MIURA, K., ITOH, Y., KADOWAKI, Y., KAGAYA, M., SASAKI, M., SHIOYA, T. and MIURA, M. Reaction of Mononuclear Cells from Patients with Bronchial Asthmato Candida albicans. Tohoku J. Exp. Med., 1991, 164 (1), 1-12-This study was undertaken to investigate cytokine production of mononuclear cells (MNCs) from patients with bronchial asthma stimulated by antigens of Candida albicans in vitro. The reaction of MNCs from corticosteroid-dependent patients was restricted to a low level. The level of tumor necrosis factor (TNF)-α released into the culture fluid was significantly higher in the high responders (HR) of the atopic corticosteroid-independent (A-CSID) group than those of other asthmatic and control groups (p<0.01). The level of IL-1β of the A-CSID group was significantly higher than that of the non-atopic corticosteroid-independent group (p<0.05), but not significantly different from the controls. In HR of the A-CSID group, the production of TNF-α and IL-1β was augmented and interferon-γ production was also increased in these patients. These results suggest that Candida albicans can contribute to the augmentation of cytokine production in bronchial asthma, especially in some of atopic type.
YOSHIDA, M., SATOH, H., KOJIMA, S. and YAMAMURA, Y. MetallothioneinConcentrations and Organ Retention of Mercury in the Liver and Kidney of theNeonatal Guinea Pig after Exposure to Mercury Vapor. Tohoku J. Exp. Med., 1991, 164 (1), 13-22-Neonatal guinea pigs were exposed to mercury vapor on the day of birth, and the following mercury distribution and concentrations of metallothioneins (MTs) in the liver and kidney were observed. In the liver, two hours after exposure, an appreciable amount of mercury accumulated and a substantial portion of this was associated with MTs. During postnatal development, the mercury concentration increased, whereas the hepatic concentration of MTs decreased. The mercury in the soluble fraction of the liver shifted from the region of MTs to the high-molecular-weight region and, finally, the mercury peak in the MT region was not detected. The kidney mercury concentration was high even 2hr after the exposure and on days 3 and 7 postpartum. The peak concentration was observed on day 3 postpartum. The mean renal concentration of MTs in the mercury-exposed neonates was significantly higher than that of the control at all times observed. The changes in both the mercury level and the concentration of MTs were strongly correlated. Furthermore, most mercury in the soluble fraction was associated with MTs on day 7. These findings indicated enhanced synthesis of MTs in the kidney, but not in the liver, after mercury vapor exposure in the neonatal period, with corresponding elevated copper and zinc concentrations in the kidney.
SOFIKITIS, N., MIYAGAWA, I., TODA, T., HARADA, T., MIO, Y. and TERAKAWA, N. The Effect of Kallikrein on Human Sperm Membrane Function. Tohoku J. Exp. Med., 1991, 164 (1), 23-28-To illustrate the influence of kallikrein on the hypoosmotic swelling test, 84 human semen samples were classified into 4 groups: normospermia (n=34, group A), oligospermia (n=18, group B), asthenospermia (n=8, group C), and oligoasthenospermia (n=24, group D). Two aliquots of 0.45 ml were prepared from each specimen in all the groups: one was incubated for 3 hr in a glass tube containing kallikrein and the other was incubated without kallikrein (control). Quantitative and qualitative assessment of sperm motility and the hypoosmotic swelling test (HOST) were subsequently performed in each pair of samples. Percentage of motile spermatozoa, speed of forward progression of motile spermatozoa and the percentage of swollen sperm were significantly lower in the control samples than in samples treated with kallikrein in all the groups. Kallikrein was also proved effective in increasing the outcome of the HOST, the percentage of motile spermatozoa and the speed of forward progression of washed spermatozoa received from normospermic men (n=15). It seems that kallikrein has a direct effect on sperm membrane and improves its properties and functions.
SAITO, H., WATANABE, K., SAHARA, M., MOCHIZUKI, R., EDO, K, and OHYAMA, Y. Triethylene-Tetramine (Trien) Therapy for Wilson's Disease. Tohoku J. Exp. Med., 1991, 164 (1), 29-35-Triethylene tetramine (trien), in increasing dose from 1.0-2.0g/day to 2.5-3.0g/day, was used for 4 Japanese patients with Wilson's disease who were intolerant of D-penicillamine (D-PC). Before the treatment, urinary copper excretion (UCE) was 70-96μg/day. UCE increased to 1, 512-2, 352μg/day on the day of initial administration, and remained at levels between 350-1, 100μg/day, thereafter. During 2 months of trien therapy, neurological deficits regressed in three patients, and only slightly in one patient. No adverse effects were observed. These results and the retrospective survey on 17 patients treated with D-PC confirmed that trien is less potent but a safer copper chelating agent than D-PC. The transient aggravation of neurological deficitsseen in two patients during the early stage of the treatment suggested that trien, as D-PC, should be started in small doses and gradually increased.
