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Biomedical subjects

H Tajima

Publications and source records attributed to H Tajima.

At least 109 records · Page 6Linked to original sources

[Transcatheter hepatic arterial embolization for the treatment of blunt hepatic injury].

To examine the indications of transcatheter arterial embolization (TAE) for blunt hepatic injury, angiographic images, CT images and medical records were reviewed. Hepatic angiography was performed in 30 patients with blunt hepatic injury. Sixteen of them who underwent TAE therapy immediately after angiography formed the TAE(+)group, while the 14 patients who were not followed by TAE formed the TAE(-)group. Angiographic extravasation of the contrast medium was confirmed in 14 of 16 patients in the TAE(+)group. On CT scan, the most common finding in the TAE(+)group was a deep hepatic laceration, which was classified as type III according to the criteria of the Japanese association for the surgery of trauma. Hemoperitoneum and fresh hematoma were visualized in most of the TAE(+)group. The preoperative hemodynamics of the TAE(+)group were markedly unstable, but were significantly improved after TAE therapy. No major complications were encountered during or after TAE. These results suggested that TAE was an effective therapeutic procedure for the control of blunt hepatic injury in patients associated with unstable hemodynamics, deep hepatic laceration shown by CT scan and extravasation confirmed by angiography.

Adolescent↗

Cell density-dependent regulation of hepatocyte growth factor receptor on adult rat hepatocytes in primary culture.

The proliferative potential of hepatocytes in the normal intact liver is highly suppressed, but they proliferate actively after liver injury. In this study, adult rat hepatocytes in primary culture were used to study mechanisms controlling hepatocyte growth in liver regeneration. DNA synthesis in hepatocytes cultured at a low cell density was highly stimulated in response to hepatocyte growth factor (HGF), but this stimulatory effect was not so obvious in hepatocytes cultured at a high cell density. In close parallel to the potency of DNA synthesis, the amounts of 125I-HGF specifically bound to hepatocytes cultured at a low cell density were much greater than in high cell density culture. Scatchard plots revealed that change in the specific binding of 125I-HGF was due to change in the number of high-affinity HGF receptors, but without change in the Kd values. Affinity cross-linking of the HGF receptor with 125I-HGF confirmed the higher expression of HGF receptor on hepatocytes cultured at a lower cell density. Since there was no significant change in the expression of c-met mRNA in hepatocytes cultured at different cell densities, the number of cell surface HGF receptors is probably regulated by post-transcriptional mechanisms. We also found that the rates of HGF-induced down-regulation and recovery of HGF receptors on hepatocytes cultured at a low cell density were much faster than in cases of a high cell density.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Heparin as an inducer of hepatocyte growth factor.

Hepatocyte growth factor (HGF) has mitogenic and unique morphoregulatory functions, and is considered to act as a hepatotrophic and a renotrophic factor for regeneration of the liver and kidney subjected to various insults. We have now obtained evidence that heparin is a potent inducer of HGF production. The addition of heparin to a culture of MRC-5 human embryonic lung fibroblasts increased the HGF concentration in the conditioned medium, in a dose-dependent manner. The maximal stimulation was obtained at 1 microgram/ml heparin and stimulation was 4-fold compared to control cultures. The rate of HGF synthesis in MRC-5 cells, as measured by pulse-labeling with [35S]methionine, and subsequent immunoprecipitation of HGF from both conditioned medium and a cell lysate, was 3-4-fold stimulated by 1 microgram/ml heparin, whereas heparin apparently had no significant effect on the HGF mRNA level. The stimulatory effect of heparin on HGF production was evident in various types of cells, such as MRC-9, IMR-90, and WI-38 human embryonic lung fibroblasts, human skin fibroblasts, HL-60 human promyelocytic leukemic cells and human umbilical vein endothelial cells. In addition to heparin, heparan sulfate also stimulated HGF production, albeit to a lesser extent than heparin; 1.7-fold stimulation with 2 micrograms/ml heparan sulfate. However, other glycosaminoglycans, such as hyaluronic acid, chondroitin sulfate, dermatan sulfate, keratan sulfate, and keratan polysulfate, had no stimulatory effect on HGF production.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Tuberculin sensitivity to purified protein derivatives from Mycobacterium other than tuberculosis (PPD-B, PPD-Y, PPD-F and PPD-C) and PPDs among patients with mycobacteriosis--cooperative study of the Research Committee for the Mycobacteriosis in Japan].

