99mTc(V)-DMSA should be performed in the detection of recurrent MTC.     

Apheresis Technologies: An International Perspective

Abstract: The developments in apheresis techniques and their clinical applications world-wide are technologically driven. In the past, apheresis survey statistics have highlighted both the differences by region in clinical practice and in the types of technologies utilized. Such differences have provided a basis for the scientific and clinical assessments of these apheresis technologies and their clinical outcomes and have stimulated the marketing and business development of new technologies world-wide. A review of the regional practices and technologies utilized provides a perspective on the future role of apheresis and its developments in clinical practice. While technology is a driving force for the development of new techniques for clinical practice, it is not the only market force. For technology introduction, several other important issues need to be considered. Regulations at the local and, most importantly, the federal level impact the timing for new technology introduction. Reimbursement by healthcare payers is critically important from the initiation of the development of a technology through its clinical use. Clinical trials are critically important to show the safety and clinical- and cost-effectiveness of the technology in order for payers to provide reimbursement for its use, but these trials are sometimes long and costly. Research funding availability at the governmental and commercial levels critically impacts new technology investigation and its introduction. Apheresis technology developments offer new hopes and promises for the clinical team; however, their development, introduction, and utilization will be influenced by the prevailing market forces.     

Biological significance of enhanced mitochondrial ketogenesis during the early stages after 70% hepatectomy in rats

Ketogenic capacity of mitochondria from the remnant liver of 70% hepatectomized rats was studied in relation to mitochondrial phosphorylative activity. Ketogenic capacity increased to a maximum of 6.04 +/- 0.39 from 3.84 +/- 0.13 of control, with an enhancement of mitochondrial phosphorylative activity 6 hr after hepatectomy, and then decreased to normal levels within 24 hr. Adenylate energy charge, (ATP + 1/2ADP)/(ATP + ADP + AMP), of the remnant liver decreased to 0.825 +/- 0.006 as compared to 0.849 +/- 0.002 of control 6 hr after operation. At 12 hr, total ketone body concentrations of the arterial blood increased concomitant with a fall in ketone body ratio (acetoacetate/3-hydroxybutyrate) which reflects the decreased liver mitochondrial redox (NAD+/NADH) state. These findings suggest that an enhancement of mitochondrial fatty acid oxidation and ketogenesis occurs concomitant with an enhancement of mitochondrial phosphorylative activity in the remnant liver in response to a decreased energy charge after 70% hepatectomy.     

Antiphospholipid antibody syndrome and vasoocclusive diseases

One hundred and thirty-four patients with vasoocclusive diseases were retrospectively tested for three kinds of antiphospholipid antibody (aPL). The mean age at onset of the disease in 58 patients with aPL was 43 years old. Seventeen, 11, and 9 patients were positive for the aCL IgA, IgM, and IgG isotypes, respectively. The rates of anti-phospholipid syndrome (APS) in patients with arterial (n=94), venous (n= 31), or both arterial and venous (n=9) occlusion were 45%, 29%, and 78%, respectively.The rates of APS in patients with autoimmune disease (n=13), thromboangiitis obliterans (TAO) (n= 36), arteriosclerosis obliterans (ASO) with lower leg involvement (n=8) or aortic arch syndrome (n=5), Raynaud's syndrome (n=15), aortitis syndrome (n= 13), ischemic heart disease (IHD) with young onset (n =12), and bilateral leg deep venous thrombosis (DVT) (n=10) were 77%, 46%, 13%, 80%, 40%, 62%, 33%, and 70%, respectively. The cumulative patency rate for reconstructive surgery in patients (n=13) with aCL was found to be considerably lower than that in those without aCL (n=13). From these results it was concluded that IgA was the most valuable aCL isotype for the diagnosis of APS and that aPL should be examined in patients with double-vessel occlusion, autoimmune disease, bilateral leg DVT, aortic arch syndrome, TAO, Raynaud's syndrome, or IHD with young onset. Furthermore, prophylaxis for graft failure is more strongly recommended for patients with aCL than for those without it.     

Urinary bladder carcinoma producing granulocyte colony stimulating factor (G-CSF): A case report with immunohistochemistry

A rare case of urinary bladder carcinoma with granulocyte colony stimulating factor (G-CSF) production was reported. In an 83-year-old female, marked neutrophilia in the peripheral blood decreased from 132,500/mm³ to 3,300/mm³ after tumour resection. The tumour was a transitional cell carcinoma. The serum G-CSF level reduced from 238 pg/ml pre-operatively to normal (60 pg/ml) after the operation. Immunohistochemical investigation of the resected tumour with monoclonal antibody specific for G-CSF revealed positive staining in the carcinoma cells, confirming G-CSF secretion.     

Effect of ceruletide on microvibration in schizophrenics

Ceruletide, a potent analogue of cholecystokinin, was administered by injection to eight schizophrenics treated with neuroleptics. We examined the dose–response effect on microvibration (MV) recorded from the chin of these patients. After 15 min of bed rest, MV was recorded for 5 min as a control recording. Subsequently, saline or ceruletide, at a dose of either 0.4 m?g/kg or at 0.8 m?g/kg, was injected according to a Latin square design with an interval of 4 weeks for washing out the drug effect and MV was recorded for 30 min. MV data obtained were subjected to the fast Fourier transform and an average power spectrum was computed. A three-way analysis of variance for these data was performed upon dose-effect, time-effect after treatment, and band-effect of the average power spectrum. The present results were similar to previous findings which had revealed effects of ceruletide on tardive dyskinesia symptoms, namely, the effects of ceruletide on MV were different according to the subjects (three cases: facilitation followed by inhibition, three cases: inhibition, two cases: no effects). The dose-response curve of ceruletide appears to be linear in some cases and an inverted U-shape in other cases. Present findings showed small doses of systemically administered ceruletide would modify muscle tonus of schizophrenics under chronic treatment of neuroleptics, and provided further reason for the therapeutic drug of tardive dyskinesia.     

Histological study of effect of bone morphogenetic protein derived from bovine tooth on periosteum in rats

Summary In this study, we examined histologically the effect of a bone morphogenetic protein (BMP) derived from bovine tooth on the periosteum. Supraperiosteal injection of crude BMP into femurs of Wistar rats (28 day old) resulted in periosteal cell proliferation with subsequent bone and cartilage formation. Moreover, proliferating periosteal cells migrated into injected BMP, and formed both cartilage and bone. These observations show that exogenous BMP stimulates mesenchymal cells of the periosteum to proliferate and differentiate into osteoblasts, and therefore BMP may be one of factors which are involved in differentiation of osteoblasts in the periosteum.