Acta Medica Okayama 46巻 2号

Radiological findings on the fate of grafted Kiel bone implants for the treatment of bone tumors were evaluated in 25 lesions. The mean follow-up period was 14.8 years, ranging from 5 to 21.8 years. We classified the radiological findings into 4 grades; Excellent (4 lesions), Good (14 lesions), Fair (2 lesions), and Poor (5 lesions). All cases of the Poor grade were polyostotic fibrous dysplasia. The younger the patient at the time of the operation, the more rapidly Kiel bone grafts tended to be incorporated. The grafted bone can become enmeshed in the structure of the recipient bed (Good or Excellent grades) within 10 years in most cases, except in polyostotic fibrous dysplasia.

The proliferative activity of various parts of normal and malignant endometrium was evaluated using an immunohistochemical approach and flow cytometry (FCM). The two monoclonal antibodies, Ki-67 and anti-DNA polymerase alpha antibody (anti-poly alpha antibody) were used to detect the proliferative activity of cells, and the percentage of the Ki-67 and anti-poly alpha positive cells were measured. Proliferative indices (PI; percentage of S and G2M phase) and DNA ploidy were measured by FCM. Normal endometrial specimens from 29 patients with benign diseases were used and three different parts (fundus, middle, and low part of the uterus) were examined. In the proliferative phase of normal endometrium, there was no significant difference in the proliferative activity in the three parts. In 20 patients with endometrial carcinomas with myometrial invasion, tissues were taken from the myometrial invasive site and the central part of the tumor tissue. In the cases of endometrial carcinoma, the myometrial invasive site had a higher proliferative activity than central part of the tissue. The proliferative activity measured by the immunohistochemistry was correlated with the histological grade of malignancy, but it was not consistent with PI by FCM. This suggests that the proliferative activity measured by the immunohistochemistry is independent of flow cytometric PI.

A new model of status epilepticus (SE), which was induced by intermittent electrical stimulation (20 Hz for 20 sec every min for 180 min) of the deep prepyriform cortex, has been developed in the conscious rat. SE was induced in 9 of 16 rats in the drug-free group. The number of stimulation trains required to induce SE in this status subgroup was 125.6 +/- 12.7 (mean +/- SEM) and the mean duration of self-sustained seizure activity (SSSA) occurring after cessation of the stimulation session was 295.4 +/- 111.4 min. Some animals showed secondary generalized seizures. Significant cell loss was observed in the hippocampal CA3 pyramidal cell layer ipsilateral to the stimulation site and bilateral CA1 areas in the status subgroup compared with the group subjected to sham operation. In addition, there was a significant negative correlation between the duration of SSSA subsequent to the stimulation session and the total number of intact pyramidal neurons observed in the bilateral CA1 and ipsilateral CA3 subfields of the status subgroup. There were significant differences between the status and non-status subgroups with respect to the number of afterdischarges (ADs) and the total AD duration during the stimulation session. Pretreatment with phenobarbital (30 mg/kg) prevented the development of SE and hippocampal cell loss completely. Pretreatment with MK-801, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist (0.25 or 1 mg/kg), also prevented hippocampal cell loss, although it did not block SE generation completely, which suggests dissociation of the mechanisms underlying the development of SE and hippocampal damage. These results indicate that prolonged SSSA actually causes hippocampal damage and it is critically dependent upon NMDA receptor participation.