Purified protein derivatives (PPDs) prepared from M. intracellulare (PPD-B), M. kansasii (PPD-Y), M. fortuitum (PPD-F), M. chelonei subsp. abscessus (PPD-C) and M. tuberculosis (PPDs) were simultaneously used in skin tests on patients diagnosed as having tuberculosis or atypical mycobacteriosis to reveal their specificity, clinical usefulness and immunological status of the patients. The mean diameter of reaction (redness) for patients with M. tuberculosis positive sputum (TB group, n = 71; age, 20-90 yrs) was PPDs, 20.4 mm; PPD-B, 7.9 mm; PPD-Y, 11.7 mm; PPD-F, 0.8 mm; and PPD-C, 0.3 mm. For M. avium complex positive patients (MAC group, n = 100; age, 31-89 yrs), the results were PPDs, 10.9; PPD-B, 16.9 mm; PPD-Y, 10.7 mm; PPD-F, 1.6 mm; and PPD-C, 0.3 mm. The M. kansasii positive patients (K group; n = 8) showed results of PPDs, 12.6 mm; PPD-B, 10.7 mm; PPD-Y, 20.8 mm; PPD-F, 0.5 mm; PPD-C, 0.0 mm. The M. fortuitum positive patients (F group; n = 5) had measurements of PPDs, 5.8 mm; PPD-B, 4.4 mm; PPD-Y, 9.8 mm; PPD-F, 17.8 mm; and PPD-C, 16.0 mm. The patients who were previously M. tbc. positive but presently negative patients (pre. TB group; n = 50) showed the following results: PPDs, 16.6 mm; PPD-B, 7.4 mm; and PPD-Y, 10.9 mm. For the patients who were previously M. avium complex positive (previous MAC group; n = 19), the results were PPDs, 10.4 mm; PPD-B, 9.9 mm; and PPD-Y, 7.7 mm. Also considering their frequency distribution curve, with exception of the previous MAC group, the patient groups showed specificity to the PPD of the bacilli detected. The previous MAC group recorded no significant difference in response to PPDs and PPD-B. Strong cross reactions were observed between PPD-F and PPD-C, and moderate reactions between PPDs, PPD-B and PPD-Y. Cross reactions were scarce between PPDs, PPD-B or PPD-Y and PPD-F or PPD-C. Though it is difficult to distinguish cross-reaction and multiple infections, majority of the patients (72-85%) showed greatest response to the PPD that corresponds with the species of bacilli detected. In conclusion, two or more PPDs applied simultaneously can be of aid in diagnosing mycobacteriosis especially in the early stages of the disease. Also, cross-reactions between atypical mycobacteria and PPDs should be taken into consideration when diagnosing infection caused by M. tuberculosis.

Adult↗

Hepatocyte growth factor transforms immortalized mouse liver epithelial cells.

Transforming activity of hepatocyte growth factor (HGF) was demonstrated utilizing immortalized but not fully transformed mouse hepatocytes (MLE-10). Rat HGF cDNA, expressed under the control of a cytomegalovirus promoter, was transfected together with the neomycin resistance gene (PSV2neo) into MLE-10 cells by the calcium phosphate method, and propagated G418-resistant colonies were harvested colony by colony. After checking for integration and expression of exogenous HGF, five cell lines (MLE-10-HGF-1-5) were established. Three cell lines transfected with the vector only (MLE-10-CMV-1-3) were also established in the same manner. All MLE-10-HGF cell lines grew much faster than the MLE-10-CMV and original MLE-10 cells in culture and produced large colonies in soft agar, which colony production was blocked by the addition of anti-HGF antibody to the agar. After addition of HGF, original and MLE-10-CMV lines produced colonies in soft agar. The high-HGF-production lines (MLE-10-HGF-4 and -5) also gave rise to tumors within 2 weeks when implanted into the nude mice subcutis. In contrast, all MLE-10-CMV and original MLE-10 cells were negative in these growth assays. A rough parallelism between the level of HGF expression and the growth rate in both soft agar and nude mice subcutis was evident among MLE-10-HGF cell lines. Those with higher HGF production tended to grow in a scattered fashion in culture. High-affinity HGF receptor, HGFR/met, was expressed in MLE-10 and all the derived cell lines. Since HGF and/or HGFR/met gene expression is seen in various tumors and the serum HGF level is elevated in patients with hepatic disease, the present results indicate a possible significance of HGF and its receptor system in carcinogenesis, most probably via autocrine and/or paracrine mechanisms.

Animals↗

[Monostotic fibrous dysplasia of the occipital bone].

A case of monostotic fibrous dysplasia of the occipital bone in a 18-year-old female is described. She was admitted to our hospital with a hard, painless mass (5 x 5 cm) in the occipital region. Neurological examination and laboratory data revealed no abnormalities. Skull x-rays showed a radiolucent lesion with a sclerotic margin in the occipital bone. CT scan revealed an intradiploic multilocular mass separated by bone trabeculae. RI bone scan showed an abnormal uptake in this lesion. T1 and T2 MR image showed an abnormal low-intensity lesion in the occipital region. Operation was performed to verify the nature of the lesion, which was histologically confirmed to be an inactive fibrous dysplasia. Postoperative course was uneventful. Although its occurrence in the occipital bone is uncommon, fibrous dysplasia should be considered in the differential diagnosis of skull tumors.

