TOMURA, K., KANG, H., MITAMURA, K., TAKEI, M., KARASAKI, M., KOYASU, S. and SAWADA, S. IL-2 Enhancing Factor(s) in B Cell Supernatants from Patientswith Rheumatoid Arthritis or Systemic Lupus Erythematosus. Tohoku J. Exp. Med., 1989, 159 (3), 171-183- Culture supernatants of B cells from patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) in the active stage enhanced interleukin 2 (IL-2) dependent proliferation of CTLL A/J cells. This activity, designated B cell-derived growth-enhancing factor-2 (BGEF-2), was recovered by gel filtration of a molecular weight between 15, 000 and 20, 000. BGEF-2 itself did not show IL-2 activity nor IL-1 activity, and BGEF-2 activity was not detected in the following cytokines: Interferon-α (IFN-α), interferon-γ (IFN-γ), tumor necrosis factor (TNF), interleukin 4 (IL-4), interleukin 5 (IL-5) and interleukin 6 (IL-6). Furthermore, BGEF-2 was distinguishable from B cell-derived growth-enhancing factor described in a previous paper [Kang et al. (1987) J. Immunol., 139, 1154-1160]. BGEF-2 was produced by B cells from patients with RA or SLE only when the patients were in the active stage. BGEF-2 enhanced IL-2-dependent growth of peripheral blood T cells from patients with active RA, but did not enhance the growth of T cells from healthy voluteers. These results suggest that BGEF-2 is a B cell-derived lymphokine which plays an important role in the pathogenesis of RA and SLE.
MINAMI, N., IMAI, Y., ABE, K., MUNAKATA, M., SAKURADA, T., YAMAMOTO, M., YOSHIDA, K., SEKINO, H. and YOSHINAGA, K. The Circadian Variation of BloodPressure and Heart Rate in Patients with Hyperthyroidism. Tohoku J. Exp. Med., 1989, 159 (3), 185-193-The circadian variation of blood pressure (BP) and heart rate (HR) was examined in 18 normal subjects, 15 patients with essential hypertension treated with β-blockers and 21 patients with hyperthyroidism. Most of the patients with hyperthyroidism were also treated with β-blockers. The 24 hr BP was measured with an ambulatory blood pressure monitoring device (UBP-100) every 5min. A nocturnal fall in BP and HR was observed in the patients with essential hypertension treated with β-blockers and the patients with mild to moderate hyperthyroidism as well as normal subjects. On the other hand, in patients with severe hyperthyroidism the nocturnal fall was observed in HR alone, and the fall was small in its amplitude. There was a significant negative correlation between triiodothyronine (T3) level and percentage amplitude of the nocturnal fall in systolic BP (n=21, r=-0.5, p<0.01). However, this relation was not significant in diastolic BP and HR. These results indicate that excess thyroid hormone may modulate the circadian variation of BP and HR.
IINUMA, K., HAGINOYA, K., HANDA, I., KOJIMA, A., FUEKI, N., AIKAWA, J., ITO, M., HATAZAWA, J. and IDO, T. Computed Tomography, Magnetic ResonanceImaging, Positron Emission Tomography and Evoked Potentials at Early Stage ofAdrenoleukodystrophy. Tohoku J. Exp. Med., 1989, 159(3), 195-203- An 8 year-old-boy with adrenoleukodystrophy (ALD) was subject to an x-ray computed tomography (CT) scan, magnetic resonance imaging (MRI), positron emission tomography (PET) using 18F-fluorodeoxy glucose and evoked potential studies, about 3 months after the onset of neurologic symptoms. A CT showed decreased radiodensity over the white matter of both occipital lobes, and high density areas on the periventricular space. No contrast enhancement was observed around the low dense white matter, while occipital grey matter seemed to be almost normal. MRI demonstrated a larger and more obvious lesion of prolonged T2 relaxation time which was 170-250msec than that detected by CT scan. The PET demonstrated wide and severe hypometabolism for glucose over the grey and the white matter of bilateral occipital lobes. The visual evoked potential (VEP) was scarcely elicitable, while the auditory brainstem response (ABR) and short latency somatosensory evoked potential (SSEP) was normal. These imaging studies suggest that extensive and profound demyelination exists in the occipital white matter. For detection of demyelinizing process, MRI may be more effective than CT in this disorder. The PET study revealed that there may have been an abnormality of the grey matter as well as the white matter in the occipital lobe. The VEP disappeared in the relatively early stage. The brainstem may not be involved at such early stage in light of normal ABR and SSEP.
