Until this report, there have been no detailed analyses of the mouse mammary tumor virus (MMTV) loci in the mammary tumor prone strain SHN. Using a probe, which hybridizes to the env sequence of MMTV, Southern blotting of genomic DNA from the brain after digestion with EcoRI revealed 5 endogenous proviruses: Mtv-1 (4.5kb), Mtv-2 (11 kb), Mtv-8 (6.7kb), Mtv-17 (8.3kb) and a newly-found 6.5-kb fragment. F1-hybrid mice (C3H/He female x SHN male) also possessed the 6.5-kb fragment. Thus, we conclude that the 6.5-kb fragment is unique to SHN mice. Genomic DNA from mammary tumors of SHN mice showed MMTV insertions, suggesting that activation of an oncogene(s) occurred in this strain.

Animals↗

PubMed1990

Tumor growth inhibitory activity of a lymphocyte blastogenesis inhibitory factor.

A lymphocyte blastogenesis inhibitory factor (LBIF) has been characterized as an immunoregulatory molecule, especially on the T-lymphocyte proliferation. Using fast protein liquid chromatography-purified LBIF, we examined the effect of LBIF on the proliferation of various 18 tumor cell lines in vitro in comparison with those of interferon-alpha, interferon-gamma, tumor necrosis factor-alpha, transforming growth factor-beta 1, or interleukin 1 alpha/beta. We showed here that LBIF strongly inhibited the proliferation of various tumor cell lines irrespective of cell lineage or species. LBIF was effective on a wider spectrum of tumor cell lines than other cytokines tested here. The inhibition resulted from cytotoxic or cytostatic effects, depending on individual characteristics of tumor cell lines. Five cell lines showed insensitivity against LBIF activity, suggesting a plausible involvement of LBIF receptor molecules to transduce LBIF signals. These results suggest that LBIF may play important roles in regulating cell growth.

Adjuvants, Immunologic↗

PubMed1990

Impaired polymorphonuclear leucocyte function in patients undergoing hepatectomy: adenylate energy charge and superoxide anion production in relation to hepatic mitochondrial redox state.

Patients undergoing hepatectomy have an increased susceptibility to infection. We therefore studied the energy metabolism of the polymorphonuclear leucocyte (PMN), focusing on energy charge and function, especially superoxide anion (O2-) generation, in relation to the hepatic mitochondrial redox state. By labelling the PMN adenine nucleotide pool with radioactive adenine and by superoxide dismutase-inhibitable reduction of ferricytochrome c, the energy charge and O2- production was measured in 18 patients with hepatoma (non-cirrhotic, seven; cirrhotic, 11) undergoing hepatectomy. Their arterial ketone body ratios (KBRs), reflecting the hepatic mitochondrial redox potential, were above 0.7 before operation. After surgery, the 18 patients were divided into two groups: group A, KBR greater than 0.7, n = 10; and group B, KBR less than 0.7, n = 8. The energy charge and O2- release in group B decreased significantly from preoperative values (P less than 0.001 and P less than 0.01 respectively) and when compared with group A (P less than 0.05 and P less than 0.01 respectively). These results suggest that impaired hepatic energy metabolism (KBR less than 0.7) in hepatectomized patients leads to impaired energy charge and O2- production in the PMNs.

Adenine Nucleotides↗

PubMed1990

Accuracy of 20-MHz Doppler catheter coronary artery velocimetry for measurement of coronary blood flow velocity.

The accuracy of 20-MHz Doppler catheter coronary artery velocimetry (Millar Instruments) was evaluated by model experiments using a turntable and a flow tube. In the turntable experiments, the flow away from the catheter tip (away flow) was significantly lower than that toward the catheter (toward flow), but the measured velocities for both away and toward flows were always lower than the known velocities. Nevertheless, the blood velocities measured at a sampling point 4 mm from the catheter tip showed excellent correlation with the known velocities irrespective of flow direction. The shape of the FFT spectra of the Doppler shift frequency from blood was broadened, and the frequency corresponding to the known velocity was always close to the maximum Doppler shift frequency. We concluded that zero-cross detection of blood velocity by the 20-MHz pulsed Doppler catheter provides a reliable measure for evaluating relative velocity changes, although it underestimates the blood velocity.

Blood Flow Velocity↗

PubMed1990

Abnormal behavior of gamma-committed B lymphocytes probed by a lymphocyte blastogenesis inhibitory factor in autoimmune MRL mice.