Adolescent↗

Negative regulation of hepatocyte growth factor gene expression in human lung fibroblasts and leukemic cells by transforming growth factor-beta 1 and glucocorticoids.

Hepatocyte growth factor (HGF), a mesenchymal-derived factor which regulates growth, motility, and morphogenesis of epithelial and endothelial cells, functions as a hepatotrophic and renotrophic factor for regeneration of the liver and kidney. We have now obtained evidence that transforming growth factor-beta 1 (TGF-beta 1) and glucocorticoids are negative regulators for HGF gene expression. When TGF-beta 1 or dexamethasone was added to cultures of MRC-5 human embryonic lung fibroblasts and HL-60 human promyelocytic leukemic cells, the amount of HGF secreted into the culture medium was inhibited to 30-40% of that of control cultures by 10 ng/ml TGF-beta 1 and to 40-50% by 10(-6) M dexamethasone. The inhibitory effect of TGF-beta 1 and dexamethasone on HGF synthesis in MRC-5 cells was additive, thereby suggesting that TGF-beta 1 and dexamethasone exert effects through distinct mechanisms. Hydrocortisone also inhibited HGF synthesis with the same potency as dexamethasone; however, testosterone, estriol, and beta-estradiol had no effect. The rate of HGF synthesis in MRC-5 cells, as measured by pulse labeling with [35S]methionine and subsequent immunoprecipitation, was suppressed to 30-40% of the control with 10 ng/ml TGF-beta 1, and to 30-45% by 10(-6) M dexamethasone. HGF mRNA levels in MRC-5 cells and HL-60 cells were dose-dependently suppressed by TGF-beta 1 and dexamethasone; 10 ng/ml TGF-beta 1 suppressed HGF mRNA levels to 32% and 35% of control culture, respectively, in MRC-5 cells and HL-60 cells, and 10(-6) M dexamethasone suppressed to 43% and 38%, respectively. Thus, TGF-beta 1 and glucocorticoids seem to inhibit HGF synthesis by suppressing the expression of the HGF gene. We propose that a negative regulation of HGF gene expression by TGF-beta 1 or glucocorticoids may be involved in physiological or pathological processes during tissue regeneration.

Animals↗

Identification and characterization of "injurin," an inducer of expression of the gene for hepatocyte growth factor.

The marked and rapid increase of hepatocyte growth factor (HGF) mRNA in the intact lung of rats after partial hepatectomy or unilateral nephrectomy suggests the existence of a humoral factor mediating a signal of injury to distal organs and may induce the expression of HGF gene in these organs. We have now identified a proteinous factor in the sera of rats with injury of liver or kidney that increases HGF mRNA in the intact lung. When the serum of rats with liver insult caused by partial hepatectomy or ischemic treatment was injected i.p. into normal noninjured rats, it induced a marked HGF mRNA expression in the lung of the recipient rats. The addition of serum from rats with various hepatic or renal injuries to MRC-5 human embryonic lung fibroblasts in culture also led to the induction of HGF mRNA expression, so that the production of HGF by MRC-5 cells after treatment with the sera was remarkably increased in the culture medium. However, serum from the normal intact rat induced no HGF production and no HGF mRNA in the lung in vivo and lung fibroblasts in vitro. This factor, which increases HGF production, was purified greater than 200-fold from sera of CCl4-treated rats. The factor proved to be an acid- and heat-stable protein with an apparent molecular mass of 10-20 kDa in SDS/PAGE. Its activity markedly increased within 3-6 hr in the plasma of rats after various treatments that injured the liver or kidney. These results suggest that the factor specifically appears in the blood of rats with organ injury and may be involved in organ regeneration through the potential to increase the synthesis of HGF. Since the factor seems to mediate various organ injuries, we named it "injurin."

Animals↗

Regulation of cell growth and motility by hepatocyte growth factor and receptor expression in various cell species.