HANDA, M., FUJIMURA, S., KONDO, T., ICHINOSE, T., SHIRAISHI, Y. and NAKADA, T. A Study of Preservation Solution for 48- and 96-Hour SimpleHypothermic Storage of Canine Lung Transplants. Tohoku J. Exp. Med., 1989, 159 (3), 205-214-Forty-eight-hr and 96-hr simple hypothermic preservations of the lung were studied on dogs using 4 kinds of solutions resembling extracellular electrolyte compositions (Ep1-Ep4). The pH of each solution was changed from 6.377 to 7.463 by HPO42-/H2PO4- ratio. Twenty dogs were prepared as donors (12 for 48-hr preservation with Ep1, Ep2 and Ep3, and 8 for 96-hr preservation with Ep3 and Ep4, respectively). The heart-lung block was removed from the donor, and flushed with 500ml of preservation solution via the pulmonary artery, then immersed in the same cold (4°C) solution, after which it was stored in a cold (4°C) room. After preservation, the left lung was separated from the heart-lung block and was transplanted into the recipient orthotopically. The function of the transplanted lung was evaluated with serial x-ray findings, contralateral pulmonary artery ligation test, and histologic findings. In the case of 48-hr preservation, all of the four recipients with Ep3 (pH: 7.225) showed good aeration of the grafted lungs on the chest x-ray in the early postoperative period. As for the 96-hr preservation cases, one with Ep3 and three with Ep4 (pH: 7.463) presented good x-ray findings. Of these successful cases, seven dogs (5 of 48-hr preservation cases, 2 of 96-hr preservation cases) underwent contralateral pulmonary artery ligation 10 to 18 days after transplantation. Excluding one of the 96-hr preservation cases, six dogs tolerated this procedure. On histopathological examination of the successful cases, the 48-hr preservation cases showed almost normal pulmonary structure, while the 96-hr preservation cases showed slight degenerative changes in the alveolar walls. From the present study, it becomes apparent that clinical application of 48-hr preservation may be possible by using a phosphate buffered extracellular solution.
YAEGASHI, N., YAJIMA, H., KONNO, R., SHIKANO, K., SATO, S. and YAJIMA, A. Detection of Human Papillomavirus Type 52b in Cervical Dysplastic Tissue. Tohoku J. Exp. Med., 1989, 159 (3), 215-219-We examined infection in the tissue of cervical dysplasia of human papillomavirus (HPV) 52b, which we recently isolated from cervical cancer. To screen a lot of samples, we used an assay system with an HPV DNA typing kit containing an HPV 33 probe that cross-hybridizes with HPV 52b DNA. DNA samples from 123 patients with cervical dysplasia were first screened with this kit. Sixteen of these appeared to be positive, and they were subjected to Southern blot hybridization with the HPV 52b probe under highly stringent conditions. Of the 16 samples, two were found to have HPV 52b genome DNA. Our results, together with the fact that HPV 52b was isolated from cervical cancer, seem to support the notion that HPV 52b infection is closely associated with the onset of cervical cancer.
ASAKI, S., NISHIMURA, T., SATO, A., SHIBUYA, D., OHARA, S., SATO, H. and MOTOGIMA, T. Efficacy of Absolute Ethanol Injection Method for Stress UlcerBleeding after Major Surgeries. Tohoku J. Exp. Med., 1989, 159 (3), 221-225-Emergency endoscopy, carried out in 342 cases of UGI overt bleeding at the Third Department of Internal Medicine, Tohoku University during the six year period from June 1979, demonstrated the necessity of endoscopic hemostasis in 171 cases (50%) with active bleeding, adhered fresh blood clot or exposed vessel with bloody gastric juice. The absolute ethanol injection method was applied to achieve hemostasis in all cases including 30 cases (18%) of postoperative stress ulcer bleeding after major surgeries. Temporary hemostasis was obtained successfully in all 30 cases and rebleeding did not develop. New bleedings in 2 cases (7%) were stopped by repeated injections of absolute ethanol. No patients died from bleeding nor underwent emergency or elective operation. Five patients (17%) died from complicated underlying diseases. Perforation developed in one case (3%). In this case new bleeding occurred on two occasions, and each time hemostasis was obtained. However, this patient showed early symptoms of perforation immediately before the third hemostasis, and was operated on after local injection of absolute ethanol. The complete hemostasis was achieved in 100% of postoperative stress ulcer cases by the ethanol method.
