SEKIZAWA, K. Enzymatic Modulation of Bronchoconstriction, Gland Secretion, Plasma Extravasation and Cough. Tohoku J. Exp. Med., 1994, 172 (4), 295-315 This review describes novel aspects of enzymes in the pertinent tissues of the airway and those associated with inflammatory cells. These include neutral endopeptidase, histamine N-methyltransferase, mast cell and neutrophil enzymes which have a potentially important role in the modulation of several airway functions such as bronchoconstriction, gland secretion, plasma extravasation and cough. Thus, regulation of enzyme activities in the airways may have new therapeutic implications in inflammatory diseases of airways
SATO, K. and BYERS, P.D. Histomorphometric Study of IntratrabecularOsteons in the Iliac Bone in Three Metabolic Bone Diseases. Tohoku J. Exp. Med., 1994, 172 (4), 317-326-Full-thickness biopsy specimens of iliac bones were submitted to morphometric analysis of intratrabecular osteons to study whether and how much the number and density of osteons increase in some metabolic bone diseases such as osteomalacia (OM), primary hyperparathyroidism (PHPT) and renal osteodystrophy (ROD). The biopsies were taken from 16 patients with OM of various causes, 18 with PHPT, 12 with ROD, and from 41 control cases. All the specimens were methacrylate-embedded, sectioned undecalcified and stained with solochrome cyanine or HE. Morphometry included measurements of the density of osteons and the volume of bone and osteoid, partially assisted with a semiautomatic digital image analyzer. Intratrabecular osteons were found to be more numerous in patients with metabolic disorder than in control. It was shown by discriminant analysis that the elevated number of osteons/cm2 tissue area contributes to the differentiation of abnormal from normal bones. The presence of blood vessels in the osteons indicated the biological significance of osteon formation which extends the metabolic surface of trabeculae, providing a basis for trabecular hypertrophy.
YOSHIDA, M. and ASANO, M. Direct Compression by MegadolichobasilarAnomaly as a Cause of Trigeminal Neuralgia, A Case Diagnosed by MRI. Tohoku J. Exp. Med., 1994, 172 (4), 327-332 A 49 year-old man with trigeminal neuralgia caused by megadolichobasilar anomaly was described. The patient having neuralgic attacks in the second branch of the right trigeminal nerve for two and a half years showed the angiographic evidence of a tortuous and elongated vertebrobasilar artery and MRI of the brain clearly visualized the root entry zone of the nerve having been compressed by the main trunk of ectatic basilar artery. Cases of trigeminal neuralgia due to the compression by the basilar artery itself have been rarely described previously. In order to evaluate trigeminal neuralgia, MRI is essential to determine the relationship of the involvedsite of nerve to the pathogenic artery.
KOJIMA, M., SAITOH, M., ITOH, H., UKIMURA, O., OHE, H. and WATANABE, H. Percutaneous Biopsy for Adrenal Tumors Using Ultrasonically Guided Puncture. Tohoku J. Exp. Med., 1994, 172 (4), 333-343-Percutaneous biopsy for adrenal tumors was performed on 12 patients using ultrasonically guided puncture. Of the 12 tumors, 11 were detected incidentally by ultrasonography or computed tomography. In 11 cases, cytological or pathological diagnosis was obtained without any complication. Among these, surgical operation was carried out in 4 cases, in which biopsy findings were confirmed by the examination of the surgical specimens. The other 7 cases were being followed up without surgery. The rate of correct discrimination between benign and malignant adrenal tumors by biopsy was 91% (10/11 cases) in this series. It is accordingly considered that adrenal biopsy is the first choice to confirm the diagnosis of nonfunctioning adrenal tumors because of itsefficacy and ease of use.
