A cross-sectional study of relationships between periodontal disease and general health: The Hitachi Oral Healthcare Survey.

BACKGROUND: This cross-sectional study performed to clarify the relationship between periodontal disease and non-communicable diseases (NCDs), such as obesity, diabetes mellitus, impaired glucose tolerance (IGT), chronic obstructive pulmonary disease (COPD), and atherosclerotic cardiovascular disease (ASCVD) by introducing dental examinations into the annual health examinations conducted by Japanese companies, and to highlights the importance of a medical system that connects dental and medical professionals. METHODS: A total of 1.022 Hitachi Ltd. employees were enrolled in this cross-sectional study. We examined correlations and odds ratios (ORs) between the dental and overall health of employees using stratification and multiple logistic regression analyses based on the periodontal health indicators, general health indicators, and occlusal force. RESULTS: The adjusted OR of PPD for obesity (OR, 1.42; 95% confidence interval [CI], 1.09-1.84; p = 0.009), IGT (OR, 1.48; 95% CI, 1.00-2.20; p = 0.049), and COPD (OR, 1.38; 95% CI, 1.02-1.88; p = 0.038) significantly differed. The adjusted OR of body mass index (OR, 1.28; 95% CI 1.15-1.42; p < 0.001), haemoglobin A1C (HbA1c) (OR, 4.34; 95% CI, 1.89-9.98; p < 0.001), fasting blood glucose (FBG) levels (OR, 1.08; 95% CI 1.04-1.11; p < 0.001), postbronchodilator forced expiratory volume in one second/forced vital capacity ratio (%FEV1) (OR, 0.95; 95% CI 0.91-1.00; p = 0.031) and smoking (OR, 2.32; 95% CI 1.62-3.33; p < 0.001) for severe periodontal disease also significantly differed. Occlusal force was significantly reduced in employees aged 50-59 years compared to those aged 40-49 years. Both PPD, HbA1c, FBG levels were significantly associated with occlusal force among employees with moderate/severe periodontitis. PPD was significantly associated with occlusal force among employees with and moderate COPD, and ASCVD. %FEV1 was significantly associated with occlusal force among employees with IGT. CONCLUSIONS: This cross-sectional study revealed mutual relationships among periodontal disease, NCDs, and occlusal force on Japanese corporate workers. We demonstrated that a comprehensive, regional healthcare system centred on annual integrated dental and physical health examinations in the workplace will benefit employees and positively impact corporate health insurance.

[Improvement of consciousness by administration of flumazenil in a patient with unexpectedly delayed emergence from general anesthesia].

A 64-year-old woman was scheduled for the removal of hepatic cystadenoarcinoma. The preoperative examination did not reveal any neurological disorders. Anesthesia was induced with midazolam (5 mg) and remifentanil (0.1.ag x kg-1 x min-1) and the trachea was intubated following administration of rocuronium. Anesthesia was maintained with propofol (1.2-4.0 mg x kg-1 x hr-1), remifentanil (0.1-0.4microg kg 1 x min-1), and rocuronium (10 mg) as needed. The dose of propofol was controlled so that bispectral index (BIS) ranged between 40 and 60 during surgery. The duration of surgery was 10 hr 29 min. Administration of propofol and remifentanil was terminated at the end of surgery. After confirmation of T2 appearance by train-of-four stimuli, sugammadex (2 mg x kg 1) was intravenously administered. Although respiratory rate and tidal volume were 12-18 breaths x min-1 and 350-450 ml, respectively, she remained unconsciousness at about 40 of BIS. We could not find any factors associated with delayed emergence from anesthesia. Flumazenil (0.5 mg) was administered intravenously 90 min after termination of anesthesia. Two min later, she became fully awake and alert with increase in BIS (above 90). Laboratory examination showed that the plasma concentrations of propofol, midazolam, and its active metabolite alpha-hydroxymidazolam before administration of flumazenil were within the range considered to have no sedative effects. From experience of this case, administration of flumazenil may be beneficial for improvement in consciousness in cases with unexpectedly delayed emergence from anesthesia.

Inhibition of Kupffer cell-mediated early proinflammatory response with carbon monoxide in transplant-induced hepatic ischemia/reperfusion injury in rats.

