Enzyme-linked Immunosorbent Assay of Pro-gastrin-releasing Peptide for Small Cell Lung Cancer Patients in Comparison with Neuron-specific Enolase Measurement

Our previous study demonstrated that pro-gastrin-releasing peptide(31–98), or ProGRP, is a specific tumor marker in patients with small cell lung carcinoma (SCLC). Using a newly developed, highly sensitive enzyme-linked immunosorbent assay (ELISA) for ProGRP, we analyzed 1,446 samples including those obtained from 478 lung cancer patients to evaluate the clinical usefulness of this ELISA. Several properties indicated that ProGRP is a useful tumor marker for SCLC. First, ProGRP was specifically elevated in SCLC patients. In non-SCLC patients and patients with non-tumorous lung diseases, its serum level was very rarely elevated. Secondly, ProGRP was a reliable marker, in terms of the marked elevation of serum ProGRP levels in SCLC patients. Thirdly, serum ProGRP levels were elevated in SCLC patients even at a relatively early stage of this disease. Fourthly, changes in the serum ProGRP level showed an excellent correlation with the therapeutic responses in SCLC patients. Neuron-specific enolase (NSE) is accepted as a tumor marker of SCLC patients. With the aim of comparing ProGRP and NSE as tumor markers for SCLC patients, we measured serum NSE levels in all samples collected in the present study. We found that ProGRP was superior to NSE in terms of sensitivity, specificity and reliability. Therefore, we consider that ProGRP can play a major role as a clinical tumor marker for SCLC patients.     

DNA analysis of two patients with a non-fluorescent y chromosome

Summary Results of DNA study on two patients of gonadal dysgenesis with a 45,X/46,X,Ynf (non-fluorescent Y chromosome) karyotype are described. In one patient who developed gonadoblastoma, all 12 loci on the non-fluorescent part of Yq were detected. Another patient did not have gonadoblastoma at 20 years, and only the proximal 6 loci out of 12 were detected.     

Genetic alterations in primary and secondary hyperparathyroidism

Hyperparathyroidism refers to a term representing a wide spectrum of parathyroid disorders that are characterized by the increased production of parathyroid hormone. Hyperparathyroidism was once thought to be tare but is now more commonly recognized, aifecting 1 in 500 women over 40 years of age. Yet the interpretation of parathyroid pathology is still controversial and confusing. Over the past 10 years, genetic changes ( ret and menin genes) involved in the pathogenesis of MEN 2 and MEN 1 have been discovered in succession. Different mutations of the calcium-sensing receptor gene have been identified in neonatal severe hyperparathyroidism and familial hypocalciuric hypercal-cemia, respectively. The HRPT 2 gene responsible for the development of heredltaty hyperparathyroidism and jaw tumors has been localized on the 1q21–31 locus. Several genetic alterations have also been characterized in primary and secondary hyperparathyroidism. Different genetic alterations appear to involve the development of different types of hyperparathyroidism. These novel advances give us new insights into the pathogenesis of hyperparathyroidism and allow better differentiation between the different types of parathyroid disorders.     

Neuronal loss and neurofibrillary degeneration in the hippocampal cortex in late-onset sporadic Alzheimer's disease

To explore more fully the relationship between neuronal death and neurofibrillary degeneration, unaffected neurons, intracellular neurofibrillary tangles (i-NFT) and extracellular NFT (e-NFT) in 22 patients with late-onset sporadic Alzheimer's disease (AD) were morphometrically evaluated in eight subdivisions of the hippocampal cortex, using the Gallyas hematoxylin-eosin stain. The subdivisions examined included CA4, CA3, CA2, CA1 (CA: cornu ammonis), prosubiculum (PRO), subiculum and presubiculum (PRE), parasubiculum (PARA) and the entorhinal cortex (ENT). The unaffected neuron density was significantly lower and both i-NFT and e-NFT densities were significantly higher in subdivisions other than CA4 and CA3 in AD patients compared with those in the aged controls. Unaffected neuron density was significantly, inversely correlated with e-NFT density and with total NFT density in all subdivisions except for PRE in AD patients. Especially in CA2, CA1, PRO and ENT, there were strong correlations between the neuron density and these NFT densities. Both unaffected neuron and e-NFT densities in CA1 and ENT were significantly correlated with the disease duration. The i/e-NFT ratio, an index of the degree and/or rate of progress of neuronal death via neurofibrillary degeneration, showed the lowest value in ENT in AD patients. The findings suggest that neuronal death via neurofibrillary degeneration starts earliest and/or most rapidly progresses in ENT. Furthermore, the i/e-NFT ratios in both ENT and CA1 were significantly correlated with the disease duration, suggesting that the neuronal death pattern in the two subdivisions parallels disease progression.     

Serial alterations of beta-adrenergic signaling in dilated cardiomyopathic hamsters: possible role of myocardial oxidative stress.

