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The nuclear matrix is an operationally defined nuclear skeletal structure that is believed to be involved in many nuclear functions including DNA replication, transcription, repair, and prem RNA processing/transport. Until relatively recently, the nuclear matrix was thought to be a rigid and static structure, but it is now thought to be dynamic. This paradigm shift was based in part on the tracking of the intranuclear movement of proteins tagged with fluorochromes. In this review, we attempt to redefine the nuclear matrix in light of recent findings and describe some useful techniques for the dynamic analysis of nuclear function.

Changes in brain vascularity in adult rats during adaptation to chronic normobaric hypoxia with or without elevated CO(2) were morphometrically investigated. Immunohistochemistry with anti-rat endothelial cell antigen (RECA-1) antibody was carried out for the vascular analysis. After the rats were subjected to hypoxia for 2 to 8 weeks (wks)(10 percent O(2) in N(2)), the total area of blood vessels was measured in 6 brain regions. After 2 wks of hypoxia, the blood vessel area was found to be significantly increased in the frontal cortex, striatum, hippocampus, thalamus, cerebellum, and medulla oblongata, by 44% , 96% , 65% , 50% , 102% and 97% , respectively. The ratio of large vessels with an area > 500 micro m(2) was also increased in all brain regions. Hypoxic adaptation in brain vascularity did not change during 8 wks of hypoxia, and the hypoxia-induced levels measured in the vasculature returned to control levels 2 wks after the termination of hypoxia in areas of the brain other than the cortex and thalamus. In addition, hypoxia-induced changes in terms of the total vascular area and vessel size distribution were significantly inhibited by the elevation in CO(2), whereas chronic hypercapnia without hypoxia had no effect on brain vascularity. These findings suggested that adaptations in brain vascularity in response to hypoxia are rapidly induced, and there are regional differences in the reversibility of such vascular changes. Carbon dioxide is a potent suppressor of hypoxia-induced vascular changes, and may play an important role in vascular remodeling during the process of adaptation to chronic hypoxia.

Spleen cells from tumor-bearing mice showed decreased natural killer (NK) activity and decreased binding to target cells with progression of the tumor. Treatment of spleen cells from tumor-bearing mice with vibrio cholerae neuraminidase (VCN) increased the cytotoxicity to a level twice or more as high as that of untreated cells, but the same treatment of spleen cells from normal mice had no or little effect. On the other hand, neither in spleen cells from tumor-bearing mice nor in those from normal mice, the VCN treatment had no effect on their binding to M-HeLa cells. The suppression of NK activity by preincubation with serum from tumor-bearing mice or prostaglandin E2 was completely abolished by VCN treatment. The above results indicate that VCN treatment of lymphocytes might augment NK activity by an antagonistic effect against an immune suppressive factor.

The elimination of fibroblast-like cells from primary cultures of fetal human livers was studied. A fibroblast-like cell line (HuF), which was obtained by subculturing fetal human liver cells 4 or more times, was briefly treated with hydrocortisone (HC) or putrescine (PUT). The growth of HuF cells was inhibited by HC at a concentration of 10(-2) M and by PUT at a concentration higher than 10(-3) M. Long-term treatment of HuF cells with 10(-3) M HC inhibited the growth of the cells. Primary cultures of fetal human livers were made in medium containing HC or PUT, and morphological and functional examinations were made. The cultures were predominantly composed of epithelial-like cells, with few fibroblast-like cells, when the HC concentration was 10(-5)M to 10(-3) M. A high amount of albumin was secreted at these concentrations of HC. On the other hand, at 10(-3) M PUT, many epithelial-like cells were seen, but albumin was undetectable. The present results indicate that albumin-producing epithelial-like cells can be selectively maintained in medium containing HC, in primary cultures of fetal human livers.