Indocyanine green (ICG) was injected into rat liver nodules induced by 2-acetylaminofluorene (2-AAF) via portal vein. The relationship between ICG staining and cell atypism of liver nodules was examined by means of histology and DNA flow cytometry. After 2-AAF administration, many small nodules appeared on the liver surface. All hyperplastic nodules were ICG stained until 10 weeks after the administration, but some nodules were not stained after 14 weeks. ICG-stained nodules histologically consisted of benign tissues and borderline lesions, and many of them showed "diploidy" in DNA cytometry. ICG-unstained nodules consisted of hepatocellular carcinoma (HCCs) and borderline lesions, and many of them showed "aneuploidy". In this way, it has been suggested that HCC could derive from hyperplastic nodules and that they might lose an ability to take up ICG in the process of hepatocarcinogenesis. Immunohistochemical staining for glutathione-S-transferase alpha (GST-alpha), a carrier protein of ICG in hepatocytes, was well correlated with ICG staining in the nodules, suggesting that the loss of ICG uptake in HCC was partly due to the decrease of GST-alpha. Moreover, the appearance of ICG unstained and aneuploid nodules was significantly inhibited in rats which were fed on diet containing Syosaiko-to after the administration of 2-AAF. Chemopreventive effect of Syo-saiko-to on hepatocarcinogenesis was identified.

We determined plasma human atrial natriuretic peptide (hANP) levels in normal pregnancy and pregnancy induced hypertension (PIH). The plasma hANP levels slightly decreased in the first trimester of normal pregnancy and tended to recover as pregnancy advanced, although these changes were slight. However, the plasma hANP level in puerperium was higher than that in the third trimester of normal pregnancy. The plasma hANP level in mild PIH was not significantly higher than that in the third trimester of normal pregnancy. In contrast, the plasma hANP level in three cases of severe PIH was approximately 200% higher than those in the normal third trimester and mild PIH.

Gross specimens are valuable sources in morphology education. In this study, we investigated how the fixation of gross specimens may be accelerated. For this purpose, whole organ specimens from freshly killed rabbits: extremities, kidney, heart, liver, stomach and uterus were fixed in a mercaptoethanol-formaldehyde mixture for 3-3.5h under the following conditions: 1, at room temperature; 2, at gradually increasing temperatures up to 45 degrees C; and 3, at a gradually increasing vacuum ranging from 20 kPa to 40 kPa. The results were compared with those of formaldehyde-fixed controls, and the mercaptoethanol-formaldehyde mixture was found to be useful in shortening the fixation time and providing good fixation. Both heat and vacuum enhanced these phenomena.

DeVega's annuloplasty was performed on 41 patients with tricuspid regurgitation (TR) associated with combined valvular disease and results were assessed based on Doppler echocardiographic findings in an attempt to examine the applicability of this surgical technique. TR was quantitatively evaluated via Doppler echocardiography before and after surgery. Clinical symptoms, cardiac function, and surgical results were assessed, and the severity of left ventricular myocardial degeneration was determined using electron microscopy. There were no differences in the following factors between the TR recurrence and TR improvement groups: previous heart surgery, number of involved valves, presence or absence of a giant left atrium, preoperative New York Heart Association (NYHA) functional class, and type of prosthetic valve (Bjork-Shiley vs. St. Jude Medical). We found no differences between these two groups in TR severity and tricuspid annulus diameter measured during surgery. Severity of myocardial degeneration was closely associated with the recurrence of TR. Clinically, most had diminished cardiac function before surgery. DeVega's technique appears to be remarkably effective in patients with well-preserved myocardium because no TR recurrence was detected even in examinations with the most accurate Doppler echocardiography. However, such long-term effectiveness of DeVega's technique cannot be expected in patients with degenerated myocardium.

In order to elucidate the role of erythrocyte catalase in the accumulation of mercury in erythrocytes, labeled erythrocytes and plasma were prepared by exposing normal and acatalasemic mice to radioactive mercury vapor (203Hg0: 6.8mg/m3) for 30 min. Labeled erythrocytes (or plasma) were mixed with unlabeled plasma (or erythrocytes) of normal or acatalasemic mice and incubated at 0 degrees C for 1 h. After incubation, the radioactivity of mercury in the erythrocytes and the plasma was measured by a gammascintillation counter. When labeled erythrocytes were incubated with unlabeled plasma, the ratio of mercury transferred from acatalasemic erythrocytes to normal plasma (11.6%) or to acatalasemic plasma (13.3%) were significantly higher than that from normal erythrocytes to normal plasma (1.8%) or to acatalasemic plasma (2.2%). When labeled normal (or acatalasemic) plasma was incubated with unlabeled normal or acatalasemic erythrocytes, the uptake of mercury by acatalasemic erythrocytes from normal plasma was 2.0%, and 1.2% from acatalasemic plasma, which tended to be lower than that by normal erythrocytes from normal plasma (3.4%) or from acatalasemic plasma (2.2%). The results indicated impaired accumulation of mercury in acatalasemic erythrocytes, suggesting the importance of catalase in taking up mercury in erythrocytes and protecting other organs from toxic effects of metallic mercury.

