[A case of severe peripheral nervous disorder due to acute idiopathic porphyria].
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Acute Disease↗
Biomedical subjects
K Sugimura
Publications and source records attributed to K Sugimura.
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↗
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↗
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↗
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↗
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↗
Cloning and nucleotide sequence of the gene encoding arginine deiminase of Mycoplasma arginini.
The existence of a mycoplasmal arginine deiminase which catalyzes the conversion of L-arginine to L-citrulline has been postulated. Here we show the partial amino acid sequence of arginine deiminase of Mycoplasma arginini and the complete nucleotide sequence of the arginine deiminase gene of M. arginini. The open reading frame deduced from this sequence consists of 1,230 bp encoding 410 amino acids. The mature form of this enzyme contains 409 amino acids after the deletion of the first methionine. In this open reading frame, TGA nonsense codons are used as tryptophan codons; this usage was verified by determination of the amino acid sequence. The molecular weight of the enzyme calculated from the deduced amino acid sequence is 46,372. Recently, the nucleotide sequence of the arginine deiminase gene of M. arginini was reported by Kondo et al. (K. Kondo, H. Sone, H. Yoshida, T. Toida, K. Kanatani, Y.-M. Hong N. Nishino, and J. Tanaka, Mol. Gen. Genet. 221:81-86, 1990). However, their sequence differed from ours in several places and especially at the C terminus.
Amino Acid Sequence↗
Identification and purification of arginine deiminase that originated from Mycoplasma arginini.
A lymphocyte blastogenesis inhibitory factor, (LBIF), was purified from the culture supernatant of human histiocytic lymphoma U937 by fast protein liquid chromatography. In this study, we demonstrated, first, that LBIF originated from a mycoplasma, Mycoplasma arginini, infecting U937 cells, and second, that LBIF bore the arginine deiminase activity. The implication of in vivo immunosuppression induced by arginine-utilizing mycoplasma species is discussed.
Animals↗
Postirradiation changes in the pelvis: assessment with MR imaging.
Magnetic resonance (MR) imaging features of pelvic radiation change were assessed in 51 patients and were correlated with tumor and critical tissue radiation dose, time after treatment, and clinical symptoms. The severity of MR tissue changes was graded. Radiation tissue toxicity increased significantly when the dose exceeded 4,500 cGy, with the incidence of marked bladder and rectal changes rising from 8% to 51% and from 24% to 48%, respectively. Similar dose-related changes were seen in other pelvic organs. All grades of tissue change were seen in the bladder and rectum regardless of the time from start of therapy. All patients who exhibited clinical grade 2 or 3 bladder and rectal changes showed moderate or severe changes on MR images. In asymptomatic patients, minimal MR changes were seen in the bladder (47%) and in the rectum (33%). The accuracy of MR imaging in differentiating between radiation damage and residual/recurrent tumor varied with the primary tumor site, being excellent for recurrent cervical cancer and less so for rectal carcinoma.
Adult↗
Multiple pulmonary metastases from renal cell carcinoma treated effectively by recombinant interleukin-2.
A 53-year old male with multiple pulmonary metastases from a renal cell carcinoma was treated with high dose recombinant interleukin-2 (rIL-2). rIL-2 was administered intravenously, and the dose was gradually increased to a subsequent daily dosage of 3 x 10(6) units for a total amount of 470 x 10(6) units. After 3 months, plain chest film and chest computerized tomography revealed a remarkable reduction in pulmonary metastases. There were no side effects except general fatigue and fever. Immunological studies revealed an increase in lymphocytes and enhancement of natural killer activity. These results suggested that rIL-2 is effective for pulmonary metastases from renal cell carcinoma.
Carcinoma, Renal Cell↗
Demyelinating changes in sural nerve biopsy of patients with HTLV-I-associated myelopathy.
We describe the sural nerve pathology in 3 patients with HTLV-I-associated myelopathy (HAM). These patients showed remarkable symptoms of myelopathy and had high HTLV-I titers in the serum and CSF. The common pathologic findings in the sural nerves were as follows: slightly decreased density in myelinated fibers (6,567/mm2, 6,488/mm2, and 7,159/mm2; control 9,999 +/- 3,446/mm2), frequent occurrence of demyelinated and remyelinated fibers, and many degenerating fibers with globule-like myelin changes. Teased-fiber analysis indicated the globule-like changes (Dyck's G change) to be accompanied by the formation of adjacent demyelinated segments. The globules result from slowly repetitive degenerative changes of myelin and are considered to be a form of demyelination. However, they have seldom been found in other demyelinating neuropathies, indicating the demyelination process with globule formation in HAM to be rather specific for this disease.
Axons↗
[Side effects of extracorporeal shock-wave exposure on the kidney in the dogs].