The cause of the death due to the atomic-bomb radiation is yet unknown definitely and the same can be said of shock brought about by the atomic-bomb. It cannot be said with certainity that infection of pathogenic bacteria concerns in the mortality, for even minor injuries did not often escape bacterial invasion from any part of the whole body. In this case the progress was same to a symptom of agranulocytosis, namely collapse, chill, fever, red throat or ulcerative stomatitis and from the reason of the heavily infected tonsils, although cultures were not made, there are reasons to consider it as agranulocytosis angina. The interpretation of the histologic changes observed in this patient, is rendered difficult not only by the factor of infection, but by the possible influence of one damaged organ upon another. From the histological changes there were the destruction of the epithelium of the gastro-intestinal organs, the atrophy of the testis and the necrosis of the tonsils, but the most noteworthy was the changes in the bone-marrow. The hyperplasia of the reticulum cells, the disappearance of the hematopoetic foci, and the great quantity of mitotic figures in the myeloid cells observecl in this case are found in many of the atomic-bomb victims died approximately one month after the exposure. This is a case of the death caused by aplastic anemia with infective complication or in orther words symptomatic agranulocytosis caused by the atomic-bomb radiation with sepsis.

1. When hemolysed blood is administered orally to rabbits, in cases of healthy and those with blocked reticulo-endothelial systems, a transient increase in the verdohemoglobin (M. Engel) is seen in circulating blood, while in that of rabbits with impaired parenchymal liver cells, no such increase occurs. 2. On irrigation of hemolysed blood through rabbit livers, in healthy rabbits production of indirect bilirubin may be demonstrated while in that with blockage of the reticulo-endothelial system or with impaired liver parenchymal cells, this may not be seen. Moreover, in this case of blockade of the reticulo-endothelial system. production of verdohemoglobin may be demonstrated. while none whatsoever may be demonstrated in cases of impaired liver parenchmal. On the other hand on irrigation of verdohemoglobin and biliverdin solutions, in healthy and in impaired liver parenchymal cell cases, production of bilirubin may be observed while absolutely none was detected in cases of blocked reticulo-endothelial systems, 3. Concluding from the results stated above and those of clinical experiments stated elsewhere, the following process is assumed: when blood is imposed on the organism it is primarily phagocytosed by the reticulo-endothelial system, next dissolved to verdohemoglobin {M. Engel) in the parenchymal cells of the liver, and then dissolved into globin, iron, and biliverdin in the reticulo-endothelial system, of which biliverdin is further reduced to bilirubin. A portion of this remains in the circulating blood as indirect bilirubin, while the majority of it is esterized in the parenchymal cells of the liver, and proceeds to the bile ducts as direct bilirubin.

To investigate the effect of exclusive breastfeeding on the likelihood of Japanese preschool children being overweight, population-based cross-sectional survey data from M town in Japan were used. Using the population registry of this town, all 616 preschool children were identified, and a self-administered questionnaire was sent to their parents. The exposure variable of interest was exclusive breastfeeding from birth to 6 months, and the outcome variable of interest was the children being overweight at preschool age. Statistical analyses used included logistic regression and sensitivity analyses. In the final analyses, we included 448 preschool children. Although all point estimates indicated a protective effect, logistic regression analyses showed no significant reduction in being overweight due to exclusive breastfeeding in the unadjusted model (odds ratio (OR)0.70, 95% confidence intervals:0.30-1.64), the model adjusted for birth weight (OR0.70, 95% CI:0.30-1.63), the model adjusted for child lifestyle (OR0.71, 95% CI:0.30-1.67), or the model adjusted for parental factors (OR0.46, 95% CI:0.15-1.37). In sensitivity analyses, point estimates were not significant, but a protective effect was observed. In conclusion, our results suggest that breastfeeding might have a protective effect on Japanese preschool children against being overweight, although statistical significance was not observed due to the limitation of the statistical power of the findings.

