Collagen abnormalities in the spinal cord from patients with amyotrophic lateral sclerosis

During the last 10 years, we have demonstrated morphological and biochemical abnormalities of skin extracellular matrices in amyotrophic lateral sclerosis (ALS). However, currently little is known concerning collagen of the spinal cord in ALS. We measured the amount of collagen and characterized collagen at light and electron microscopic levels in posterior funiculus, posterior half of lateral funiculus and anterior horn of cervical enlargement of the spinal cord obtained from ten patients with ALS, 11 patients with other neurologic diseases (control group A), and ten patients without neurologic ones (control group B). In posterior half of lateral funiculus and anterior horn, (1) by light microscopy, there was no significant difference in vessel wall area between ALS patients and control groups A and B; (2) ultrastructurally, collagen bundles were more fragmented and widely separated, and the fibrils were randomly oriented in the perivascular space of capillaries in ALS patients, which were not observed in any areas of control groups or in posterior funiculus of ALS patients; and (3) the collagen contents in ALS were significantly lower (P<0.001 and P<0.001, respectively) than those in control groups A and B. Fragmented and widely separated collagen bundles in the interstitial tissue surrounding capillaries and markedly decreased amount of collagen in posterior half of lateral funiculus and in anterior horn of ALS could be related to the degeneration of the upper and lower motor neurons in the spinal cord in ALS, that is, selective neuronal vulnerability in ALS.     

A case of serous cystadenoma of the pancreas with focal malignant changes

Summary We present a serous cystadenoma of the pancreas with focal malignant changes, and describe its characteristic histological features. On gross examination, a tumor was present on the anterior surface of the body of the pancreas and measured approx 25×25⋻20, mm. Microscopically, most tumor cells showed the typical histological features of serous cystadenoma, characterized by a microcystic architecture and glycogenrich cells with a uniform and bland appearance. However, in some areas, a tendency to papillary structures with fibrovascular cores was noted. These papillary lesions were composed mainly of nonmucinous, glycogen-poor epithelial cells, the nuclei of which showed a mild atypia. In addition, vascular and perivascular invasion was focally observed. However, there was no clinical evidence of local or distant metastasis. From these findings, we diagnosed this lesion as a serous cystadenoma of the pancreas with focal malignant changes rather than a serous cystadenocarcinoma of the pancreas.     

Detection of platelet-activating factor in exudates of rats with phorbol myristate acetate-induced pleurisy

PAF-likely activity, detected as aggregation of washed platelets, was found in the exudate of rats with pleurisy induced by phorbol myristate acetate (PMA, 1 nmol). At 30 min after the injection of PMA, 400-500 pg of PAF was detected in the pleural exudate. An extract of the exudate was made and analysed by HPLC and by rabbit platelet aggregation. The activity was characterized as that of PAF as a result of the inhibition seen with the PAF-antagonist CV-3988 and the loss of activity by treatment with phospholipase A2. Indirect evidence was previously reported in that CV-3988 suppressed the pleural fluid accumulation in the pleurisy induced by PMA. Taken together these facts it indicates that PAF could be an important mediator of acute inflammation, especially of the plasma exudation resulting from an increase in vascular permeability. Evidence that pleural cells produce PAF was also examined in an in vitro experiment. PAF was found in the supernatant and cellular fractions of the incubation mixture of the pleural cells from normal rats when stimulated by PMA (1 microM) or A23187 (5 microM), and the results indicate that the pleural cells produce PAF and release a portion of it.     

A new method to induce topical cooling of the right atrium for treatment of supraventricular tachyarrhythmia: an experimental study

Supraventricular tachyarrhythmia (SVT) such as sinus tachycardia and atrial dysrhythmia is a life-threatening problem in the period immediately following an open-heart operation. Because of their negative inotropic effects, antiarrhythmic agents are not recommended for patients with low cardiac output syndrome. A device was developed that topically cools the right atrial surface for antiarrhythmic treatment. In experiments, this device lowered right atrial temperature and did not affect the temperature of the right ventricle or the whole body. When right atrial temperature decreased from 37 degrees to 28 degrees C, heart rate was reduced from 146.3 to 109.7 beats per minute (p less than .001). Meanwhile, cardiac output and blood pressure remained within control levels. In the treatment of experimental SVT induced by the intravenous infusion of isoproterenol hydrochloride and by direct application of aconitine, this method worked effectively and was reproducible. The results demonstrated the beneficial effects of this method in the treatment of SVT in experimental studies and suggested its future clinical application following open-heart operations.     