WANG, J., MASUKO, T., UENO, H., HOJO, H. and HASHIMOTO, Y. Derivationand Application of Monoclonal Antibodies Recognizing Several Epitopes on BovineSerum Albumin. Tohoku J. Exp. Med., 1994, 172 (4), 345-353-Three (AB-3, AB-4 and AB-6) monoclonal antibodies (mAb) to bovine serum albumin (BSA) were derived and characterized for their physicochemical and immunological properties. AB-3 recognized an epitope distinct from epitopes recognized by AB-4 and AB-6 as determined by binding inhibition assay. AB-4 and AB-6 mAbs recognized similar but not identical epitopes on BSA. Based on the antigenic specificity, we applied these mAbs to quantitative analysis of BSA in medium and to depletion of BSA from culture medium containing fetal calf serum (FCS). For quantitative analysis, we employed a sandwich enzyme-linked immunosorbent assay (ELISA) using biotinylated AB-3, solid-phase of AB-6 and an avidin-biotin-peroxidase complex system. This assay was highly sensitive and quantitative in the range of BSA concentration at 10 to 1, 500ng/ml. To deplete BSA from medium, we prepared affinity-gel coupled to AB-6. Repeated treatment of FCS-containing medium with the affinity-gel efficiently depleted BSA from the medium. The depletion capacity was 0.74 to 1.0 moles of BSA/mole of coupled mAb.
ABE, S., YAMAZAKI, K., TAKIKAWA, S. and SUZUKI, K. Impaired BiliaryExcretion of Copper and Lysosomal Enzymes in Long-Evans Cinnamon Rat. Tohoku J. Exp. Med., 1994, 172 (4), 355-367-Although impaired biliary excretion of copper through hepatocyte lysosomes has been postulated as a pathogenesis of Wilson's disease, direct evidence has been lacking. Our aim was to investigate the dynamics of biliary excretion of copper and lysosomal enzymes in the Long-Evans Cinnamon (LEC) rat, a recently established rodent model of Wilson's disease. Liver homogenate and bile were obtained from 12 week-old LEC rats (n=7), Long-Evans Agouti rats (n=3) and Sprague-Dawley rats (n=8) and analyzed for copper and lysosomal enzymes. Structural integrity of hepatic lysosomes was assessed by the latency of N-acetyl-β-glucosaminidase. Compared with the controls, LEC rats exhibited a 43-fold increase in hepatic copper concentration (p<0.001), a signficant increase in hepatic activities of lysosomal enzymes (p<0.001) and reduction of lysosomal latency (p<0.05). In contrast, biliary excretion of copper and lysosomal enzymes were significantly impaired in LEC rats (p<0.05). These results suggest a coupled alteration between copper and lysosomal enzymes in both the liver and bile of LEC rats (i.e., increase in liver and decrease in bile). Defective biliary excretion of copper via hepatocyte lysosomes may play a role in part in spontaneous copper accumulation in LEC rats.
ONUMA, T., TSUTSUI, M., UEHARA, O., MASUDA, M., KIKUCHI, T., ISHIGAME, M., SUZUKI, K. and TAKEBE, K. Clinical Characteristics in Non-Insulin-DependentDiabetic Patients with Long Duration in Japan-Relation to Risk Factors forVascular Complications. Tohoku J. Exp. Med., 1994, 172 (4), 369-374-In this study, we evaluated the control state of body weight, blood pressure, and blood glucose during the recent 10 years in 82 patients of non-insulin-dependent diabetes mellitus (NIDDM) who had long duration of diabetes for 20-25 years without ischemic heart disease (IHD) and diabetic nephropathy (Neph). The patients without either IHD or Neph showed significantly lower incidences of obese (11 vs. 40%, p<0.05), hypertensive (0 vs. 20%, p<0.05) and poor glycemic control state (7 vs. 27%, p<0.05) for 10 years than the patients with IHD alone, and showed significantly lower incidences of hypertensive (0 vs. 20%, p<0.05) and poor glycemic control state (7 vs. 33%, p<0.01) than the patients with Neph alone. The control state of body weight was similar between the patients without either IHD or Neph and with Neph alone. In addition, the patients without either IHD or Neph showed significantly lower incidences of obese (11 vs. 56%, p<0.01) and hypertensive control state (0 vs. 40%, p<0.01) for 10 years than the patients with both IHD and Neph. The control state of blood glucose was similar between the two groups. These results suggest that for long survival of NIDDM patients without development or progression of IHD and Neph, non-obese and non-hypertensive state as well as good glycemic control should be maintained for long time.