UNLABELLED: Proinflammatory responses play critical roles in hepatic ischemia/reperfusion (I/R) injury associating with liver transplantation (LTx), and carbon monoxide (CO) can effectively down-regulate them. Using wild-type (WT) to enhanced green fluorescent protein (EGFP)-transgenic rat LTx with 18-hour cold preservation in University of Wisconsin solution, this study analyzed the relative contribution of donor and host cells during early posttransplantation period and elucidated the mechanism of hepatic protection by CO. CO inhibited hepatic I/R injury and reduced peak alanine aminotransferase levels at 24 hours and hepatic necrosis at 48 hours. Abundant EGFP(+) host cells were found in untreated WT liver grafts at 1 hour and included nucleated CD45(+) leukocytes (myeloid, T, B, and natural killer cells) and EGFP(+) platelet-like depositions in the sinusoids. However, reverse transcription polymerase chain reaction (RT-PCR) analysis of isolated graft nonparenchymal cells (NPCs) revealed that I/R injury-induced proinflammatory mediators [for example, tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and inducible nitric oxide synthase (iNOS)] were not up-regulated in purified CD45(+) cells of donor or host origin. Instead, TNF-alpha and IL-6 messenger RNA (mRNA) elevation was exclusively seen in isolated CD68(+) cells, whereas iNOS mRNA up-regulation was seen in hepatocytes. Nearly all CD68(+) cells at 1 hour after LTx were EGFP(-) donor Kupffer cells, and CO efficiently inhibited TNF-alpha and IL-6 up-regulation in the CD68(+) Kupffer cell fraction. When graft Kupffer cells were inactivated with gadolinium chloride, activation of inflammatory mediators in liver grafts was significantly inhibited. Furthermore, in vitro rat primary Kupffer cell culture also showed significant down-regulation of lipopolysaccharide (LPS)-induced inflammatory responses by CO. CONCLUSION: These results indicate that CO ameliorates hepatic I/R injury by down-regulating graft Kupffer cells in early postreperfusion period. The study also suggests that different cell populations play diverse roles by up-regulating distinctive sets of mediators in the acute phase of hepatic I/R injury.

Administration of granulocyte colony-stimulating factor to recipients followed by intra-bone marrow-bone marrow transplantation accelerates acceptance of allogeneic bone marrow cells in mice.

We have recently established a novel method for bone marrow transplantation: intra-bone marrow-bone marrow transplantation (IBM-BMT), by which the rapid recovery of donor-derived hematopoiesis can be expected even when reduced radiation doses are used. In this paper, we examine, using mice, whether the combination of pretreatment of recipients with granulocyte-colony-stimulating factor (G-CSF) and IBM-BMT can induce a more rapid recovery of donor-derived hematopoiesis than IBM-BMT alone. We first pretreated recipients with recombinant human (rh) G-CSF (250 microg/kg/day) for 5 consecutive days (days -6 to -2). On day -1, the recipients were irradiated, and IBM-BMT was carried out on day 0. On day 12, we performed colony-forming units of spleen (CFU-S) assays. The combination of G-CSF pretreatment and IBM-BMT augmented the CFU-S counts, the weight of spleens, and the numbers of donor-derived hematopoietic cells. We next analyzed the mechanisms underlying these effects of G-CSF and found that (i) G-CSF induces Th2 polarization, which can prevent graft rejection, and (ii) G-CSF augments natural suppressor activity, which suppresses graft rejection. The combination of G-CSF pretreatment and IBM-BMT can produce the rapid recovery of donor-derived hematopoiesis and suppress graft rejection. This method would lighten the burden on patients in allogeneic BMT.

Immunotherapy for malignant tumors using combination of allogeneic intra-bone marrow-bone marrow transplantation, donor lymphocyte infusion and dendritic cells.

We have previously shown that the combination of allogeneic intra-bone marrow-bone marrow transplantation (IBM-BMT) and donor lymphocyte infusion (DLI) using CD4+ cell-depleted spleen cells is effective in suppressing tumor growth, but that this does not induce graft-versus-host disease (GVHD) in mice. In this report, we show that formalin-fixed tumor cell-pulsed dendritic cells (FFTCP DCs) have an additive effect with IBM-BMT plus DLI on the suppression of tumor growth, but that the DCs do not augment GVHD. BALB/c mice, which had been subcutaneously inoculated with Meth A (BALB/c-derived fibrosarcoma), were irradiated at a low dose (5 Gy) and were transplanted with bone marrow cells (BMCs) from C57BL/6 (B6) mice into the bone marrow cavity (IBM-BMT). Simultaneously, the mice were intravenously injected with spleen cells from B6 mice, and subcutaneously injected with FFTCP DCs derived from the bone marrow (BM) of B6 mice. At the point of the induction of DCs from BMCs, formalin-fixed Meth A cells were added into the culture. The mice treated with the combination of FFTCP DCs, IBM-BMT and DLI using CD4+ cell-depleted spleen cells showed smaller tumor sizes and longer survival than the mice treated with IBM-BMT plus FFTCP DCs or IBM-BMT plus DLI using CD4+ cell-depleted spleen cells. These results suggest that the combination of FFTCP DCs, IBM-BMT plus DLI using CD4+ cell-depleted spleen cells has potent anti-tumor effects without showing GVHD.

