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The effects of 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ), green tea catechins (GTC), alpha-tocopherol, beta-carotene, chlorophyllin, phenylethylisothiocyanate (PEITC), 3-O-ethylascorbic acid (EAsA), 3-O-dodecylcarbomethyl ascorbic acid (DAsA), n-tritriacontane-16,18-dione (TTAD) and d-limonene on 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1)- or dimethylnitrosamine (DMN)-induced hepatocarcinogenesis, and the dose dependence of HTHQ inhibition of Glu-P-1- or 2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline (MeIQx)-influence on lesion development were examined in a rat medium-term liver bioassay system featuring diethylnitrosamine initiation and partial hepatectomy. At the end of week 8, the number and total area of glutathione S-transferase placental form (GST-P) positive liver foci in rats treated with 0.03% Glu-P-1 alone were increased significantly (46.8 +/- 11.0 and 12.0 +/- 5.6 respectively) as compared to the control values (3.8 +/- 1.6 and 0.4 +/- 0.2). Combined treatment with 1% HTHQ remarkably reduced both of these parameters (8.1 +/- 2.1 and 0.6 +/- 0.2). GTC (1%), PEITC (0.1%), beta-carotene (0.1%) and DAsA (1%) also demonstrated inhibition but less than HTHQ. On the other hand, these antioxidants did not influence development of foci initiated by 0.002% DMN. In the dose-response study, up to 0.125% HTHQ significantly reduced the effects of 0.02% Glu-P-1 or 0.03% MeIQx on the number and area of foci. These results indicate that several antioxidants exert chemopreventive effects against heterocyclic amine (HCA)-induced hepatocarcinogenesis, and particularly HTHQ which thus deserves further attention as a chemopreventor in the contest of the environmentally important HCA group of carcinogens.

Effects of transplacental and trans-breast milk exposure to a food-derived mammary and colon carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), were investigated in rats. Female Sprague-Dawley rats were administered PhIP in the diet (100 ppm) for 4 weeks before mating with nontreated males and also during gestation and lactation. As controls, additional females were maintained on the basal diet without PhIP and mated as with the treated animals. The offspring of both groups were subdivided for each sex at weaning into three dietary groups receiving 100, 25, and 0 ppm and were killed at 47 weeks of age. Effects of the transplacental and neonatal exposure to PhIP on mammary carcinogenesis were most evident in females administered 25 ppm PhIP after weaning; the incidence and multiplicity of adenocarcinomas in offspring from the PhIP fed dams (42.9%, 0.62/rat) was significantly higher than the value for offspring from nontreated dams (4.8%, 0.05/rat). Furthermore, in the basal diet groups, the incidence of adenocarcinomas in females was higher, albeit not significantly, in offspring of the PhIP-treated than the nontreated dams (16.7%, 0.22/rat as compared with 3.3%, 0.07/rat). Although the highest incidence of mammary adenocarcinomas was found in the female progeny given 100 ppm PhIP from PhIP-treated dams (70.0%, 1.55/rat), this was only slightly higher than the 61.9% and 0.90/rat of the same dose group from the nontreated dams. In males, no apparent effects of transplacental and neonatal exposures were evident. In a separate experiment, excretion of PhIP into breast milk and transfer of PhIP to fetuses and neonates with resultant hepatic PhIP-DNA adduct formation were demonstrated. Thus, maternal exposure to this food-derived carcinogen may be a critical risk factor for generation of mammary carcinomas.

To obtain basic data concerning the availability of medical care for intractable diseases in a large city and its environs, we analyzed the data of Saitama Prefecture. These data were selected from a nationwide survey conducted by the Epidemiology of Intractable Diseases Research Committee of the Ministry of Health and Welfare in Japan. The characteristics of medical institutions visited by patients with 26 intractable diseases were analyzed. The patients were receiving financial aid for treatment. The subjects were 4234 patients in 1984 and 6804 patients in 1988. In addition, we compared the data of 1984 with those of 1988. The results are as follows: 1) In both years, the characteristics of medical institutions which were visited varied in terms of the individual disease. The proportion of patients who visited medical institutions in the same medical service area and in the same prefecture were both very low. The percentage of patients who visited medical institutions in Tokyo was more than 30% of the total, and was more than 50% for the disease with the highest proportion of patients. The dependency on Tokyo for medical institutions was inversely proportional to the distance from Tokyo. Most patients were highly dependent on a large hospital, but the proportion of patients with SMON and ulcerative colitis who visited a large hospital was markedly lower than that for other diseases. 2) A comparison of the data of 1984 with those of 1988 showed that in most of medical service areas, the proportion of patients who visited medical institutions in the same medical service area and in Saitama Prefecture increased, but in Tokyo Prefecture the proportion decreased. We continuously observed a high dependency on a university hospital located about 60km distance from downtown Tokyo, but the dependency slightly decreased in 1988. When a new branch of a university hospital opened, many intractable disease patients then depended on that branch. These results suggest that the self-sufficiency levels of medical services for intractable diseases gradually rose in Saitama Prefecture. The illness behavior of intractable disease patients in Saitama Prefecture did not show any remarkable changes, therefore those results in Saitama Prefecture might indicate a universal characteristic of medical institutions visited by intractable disease patients who live in the envirous of a large city (Tokyo).

To investigate whether waist-hip ratio (WHR) influences glucose tolerance, blood pressure, and serum lipids independently of body mass index (BMI).Cross-sectional study.2,228 male self-defense officials aged 49-55 years in Japan.BMI, WHR, serum lipids, systolic and diastolic blood pressure, and glucose tolerance status according to World Health Organization (WHO) criteria.Adjustment was made for smoking, alcohol use, physical activity, and inter-hospital variation in statistical analysis. Adjusted odds ratios of non-insulin-dependent diabetes mellitus (NIDDM) were progressively increased with increasing levels of WHR, but not BMI. Both BMI and WHR were independently positively associated with impaired glucose tolerance to almost the same degree. Adjusted means of blood pressure, total cholesterol, and triglycerides were almost linearly increased with increasing levels of both BMI and WHR, and high-density lipoprotein cholesterol was progressively decreased. Although the associations of BMI and WHR with blood pressure and serum lipids attenuated after mutual adjustment for each, BMI was less influenced by WHR than vice versa, except for triglycerides.WHR is an important contributor not only to NIDDM but also to impaired glucose tolerance, blood pressure, and serum lipids, although the associations of WHR with blood pressure and serum lipids were generally weaker than those of BMI, except for triglycerides.