YAMASHITA, H., NAKANISHI, K., TAJIMA, F., SATO, Y., KIZAKI, T., OH-ISHI, S. and OHNO, H. Chronic Exposure to Simulated Altitude Does Not Increase AngiogenicActivity in Skeletal Muscle of Rats. Tohoku J. Exp. Med., 1994, 172 (4), 375-379-In order to examine whether the hypoxia of high altitude increases angiogenic activity in skeletal muscle, six male Wistar rats were subjected to a simulated altitude of about 5, 500 m (ambient pressure 380 mmHg) for 3 weeks, and the whole soleus, gastrocnemius, and extensor digitorum longus muscles were collected. As a result, any muscle extracts from high altitude rats did not significantly enhance the capillary growth in an in vitro angiogenesis model compared with those from sea-level rats. This appeared to confirm previous morphological studies that hypobaric-hypoxic environment did not cause the formation of new capillaries in skeletal muscles.
KONDO, S., MORITA, T. and TASHIMA, Y. Endothelin Receptor Density inHuman Hypertrophic and Non-Hypertrophic Prostate Tissue. Tohoku J. Exp. Med., 1994, 172 (4), 381-384-The amount of endothelin receptors in human prostate tissue was measured by radioligand binding techniques using 125I-Endothelin -1 and -3 (125I-ET-1, -3). Specimens of the non-hypertrophy group were obtained from 6 patients who underwent total cystectomy under the diagnosis of bladder cancer and those of the hypertrophy group from 6 prostatic hypertrophy patients who underwent open prostatectomy. 125I-ET-1 bound to the prostate tissue with the KD value of 0.033±0.012nM in the non-hypertrophy group and with the KD value of 0.035±0.012nM in the hypertrophy group. 125I-ET-3 bound to the prostate tissue with the KD value of 0.023±0.011nM in the non-hypertrophy group and with the KD value of 0.029±0.016nM in the hypertrophy group. The RD values were not significantly different between the hypertrophy and non-hypertrophy groups. The KD values of 125I-ET-1 and 125I-ET-3 were similar. The Bmax values (fmol/mg protein) of 125I-ET-1 binding to the prostate tissue were 32.18±3.69 to the non-hypertrophy group and 85.66±20.65 to the hypertrophy group. The Bmax values (fmol/mg protein) of 125I-ET-3 binding to the prostate tissue were 27.48±5.25 to the non-hypertrophy group and 75.90±13.46 to the hypertrophy group. The Bmax values of both 125I-ET-1 and 125I-ET-3 were significantly higher in the hypertrophy group than in the non-hypertrophy group. Benign prostatic hypertrophy was found to increase the density of endothelin receptors in human prostate tissue, suggesting that endothelins modulate the pathophysiology of benign prostatic hypertrophy.
OKUYAMA, S., SUzuKI, Y, and KATO, M. Cisplatin Pasting for Radiotherapyof Penile Cancer. Tohoku J. Exp. Med., 1994, 172 (4), 385-387-A case of penile cancer (Jackson's stage II) was treated with cisplatin pasta along with radiotherapy. The cancerous masses dissolved by the time of 27 Gy (913 ret) of radiotherapy, and the initial plan of penile amputation was abandoned. This cisplatin pasting would probably be a useful technique in radiotherapy of penile cancer, preserving the function of the organ
KUWANO, A, IKEDA, H., TAKEDA, K., NAKAI, H., KONDO, I. and SHIBAHARA, S. Mapping of the Human Gene for Inducible Heme Oxygenase to Chromosome22q12. Tohoku J. Exp. Med., 1994, 172 (4), 389-392-Heme oxygenase is an essential enzyme in heme catabolism that cleaves heme to form biliverdin, releasing carbon monoxide and iron. There are two isozymes of heme oxygenase: heme oxygenase 1 (HO-1) and heme oxygenase 2, each of which is encoded by a separate gene. It is noteworthy that HO-1 is Inducible by various environmental factors, while heme oxygenase 2 is not. Here we have localized the human HO-1 gene to chromosome 22 by polymerase chain reaction (PCR) analysis of human-hamster somatic cell hybrids. The precise region of the HO-1 locus was then determined by fluorescence in situ hybridization, revealing that the human HO-1 gene is localized to 22q12.