Die oben erwahnten Ergebnisse lassen sich dahin zusammenfassen, daB das Hynobius aus Okayama-Ken bei einem 8 mm langen Embryo etwa vor dem 1 . Kiemengang, fast an ihn angrenzend, beiderseitig symmetrisch je eine Verdickung des Epithels zum Vorschein bringt. Diese Verdickung besteht wie die anderen Abschnitte der Oberhaut aus zweischichtigem Epithel, aber die Zellen des Epithels sind sehr verdickt. Dies ist die erste Anlage der Balancier stangen. Mit der Entwicklung des Organismus verlangert sich diese Verdickung ventrokaudalwarts, nimmt eine rundlich kanalartige Stabchenform an, welche mit den Zellen der zwei Schichten bedeckt ist und in ihr Kanallumen Mesenchymzellen und BlutgefaBe in kleiner Anzahl einschlieBt. Bei einem Embryo von 12mm Lange wird sodann innerhalb des Kanallumens unmittelbar unter den Innenschichtzellen eine strukturlose, stark lichtbrechende Basalmembran gebildet, bei einem Embryo von 18mm Lange entspringen aus dem ventralen Rand des Palatoquadratums und des M. depressor mandibularis eine kleine Menge Mesenchymzellen, die den Anschein haben, als ob sie die Wurzel der Stange abschnuren wollten. Bei einem Embryo von 19mm Lange ist die rechtsseitige Stange noch unbeschadigt vorhanden, wahrend die linksseitige fast ganzlich verloren gegangen ist und eine kleine Vorwolbung der am Basalteil befindlichen Oberhaut als Uberrest zuruckgelassen hat. An dieser Vorwolbung findet man, daB der mit der Innenschicht der Oberhaut kombinierte Abschnitt eine erhebliche Zellwucherung erfahrt und infolge von Anhaufung der Zellen sich zu einer Kugel gestaltet, die mit einer Schicht der AuBenschichtzellen bedeckt ist. Die Innenschichtzellen dieses Abschnittes scheinen also durch ihre betrachtliche Wucherung den Basalteil der Balancierstangen zu verschlieBen.

Trimebutine at low concentrations (6 X 10(-9)-1.4 X 10(-8) M) slightly enhanced the twitch response of isolated guinea pig ileum induced by transmural stimulation. At high concentrations (2 X 10(-8)-2 X 10(-7) M), however, it inhibited the twitch response in a dose dependent manner. This inhibitory effect of trimebutine was reversed by naloxone (8.1 X 10(-9) M). These results suggest that trimebutine has an opiate-like action on the myenteric plexus.

A clinical trial was performed to investigate the efficacy of hyperthermia in combination with chemotherapy for gynecological malignancies. Sixty-nine patients with vaginal or vulvar malignancies (9 primary vulvar, 3 recurrent vulvar, 11 primary vaginal, 4 primary cervical, 40 recurrent cervical, and 2 recurrent ovarian carcinomas) were treated by thermochemotherapy (42 cases) or chemotherapy alone (27 cases). After treatment, 7 patients underwent surgery and 46 patients irradiation. The chemotherapeutic schedule was mainly a combination therapy with bleomycin and mitomycin C (B-M). Microwaves of 2.45 GHz were applied to induce local hyperthermia. The side effects of chemotherapy were not increased by hyperthermia. The rate of partial response plus complete response increased to 84% (16/19) in primary cancers and 45% in recurrent cancers by hyperthermia, compared to the respective values of 40% (2/5) and 17% (3/17) for chemotherapy alone. However, a satisfactory prognosis cannot be expected with thermochemotherapy, unless additional treatments are performed. Subsequent surgery or radiation treatment improved the progression-free interval.

Gastroparesis is a frequent and sometimes life-threatening complication of diabetes mellitus. Autonomic neuropathy seems to be one of the most important mechanisms underlying this entity, together with the other probable pathologies. The present study was performed in order to identify an alternative to gastric scintigraphy as a screening test. The gastric emptying times of 60 subjects (Group 1: 20 insulin-dependent patients, Group 2: 20 non-insulin-dependent diabetes mellitus patients, and Group 3: 20 healthy volunteers) were monitored by gastric scintigraphy. Perception thresholds for cold, heat, and vibration were tested by a quantitative sensory test, and QTc dispersions were calculated from standard electrocardiography recordings. In addition, fasting blood glucose, hemoglobin A1c and urine beta2-microglobulin and microalbumin concentrations were determined for the patient groups. Funduscopic examination was performed by an independent ophthalmologist. Gastroparesis was determined in both patient groups, regardless of fasting blood glucose and hemoglobin A1c concentrations. A strong correlation was observed between nephropathy, retinopathy, and cardiac autonomic denervation (QTc) and gastroparesis. In conclusion, retinal and renal microvasculopathy parameters and cardiac autonomic function tests may be useful for screening diabetic patients for gastroparesis.