Disc grafting is a new surgical procedure that may be suitable for preserving mobility of the spine. This experimental study was designed to determine a method of favorably preserving a disc prior to allografting. The lumber vertebrae of adult mongrel dogs were aseptically excised, regarded as the vertebral body-disc unit, and preserved at -80 degrees C, or at 4 degrees C. In the preservation at 4 degrees C, UW solution, Euro-Collins solution, EP-II solution, Ham's F-12, or physiological saline solution was used for preservation. Isotopes were used for determining the activities of the disc cells. In the preservation at -80 degrees C, it was difficult to maintain the activity regardless of the preservation period. There was no difference among these preservative solutions in the preservation at 4 degrees C on the nucleus pulposus, but the 2-day preservation in UW solution provided the best results in terms of the annulus fibrosus. Based on the results of these experiments, at -80 degrees C it was difficult to maintain the activity of disc cells while at 4 degrees C the UW solution was the most effective for preserving the anulus fibrosus. However the period of preservation was very short, and a new method to enable longer periods of preservation should be developed.

Parathyroid cysts are grouped into two: functioning and non-functioning cysts. Most of the functioning cysts result from the cystic degeneration of parathyroid adenoma, while, non-functioning cysts, in many cases, originate from Kürsteiner's canal on the third branchial cleft. It is difficult to differentiate parathyroid from thyroid cysts morphologically. However, the measurement of assay of parathyroid and thyroid hormone in the aspirated fluid enables differentiation. Hypercalcemic crisis occurs frequently in the functioning cysts. Moreover, we propose sclerotherapy as the treatment for the non-functioning cysts.

We have shown for the first time that the myosin head (subfragment-1, S1), the energy-transducing component in the actomyosin motor system undergoes a distinct shape change during hydrolysis of ATP using x-ray solution scattering techniques. Among various analogs for intermediate states of the S1 ATPase cycle, the complexes with MgADP and vanadate (S1.ADP.Vi), MgADP and beryllium fluoride (S1.ADP.BeF3), or MgADP and aluminum fluoride (S1.ADP.AIF4) showed a shape change similar to that in the presence of MgATP, but the complexes with ATP gamma S (S1.ADP gamma S) and MgADP trapped by cross-linking with pPDM (S1.ADP-pPDM) seemed to have a shape similar to that of nucleotide-free S1. These results indicate that the shape of an S1**.ADP.Pi state is more rounded or bent than in other intermediate states of the S1 ATPase cycle. Such changes occur in light chain 2-deficient S1 and also in smooth muscle S1. However, MgADP-fluoride complexes with smooth muscle S1 (without phosphorylation of a regulatory light chain) seemed to have a structure similar to that of nucleotide-free S1. Analysis of x-ray scattering data indicated that a conformational change of S1 in the presence of MgATP might be caused by a hinge-like bending movement between the catalytic and regulatory domains. The global change of S1 is correlated with some specific changes of a nucleotide-binding moiety.

The author discusses women's status in China with reference to family characteristics and lineage customs. Aspects considered include changes in the size and makeup of the traditional family; increases in divorce and female suicide; population statistics on women; the inheritance system and support of aged men; eugenics and human rights; and the UN World Conference on Women. (SUMMARY IN JPN)

Endothelin (ET) is a 21-residue potent vasoconstrictive peptide produced by vascular endothelial cells and formed from its precursor, big endothelin (big ET), by endothelin-converting enzyme (ECE). This paper describes the cloning and functional expression of a cDNA encoding a human ECE from human umbilical vein endothelial cells (HUVEC). Human ECE consists of 758 amino acid residues and has high homology to rat and bovine ECE. Immunoblot analysis using a monoclonal antibody risen against rat lung ECE showed the presence of immunoreactive protein in membrane fraction prepared from both HUVEC and COS-1 cells transfected with human ECE cDNA. Both COS-1 cells expressing human ECE and its membrane fraction converted big ET-1 most efficiently among big ETs.

Spontaneously hypercholesterolemic (SHC) rats become hypercholesterolemic on normal diets. SHC rats, especially males, exhibit renal lesions similar to those found in focal segmental hyalinosis/sclerosis (FGS). We presented here a detailed natural history of serum lipid, renal function and pathological changes in male SHC rats from 5 to 40 weeks of age. Increased urinary protein excretion and glomerular injury were apparent before the detection of lipid or immune deposits, indicating that the renal lesions were not caused by these deposits. Serum total cholesterol levels, already high at 5 weeks, abruptly increased in concurrence with increased urinary protein excretion, suggesting that the severe hyperlipidemia of this strain is modified by a nephrotic syndrome. By 30 weeks of age, glomerular sclerosis was evident in more than half of the glomeruli and tubular dilatation was prominent, with an abrupt increase of BUN, SCr, and urinary volume; these findings indicate a rapid progression to renal failure. Our results suggest that SHC rats would be a very useful model to investigate the process leading to glomerular sclerotic lesion and renal failure, as well as the effect of hyperlipidemia on glomerular injury.