Extensive studies on perfusion method plus intra-bone marrow-bone marrow transplantation using cynomolgus monkeys.

The collection of bone marrow cells (BMCs) using a perfusion method has been advantageous not only because of the low contamination of BMCs with T cells from the peripheral blood but also the enrichment of stromal cells, which support hemopoiesis. Before the application of this new method to humans, its safety needed to be confirmed using cynomolgus monkeys. We therefore performed the perfusion method on more than 100 cynomolgus monkeys using the long bones (such as the humerus and femur) and also the iliac bones (for human application); in the more than 150 trials to date, there have been no accidental deaths. Furthermore, the technical safety of a new method for the intra-bone marrow (IBM) injection of BMCs (termed IBM-bone marrow transplantation) has also been confirmed using 30 monkeys. Disclosure of potential conflicts of interest is found at the end of this article.

Allogeneic intrabone marrow-bone marrow transplantation plus donor lymphocyte infusion suppresses growth of colon cancer cells implanted in skin and liver of rats.

We have recently found that allogeneic intrabone marrow-bone marrow transplantation (IBM-BMT) + donor lymphocyte infusion (DLI) using CD4(+) cell-depleted spleen cells (CD4(-) cells) can prevent graft-versus-host disease (GvHD) but suppress tumor growth (Meth A: fibrosarcoma) in mice. In the present study, we show that allogeneic IBM-BMT + DLI using CD4(-) cells also has suppressive effects on the growth of colon cancer cells implanted not only in the skin but also in the liver of rats. First, we examined the effects of allogeneic IBM-BMT + DLI on the subcutaneously inoculated ACL-15 (rat colon cancer cell line). Lethally irradiated Fischer rats (F344 rats) were transplanted with T-cell-depleted bone marrow cells (BMCs) from Brown Norway (BN) rats. Simultaneously, DLI was performed using whole spleen cells (whole cells), CD4(+) cell-depleted spleen cells (CD4(-) cells) or CD8(+) cell-depleted spleen cells (CD8(-) cells) of BN rats. Although allogeneic IBM-BMT + DLI suppressed tumor growth, a considerable number of rats treated with allogeneic IBM-BMT + DLI using whole cells or CD8(-) cells died due to GvHD. In contrast, allogeneic IBM-BMT + DLI using CD4(-) cells also suppressed tumor growth, but there was no GvHD. Based on these findings, we next examined the effects of allogeneic IBM-BMT + DLI using CD4(-) cells on the cancer cells implanted in the liver. Allogeneic IBM-BMT + DLI using CD4(-) cells via the portal vein significantly prolonged the survival. These results suggest that allogeneic IBM-BMT + DLI using CD4(-) cells could become a new strategy for the treatment of solid tumors.

An innovative approach to bone marrow collection and transplantation in a patient with beta-thalassemia major: marrow collection using a perfusion method followed by intra-bone marrow injection of collected bone marrow cells.

Using small animals (mice and rats) and monkeys, we have found that the combination of bone marrow collection using the perfusion method (PM) and intra-bone marrow-bone marrow transplantation (IBM-BMT) of the collected cells is safe and effective in treating various intractable diseases. Based on these findings, we attempted to apply this method to humans. We report here the first case of a patient (6 years old) with beta-thalassemia major who underwent allogeneic BMT using this new PM + IBM-BMT method. The white blood cell counts of the patient gradually increased to more than 1500/microL by day 47 and continued to increase, reaching the highest level (8600/microL) on day +55. Fluorescence in situ hybridization data on day +33 showed that 98% of the peripheral blood cells were from the donor. Notably, there were no symptoms of graft-versus-host disease (GvHD). However, on day +56, the patient regrettably died of asphyxia resulting from sticky sputum. There was no evidence of infection (in the lung or liver) or GvHD (in the skin) by necropsy. We hope that this case report will help make our new strategies more readily available for the treatment of patients with various intractable diseases.