ASAKI, S., NAKAYAMA, Y., OHARA, M., HIRASAWA, Y., KANAZAWA, N. and OTA K. Comparison of Efficacy of Endoscopic Ultrasonography and Submucosographyin Diagnosing the Depth of Gastric Cancer Invasion. Tohoku J. Exp. Med., 1989, 159 (3), 227-235-Diagnosis of the depth of the cancer invasion is necessary to select the indication of endoscopic treatment. We used endoscopic ultrasonography (EUS) and Submucosograhy (SMG) to diagnose the depth of cancer invasion and compared their efficacy against 63 lesions in 60 cases of gastric and esophageal cancers. SMG could diagnose the invasion correctly in 97% of m (mucosa) cancers, 88% of sm (submucosa) cancers and 100% of advanced cancers. On the other hand, linear-type EUS could diagnose the cancer invasion correctly in 60% of the m cancers, 83% of the sm cancers and 100% of the advanced cancers. The results of the comparison of radial-type EUS and SMG showed similar results. Both EUS and SMG are appropriate for the judgement of endoscopic treatments. However, for the selection of the indication of endoscopic treatment which is applied to relatively small sized lesions in general, SMG appears to be superior to EUS in both resolution power and accuracy in shooting.
HIROKAWA, M., TAKATSU, H., NIITSU, H., NISHINARI, T., NIMURA, T., ITOH, T., CHUBACHI, A., MIURA, I., YOSHIDA, K., ENDO, Y. and MIURA, A.B. Serum TumorNecrosis Factor-α Levels in Allogeneic Bone Marrow Transplant Recipients withAcute Leukemia. Tohoku J. Exp. Med., 1989, 159 (3), 237-244-We determined the serum levels of tumor necrosis factor-α (TNF) in allogeneic bone marrow transplant recipients in order to evaluate the relationship between TNF and graft-versus-host disease (GVHD). Eight patients with acute leukemia receiving an HLA-identical marrow graft were studied. Samples from healthy subjects and pretransplant recipients were all negative for TNF. Six of eight patients had detectable levels of TNF in serum after transplantation. All three patients with acute GVHD, and three of five patients without acute GVHD had elevated TNF levels in serum. Among the patients with increased TNF levels, documented infection was demonstrated in only one patient, with a clinical diagnosis of B 19 parvovirus infection. Serum TNF levels were elevated when the WBC counts were more than 2, 000/μl. However, serum concentrations of TNF significantly correlated with body temperature. Although we could not conclude definitely that serum TNF levels correlated with severity of GVHD, it was suggested that TNF may be produced as a result of latent infections or immunological reaction against non-HLA allogeneic antigens.
YAMAUCHI, H., ICHINOHASAMA, R., KAKIZAKI, K., YAMADA, Y. and TANAKA, N. Cytofluorometric Analysis of Nuclear DNA and Cell Protein in PancreaticCarcinoma. Tohoku J. Exp. Med., 1989, 159 (3), 245-246-Cytofluorometric analysis of pancreatic carcinoma was performed in six patients, using a method for simultaneous one-step staining of nuclear DNA and cell protein. All carcinoma cells demonstrated ploidy abnormalities in DNA histogram; polyploid with or without aneuploidization. The carcinoma cells of two patients who died within one year after resection showed significantly higher polyploidization of DNA and bigger amount of cell protein than those of four patients who survived longer than one year after surgical managements.
KOIWA, Y., OHYAMA, T., TAKAGI, T., KIKUCHI, J., HONDA, H., HOSHI, N. and TAKISHIMA, T. Clinical Demonstration of Vibration-Induced Depression of LeftVentricular Function. Tohoku J. Exp. Med., 1989, 159 (3), 247-248-In experimental studies, minute sinusoidal vibration has been reported to induce functional depression of the left ventricle and to be an index for evaluation of myocardial crossbridge kinetics. Therefore, to examine whether or not this vibration-induced functional depression could also be observed in the human ventricle, motion of the left ventricular (LV) wall or LV pressure was measured by echocardiography (n=16) or by left heart catheterization (n=4), in which 100Hz, 2.07mm-amplitude sinusoidal vibration was applied to the subject's precordium. In the echocardiographic study, left ventricular wall shortening did not change by vibration in nine healthy volunteers, but was depressed in two patients with aortic regurgitation (AR) and in one patient with ischemic heart disease (IHD). In measurement of LV pressure, the decrease in LV systolic pressure caused by vibration was obviously observed in two patients (AR and IHD) but was not observed in two patients with hypertrophic cardiomyopathy. These results suggest that we might be able to extend previously proposed experimental idea on early detection of the abnormality in myocardial crossbridge kinetics to the clinical setting.