EPIDEMIOLOGICAL CHARACTERISTICS OF PROSTATE CANCER IN GUNMA PREFECTURE, JAPAN

Background Prostate cancer is rare in Asia, but the number of patients is increasing in Japan. We conducted an epidemiological study of prostate cancer in Gunma Prefecture, Japan, to investigate the trends and characteristics of the disease.
Methods: The subjects were 1.411 prostate cancer patients newly diagnosed between 1985 and and 656 patients who died from prostate cancer between 1981 and 1992. The incidence and mortality rates were calculated by year, demographic region and age.
Results: The yearly incidence rate showed an increase but the mortality rate showed no marked fluctuations. There was no significant difference between urban and ruraI districts in either incidence or mortality rate. The incidence rate tended to be high in the northern part of the prefecture, but no marked variation in mortality rate was seen. The incidence and mortality rates in districts with a history of manganese mining were high compared to those in districts without mining. In contrast, the incidence and mortality rates in districts with a history of zinc mining were comparatively lower. Both incidence and mortality rates showed a marked increase with age. The age-specific incidence showed a double logarithmic relationship to age.
Conclusions: The increase of the yearly incidence rate might be due to changes in lifestyle and environmental factors, improved diagnostic techniques, and increased awareness among the general public regarding prostate disease. Further investigation is needed to clarify the pattern and the causes of regional differences in the incidence and mortality rates. The possibilities that manganese and zinc might be related to prostatic carcinogenesis are suggested. Int J Urol 1995:2:191–197     

Human leukocyte antigens in Fisher's syundrome

We performed human leukocyte antigens(HLA)typing for class I antigens on 19 Japanese patients with Fisher's syndrome. We demonstrated a statistically significant association between the disease and the HLA-B39 antigen.     

Clinical similarities of hereditary progressive/dopa responsive dystonia caused by different types of mutations in the GTP cyclohydrolase I gene

OBJECTIVE—Hereditary progressive dystonia withpronounced diurnal fluctuation ((HPD)/dopa responsive dystonia (DRD))is a childhood onset dystonia which responds to levodopa. Variousclinical signs and symptoms of HPD/DRD have been recognised to date.Mutations in the GTP cyclohydrolase I (GTP-CH-I) gene were recentlyidentified as the cause of HPD/DRD. In the present study, the GTP-CH-Igene and the clinical features of eight HPD/DRD patients from sixfamilies were analysed to determine the correlationsbetween clinical expression and the mutations in the GTP-CH-I gene.
METHODS—The exons, exon-intron junctions, and anindispensable part of the 5' flanking region of the GTP-CH-I gene weresequenced in the eight clinically diagnosed patients with HPD/DRD andtheir asymptomatic parents.
RESULTS—Three independent mutations in theGTP-CH-I gene were found in three patients. One of the patients and herasymptomatic mother were heterozygous for a novel mutation at theinitiation codon. The three patients with dissimilar GTP-CH-I mutationsexhibited similar clinical features. The other five patients withnormal sequences presented several features not manifested by the three patients with the mutations. No mutation was found in the 5' flanking region of any patients or their parents.
CONCLUSIONS—A novel initiation codon mutation wasfound in a Japanese patient with HPD/DRD. The clinical manifestationscommon to the patients with HPD/DRD with a mutated GTP-CH-I gene werealso identified. Although focal manifestations of HPD/DRD associatedwith the mutations of this gene will be broadened, it is inferred thatthese clinical features are fundamental to HPD/DRD caused by mutationsin this gene.

     

Expression of intercellular adhesion molecule-1 on transitional cell cancer. Possible significance in immunity against tumor cells.

Immunohistochemical examination demonstrated expression of intercellular adhesion molecule-1 (ICAM-1) on 17 of 44 transitional cell cancers (TCCs) but not on normal transitional cells. ICAM-1 was frequently expressed in higher stage tumors, especially in those with abundant immune cells scattered within tumor. Analysis of infiltrating immune cells showed that they were composed mainly of T lymphocytes and a smaller number of macrophages bearing the lymphocyte function-associated antigen-1 (LFA-1). Expression of ICAM-1 on transitional cell cancer cell lines was augmented by in vitro treatment with interferon-gamma, tumor necrosis factor-alpha, and interleukin-1 beta. Furthermore, Northern blot analysis revealed higher quantities of a 3.3-kb RNA in T24 cells exposed to interferon-gamma or tumor necrosis factor-alpha. These results suggest that the expression of ICAM-1 on transitional cell cancers might be modified by cytokines produced by infiltrating immune cells, which might facilitate immune responses against cancer cells.