The effects of extracorporeal shock-wave (SW) exposure on the kidney were investigated in dogs using a Dornier kidney lithotriptor HM3. The SW was generated by spark discharge at 20 KV and was focused on the lower part of either kidney. Before and after the exposure of 500 and 1000 shots of SW, the renal blood flow of the affected and contralateral kidney was measured by the microsphere method. The blood flow of the affected kidney decreased, but was comparable to that of the contralateral kidney immediately after the 1000 shots of SW. Renal scintigraphy using 99mTc-DTPA was performed before the exposure of SW, and 30 minutes, 1 week, 2 weeks and 4 weeks after the exposure. The renograms were evaluated by the following parameters: Tmax (time required to reach maximum radioactivity), RAmax ratio (maximum radioactivity of the affected kidney/that of the contralateral kidney) and T1/2 (the half-life of elimination). Tmax was significantly prolonged for the affected kidney 30 minutes after the exposure, while that for the contralateral kidney was shortened. The RAmax ratio was decreased 1 week after the exposure. T1/2 was significantly prolonged 30 minutes after the exposure, which was observed till 2 weeks later. The scintigraphy also showed a slight enlargement of affected site. The histological study showed a hemorrhage in the peritubular space, indicating rupture of the peritubular capillaries. In conclusion, the main effect of SW exposure on the kidney was the rupture of the peritubular capillaries, resulting in temporary and reversible deterioration of renal function.
Animals↗
[A case of Down's syndrome with chronic inflammatory demyelinating polyradiculoneuropathy].
A 19-year-old male patient with Down's syndrome accompanied by relapsing and steroid-dependent chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) was reported. He had been well until the beginning of June 1988, and he rapidly developed a gait disturbance and symmetrical numbness in his arms and legs at the end of that month. He also suffered from difficulty in swallowing and dyspnea soon afterward. A physical examination revealed the specific clinical features of Down's syndrome, but no particular signs. Neurological examination showed the following abnormal findings; fixed nystagmus, diminished gag reflex, flaccid tetraparesis, and distal dominant dysesthesia of upper and lower extremities. Deep tendon reflexes were diminished and Babinski's sign was negative. No autonomic dysfunction was detected. Routine hematology and biochemistry screening test revealed normal level except for increasing GPT and IgG. Protein and gamma globulin values in cerebrospinal fluid (CSF) were elevated without pleocytosis. Nerve conduction velocities were slighty reduced. Pulse therapy and corticosteroid treatment improved on clinical course and CSF results. CIDP probably results from an abnormal immune responsiveness. Down's syndrome has often been taken for autoimmune abnormality. It is of great interest whether there is a close connection of autoimmune abnormality between Down's syndrome and CIDP. This might be the first case report of Down's syndrome associated with CIDP, judging from our survey of the literature in Japan and other countries.
Adult↗
Inhibition of the metastasis of murine malignant melanoma by synthetic polymeric peptides containing core sequences of cell-adhesive molecules.
We investigated that the antimetastatic and antiadhesive activities of peptides based on Arg-Gly-Asp adhesive signal in fibronectin could be augmented by their polymerization. Poly(Arg-Gly-Asp), which consists of a repetitive sequence of Arg-Gly-Asp, inhibited lung metastases in C57BL/6 mice more effectively than Arg-Gly-Asp tripeptide was able to do, when coinjected or separately injected with B16-BL6 cells. The adhesion of tumor cells to fibronectin was specifically inhibited by adding poly(Arg-Gly-Asp) but not unrelated peptides. In contrast, poly(Arg, Gly, Asp), in which three amino acids are randomly arranged, showed neither inhibition of lung metastases nor any adhesive ability to attach to tumor cells. The inhibitory effect of polymeric peptides containing the Arg-Gly-Asp sequence on lung metastases decreased according to the decreasing repeat units of the Arg-Gly-Asp core sequence. Polymeric peptides with Arg-Gly-Asp entrapped within the liposome membranes also caused a remarkable reduction of metastatic colonies. In a spontaneous metastasis model, multiple i.v. administrations of poly(Arg-Gly-Asp) after tumor inoculation caused the significant reduction of metastatic colonies in the lung but did not affect the growth (size) of primary tumor. We found that the polymerization (multivalency) of the Arg-Gly-Asp core sequence was able to augment the inhibition of tumor lung metastases in experimental and spontaneous metastasis models as well as the cell-adhesive property more effectively than a monovalent unit of Arg-Gly-Asp peptide.
Amino Acid Sequence↗
[Magnetic resonance imaging of the metastatic vertebral tumor].
Fourty two patients underwent MR studies for a variety of lesions in the vertebral body. A 0.15-T MR system was employed. Twenty five patients were found to have malignant metastatic lesions (group 1); 16 had non-neoplastic lesions (group 2). The ability to discriminate between group 1 and group 2 with MR imaging was evaluated. All malignant metastatic lesions appeared as low intensity areas on both T1-weighted spin echo image and inversion recovery image, but 44 to 53% of the non-neoplastic lesions appeared as low intensity areas, respectively. The diagnostic ability with signal intensity of the vertebral column was evaluated on various pulse sequences; sensitivity of inversion recovery and T1-weighted spin echo image was 100%, in contrast specificity of these pulse sequences was 47 to 56%, overall accuracy was the highest on T1-weighted spin echo image (86%). The signal intensity of intervertebral disk was also evaluated in both groups. The intervertebral disks adjacent to the all malignant metastatic lesions showed normal intensity on both T1-weighted spin echo image and inversion recovery image, but non-neoplastic lesions showed variable intensities on images with all pulse sequences. The diagnostic ability with the signal intensities of the vertebral column and intervertebral disk was higher than that of the vertebral columns alone. Consequently accuracy was the highest in that case of both intervertebral disk and bone marrow which were imaged on T1-weighted spin echo (93%). We concluded that this diagnostic method was useful in distinguishing malignant metastatic from non-neoplastic lesions.