Effects of low-dose irradiation on enhancement of immunity by dendritic cells.

Low-doses of irradiation have been reported to have beneficial effects, particularly anti-tumor effects. In this paper, we show the effects of the low-dose irradiation on T cell activation induced by dendritic cells (DCs). DCs, which had been pre-irradiated at 0.02-1.0 Gy from a (137)Cs source, were cultured with allogeneic T cells, and the proliferation of T cells was then examined. The 0.05Gy-pre-irradiated DCs showed the highest proliferation capacity of T cells. The 0.05Gy-irradiation does not augment the expression of major histocompatibility complexes (MHCs) or costimulatory molecules on DCs, as with non-irradiated DCs or 1Gy-irradiated DCs, but does augment the production of IL-2, IL-12 and IFN-gamma DCs. These results suggest that the low-dose irradiation augments T cell-activation capacity through cytokine production by DCs, which might shift naïve helper T cells to Th1 cells.

Human cord blood cells can differentiate into retinal nerve cells.

Retinal degeneration and dystrophy are the major causes of blindness in the developed world. It has been reported that human cord blood cells (HCBCs) can differentiate into neuron-like cells in vitro. We have recently demonstrated that bone marrow cells (BMCs) of both mice and rats can differentiate into retinal nerve cells (RNCs). In the present study, we show the differentiation capacity of HCBCs into RNCs in vivo. We transplanted lineage-negative HCBCs into the subretinal space of severe combined immunodeficiency (SCID) mice. Two weeks after the transplantation, some of the transplanted cells expressed human nestin, human MAP2, human neuron specific enolase (NSE), beta-III tubulin and also rhodopsin. These results indicate that HCBCs can differentiate into RNCs and suggest that our new strategy could be used for the regeneration of retinal nerve cells in degenerative or dystrophic diseases.

Synergistic effects of granulocyte-colony stimulating factor and macrophage-colony stimulating factor on recovery of donor hematopoietic cells in allogeneic bone marrow transplantation.

G-CSF and M-CSF are used clinically to augment hematopoiesis after bone marrow transplantation (BMT) and chemotherapy. In this paper, we examined the synergistic effect of G-CSF and M-CSF on hematopoietic recovery in allogeneic BMT as a model of human BMT. We performed BMT from eGFP-transgenic mice (C57BL/6 background; H-2b) into lethally-irradiated C3H (H-2k). From the day after BMT, G-CSF and/or M-CSF were injected for 5 consecutive days. Not only the numbers of day 12 CFU-S and spleen weight, but also white blood cell (WBC) counts in the peripheral blood (PB) and nuclear cells in the bone marrow (BM) increased in the mice treated with G-CSF and/or M-CSF 12 days after BMT. Moreover, the number of donor-type WBCs in the PB and donor-type nuclear cells in the BM also increased in the mice treated with G-CSF and/or M-CSF. The effects were pronounced when G-CSF and M-CSF were used together rather than independently. These results suggest that treatment with the combination of G-CSF and M-CSF has a synergistic effect on hematopoiesis in allogeneic BMT.

Treatment and transfer of emphysema by a new bone marrow transplantation method from normal mice to Tsk mice and vice versa.

We have recently established a new bone marrow transplantation (BMT) method in which bone marrow cells are injected into the intrabone marrow (IBM). In the present study, we used an animal model for emphysema (tight-skin [Tsk] mouse) to examine whether IBM-BMT could be used to treat emphysema in Tsk mice. IBM-BMT was carried out from C3H mice into Tsk mice (8-10 weeks old) that had already shown emphysema. Six months after transplantation, the lungs of all the Tsk mice treated with IBM-BMT [C3H-->Tsk] showed similar structures to those of normal mice, whereas the [Tsk-->Tsk] mice showed emphysema, as seen in age-matched Tsk mice. Next, we attempted to transfer emphysema from Tsk mice to C3H mice by IBM-BMT. Six months after IBM-BMT, the [Tsk-->C3H] mice showed emphysema. These results strongly suggest that emphysema in Tsk mice originates from defects of stem cells in the bone marrow.

G-CSF and/or M-CSF accelerate differentiation of bone marrow cells into endothelial progenitor cells in vitro.