2-amino-1-methyl-6-(4-hydroxyphenyl)imidazo[4,5-b]pyridine (4'-OH-PhIP) was mutagenic, inducing 180 revertants of Salmonella typhimurium TA98 per 100 micrograms with S9 mix and was formed by heating a mixture of creatine, tyrosine and glucose. It was detected in broiled beef at a level of 21.0 ng per g of broiled beef, which is comparable to the level of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Two new mutagens were isolated from bacteriological-grade beef extract using a new Salmonella tester strain, YG1024, which has a much higher O-acetyltransferase level than TA98. These mutagens were identified as 2-amino-4-hydroxymethyl-3,8-dimethylimidazo[4,5-g]quinoxaline (4-CH2OH-8-MeIQx) and 2-amino-1,7,9-trimethylimidazo[4,5-g]quinoxaline(7,9-DiMeIgQx++ +). The amounts of these mutagenic heterocyclic amines (HCAs) in beef extract were 6.0 ng and 53 ng per g of beef extract, respectively. 4-CH2OH-8-MeIQx induced 326,000 revertants of YG1024 and 99,000 revertants of TA98 per microgram with S9 mix, while 7,9-DiMeIgQx induced 13,800 and 670 revertants of YG1024 and TA98, respectively, per microgram in the presence of S9 mix. The levels of nine previously reported HCAs in cooked meats and fish and in beef extract were determined quantitatively. The level of PhIP was highest (0.56 approximately 69.2 ng/g), followed by that of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) (0.64 approximately 6.44 ng/g), and those of other HCAs were 0.03 approximately 2.50 ng/g. Mainstream smoke condensates of five Japanese brands of cigarettes contained four HCAs, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-9H-pyrido[2,3-b]indole (A alpha C) and 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C), at levels of 0.02 approximately 13.5 ng per cigarette and sidestream smoke condensates of two brands of cigarettes contained these HCAs at levels of 0.14 approximately 2.72 ng per cigarette. PhIP was not detected in any sample of mainstream or sidestream smoke condensate.

Xylanase J from alkaliphilic Bacillus sp. strain 41M-1 contains a family G catalytic domain at the N-terminus, followed by a linker sequence and a functionally-unknown C-terminal domain. The mutational analysis of xylanase J indicated that Glu-93, Glu-183, Trp-18, Trp-86, Tyr-84 and Tyr-95 play an important role in the catalytic activity. A deletion derivative of xylanase J lacking the C-terminal domain retained its activity, suggesting that the C-terminal domain does not directly involved in catalysis.

A compact 550 kV gas-insulated substation (GIS) is developed by applying new single break gas circuit breaker (GCB). The interrupter for the single break GCB has to cope with nearly twice the voltage compared with the double break GCB. This paper discusses mainly the development of the single break 550 kV GCB which had its focal point on the interrupter design and the arrangement of the resistor unit. Furthermore, discussions are made on the various advantages of employing the single break GCB on the layout of 550 kV GIS.

Microsatellite instability in rat colon tumors induced by heterocyclic amines was examined by studies on the lengths of 85 microsatellite sequences, covering most of the rat chromosomes in tumors and normal tissues. Seven of eight colon tumors induced by 2-amino-1-methyl-6- phenylimidazo-[4,5-b]pyridine showed alterations at least at one locus of microsatellite sequences, whereas no mutations were observed in colon tumors induced by 2-amino-3-methylimidazo[4,5-f]quinoline. Three 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine-induced colon tumors had mutations in more than one microsatellite, their mutation rates being 2 of 85, 2 of 85, and 3 of 85 allele/mircrosatellite sequence, respectively. These data suggest that rat colon adenocarcinomas induced by 2-amino-1-methyl-6- phenylimidazo-[4,5-b]pyridine but not 2-amino-3-methylimidazo[4,5-f] quinoline show a trait of microsatellite instability. This is the first systematic study of microsatellite instability in experimental animal models of carcinogenesis.

The elongation of thin and thick filaments during isometric contraction of a molluscan smooth muscle was studied by measuring spacing changes of meridional reflections in the medium-angle X-ray diffraction pattern. X-ray patterns from the anterior byssus retractor muscle of Mytilus edulis in the resting, active, and catch states were taken from the same part of a muscle bundle at a fixed specimen-to-detector distance, using imaging plates and 10 s exposure to synchrotron radiation. The third-order reflection (9.2 A) of the axial period of actin, and the fourteenth-order reflection (10.4 A) of the axial subunit-repeat of the thick filament are increased in spacing in the active and catch states. From accurately measured changes in the axial distance of the 9.2 A layer line from the origin, thin filament elongations in the active and catch states are estimated to be 0.48 and 0.32%, respectively, in a muscle that maintains a tension of 12.2 kg cm-2 in the active state and 9.8 kg cm-2 in the catch state. Thick filament elongations in the active and catch states are similarly estimated to be 0.33, and 0.28%, respectively, based on the axial shift of the 10.4 A reflection. The 0.48% elongation of the thin filament in the active state agrees with an elongation that is presumed by White and Thorson (1973) to estimate the lower limit of the thin-filament stiffness. It seems that in the catch state the activated and resting thin filament structures are intermixed. The activated parts of the thin filament are probably more elongated than the apparent value, 0.32%.

Induction of endometrial adenocarcinomas in persistent estrous Donryu rats by a single intra-uterine administration of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) was examined. Female Donryu rats were divided into four groups at 7 weeks of age. Rats in Croup 1 were controls under a 12-h light/12-h dark regimen while Groups 2-4 were persistent estrous animals maintained under 24-h light conditions. At 10 weeks of age, rats in Group 1 and 2 were given a single intra-uterine administration of polyethylene glycol(PEG), and those in Groups 3 and 4 received ENNG(20 mg/kg body weight), dissolved in PEG, in the same manner. Group 4 rats also received an s.c. 17 beta-estradiol(E2) implant one week thereafter. At the termination of the experiment (week 42 after the ENNG-treatment), all surviving rats were killed and the development of uterine proliferative lesions assessed. All groups demonstrated hyperplasias, the incidence and severity being higher in ENNG-treated animals. The incidence of uterine adenocarcinomas in Group 2(2/20, 10%) was slightly higher than that in Group 1(0/16, 0%), although this difference was not significant. In Groups 3(7/19, 37%) and 4(6/20, 30%) statistically significant induction of adenocarcinomas was noted, two lesions in the latter case being very large with prominent invasion of tumor cells into the perimetrium. At 10 and 25 weeks after ENNG-treatment, the E2-progesterone(E2:P) ratios in Groups 2, 3 and 4 were significantly higher than in Group 1.(ABSTRACT TRUNCATED AT 250 WORDS)