BACKGROUND: The relationship between enhanced myocardial oxidative stress and impaired beta-adrenergic signaling remains to be characterized during the development of dilated cardiomyopathy. METHODS AND RESULTS: Alterations in myocardial oxidative stress and beta-adrenergic signaling, as well as left ventricular (LV) functional and structural changes, were evaluated during the development of cardiomyopathy in TO-2 hamsters; F1B hamsters served as controls. LV dysfunction was first apparent at 8 weeks of age and deteriorated thereafter in the TO-2 hamsters. At 32 weeks, the animals exhibited heart failure with an increased plasma norepinephrine concentration. Cardiac myolysis, as demonstrated by elevated plasma concentration of cardiac troponin T, peaked at 8 weeks. The glutathione redox ratio revealed increased oxidative stress in the LV myocardium in TO-2 hamsters even at 4 weeks and became manifest after 8 weeks. The hearts of TO-2 hamsters had significantly reduced superoxide dismutase activity from 8 weeks onward compared with control hamsters. However, glutathione peroxidase activity was unchanged at any time point. The LV functional response to isoproterenol was markedly reduced at 8 weeks, without any apparent changes in the amount of beta-adrenergic signaling molecules, and it deteriorated thereafter. Adenylyl cyclase activity was significantly decreased, despite increased amounts of both G(s) alpha mRNA and protein, in the LV myocardium at 18 weeks. CONCLUSIONS: Myocardial oxidative stress is actually enhanced in the initial development of LV dysfunction. Both activation of myocardial oxidative stress and impairment of beta-adrenergic signaling become prominent at the stage of severe LV dysfunction. Myocardial oxidative stress may be involved in the development of beta-adrenergic desensitization.     

Pathomorphological description of the shunted portion of a filum terminale arteriovenous fistula

Background contextThe clinical morphology of a filum terminale arteriovenous fistula (f-AVF) is well known; however, pathological details of the fistulized portion are unknown. Herein, we report the pathological findings of the f-AVF.Study designCase report and literature review.PurposeTo present a detailed pathological examination of the fistulized portion of the f-AVF.MethodsA 71-year-old man presented with gradually worsening bilateral foot paresthesias and anal dysesthesia. T2-weighted magnetic resonance imaging showed flow voids surrounding an edematous conus medullaris and cauda equina with spinal stenosis at L3–L4 and L4–L5. Spinal digital subtraction angiography demonstrated an f-AVF fed by the left T9 intercostal artery.ResultsWe performed laminotomies of L3 and L4 to open the dura mater and found a hypertrophic filum terminale. It was resected, leaving a length of 2 cm between the abnormal proximal end and normal distal end. The f-AVF completely disappeared after the surgery. On pathological examination, the filum terminale included two vessels at the proximal end and one at the distal end. At the proximal end, immunostaining showed one vessel that was definitively an artery with both an internal elastic membrane (IEM) and smooth muscle. The other was a vein and lacked an IEM. On the distal side, the collagen fibers gradually increased, the IEM partially disappeared from the arterial wall, and the vein became arterialized with a thin IEM. At the distal end the two vessels joined. Therefore, we speculated that the fistulized portion of the f-AVF was not a fistula point but had some lengths where the artery had characteristics of a vein and there was venous arterialization.ConclusionsThe filum arteriovenous shunting occurred at the portion where there was venous arterialization and the artery had the characteristics of a vein. Therefore, resecting the filum terminale requires more proximal from the normal distal end.     

Are there sequential morphometrical changes in the nucleus basalis in Alzheimer's disease?

Degenerated neurons of the nucleus basalis of Meynert (nbM) were quantitatively analyzed in 3 normal and 3 Alzheimer's disease (AD) subjects. In this study, the Ch4 of the nbM was examined using the indirect immunoperoxidase method with a monoclonal antibody to acetylcholinesterase (AChE) counterstained with cresyl violet. AChE-rich neurons were designated as the cholinergic neurons. The cross-sectional area of all the Ch4 neurons with clearly visible nucleoli in one preparation was measured using a computer image analyzing system. Furthermore, we compared these data with the numbers of neurofibrillary tangles (NFTs) and neuritic plaques (NPs) in the temporal cortex by Gallyas silver stain. The cholinergic neurons decreased in number and size according to the length of the disease duration but the surviving cholinergic neurons in the size range from 800 to 1,000 micron 2 in a case with short clinical duration were increased in number. The non-cholinergic neurons showed only atrophy without definite neuronal cell depletion. The 400- to 1,000-microns 2-sized non-cholinergic neurons were markedly decreased in number, and the number of 300-microns 2-sized non-cholinergic neurons remained unchanged. Although there was an inverse correlation between the degree of atrophy and depletion of the cholinergic neurons with the number of NFTs and NPs in 2 AD cases with 3 and 6 years of disease duration, this correlation was not found in an AD case with 12 years of disease duration, probably due to extensive and profound grey matter degeneration.