It has been reported that granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage-colony stimulating factor (GM-CSF) can mobilize endothelial progenitor cells (EPCs) in bone marrow cells (BMCs) into peripheral blood (PB) in vivo. Previously, we also reported that macrophage-colony stimulating factor (M-CSF) can mobilize EPCs into PB, which results in the rapid recovery of blood flow in induced-ischemia limbs by augmenting the number of intramuscular capillaries in vivo. In the present study, we demonstrate that M-CSF and/or G-CSF can increase EPCs from lineage (CD3, B220, Gr-1, Mac-1, CD11c, Ter119, NK1.1 or CD31)-negative BMCs in vitro. Lineage-negative BMCs were cultured with or without M-CSF and/or G-CSF. Three days after culture with M-CSF and/or G-CSF, the number of Flk-1+/CD45-, Sca-1+/CD45-, CD31+/CD45- or CD146+/CD45- cells increased in comparison with no cytokines. When the cultured BMCs with or without G-CSF and/or M-CSF were intravenously injected into ischemia-induced hindlimbs of mice, the number of intramuscular capillaries in the ischemia-induced legs increased; BMCs cultured with G-CSF and/or M-CSF were more effective than those of cytokine non-treated BMCs. These results suggest that M-CSF and/or G-CSF can induce the differentiation of BMCs into EPCs, even in vitro.

Mechanisms underlying acceleration of blood flow recovery in ischemic limbs by macrophage colony-stimulating factor.

Recently we reported that macrophage colony-stimulating factor (M-CSF) can mobilize endothelial progenitor cells (EPCs) from the bone marrow into the peripheral blood, resulting in an increase in the number of blood vessels and augmentation of blood flow in the ischemia-induced legs. M-CSF accelerates neovascularization of ischemic lesions resulting from the mobilization of EPCs. In the present paper, we analyze the mechanisms underling the mobilization of EPCs by M-CSF. M-CSF augments the production of vascular endothelial growth factor (VEGF) from the bone marrow cells, especially from myeloid lineage cells. In vivo administration of anti-VEGF antibody abrogates both the acceleration of the recovery of blood flow in the ischemia-induced limbs by M-CSF and the augmentation of the mobilization of EPCs induced by M-CSF. These results suggest that the M-CSF contributes to rapid recovery of blood flow in ischemic lesions by mobilization of EPCs from the bone marrow through augmentation of VEGF production in the bone marrow and that the VEGF is mainly produced by myeloid lineage cells.

Infrarenal abdominal aortic aneurysm complicated by persistent endotension after endovascular repair: report of a case.

Endoleak and endotension may prevent the successful exclusion of an aneurysm after endovascular aortic aneurysm repair (EVAR). The pressurization in the excluded aneurysm sac caused by endotension may lead to rupture of the aneurysm; however, the cause of endotension and its underlying mechanisms remain unclear. We report a case of infrarenal abdominal aortic aneurysm (AAA) complicated by persistent endotension after EVAR. Although no endoleaks were found on conventional double-phase computed tomographic scans, a thrombosed endoleak existed in the side branch and attachment site of the endograft. After treating the undetectable thrombosed endoleaks, physical examination revealed that the pressure of the excluded aneurysm had diminished, with shrinkage of the aneurysm. This case report suggests that a high-pressure undetectable type I or type II endoleak could be a major cause of endotension. Thus, postoperative evaluation of the attachment site of an endograft is important after EVAR.

Long-term observation after simultaneous lung and intra-bone marrow-bone marrow transplantation.

BACKGROUND: Although lung transplantation is now an established treatment for end-stage lung diseases, allogeneic transplantation of parenchymal organs requires immunosuppressive therapy to prevent rejection. It has been reported that bone marrow transplantation (BMT) induces specific tolerance to donor organs. We have recently discovered a new method for BMT, which is called intra-bone marrow (IBM) BMT, in which bone marrow cells (BMCs) are injected directly into the bone marrow cavity. We demonstrate that IBM-BMT can be used to induce tolerance even in simultaneous lung transplantations in rats without administering any immunosuppressants. METHODS: Allogeneic lung transplantation was carried out from Brown Norway to Lewis rats. Simultaneously, IBM-BMT was carried out. RESULTS: Transplantation of nonirradiated lung or nontreated BMCs (T cell-containing BMCs) induced graft vs host disease. Therefore, the donor lung was irradiated, and T cells in the BMCs were depleted by anti-CD4, anti-CD5, and anti-CD8 antibodies plus anti-mouse antibody-coated magnetic beads. Lung allografts with conventional (intravenous) BMT failed to induce tolerance. However, the recipients treated with lung allografts plus IBM-BMT, which showed either mixed chimerism or full chimerism of hematopoietic cells, did not show symptoms of graft rejection or graft vs host disease, even without the use of immunosuppressants. CONCLUSIONS: These results suggest that simultaneous lung transplantation and IBM-BMT (but not conventional BMT) is effective in inducing persistent tolerance without the use of immunosuppressants.