From 1946 to 1990, 10,485 patients with gastric cancer were been surgically treated in the Cancer Institute Hospital, Tokyo. Retrospectively, we analyzed prognostic factors, especially in those without distant metastasis. Prognosis of the patients with tumors which invaded the proper muscle layer improved dramatically (from 70% to 90%). However, patients who had advanced tumors with serosal invasion did not show good survived (from 20% to 40%). To improve the prognosis of patients with serosal positive gastric cancer, a new and effective prophylactic therapy for peritoneal recurrence is needed.

We discussed the advances and clinical issue including complications in the treatment of gastric cancer infiltrating the adjacent organs. Recent years, the proportion of the patients with gastric cancer infiltrating the adjacent organs are decreasing, but there isn't remarkable advances in the treatment result of them. That is due to the fact that about one half of them has distant metastasis, such as peritoneal dissemination or liver metastasis. Whatever the survival rate of the patients who was performed combined resection is better than unresected cases. The postoperative complications of the combined resection cases is two times as much as the uncombined resected cases. Therefore we should perform combined radical resection for the patients without distant metastasis, and for the patients with distant metastasis, we should perform palliative surgery for the purpose of improving QOL.

A total of 8,993 cases of gastric cancer which were undergone gastrectomy at Cancer Institute Hospital, Tokyo were subjected to the multi-variate analysis of prognostic factors in gastric cancer. Relative ratio of hazard risk indicated the rank of importance in prognostic factors as the following order: Hepatic metastasis, radicality of surgery, macroscopic tumor type, serosal involvement, number of involved lymph node, and grade of lymph node metastasis. Difference in the results of analysis was observed between mono- and multi-variate analysis in the following categories: site of primary lesion, type of resection, and chemotherapy. These results suggested the importance of multimodality therapy to achieve the absolute curative surgery for advanced cancer, and also the importance of multi-variate analysis for the proper evaluation of prognostic factors.

Now we use the nodal grade (N, n) as a prognostic indicator in patients with gastric cancer according to the general rules for the gastric cancer study. But there are both of patients with good and poor prognosis in the same nodal grade. Then we analyzed the survival of patients with gastric cancer based on the nodal grade and the number involved lymph nodes, and discussed the new prognostic indicator with both of them. We classified the three groups based on the number of involved nodes as follows: 0.1-4.5-. There is the differences in survival between each pair of groups statistically. The relationship between the nodal grade (N, n) and the number of lymph node metastasis is that the survival of patients with involved nodes more than five is equal to the survival of the patients with high nodal grade and involved nodes 1-4. Therefore it suggest that the new grading consisting of them will be more better prognostic indicator.

The recurrence rate of resected gastric cancer was 31.9%. The rate was in creasingly higher in proportion to the lack of radicality. The most common type of recurrence was peritoneal dissemination, followed by hematogeneous metastasis, local recurrence, and distant lymph node metastasis. The treatments for recurrence were surgery (9.3%) and chemotherapy (16.1%). Systemic chemotherapy (intravenous iv) was common, and local chemotherapy (intraarterial ia, intraperitoneal ip) was rate. The efficacy of systemic chemotherapy (iv) for recurrent gastric cancer without local recurrence was suggested. The efficacy of local chemotherapy (ia) was suggested for peritoneal dissemination and local recurrence.

To evaluate the clinical significance of the surgical procedure of left upper abdominal evisceration (LUAE), we analysed the prognosis of patients who received LUAE in the Cancer Institute Hospital from 1980 to 1990 using pair matching analysis. Survival benefits were observed in the patients with the tumor located in the upper or middle part of the stomach, and especially in those with Borrmann type 4 gastric cancer. Even in cases of peritoneal dissemination, patients who received LUAE survived longer than those with conventional total gastrectomy. These results indicated that LUAE should be a standard surgical approach for Bormann type 4 gastric cancer.

A 16-year-old female patient with gastric cancer was recently treated at our institute. She had macroscopically curative surgery, but relapsed to die 7 months after surgery due to peritoneal dissemination. We experienced three teen-agers over past 45 years, who were 0.019% of all cases treated in our institute. Histological type of these cases was undifferentiated adenocarcinoma, exposing to serosa. Though they had suffered abdominal discomfort for long time, proper diagnosis was not done due to their young age. Even the teen-ager who has abdominal complaints should be subjected to a thorough examination of gastrointestinal tract. Oncogene analysis should be done for the familial strain of gastric cancer.

Long-term oral administration of fluoropyrimidines such as 5-fluorouracil (5-FU) or tegafur is commonly used as an adjuvant chemotherapy for gastric cancer, but the optimal period or optimal total doses of fluoropyrimidines have not been studied. Two hundred cases of macroscopical Stage II and III curatively resected gastric cancer patients were entered in this study, and divided into three groups (6 months group: mitomycin C was given i.v. at day 0 and day 1 and 5-FU tablets were orally administered at a dose of 200 mg/day for 6 months. 12 months group: MMC was given the same as for the 6 months group and 5-FU tablets were administered for 12 months. Surgery alone group: No chemotherapy, operation only). As the result, 185 cases were eligible. There was no significant difference between the 6 months group and the 12 months group among Stage II patients. Although there was also no significant difference between the 2 groups in Stage III patients, the survival curve of 12 months group was always higher than in the 6 months group. When comparing with surgery alone group, 5-year survival of the 12 months group was always higher than in the surgery alone group of Stage III patients; however, the survival rate in the 6 months group was worse than in the surgery alone group at Stage II and III. These results suggest that MMC i.v. and 12 months or over administration of 5-FU tablets is useful for Stage III gastric cancer patients, and that cooperative study is required comparing with surgery alone in Stage II patients.