Since December 1988, a centrifugal ventricular assist device (VAD) was used to support the circulation in 5 patients who could not be weaned from cardiopulmonary bypass (CPB) or developed cardiogenic shock after removal from CPB. Three patients required a left VAD, one needed a right VAD. One patient had biventricular support using a centrifugal left VAD and a diaphragm type right VAD. The duration of the centrifugal VAD support ranged from 6 to 136 (mean 72)h. All patients were weaned from the VAD, but only 2 patients were discharged from the hospital. Two patients died of multiple organ failure, and one died of cardiogenic shock caused by intractable arrhythmia. Infection occurred in all non-survivors, and 2 of them developed renal failure. We conclude that the centrifugal VAD is effective to recover a failing ventricle. The factors related to the unsuccessful recovery were delayed start of the VAD support and major complications such as infection as infection and renal failure.

Synergistic enhancement of anti-tumor effects through the combined use of natural human interferon-alpha (nHuIFN-alpha) and natural human tumor necrosis factor-alpha (nHuTNF-alpha) enabled us to decrease the effective dose of each cytokine and consequently to reduce side effects. One hundred and twenty patients with advanced or recurrent solid cancer were entered in the trial from April 1985 to January 1988, of whom 112 patients were evaluable. A mixture of nHuINF-alpha and nHuTNF-alpha was injected intravenously as the maintenance dose 1 x 10(6)U or more/day for over 8 weeks. There was no response in 40 patients injected with the maintenance dose of 1 x 10(6)U/day, but of 72 patients receiving more than 2 x 10(6)U/day (10 micrograms of nHuIFN-alpha and 3 micrograms of nHuTNF-alpha), 4 had complete responses, 10 had partial responses, and 4 had minor responses. The overall response rate was 12.5% (14/112) and the rate was 19.5% in 72 patients with more than 2 x 10(6)U/day. Positive responses were as follows: hepatoma 3/8), renal cell cancer (4/11), breast cancer (4/17), ovarian cancer (1/2), malignant thymoma (1/1) and liposarcoma (1/1). Serious adverse effects like hypotension, oliguria and severe hepatobiliary toxicity were never experienced. The effective and adequate dose of the mixed preparation was considered 2 to 4 x 10(6)U/day/body.

Using 6 fractions differing in molecular weight of Dermatophagoides pteronyssinus (Dp)-antigen, we measured by enzyme-linked immunosorbent assay (ELISA) the titers of specific IgE, IgG and IgG4 antibodies against Dp antigen in sera of allergic subjects who were sensitive to house dust mite. We intended to evaluate which Dp fraction acts as the major antigenicity for allergic subjects. Results were as follows: 1) In comparison with normal controls, the titer of IgE antibody specific to crude Dp antigen was evaluated, but no significant difference was found among the titers of IgE antibody against each Dp fraction. 2) The titer of IgG antibody against the fraction with a high molecular weight (190 KD, 95 KD) was significantly higher than the titer of the 15 KD fraction in the nasal allergy patients. 3) The 15 KD fraction induced significant elevation of the titer of IgG4 antibody. It suggests that the low molecular weight fraction may act as the major allergenicity of Dp-antigen for inducing both IgE and competitive IgG4 antibodies, although other fractions induce significant IgE responses in patients with nasal allergy.