Pathologic features of Mycoplasma pneumoniae infection (M. pneumonia) are generally non-specific, and the literature regarding the pathologic features of M. pneumonia with intraalveolar exudates is limited. Clinical and histopathological studies were performed in 3 patients with M. pneumonia which did not respond to erythromycin and minocycline, but all rapidly recovered after corticosteroid therapy. In pathologic findings, we observed intraalveolar exudates and focal organization in M. pneumonia, and its intraalveolar lesions were compared between M. pneumonia and bronchiolitis obliterans organizing pneumonia containing fibrin (BOOP). Immunohistochemical studies were performed using the streptavidin biotin peroxidase complex method with anti-alpha-smooth muscle actin antibody and anti-pancytokeratin AE1/AE3 antibody. In pathologic findings, more fibrin deposits in intaalveolar lesions were observed in M. pneumonia than in BOOP. In intaalveolar lesions of M. pneumonia, a larger amount of nuclear debris, more neutrophils, and more erythrocytes were noted. Myofibroblasts were observed in the organization of BOOP, while in the intaalveolar lesions of M. pneumonia, myofibroblasts were not observed. These results suggest that M. pneumonia with intraalveolar exudates responds well to corticosteroid and its intraalveolar lesions apparently differed from those in BOOP.

The association between depressed mood and condom use was examined among incarcerated male adolescents. One hundred and eighty male adolescents who were detained in Birmingham, Alabama in the United States were interviewed during a period of incarceration. Contrary to patterns generally found in adult samples, nearly 50% of this adolescent sample that did not use condoms regularly actually recognized the advantages of condom use. This behavior pattern was deemed "inconsistent," and those engaging in this "inconsistent" behavior pattern were found to have a higher score of depressed mood compared to participants with a "consistent" behavior pattern. As a result, a relationship between depressed mood and decisional balance for condom use within adolescents was evident. These findings suggest that assessment and treatment of depressed mood within this high-risk population could potentially contribute to a reduction in high-risk sexual behaviors.

Separation of the urinary ester-form bilirubin was attempted, and the results obtained may be summarized as follows: 1. A brown pigment was obtained from jaundiced urine by the following procedures; namely, salting out, methanol extraction, chloroform flocculation, and separation on cellulose column. The pigment has been found to be easily soluble in water, displaying the absorption maximum at 420 - 410 mμ at pH 7.0, and it also gave a positive reaction both to GMELIN's and EHRLICH's diazo reagents within a minute without the addition of alcohol. These characteristics agree well with those of the socalled ester-form bilirubin. 2. On the basis of the results of paper chromatography and paper electrophoresis, the pigment has been determined to contain no amino acid, steroid, nor reducing substance. Moreover, no glucuronic acid could be detected whether examined in vitro or by paper chromatography together with paper electrophoresis, either.

The effects of thimerosal, a sulfhydryl oxidizing agent on nitrergic, endothelium-dependent and -independent relaxations were investigated to examine the possibility that the nitrergic neurotransmitter and endothelium-derived relaxing factor (EDRF) could be S-nitrosothiol or free nitric oxide (NO) in the isolated mouse corpus cavernosum. Thimerosal (5 x 10(-6)-2 x 10(-5) M) inhibited or almost abolished electrical field stimulation--(EFS, 30V, 0.5 ms, 15 sec, 1, 2, 4, 8, 16 Hz), acetylcholine--(ACh, 5 x 10(-8)-1.25 x 10(-6) M), glyceryl trinitrate--(GTN, 3 x 10(-7)-3 x 10(-6) M), and S-nitrosoglutathione--(GSNO, 5 x 10(-6)-1.25 x 10(-4) M) induced relaxations. Thiomerosal inhibition seems to be specific to L-arginine NO pathways since it had no effect on acidified sodium nitrite--(10(-4)-5 x 10(-4) M), photoactivated sodium nitrite--(2 x 10(-4) M), isoprenaline--(10(-6) M), or papaverine--(10(-4) M) elicited relaxations. Moreover, the inhibitory effect of thimerosal on the nitrergic, ACh- or GTN-induced relaxations were partly reversed by sulfhydryl-containing compounds, L-cysteine (10(-3) M), dithiothreitol (10(-3) M), or glutathione (10(-3) M). However L-methionine (10(-3) M), which contains a methyl group on the sulphur atom, failed to restore the thimerosal inhibition. Thimerosal did not change the contraction produced by 10(-4) M NG-nitro-L-arginine methyl ester. These findings indicate that the nitrergic neurotransmitter as well as EDRF may not be free NO but NO-transferring molecules, probably S-nitrosothiols, in the mouse corpus cavernosum.