Quantitative analysis of the positive and negative feedback actions of testosterone (T) was carried out using intact rats, and orchidectomized rats implanted with T-filled Silastic capsules. Target organ weights and serum levels of LH and T were examined 7 days later, and response ratios of positive and negative actions were plotted against logarithm of serum T. From x-intercepts and slopes of regression lines, thresholds and responsiveness of reactions were calculated, respectively. Maintenance T levels necessary to maintain onset weights of the organ were also calculated from the regression lines. We compared 5 parameters at various ages, 1) thresholds for lowering serum LH, 2) mean T concentration of intact animals, 3) upper limit of serum T (mean + 2SD), 4) maintenance T levels, and 5) lower 95% limit of the thresholds for target organ response in orchidectomized animals. Though T can act between thresholds for target organ response and upper limit of serum T, the action range of T to induce organ growth over the onset organ weight (growth-inducing range) should be the area between the maintenance T level and the upper limit for serum T. At 3 weeks of age, the threshold for serum LH was very low, which makes the upper limit of serum T lower than maintenance T, allowing no growth-inducing range. From 5 weeks of age, the threshold for serum LH increased, and the serum T level with its upper limit also increased over the maintenance T level, allowing the presence of a growth-inducing range of T to make the growth of target organs possible.

We examined the equatorial X-ray diffraction of skinned fibers from rat psoas muscle in isometric contraction induced by photorelease of 1.1 mM ATP at 24 degrees C in the absence of Ca2+. At 15-20 ms after release of ATP, tension peaked at 21% of the maximum active tension. From the equatorial intensity ratio (I1,0/I1,1), we estimated the amount of myosin heads associated with actin filaments (A.M) at the tension peak. It was 32% of that in rigor and about half of that in the maximum contraction. ADP (0.7 mM) enhanced the contraction: tension peaked at 47% of the maximum at 25-30 ms. The estimated A.M at this peak was 50% of that in rigor, which was close to that in the maximum contraction. These results indicate that the association of myosin heads with the actin filaments in the Ca(2+)-free contraction is more than expected from the tension size, both in the absence and presence of ADP.

In previous studies of invertebrate rhabdomes by X-ray diffraction, glutaraldehyde fixation of the retina was used because this tissue is very labile and, without fixation, disintegrates within an hour of dissection. However, with conventional X-ray apparatus more than ten hours exposure time was needed to record a diffraction pattern. In this study, X-ray diffraction patterns from unfixed squid retina could be successfully obtained by use of synchrotron radiation and a storage phosphor screen as detector. The diffraction spots were indexed on a two-dimensional hexagonal lattice of 60 nm. X-ray data was analysed by comparing Patterson functions calculated from the diffraction intensities with those based on model building. The hexagonal shape of microvillar cross section was suggested by the systematic weakness of (0, k ) reflections beyond k =4 and the appearance of the six symmetry-related diffused maxima around (4 nm) -1 . The best-fitting model showed a large gap between adjacent microvilli (∼12 nm), which has been expected (for ionic current flow through the inter-microvillus space to generate the membrane potential) but not observed with the chemically fixed retina, possibly due to an artifact of fixation. Also, the existence of massive inter-microvillus materials, scarcely observed by conventional electron microscopy, has been confirmed.

The authors present some of the major findings from the Third Japanese National Survey on Migration, which was conducted in 1991 and covered a representative sample of 34,781 persons. Data are included on interregional migration, origins and destinations, urban migration, household characteristics, place of birth, return migration, and norms of family formation. (SUMMARY IN ENG)

This study presents a precision tunable cycle-accurate register transfer level (RTL) power estimation method based on a hybrid lookup table (LUT) and linear regression model. The authors' method pre-characterises the power profile for a set of atomic units (i.e. adder, multipliers, multiplexers) into an RTL library. This library consists of two parts: (1) an LUT to capture the non-linear behaviour of the atomic unit and (2) a linear regression equation for its regular activity. These non-linearities are treated as outliers of the linear regression and therefore removed from the linear regression data set into the LUT. Based on the precision requirements (quality of the estimation) their method stores more or less discrete values in the LUT library part. This method has been integrated into a high level synthesis (HLS) tool that generates specific RTL for power estimation where each atomic unit is instantiated with a shadow components that outputs its power consumption based on its inputs' activity. Experimental results for different precision requirements (outliers 3', 2' and 1' from the linear regression equation) show an improvement of the RMSE by 78, 82 and 90' and a maximum error reduction of 30, 34 and 54', respectively, at the expense of having to store 0.69, 4.05 and 15.09' of all the training set combination, respectively, in the LUT power library compared to the pure linear regression method.

Two types of cDNA (GTH alpha 1 and -alpha 2) encoding the alpha subunits of masu salmon (Oncorhynchus masou) gonadotrophin were cloned by the reverse transcription-polymerase chain reaction for pituitary mRNAs. The nucleotide sequences showed that the GTH alpha 1 cDNA was 380 bp long, encoding 119 amino acids, and that GTH alpha 2 cDNA was 365 bp long, encoding 114 amino acids. The masu salmon alpha subunit types had a few differences between the sequences, with homologies of 80% (nucleotide sequence) and 72% (amino acid sequence). The structural difference between the alpha 1 and alpha 2 subunits was predicted using hydropathic analysis. The evolutionary interval between masu and chum salmon was estimated to be 4.0 and 2.3 million years by comparing their GTH alpha 1 and -alpha 2 subunits respectively. These time values are roughly consistent with the evolutionary time interval (3.0 million years) estimated from fossil records and an isozyme study. Specific synthetic oligonucleotide probes were constructed and used for genomic Southern blot analyses. The restriction fragment sizes of the GTH alpha 1 and -alpha 2 genes were similar, and when their patterns were compared with those from four other teleosts, each species showed a different pattern from the others, but no difference between their respective alpha 1 and alpha 2 genes. Therefore, the structural features of the GTH alpha 1 and -alpha 2 genes may have diverged in a similar manner in these five teleosts.