Adenocarcinoma↗
A cytokine, lymphocyte blastogenesis inhibitory factor (LBIF), arrests mitogen-stimulated T lymphocytes at early G1 phase with no influence on interleukin 2 production and interleukin 2 receptor light chain expression.
The function of a human cytokine, lymphocyte blastogenesis inhibitory factor (LBIF), was characterized. To this end, LBIF was purified from crude supernatant of U-937 cells, a human macrophage-like cell line, by using fast protein liquid chromatography (FPLC). We demonstrated here that (a) the LBIF preparation completely inhibited phytohemagglutinin (PHA)-stimulated T cell proliferation; (b) however, in PHA-stimulated T lymphocytes LBIF inhibited neither interleukin (IL)2 production nor the expression of IL2 receptor (IL2R) light chain (CD25) which play a critical role for T cell proliferation; (c) LBIF arrested PHA-stimulated T lymphocytes at the G1 phase of cell cycle and inhibited entry into S phase, thus inhibiting lymphocyte proliferation. Wright-Giemsa's staining of the cells showed that PHA/LBIF-stimulated cells were arrested in early G1. In agreement with this result, LBIF strongly inhibited PHA-induced RNA synthesis. Further, LBIF inhibited the induction of the transferrin receptor which is normally expressed at the late G1 phase of the cell cycle. The inhibitory activity of LBIF was reversible. Thus, this study elucidated that LBIF arrests PHA-stimulated T lymphocytes at a point between the stages of IL2 production or IL2R light chain expression (in early G1) and transferrin receptor expression (in late G1). Taken together, these results suggest that there might be a control system of T cell proliferation distinct from the previously reported mechanisms, such as the inhibition of IL2 production or the inhibition of IL2R light chain (CD25) expression, and that LBIF might be an important molecule in the regulation of normal lymphocyte proliferation.
Biological Factors↗
Immunohistochemical differential distribution of S-100 alpha and S-100 beta in the peripheral nervous system of the rat.
The localization of the alpha subunit of the S-100 protein (S-100 alpha) and beta subunit (S-100 beta) was studied in the peripheral nervous system of the rat. In peripheral nerves, S-100 alpha and S-100 beta were found in the cytoplasm of Schwann cells. Axons were positively stained in part by S-100 alpha and almost totally by S-100 beta. In the dorsal root ganglia, S-100 alpha was found in satellite cells and their processes and in some neurons. S-100 beta was found in more of the large neurons, but almost all of the small neurons were negative for S-100 beta. In the anterior horn cells, S-100 beta staining was stronger than that of S-100 alpha. In Schwann cells, both S-100 alpha and S-100 beta were present on the rough endoplasmic reticulum, free ribosomes, and nucleus, as seen by electron microscopy. The S-100 alpha and S-100 beta in axons were associated with microtubules and neurofilaments.
Animals↗
Effects of chronic n-hexane exposure on nervous system-specific and muscle-specific proteins.
Two kinds of nervous system-specific and muscle-specific proteins, enolase and S-100 protein, were quantitatively determined in peripheral nerves and skeletal muscles of rats chronically exposed to a neurotoxic solvent - n-hexane. Three groups of animals were exposed to n-hexane vapor at three different solvent concentrations (500 ppm, 1200 ppm, 3000 ppm) for 12 h/day, 7 days/week for 16 weeks. The body weight gain and motor nerve conduction velocity (MCV) in exposure groups show progressively concentration-dependent decreases compared to control values. Histopathological examination also demonstrates the degeneration of peripheral nerves in 3000 ppm- and 1200 ppm-exposed rats. The significant decrease in the amount of S-100 protein in peripheral nerves was observed not only in the high level exposure groups (3000 ppm and 1200 ppm), but also in the lowest level group (500 ppm), although the MCV and morphological examination remained unchanged at this level. In addition, the muscle-specific S-100 protein in 3000 ppm exposed rats' soleus also displayed a significant reduction. In contrast to this, however, enolase isozymes were not significantly changed by either dosage level in both nervous tissue and skeletal muscle. The experiment suggests that beta- and alpha-S-100 proteins which are specifically localized in nervous system and muscles, respectively, are more vulnerable than enolase isozymes under treatment with n-hexane, and may possibly serve as a specific indicator to evaluate the neurotoxic effects. Further research would be worthwhile to elucidate the role of the specific S-100 protein in evaluating the neurologic damage induced by various industrial chemicals.
Animals↗