SUZUKI, O., NAKAMURA, M., MIYASAKA, Y., KAGAYAMA, M. and SAKURAI, M. Bone Formation on Synthetic Precursors of Hydroxyapatite. Tohoku J. Exp. Med., 1991, 164 (1), 37-50-The aim of this study was to investigate the reaction of skeletal tissue to various synthetic calcium phosphate (Ca-P) compounds in vivo.Five synthetic Ca-P compounds were implanted into the subperiosteal area of the calvaria of 7-week-old BALB/c mice for one to 15 weeks. Synthetic compounds were dicalcium phosphate (DCP), octacalcium phosphate (OCP), amorphous calcium phosphate (ACP), Ca-deficient hydroxyapatile and hydroxyapatile (HA). Implanted DCP, OCP and ACP were found to be converted to apatitic phase by x-ray microdiffraction analysis using undecalcified specimens. Structure of bone was found out on all of Ca-P compounds eventually at late stage under the light microscope, but the rate of bone formation calculated from a number of experiments varied on respective synthetic Ca-P compound. It was high as 80% for DCP, OCP and ACP, but was low as 5.6% for Ca-deficient HA, and no reaction was found for HA at the stage of 3 weeks. Fine filaments and granular materials in the newly formed bone matrix were detected at 7 days around the remnants of OCP particles which already converted to apatitic phase by ultrastructural study of decalcified specimens. These structures were very similar to the components of bone nodules seen in intramembranous osteogenesis. It is postulated that the precursors of HA have an important role in intramembranous osteogenesis.
KAKIZAKI, K. and YAMAUCHI, H. Simultaneous Analysis of the Patterns ofNuclear DNA and Cell Protein Contents in Pancreatic Carcinoma with Referenceto Prognosis. Tohoku J. Exp. Med., 1991, 164 (1), 51-58-Simultaneous analysis of the patterns of nuclear DNA and cell protein contents was performed in 13 patients with pancreatic carcinoma to evaluate their prognostic significance. The patients were divided into two groups according to clinical outcome. Namely, six died of the primary disease within one year (group A), and six survived longer than 16 months and one died of other cause (liver abscess) at 9 months after operation (group B). The cell suspensions prepared from paraffin-embedded specimens were stained with diamidino-phenylindole and hematoporphyrin for nuclear DNA and cell protein, respectively. Fluorescence intensities of 20 lymphocytes as control and 200 carcinoma cells of each case were measured. The nuclear DNA pattern was mainly diploid or tetraploid in group B. Group A showed aneuploid and polyploid patterns. Furthermore, mean DNA content of group A was significantly higher than that of group B. Cell protein content was widely scattered and higher in group A than group B. Analysis of nuclear DNA ploidy, relative value of DNA and cell protein content may be a reliable tool to predict prognosis of patients with carcinoma of the pancreas.
OHARA, T., OGATA, H. and TEZUKA, F. Histological Study of PulmonaryVasculature in Fatal Cases of Persistent Pulmonary Hypertension of the Newborn. Tohoku J. Exp. Med., 1991, 164 (1), 59-66-Using our own morphometric technique, we examined pulmonary vasculature in eight neonates who died of persistent pulmonary hypertension of the newborn (PPHN). PPHN was judged to be idiopathic in three neonates and was associated with fatal meconium aspiration in the other five. Two characteristic structural features of PPHN were revealed in this study. First, medial thickening of the normally fully-muscularized pulmonary vessels occurred in the smaller and more peripherally located arteries. Second, fully-muscularized vessels extended as far as the intraacinar arteries, which are normally non-muscular vesseles at this age. This structural abnormality appears not to merely represent a failure of the fetal pattern to regress, and it is suggested that PPHN is due to a structural abnormality of the pulmonary microcirculation in fatal cases.
OHARA, T., OGATA, H. and TEZUKA, F. Effects of Indomethacin in Utero onthe Pulmonary Vasculature of the Newborn Lambs. Tohoku J. Exp. Med., 1991, 164 (1), 67-79-Exposure of the fetus to indomethacin and the resultant closure of the ductus arteriosus in utero has been suggested to be one possible cause of persistent pulmonary hypertension of the newborn (PPHN). We examined whether or not closing the ductus arteriosus of fetal lambs by the administration of in-domethacin to the fetus and ewe could produce the functional and structural changes of PPHN. Three treated and four non-treated lambs were delivered by cesarean section. Postnatal hemodynamics were studied in two of the treated lambs. Pulmonary arterial pressure gradually decreased after delivery and did not reveal features compatible with PPHN, while the blood gases remained within the physiological range. However, acute hypoxemia produced a re-elevation in pulmonary arterial pressure. Morphometric analysis showed the medial thickening of normally fully-muscularized pulmonary arteries, but there was no abnormal extension of fully-muscularized arteries to the intraacinar level in the treated lambs. In conclusion, we could not reproduce functional and structural changes of PPHN in newborn lambs by the administration of indomethacin in utero. However, our experimental animal model with excessive muscularization of the pulmonary vasculature appears to be useful for studying vasoconstriction in response to hypoxemia.
TSAI, J., KOBARI, M., TAKEDA, K., MIYASHITA, E., RAHMAN, M.M, and MATSUNO, S. Changes of Duodenal pH and Pancreatic Exocrine Function afterUpper G-I Intraluminal Ethanol Administration. Tohoku J. Exp. Med., 1991, 164 (1), 81-91-Using 3 outbred dogs with pancreatic, gastric and jejunal fistulas, we examined changes in pancreatic exocrine secretion, duodenal pH and plasma CCK concentration after intragastric or intrajejunal administration of ethanol. Intragastric administration of 20% or 40% ethanol significantly lowered the pH in the duodenal cavity, and pancreatic fluid secretion and bicarbonate excretion were stimulated. Intrajejunal administration of ethanol elicited stronger responses. Plasma CCK concentration was not changed or was only slightly lowered by ethanol administration in the digestive tract. It is assumed that stimulation of pancreatic exocrine secretion was mediated by the secretion of gastric acid.