The Lewy body (LB) is a cytoplasmic neuronal inclusion that is constantly found in the substantia nigra and locus ceruleus, and other specific brain regions in Parkinson's disease (PD). In the present study, the significance of non-parkinsonian cases in which the LBs were an incidental finding was investigated. In 1,452 autopsy series (age range, 1-89 years), 27 incidental cases of LBs and 21 patients with PD were found. The age-specific prevalence of incidental LBs steadily increased from 0.7% to 6.5% between the sixth and ninth decades. The distribution of LBs in incidental cases was similar to that in PD. The number of neurons in the substantia nigra and locus ceruleus was determined in 8 incidental cases (age range, 60-81 years), 9 patients with PD (range, 56-81 years) and 9 control subjects (range, 60-81 years). In incidental cases, the average numbers of pigmented neurons in the substantia nigra and locus ceruleus was 83% and 77% of those in control subjects, respectively. In PD, the average numbers of pigmented neurons in the substantia nigra and locus ceruleus was 28% and 19% those of controls, respectively. However, the number of nonpigmented neurons in the substantia nigra was not reduced in incidental cases and PD. From the above findings, it is suggested that there exists a close relationship between the occurrence of LBs and aging. However, in the brains of elderly patients, incidental LBs were considered to be pathological findings rather than simple aging phenomenon. Therefore, it has been suggested that incidental cases may represent early and presymptomatic cases of PD.

A 85-year-old man had undergone implantation of a transvenous pacemaker system in 1982. Nine years later the generator was explanted and he was underwent implantation of a new generator and electrode. After one year of the second operation, infection of the old electrode had been noted and it was not cured in spite of partial explantation of the infected electrode and appropriate antibiotic therapy. We decided to remove the infected electrode and succeeded in extraction using catheter and snare. The patient's recovery was uneventful. We suggest catheter and snare is useful for explantation of chronic transvenous pacemaker electrodes.

Polyclonal antibody was raised in rabbits against a synthetic hexapeptide R-K-V-D-V-R corresponding to a unique amino acid sequence of the neuron-specific c-src gene product pp60c-src(+). The antibody was purified by affinity chromatography. A single band with an apparent molecular mass of 60 kDa was recognized when the supernatant of homogenates of brain and spinal cord from chick embryos and chicks was probed with the affinity purified anti-hexapeptide antibody after SDS-polyacrylamide gel electrophoresis followed by Western blotting. Specificity of the antibody was further characterized by autophosphorylation assay of immunoprecipitate in comparison with the monoclonal antibody 327. Immunocytochemical studies by light microscopy revealed that pp60c-src(+) was localized in flake-like aggregates in neuronal cell bodies of the spinal cord in 7-15-day-incubated chick embryos and newly hatched chicks. Developing spinal ganglia and muscle cells were also immunoreactive at early developmental stages. By electron microscopy, the reaction product was observed mainly in two regions. One region was at polysomes and along the membranes of the rough endoplasmic reticulum. The other region was along the neuronal plasma membrane--at subsurface cisterns and at synapses. At synapses, the postsynaptic density, presynaptic membrane and synaptic vesicle membranes were immunostained. Immunoreactivity at synapses were more frequently observed at earlier stages than at later stages of development. These findings suggest that pp60c-src(+) is actively produced in developing neurons and has some important roles in synaptogenesis. In mature synapses, pp60c-src(+) may be involved in the interaction of synaptic vesicles with the presynaptic membrane.

During isometric contraction/activation of full-overlap and non-overlap live frog skeletal muscles, the intensity of the first thin filament layer line at the axial spacing of approximately 1/37 nm-1, when separated from the partially overlapping first thick filament layer-line at approximately 1/43 nm-1, remained unchanged in the inner radial region (0.02-0.08 nm-1) where a large intensity increase is observed in the rigor state. The intensity decreased in the outer radial region (0.08-0.18 nm-1) where this layer line is expected to peak in the resting state. The intensity decrease in the outer region became larger with increasing filament overlap; on activation of the non-overlap muscle, it was about half that of the full-overlap muscle. Thus the first thin filament layer line decreases in intensity and any indication of the rigor-like intensification is not observed at all during contraction. This intensity decrease can be attributed to the same structural changes giving rise to the intensity increase of the second thin filament layer line. The results indicate that the configuration of the myosin heads interacting with actin during contraction differs significantly from that of the rigor state. Four-fold rotational symmetry of the thin filament structure as a whole becomes more pronounced during isometric contraction of the overlap muscle.

We examined the reactivity of the N‐hydroxyamino derivative of a carcinogenic heterocyclic amine, 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP), after its O‐acetylation with four 2′‐deoxyribonucleoside 3′‐monophosphates. 32P‐Postlabeling analysis demonstrated that the levels of adducts with 2′‐deoxyguanosine 3′‐moiiophosphate were much higher than those with the other three nucleotides. 1H‐NMR, mass spectral and UV absorption spectral analyses of the major adducts formed by N‐acetoxy‐PhIP with 2′‐deoxyguanosine and with its phosphate esters indicated that PhIP bound at the C‐8 position of guanine, as previously demonstrated with other heterocyclic amines.