Recently, we have characterized a lymphocyte blastogenesis inhibitory factor (LBIF) which was purified from the culture supernatant of a human histiocytic lymphoma U-937 (Sugimura, K. et al., Eur. J. Immunol. 1989. 19: 1357). In this study, we investigated the effect of LBIF on the antibody production of autoimmune MRL mice in vitro. We demonstrated here that (a) LBIF inhibited the IgM, IgG and IgA antibody responses of lipopolysaccharide (LPS)-stimulated spleen cells of normal BALB/c mice, (b) in the case of old autoimmune MRL/Mp-lpr/lpr (MRL/l) and MRL/Mp-(+)/+ mice, however, LBIF inhibited IgM and IgA but not IgG responses of LPS-stimulated spleen cells, (c) the antibody production of all IgG subclasses, IgG3, IgG1, IgG2b and IgG2a, was not sensitive to LBIF inhibitory activity in these autoimmune mice, (d) in young MRL mice (3-5-week-old MRL/l), which were phenotypically normal, LPS-induced antibody production of all isotypes (IgM, IgG and IgA) was strongly inhibited by LBIF as shown in normal BALB/c mice and (e) in the case of 7-week-old MRL/l the insensitivity to LBIF was concomitant with the appearance of gamma + B lymphocytes. Thus, by employing LBIF as a probe, this study showed a correlation between the pathogenesis of MRL autoimmune disease and the lack of LBIF sensitivity of hyperactive B lymphocytes and suggested that the intrinsic abnormality of autoimmune MRL B lymphocytes might be confined to gamma- but not mu- or alpha-committed B cells.

Animals↗

PubMed1990

"Quadriceps myopathy": a clinical variant form of Becker muscular dystrophy.

A 26-year-old male with "quadriceps myopathy" is presented. He had a family history and only the bilateral quadriceps were wasted, without symptomatic weakness. The specimen of the muscle biopsy showed typical myopathic features without inflammatory reactions. The patchy defect of muscular dystrophin was proved by immunohistochemical study. Dystrophin analysis revealed abnormal 380 kDa dystrophin. Gene deletion was proved at exon 45-48 of Xp21 without frameshift. This case was considered to be a clinical variant form of Becker muscular dystrophy.

Adult↗

PubMed1990

A lymphocyte blastogenesis inhibitory factor (LBIF) reversibly arrests a human melanoma cell line, A375, at G1 and G2 phases of cell cycle.

A lymphocyte blastogenesis inhibitory factor, LBIF, has been found in the culture supernatant of a human macrophage-like cell line, U937. The factor has been purified by fast protein liquid chromatography. Partial amino acid sequencing analysis showed that LBIF was a novel immunoregulatory factor. Recent study has demonstrated that LBIF possesses a remarkable tumor growth inhibitory activity. In this study, the cell growth inhibitory activity of LBIF was characterized on the proliferation of a human melanoma cell line A375 in vitro. LBIF strongly inhibits the proliferation of A375 cells. The inhibitory activity was cytostatic and reversible by Day 5 although the lethal effect became apparent at Day 7. Cell cycle analysis by flow cytometry showed that LBIF arrested A375 cells at both G1 and G2/M phases. Mitotic index analysis indicated that A375 cells were arrested in G1 and G2 phases. LBIF function was not attributed to the elevation of intracytoplasmic cyclic-AMP levels. Thus, these results suggest that LBIF plays an important role in controlling cell cycle and there is a similarity between the mechanisms of G1 and G2 arrests in eukaryotic cell proliferation. LBIF-induced reversible cell-cycle arrest of A375 cells can be a useful system to analyze the signal transduction for cell proliferation and cell-cycle arrest.

Cell Division↗

PubMed1990

Massive pancreatic pleural effusion: pathogenesis of pancreatic duct disruption.

Massive pancreatic pleural effusion is believed to be caused by pancreatic duct disruption. To elucidate the cause of the duct disruption, pancreas specimens resected from three cases of massive pancreatic pleural effusion were investigated histopathologically. There was no evidence of either chronic or acute pancreatitis except focal fibrosis along a single dilated duct in the resected pancreas. From our study, the pathogenesis of pancreatic duct disruption is suggested as follows: (a) alcohol ingestion can induce focal acute inflammation on a single branch of the duct system and elicit protein plug formation; and (b) focal stenotic change occurs on this branch at a point near the main pancreatic duct, and transient obstruction can occur by means of the protein plugs. The "upstream" extent of this branch will then dilate until it ruptures. However, on the frequency of this atypical pancreatitis, we have no clues to mention.

Acute Disease↗

PubMed1990

Elevated argininosuccinate synthetase activity in adult T leukemia cell lines.

Argininosuccinate synthetase (ASS) is a ATP-dependent and rate-limiting enzyme of the urea cycle which catalyzes L-citrulline to L-arginine in combination with argininosuccinate lyase (ASL). We demonstrate here that (a) human normal T and B lymphocytes did not express ASS activity, (b) however, three adult T leukemia (ATL) cell lines tested here exhibited significant elevation of ASS activity, and (c) ASL activity remained relatively constant in normal lymphocytes and various leukemia cell lines. These results suggest that the ASS expression of peripheral blood lymphocytes is of value as a diagnostic marker of leukemia including ATL. The implication of these results is discussed.