The effects of levocabastine, a novel histamine H1-receptor antagonist, on lipid mediator release induced by antigen-antibody reaction from actively sensitized guinea pig lung fragments were studied. Levocabastine dose-dependently inhibited the release of leukotriene C4 from guinea pig lung fragments induced by antigen. A significant effect was observed with levocabastine at a concentration of 10(-4) M. On the other hand, levocabastine produced no effect on the release of leukotriene E4 or thromoboxane B2. From these findings, it was concluded that levocabastine may be useful for relieving the nasal obstruction in allergic rhinitis caused by inhibition of leukotriene C4 release.

The influence of mild exercise on skeletal muscle fibers was investigated histochemically to assess the effects of exercise on steroid myopathy and its efficacy for preventing this disease. Twenty male Wistar rats were divided into 4 groups of 5 each: group T, which received exercise alone; group S which received steroid alone; group ST which received both exercise and steroid; and group C, the control group. In groups S and ST, hydrocortisone was administered subcutaneously at a dose of 10 mg/kg/day for 4 weeks. In the exercise groups, the animals were made to run at a speed of 15 m/min for about 1 h/day for 5 days a week on a treadmill. After the completion of treadmill exercise and steroid administration for 4 weeks, the rats were anesthetized with Nembutal, the soleus muscle (SOL) and the extensor digitorum longus muscle (EDL) were removed and prepared for examinations. The area of type I fibers in the SOL was significantly larger in group ST than in group S. The area of type IIa fibers in the EDL was significantly larger in group ST than in group S. In group S, the proportion of type I fibers in the SOL was significantly lower than in the other three groups. There was little difference in fiber type distribution between groups ST and C. These results suggest that steroid myopathy can be prevented by even mild exercise.

Doppler left ventricular (LV) inflow is reportedly affected by LV diastolic properties. We evaluated 48 subjects consisting of 27 patients with chronic mitral regurgitation (MR) and 21 patients with noncardiac disorders who received echocardiographic examinations. The deceleration rate divided by diastolic dimension (DR/Dd) derived from Doppler early diastolic LV inflow was correlated with the peak diastolic velocity divided by diastolic dimension (peak DV/Dd), a conventional index of LV diastolic function derived from the M-mode echocardiogram in the 48 patients, regardless of the presence of normal sinus rhythm or atrial fibrillation. LV diastolic function was then estimated by comparing perioperative echocardiographic examination and LV micro-and ultrastructural findings of biopsy specimens from 12 patients with MR who received mitral valve replacement. Fiber diameter, volume fraction of interstitial fibrosis (int. % Fib), and volume fractions of three intracellular components; the myofibrils (% MF), the sarcoplasmic reticulum (% SR) and the mitochondria (% MT), were measured in LV transmural biopsy specimens. DR/Dd was significantly correlated with peak DV/Dd before and after operation. Peak DV/Dd and DR/Dd were inversely correlated with int. % Fib and % SR, and were positively correlated with % MF. We subdivided the 12 MR patients according to their postoperative DR/Dd values as "recovered", and "non-recovered" based on their postoperative LV diastolic function. % MF was significantly lower in the 'non-recovered' group. Thus, DR/Dd can serve as an index of LV diastolic function. A decrease in % MF may inhibit the recovery of postoperative LV diastolic function.

1. When the various anticancer agents are injected intravenously to normal rabbits and intraperitoneally to normal mice, it seems that the serum properdin levels fall transitorily for some hours after administration with a small dose and then keep rising, but with a massive dose it continues to fall from the beginning. 2. The properdin level is decreased considerably by Thio-TEPA and Carzinophilin; moderately by Mitomycin C; and slightly by M. H. OX-substance hardly changes the level and 8-azaguanine rather has a tendency to raise the level. 3. The administration of most anticancer agents seems to suppress the properdin system. 4. The influence of these agents on human serum properdin is similar to that of rabbits. 5. The properdin levels keep at high titers in the group to which the agents act effectively on the cancer, but the levels fall down more rapidly and animals die earlier in the group to which the agents act ineffectively on the cancer as compared with the control group.

The author examined with electron microscope the rod-shaped bacteria obtained from the human mouth, which were peritrichous and Gram stain positive. Observations revaled the granules of 15 mμ-25 mμ in size being arranged neatly and hexagonally in the cell wall. Moreover, these granules were found to detach themselves quite readily by a slight physical process, disclosing the underlying layer. These seemed to show most probably a portion of the fine structure in the cell wall of an unidentified bacterium from the human mouth.