Cooked food contains a variety of mutagenic heterocyclic amines. All the mutagenic heterocyclic amines tested were carcinogenic in rodents when given in the diet at 0.01-0.08%. Most of them induced cancer in the liver and in other organs. It is noteworthy that the most abundant heterocyclic amine in cooked food, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, produced colon and mammary carcinomas in rats and lymphomas in mice but no hepatomas in either. 2-Amino-3-methylimidazo[4,5-f]quinoline induced liver cancer in monkeys. Formation of adducts with guanine by heterocyclic amines is presumably involved in their carcinogenesis. Quantification of heterocyclic amines in cooked foods and in human urine indicated that humans are continuously exposed to low levels of them in the diet. These low levels of heterocyclic amines are probably insufficient to produce human cancers by themselves. However, a linear relationship between DNA adduct levels and a wide range of doses of a heterocyclic amine was demonstrated in animals. It suggests that even very low doses of heterocyclic amines form DNA adducts and may be implicated in the development of human cancer under conditions in which many other mutagens-carcinogens, tumor promoters, and factors stimulating cancer progression exist.

UFT was orally administered at a dose of 600 mg/day as a preoperative chemotherapy for a 44-year old male with colon cancer. On the seventh day of the administration, severe anal bleeding occurred, and an emergent colectomy was performed. The macroscopic findings of the resected tumor were different from the first endoscopic picture, and the histopathological findings showed the significant effects of preoperative chemotherapy.

We carried out the ultracytochemical study of Ca(2+)-ATPase activity for the developing rat brain at embryonic day 11 (E 11), E 14, E 19 and postnatal day 5(P 5), and for the adult rat cerebrum. Matrix cells at E 11 and neuroblasts at E 14 showed no cytochemical reaction (CR) for Ca(2+)-ATPase activity. Glioblasts at E 19 showed very weak CR. Reaction product (RP) was observed on the surfaces of the neuronal and glial cells at P 5 and adult rat cerebrum. Microvessels at E 14 demonstrated no CR, but microvessels at E 19 showed CR, in which RP was, of a fine granular appearance, diffusely observed along the luminal and abluminal surfaces. At P 5, coarsened RP was diffusely observed on the luminal and abluminal surfaces. The CR for capillary Ca(2+)-ATPase activity in the adult rat cerebrum was found to be mild and the RP formed continuous and discontinuous thin layer on the abluminal surface. The results suggest that Ca(2+)-ATPase activity is closely related with development of the cells in the central nervous system.

To develop a homologous radioimmunoassay (RIA) for a hormone of a small or rare animal often meets difficulty in collecting a large amount of purified antigen required for antibody production. On the other hand, to employ a heterologous RIA to estimate the hormone often gives poor sensitivity. To overcome this difficulty, a "hetero-antibody" RIA was studied. In a hetero-antibody RIA system, a purified preparation of a hormone is used for radioiodination and standardization and a heterologous antibody to the hormone is used for the first antibody. Canine motilin and rat LH were selected as examples, and anti-porcine motilin and anti-hCG, anti-hCG beta or anti-ovine LH beta was used as the heterologous antibody. The sensitivities of the hetero-antibody RIAs were much higher than those of heterologous RIAs in any case, showing that these hetero-antibody RIA systems were suitable for practical use. To clarify the principle of hetero-antibody RIA, antiserum to porcine motilin was fractionated on an affinity column where canine motilin was immobilized. The fraction bound had greater constants of affinity with both porcine and canine motilins than the rest of the antibody fractions. This fraction also reacted with a synthetic peptide corresponding to the C-terminal sequence common to porcine and canine motilins in a competitive binding test with labeled canine motilin. These results suggest that an antibody population having high affinity and cross-reactivity is present in polyclonal antiserum and indicate that the population can be used in hetero-antibody RIA at an appropriate concentration.

China conducted its 4th national population census in July 1990 for entire population. Its population count, numbering 1,133,682,501, was obtained in face-to-face interviews with people holding citizenship in the People's Republic of China and who resided on the mainland. Compared with the figures in the 1982 census, 6 minority nationalities have increased their populations by 100% over the past 8 years. This was due to the changes in historical policies and the special protection and privileges they have obtained since 1978. These groups may have 2 children and even 3 under certain special conditions through the practice of family planning. They may also marry 2 years earlier than the marriage age prescribed by law. These differences have come from the 1-child policy which has excluded minority nationalities since 1979. Secondly, marriages between the Han and the minority nationalities have increased. Their children are reported mostly as minority nationalities so that their numbers have been on the increase. The preferential policies for minority nationalities have raised their potential, social, and economic standing from one of being discriminated against to one of autonomy. Concrete examples are: relaxation of family planning guidelines; preferential treatment in admission to higher schools; preferential treatment for dormitory expenses and scholarship; advantages in getting jobs or positions of a cadre; and grant-in-aid. Thirdly, prior to 1978, minority nationalities were looked down upon and thus, they frequently concealed their origins and lived as the Han. Later, most of them officially admitted and reported their backgrounds, which resulted in an increase in numbers. There were many people who revised their nationalities since 1978 and most of them changed from the Han to minority nationalities. (author's modified)

The author discusses some results from the 1990 census of China and makes comparisons with data from the 1982 census.

2‐Amino‐l‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP), the most abundant mutagenic heterocyclic amine in cooked foods, was examined for carcinogenic potential using Nagase analbuminemic rats (NARs), which are sensitive to various carcinogens. The concentration of PhIP in the diet was 0.04% at the beginning of the experiment, this being subsequently gradually reduced to 0.01% to avoid severe body weight loss. Ten of 13 treated NARs developed a total of 36 intestinal tumors within the 311‐day experimental period. Among these, 22 were adenocarcinomas and 2 were adenomas of the small intestine, 4 were adenocarcinomas of the cecum and 8 were adenocarcinomas of the large intestine. The results suggest that PhIP could represent a significant risk to human populations exposed to foods containing heterocyclic amines.

