There is a compelling need to develop biological marker(s) to confirm a clinical diagnosis of Alzheimer's disease (AD) during life in order to unequivocally identify AD patients for emerging therapeutic interventions. This review describes recent advances in the development of diagnostic marker(s) for AD. They include polymorphism of apolipoprotein E (ApoE) and α1-antichymotrypsin as well as cerebrospinal fluid (CSF) tau and CSF-amyloid β-protein levels, skin biopsy, and pupil dilatation assay by anti-cholinergic agent. In conclusion, ApoE genotyping should not be used as a sole diagnostic test for AD, and that monitoring of CSF-tau appeared to be most promising and reliable diagnostic aid.
To clarify the role of microvessels in the development of pulmonary hypertension of acute lung injury, we induced lung edema by oleic acid (OA) in ten artificially perfused cat lungs and measured microvascular pressure. Pulmonary artery pressure (Ppa) and pressure of 30-50 μm arteriole (Parteriole) increased from 19.2±1.4 and 15.7±1.0 cmH2O before to 30.5±5.0 cmH2O and 22.7±2.4 cmH2O after edema, respectively. Pressure of 30-50 μm venule (Pvenule) and venous occlusion pressure (Pvo) did not change significantly after edema. Double occlusion pressure (Pdo) which represents pulmonary microvascular pressure increased from 14.5±0.6 to 17.7±2.0 cmH2O. Pressure gradient in the artery, i.e., between Ppa and Parteriole and in the microvessels, i.e., between Parteriole and Pvenule increased when lung became edematous. Pressure gradient in vein, i.e., between Pvenule to left atrium was not affected by edema. Pdo was in the midst of Parteriole and Pvenule in both edematous and non-edematous lung. In acute lung injury, increase of microvascular resistance was followed by an increase of arterial resistance and caused pulmonary hypertension.
The clinicopathological features of 31 young patients with early gastric cancer, defined as under 40 years of age, were reviewed retrospectively from hospital records between 1969 and 1993. The results were compared with those for 549 patients 40 years of age or older. Early gastric cancer was found in 36.0% of the younger patients with gastric cancers and in 36.3% of the older patients with those. The gender ratio of m/f was 1.21 for the younger patients and 2.37 for the older patients. The macroscopic characteristics of early gastric cancer for the younger patients were superficial depressed lesions and a larger tumor size. The distinguished histologic features of early gastric cancer for the younger patients were a diffuse type of cancer and infiltrative tumor growth with a scirrhous stroma. More extensive lymph node dissection was performed on the younger patients than on the older patients. The younger patients had a prognosis similar to that of the older patients. We conclude that early gastric cancer in young patients possesses histological aggressiveness, but those patients rather show a similar survival to older patients.
In isovaleric acidemia (IVA), accumulated isovaleryl-CoA in the mitochondrion induces variable metabolic disturbances. To remove intramitochondrial isovaleryl groups, glycine therapy has been advocated primarily. On the other hand, secondary carnitine deficiency has been documented in this disorder and carnitine supplementation alone has been reported to be effective. In the present study, we administered carnitine and glycine to patients with IVA, and investigated serum carnitine and urinary excretion of total and free carnitine, acylcarnitine profile (i.e., isovalerylcarnitine and acetylcarnitine), and isovalerylglycine. By adding carnitine to glycine supplementation, more isovalerylglycine, not only isovalerylcarnitine, was excreted in the urine. Acetylcarnitine was detected in the urine only when sufficient carnitine was supplemented. We concluded that combined therapy of glycine and carnitine is more effective and safer to eliminate isovaleryl-CoA in IVA than conventional therapy using either glycine or carnitine. Urinary acetylcarnitine concentration might be a good marker indicating the optimal dose of L-carnitine supplementation.
Using a quantitative culture of sputum, the incidence of pathogenic bacteria in respiratory infection in our laboratory between 1990 and 1993 were investigated. While Haemophilus influenzae, Streptococcus pneumoniae and Moraxella (Branhamella) catarrhalis were isolated at high rates (67∼78%) from the specimens of outpatients throughout the study period, the incidence of S. pneumoniae has increased gradually. The antimicrobial susceptibilities of these three pathogens were examined with the agar dilution method. A marked increase of penicillin (PC) resistant S. pneumoniae (MIC≥0.1 μg/ml) was observed with a resistance rate of 2.1% in 1990 and 25% in 1993. Resistance to erythromycin (EM, MIC≥1.56 μg/ml) was 8.5% in 1990 but then increased to 34% in 1992. Most of the PC resistant isolates were resistant to multidrugs such as EM, minocycline and clindamycin. The MICs of all β-lactams examined for S. pneumoniae increased along with the MICs of PC, though the level varied between drugs. The rates of β-lactamase positive H. influenzae gradually decreased, being 14.3% in 1990 and 7.4% in 1993, whereas those of M. (B) catarrhalis were consistently high (>90%) every year. In addition to β-lactamase production, the emergence of strains of H. influenzae and M. (B) catarrhalis resistant to new quinolone drugs should be noted.
Bilateral adrenal aldosterone-producing adenomas (APA) are rare. It is important to distinguish bilateral APA from idiopathic hyperaldosteronism (IHA), which is due to bilateral hyperplasia of the adrenal cortex. We present two patients with bilateral APA in whom the diagnosis was made histochemically by analyzing steroidogenic enzymes. They showed hypokalemia, high plasma aldosterone concentration (PAC) and suppressed plasma renin activity (PRA). Bilateral adrenal tumors were represented by computed tomography, and surgical resection was performed. In both cases, cytochrome P-450 and other enzymes that were involved in aldosterone synthesis were found mainly in tumor, but little in the zona glomerulosa of the adjacent adrenals, which showed paradoxical hyperplasia. Such cases are difficult to distinguish from IHA. The two disorders were differentiated by immunohistochemical analysis of steroidogenic enzymes.
To study the fine structure of fragmentary marker chromosomes, we performed scanning electron microscopy (SEM) on samples isolated from two carriers (Case 1: 46, XY/47, XY, +mar/48, XY, +mar, +mar; Case 2: 47, XY, +mar). In both cases, light microscopic observation revealed that marker chromosomes lacked a centromere and were fragmented in appearance. However, SEM observation of the metaphasic cells in both cases showed three variations. One variation was a structure that seemed to be metacentric, another was a structure that seemed to be submetacentric, and the remaining one was essentially fragmentary. However, neither the usual chromatid nor centromere formations were observed in the metacentric-like and submetacentric-like structures, even when both cases were observed by SEM. Moreover, the marker chromosomes of the boy of Case 1, who suffered from various clinical troubles, included a greater population of metacentric-like or submetacentric-like structures than of essentially fragmentary structures. The marker chromosomes of the fetus of Case 2, who suffered from no clinical problems, included a much greater population of essentially fragmentary structures than metacentric-like or submetacentric like structures. Therefore, SEM observation of fragmentary marker chromosomes that are visible on light microscopy might be used to define specific structures. Moreover, SEM observation might provide clinical criteria relating to the pathogenesis of fragmentary marker chromosomes found on light microscopy.