Arginine↗

PubMed1990

Evidence of clonal proliferation of hepatocytes after carbon-tetrachloride-induced hepatic injury in PGK-1 mosaic mice.

During aging processes, the liver is exposed continuously to both endogenous and exogenous chemicals which result in various degrees of hepatic damage. Hepatocytes maintain mitotic potential so that damaged cells are replaced by proliferation of selected clones of cells. Changes in the clonality after hepatic damage were investigated using carbon tetrachloride (CCl4) as a model hepatotoxin. The changes in clonality were determined by the alteration of the electrophoretic patterns of the allozyme, phosphoglycerate kinase-1A/1B (PGK-1A/1B), the locus of which is on the X-chromosome. In mammalian females random inactivation of one of the two X-chromosomes, of either paternal or maternal origin, are known to result in phenotype mosaicism. Heterozygous female (PGK-1a/1b) mice were obtained by crossing female (PGK-1b/1b) and male (PGK-1a/-) C3H/He mice. Liver samples were collected from these mice 5 days before (by biopsy) and 18 days after dosing with CCl4 (1 ml/kg, i.p.). Quantitative evaluation of the electrophoretic bands showed significant changes (percent change more than 7.2%, P less than 0.01) in the relative PGK-1A activity in 4 out of 10 cases. In one mouse a remarkable change, from 83.0 to 59.2%, was observed. Thus we concluded that selective hepatocyte proliferation occurs after cellular damage. We speculated that this process may play an important role in the aging of the liver.

Aging↗

PubMed1990

Effect of a novel anticonvulsant, zonisamide (AD-810, CI-912), in an experimental model of photosensitive epilepsy.

The effects of a novel anticonvulsant, zonisamide (3-sulfamoylmethyl-1,2-benzisoxazole), on photically induced seizures were studied in the lateral geniculate-kindled cat. Zonisamide was found to reduce the behavioral severity of seizure responses to photic stimulation in a dose-related manner. This anticonvulsant effect was only observed with doses that caused behavioral toxicity, but anticonvulsant action outlasted behavioral effects. The present results suggest that zonisamide may be effective in the treatment of human photosensitive epilepsy.

Animals↗

PubMed1990

Sequential decrease in platelet energy charge after hepatic resection in cirrhotics.

The adenylate energy charge of human platelets was measured in the early postoperative period after hepatic resection in cirrhotic and noncirrhotic patients to evaluate the metabolic status of platelets in this period. The adenylate energy charge of platelets decreased on the first, second, and third postoperative days in the cirrhotic group, whereas no significant decrease was found in the noncirrhotic group. A decrease in the percentage of adenosine triphosphate and an increase in that of hypoxanthine also occurred concomitant with a decrease in the adenylate energy charge, which was considered to be the result of an increased utilization of adenosine triphosphate. These findings indicate that in cirrhotic patients, the intravascular activation of platelets takes place and platelet function is damaged during the period immediately after hepatic resection, even when there is no clinical evidence of intravascular coagulation.

Adenine↗

PubMed1990

Anticonvulsant effects of zonisamide and phenytoin on seizure activity of the feline visual cortex.

The acute anticonvulsant effects of zonisamide (ZNS) and phenytoin (PHT) on seizure activity produced by electrical stimulation of the feline visual cortex were studied. The intravenous administration of ZNS 60 mg/kg reduced kindled generalized seizures into partial seizures, with marked reduction in the afterdischarge duration. ZNS also suppressed focal seizure activity of the visual cortex and produced a dose-related increase in the afterdischarge threshold. The anticonvulsant effect of ZNS (60 mg/kg) was comparable to that of PHT (15 mg/kg) and was observed in the absence of neurological toxicity and background EEG changes. The present findings demonstrated that ZNS possesses potent anticonvulsant action against focal seizure and its secondary generalization from the visual cortex.

Animals↗

PubMed1990

Inherited hyperactivation of L-arginine synthesis in gamma + B lymphocytes of systemic autoimmune MRL mice.

The hyperactivation of B lymphocytes of MRL mice, which are an animal model for human systemic lupus erythematosus (SLE), is characterized as the preferential propagation of gamma + B lymphocytes and IgG overproduction followed by aging. Little is known about the molecular mechanisms, although the involvement of cytokines has been extensively investigated. Here we now show that gamma-committed B lymphocytes selectively exhibit a highly elevated L-citrulline metabolism while mu or alpha-committed B lymphocytes show a normal level in autoimmune MRL mice. L-Arginine proportionally supports the lymphocyte proliferation and antibody production in a concentration-dependent fashion (approximately 100 microM). However, normal murine lymphocytes show an extremely low activity of citrulline metabolism, which converts L-citrulline to L-arginine. Thus, these results suggest that the overexpression of elevated citrulline metabolism is associated with gamma chain expression, and this elevation may enable gamma-committed B lymphocytes to preferentially propagate and overproduce IgG compared with mu or alpha-committed B lymphocytes.

Animals↗