In order to evaluate the possibility of left ventricular assistance by latissimus dorsi (LD) myograft, we have studied contractile property and fatigue rates of skeletal muscle ventricle (SMV) constructed using canine LD muscles. Twenty three dogs were divided into 3 groups depending on the conditioning protocol of LD muscles; Group I (Control n = 12), Group II (Vascular delay n = 4) and Group III (Vascular delay and electrical preconditioning n = 7). SMVs in GIII dogs generated sufficient pressure and forward flow in a hydraulic test system with muscle stimulation at a burst-frequency of 50 Hz (SMV pressure 131 +/- 42 mmHg, Stroke volume 7.0 +/- 3.0 ml/beat). Although SMVs in GI and GII dogs could sustain flow for only 4.0 +/- 1.1 minutes and 32.4 +/- 14.0 minutes, respectively, SMVs in GIII were able to pump continuously for 107.5 +/- 15.0 minutes (p less than 0.01, vs GI and GII). Thermography surface temperature mapping revealed marked improvement of blood distribution of LD muscles in GII and GIII dogs. Flow rates of thoracodorsal artery during SMV stimulation were GI: 10.0 +/- 3.1 ml/minute/LD 100 g, GII: 15.0 +/- 3.7 ml/minutes/100 g and GIII: 20.7 +/- 2.5 ml/minutes/100 g (p less than 0.01 vs GI). The ratio of oxygen consumption to lactate output was GI: 0.33 +/- 0.10, GII: 0.36 +/- 0.09 and GIII: 1.56 +/- 0.97 (p less than 0.01 vs GI, p less than 0.05 vs GII). Histochemical examination of LD muscles using alkaline ATPase stain revealed muscle fiber type transformation of GIII muscles. These results suggest electrically preconditioned LD muscles have sufficient contractile property for partial left ventricular assistance, and highly fatigue-resistant properties resulted from muscle fiber transformation, improved muscle perfusion and metabolic changes.

Time-resolved X-ray equatorial diffraction studies on a single frog skeletal muscle fiber were performed with a 10 ms time resolution using synchrotron radiation in order to compare the time courses of the molecular changes of contractile proteins and the intracellular Ca2+ transient during an isometric twitch contraction at 2.7 degrees C. Measurements of the Ca2+ transient using aequorin as an intracellular Ca2+ indicator were conducted separately just before and after the X-ray experiments under very similar experimental conditions. The results, which showed a similar time course of tension to that observed in the X-ray experiment, were compared with the aequorin light signal, tension and the intensity changes of the 1,0 and 1,1 equatorial reflections. No appreciable change in both reflection spacings indicated that the effect of internal shortening of the muscle was minimized during contraction. The intensity change of the equatorial reflections generally occurred after the aequorin light signal. In the rising phase, the time course of increase in the 1,1 intensity paralleled that of the rise of the light signal and the intensity peak occurred 20-30 ms after the peak of the light signal. The decrease in the 1,0 intensity showed a time course similar to that of tension and the intensity minimum roughly coincided with the tension peak, coming at 80-90 ms and about 60 ms after the peaks of the light signal and the 1,1 intensity change, respectively. In the relaxation phase, the 1,1 intensity seemed to fall rapidly just before the tension peak and then returned to the original level in parallel with the decay of tension. The 1,0 intensity returned more slowly than the tension relaxation. Thus, the change of the 1,1 intensity was faster than that of the 1,0 intensity in both the rising and relaxation phases. When the measured aequorin light signal was corrected for the kinetic delay of the aequorin reaction with a first-order rate constant of either 50 or 17 s-1, the peak of the corrected light signal preceded that of the measured one by approx. 30 ms. Thus, the peak of the Ca2+ transient appeared earlier than the peaks of the 1,1 and 1,0 intensity changes by 50-60 and 110-120 ms, respectively. The time lag between the extent of structural change and the Ca2+ transient is discussed in relation to the double-headed attachment of a cross-bridge to actin.

We have studied contractile property and fatigue rates of skeletal muscle ventricle (SMV) constructed using the latissimus dorsi muscles of 11 dogs. The role of early interruption of collateral blood supply in the prevention of muscle ischemia and SMV fatigue was evaluated. Systolic function of SMV was measured in a hydraulic test system; afterload was set at 70 mmHg and preload 15 or 25 mmHg. Control SMV (GI: N = 7), which was fashioned immediately after interruption of collateral blood supply, generated an initial SMV pressure of 222 +/- 50 mmHg and stroke volume of 15 +/- 7 ml/beat with muscle stimulation at a burst-frequency of 50 Hz, but could sustain flow for only 3.5 +/- 0.8 minutes. SMV subjected to a vascular delay (Group II: N = 4) demonstrated improvement of fatigue rates; duration of flow 32.4 +/- 14.0 and sufficient contractile property (initial SMV pressure 182 +/- 17 mmHg, stroke volume 1- +/- 2 ml/beat). Thermography surface temperature mapping revealed remarkable improvement of blood distribution in GII muscles. Flow rates of thoracodorsal artery were significantly greater in GII muscles compared to those in GI muscles (15.0 +/- 3.7 ml/min/LD 100 g, 10.1 +/- 3.1 ml/min/LD 100 g, p less than 0.05, respectively). Despite significant improvement of functional durability in GII muscles, the ratio of oxygen consumption to lactate output was not different between 2 groups. These results suggest that early interruption of collateral blood supply can minimize muscle ischemia, resulting in diminishing fatigue of latissimus dorsi muscles without changes in skeletal muscle metabolism.

The retinal toxicity of vancomycin and ofloxacin was studied by electroretinogram (ERG) recorded before and after intravitreal injection in rabbits. A dose of 1.0 mg vancomycin caused no change in the ERG for at least 8 weeks after the injection. The ERG was nonrecordable during one to four weeks after an intravitreal injection of 10 mg vancomycin, with recovery of only the c-wave. A dose of 200 micrograms ofloxacin did not cause deterioration of the b-wave, the c-wave or the oscillatory potentials throughout the follow-up period of 8 weeks. Considering the individual susceptibility of the ERG components to these antimicrobial agents and taking into account the difference in vitreous volume between the rabbit and man, the results of this study indicate the recommended intravitreal doses of these antimicrobial agents for clinical use are as follows: vancomycin 1.0 mg/0.1 ml, and ofloxacin 200 micrograms/0.1 ml.