Hepatocyte growth factor delivered by ultrasound-mediated destruction of microbubbles induces proliferation of cardiomyocytes and amelioration of left ventricular contractile function in Doxorubicin-induced cardiomyopathy.

At present, there is no curative strategy for advanced cardiomyopathy except for cardiac transplantation, which is not easily performed, mainly due to a shortage of donors. It has been reported that myocardial progenitor cells exist even in the postnatal heart, suggesting that myocardial progenitor cells could proliferate under some situations and might improve cardiac function in cardiomyopathy-induced hearts. In this study, recombinant human hepatocyte growth factor (rhHGF) was delivered using ultrasound-mediated destruction of microbubbles (UMDM) into the cardiomyopathy-induced heart by doxorubicin (20 mg/kg). Intravenous injection of rhHGF (IV-rhHGF) alone or UMDM alone failed to improve the morphology or the function of the cardiomyopathy-induced heart, but (IV-rhHGF + UMDM) treatment significantly improved the heart morphologically and functionally, and repetitive treatments of (IV-rhHGF + UMDM) enhanced the effects. The number of bromodeoxy-uridine-positive cardiomyocytes significantly increased in the (IV-rhHGF + UMDM)-treated hearts compared with the untreated hearts. Moreover, Sca-1+ myocardial progenitor cells express c-Met, a receptor for HGF. These results suggest that (IV-rhHGF + UMDM) treatment could morphologically and functionally improve the heart in the case of doxorubicin-induced cardiomyopathy through the proliferation of the myocardial progenitor cells.

Long-term survival of bone marrow-derived retinal nerve cells in the retina.

Recently, we have demonstrated that bone marrow stem cells can differentiate into retinal nerve cells. In the present study, we show a new and efficient strategy for transplanting bone marrow stem cells into the retina. When bone marrow stem cells were injected into the vitreous cavity of untreated eyes, only very few cells were found in the retina 2 weeks after injection. In contrast, when laser photocoagulation was performed just before the injection of bone marrow stem cells, a large number of the injected cells survived 2 weeks after injection and the cells expressed neural cell-specific or retinal nerve cell-specific antigens. Moreover, we still detected bone marrow stem cell-derived retinal nerve cells in the retina 1 year after injection in the retina.

Autopsy case of primary choriocarcinoma of the urinary bladder.

Choriocarcinomas usually develop in the uterus and ovaries in the female, being extremely rare in the extragenital organs in the male. Extragenital choriocarcinomas in the male usually develop in the mediastinum or retroperitoneum. The frequency of choriocarcinoma in the urinary bladder is extremely low. The purpose of the present paper was to report an autopsy case of choriocarcinoma in the urinary bladder in the male. An 81-year-old male patient with macrohematuria was first diagnosed with transitional cell carcinoma (TCC). At autopsy a hemorrhagic necrotic tumor, which was found in the urinary bladder with metastatic lesions in the lungs, was diagnosed as choriocarcinoma microscopically. There was no evidence for choriocarcinoma derived from any other organs than the urinary bladder, although there were metastatic lesions in both lungs and the direct invasion into the prostate. From these findings it is concluded that the tumor was a primary choriocarcinoma in the urinary bladder in a male patient. Choriocarcinoma of the urinary bladder is very rare, but the prognosis is extremely poor in comparison with TCC even in the urinary bladder. Therefore, it is essential to clearly discriminate between choriocarcinomas and TCC.

Macrophage colony-stimulating factor (M-CSF), as well as granulocyte colony-stimulating factor (G-CSF), accelerates neovascularization.

It has been reported that bone marrow cells (BMCs) differentiate into endothelial cells of blood vessels, and that granulocyte colony-stimulating factor (G-CSF) mobilizes progenitors in the BMCs to the peripheral blood, while macrophage colony-stimulating factor (M-CSF) augments the production of monocytes. We examined whether M-CSF augments the differentiation of BMCs into endothelial cells of blood vessels using a hindlimb-ischemic model. Either G-CSF or M-CSF, or both, was administered to the hindlimb-ischemic mice for 3 days. Both M-CSF and G-CSF augmented the differentiation of BMCs into endothelial cells of blood vessels through vascular endothelial cell growth factor (VEGF), resulting in early recovery of blood flow in the ischemic limbs.