Hepatocyte growth factor (HGF), a humoral mediator for regeneration of liver and kidney, possesses multiple biological activities. To investigate target cell specificity and to examine whether multiple actions of HGF are related to properties of the HGF receptor on target cells, we examined the effects of HGF on cell growth and motility and analyzed the HGF receptor in various species of cells. HGF stimulated growth and DNA synthesis of PAM212 (naturally immortalized mouse keratinocytes), Mv1Lu (mink lung epithelia), and A431 (human epidermoid carcinoma) cells, as well as mature hepatocytes, but inhibited those of IM-9 (human B-lymphoblasts). Conversely, HGF had a marked stimulatory effect on cell motility of MDCK (Mardin-Darby canine kidney epithelia) cells, but not on their growth. Also, HGF enhanced the motility of various species of cells, including A431, PAM212, HepG2 (human hepatoma), KB (human epidermoid carcinoma), and J-111 (human monocytes) cells. Scatchard analysis of 125I-HGF binding to hepatocytes indicated that the cells expressed both high- and low-affinity binding sites for HGF with Kd values of 23 and 260 pM, respectively. High-affinity HGF receptor with Kd values of 20-25 pM was detected at 40-720 sites/cell in MDCK, A431, PAM212, Lu99, and IM-9 cells, but not in fibroblasts and hematopoietic cells. In contrast, low-affinity binding sites were detected in all cell lines examined, even in those not responsive to HGF. Northern blots revealed that cells possessing a high-affinity HGF receptor expressed c-MET/HGF receptor mRNA. Therefore, HGF probably regulates both cell growth and motility of various types of epithelial cells and some types of mesenchymal cells. The multiple biological activities of HGF may be exerted through a high-affinity HGF receptor linked to multiple distinct intracellular signaling pathways.

Animals↗

Tissue distribution of hepatocyte growth factor receptor and its exclusive down-regulation in a regenerating organ after injury.

Using 125I-labeled hepatocyte growth factor (HGF) as a ligand, we examined the tissue distribution of the HGF receptor in adult rats. Specific binding of 125I-HGF was detected in the plasma membranes of liver, spleen, kidney, lung, adrenal gland, pituitary, and thyroid. Scatchard analysis of HGF binding in liver, spleen, kidney, lung, and adrenal gland revealed the presence of a single class of high affinity receptor with a dissociation constant (Kd) of 20-30 pM. The maximum number of binding sites (Bmax) was determined to be 400-3,000 sites per ng of plasma membrane protein, the highest number being in the liver. Such a wide distribution of a high affinity HGF receptor indicates that HGF may be a multifunctional growth factor, targeting to a variety of organs, and not restricted to liver. After 70% partial hepatectomy, specific binding of 125I-HGF to membranes of the residual liver rapidly decreased, but there was no change in the kidney, lung, and spleen. On the other hand, after unilateral nephrectomy rapid down-regulation of the HGF receptor was clearly evident in the remaining kidney, but not in other organs including the liver. These findings suggest the presence of control mechanisms governing HGF receptor function only in a regenerating organ after injury.

Animals↗

[Elemental analysis of hilar and mediastinal lymph nodes in idiopathic pulmonary fibrosis].

Elemental analysis of hilar and mediastinal lymph node tissues was performed to determine whether some inhaled atmospheric elements are implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). IPF was divided into two types; typical and atypical, according to our criteria. Lymph nodes were selected as the study material rather than lung tissue, because inhaled elements are concentrated in the hilar and mediastinal lymph nodes, and increase in lung weight due to fibrosis may influence the estimated values of element per unit weight of lung tissue. The hilar and mediastinal lymph nodes collected from 40 IPF cases and 43 non-IPF control cases were examined to determine the concentration of 13 elements in 100 mg dry tissue, using the X-ray fluorescent analysis method. For aluminium, 50 mg dry tissue was examined by an atomic absorption analysis method. Among the 14 elements, Ni in IPF lymph nodes showed a significantly higher level than in control nodes (mean +/- SD: 8.2 +/- 21.3 ppm versus 1.1 +/- 2.1 ppm, respectively. p < 0.01). No difference in each of the examined elements was noted between smokers and non-smokers or between typical and atypical IPF cases. Exogenous elements such as Ni may play a role as triggering substances in the pathogenesis of IPF.

Aged↗

[Function, molecular structure and gene expression regulation of hepatocyte growth factor and its receptor].

Hepatocyte growth factor (HGF), a potent mitogen of mature hepatocytes in primary culture, is composed of 69 kDa alpha-chain with four kringle domains and 34 kDa beta-chain. HGF is currently thought to be a pleiotropic factor, that stimulates the growth and motility of various epithelial cells, and that inhibits the growth of some carcinoma cells. These cells have a single class of high affinity receptor with a dissociation constant (Kd) of 20-30 pM. The maximum number of binding sites (Bmax) was determined to be 100-1500 sites/cell. After 70% partial hepatectomy and unilateral nephrectomy, HGF activity in serum and their tissues increased markedly and HGF receptors of the injured organ rapidly decreased, but not in other normal organs. These results suggest that HGF acts only in a regenerating organ after injury through the control mechanisms governing HGF receptor.

Animals↗