Long-Term Results and Follow-Up Examinations after Endovascular Embolization for Unruptured Cerebral Aneurysms.

BACKGROUND AND PURPOSE: The appropriate period of follow-up examinations after endovascular embolization for cerebral aneurysms using time-of-flight MR angiography is not well-known. We retrospectively investigated long-term results after endovascular embolization for unruptured cerebral aneurysms and evaluated the periods from embolization to recanalization and retreatment. MATERIALS AND METHODS: Between April 2006 and March 2011, one hundred forty-eight unruptured aneurysms were treated with endovascular coil embolization. Among them, we investigated 116 unruptured aneurysms, which were followed up for >5 years. Time-of-flight MR angiography was performed at 1 day, 3-6 months, 1 year after the procedure, and every year thereafter. RESULTS: The mean follow-up period was 7.0 ± 1.4 years. Recanalization was observed in 19 (16.3%) aneurysms within 2 years. Among them, retreatment for recanalization was performed in 8 (6.8%) aneurysms. No recanalization was detected in any aneurysms that had been stable in the first 2 years after embolization. A larger maximum aneurysm size was significantly correlated with recanalization (P = .019). CONCLUSIONS: Aneurysms in which recanalization was not observed within 2 years after endovascular coil embolization were stable during a mean follow-up of 7 years. This result may be helpful in considering the appropriate span or frequency of follow-up imaging for embolized cerebral aneurysms.

Changes in penile length after radical prostatectomy: effect of neoadjuvant androgen deprivation therapy.

Although reports have shown evidence for penile length (PL) shortening after radical prostatectomy (RP), the association between neoadjuvant androgen deprivation therapy (NADT) and PL after RP has yet to be determined. This study evaluates chronological changes in PL after NADT and RP. Stretched PLs (SPLs) of 143 patients, 41 of whom had undergone NADT, were measured before, 10 days after, and 1, 3, 6, 9, 12, 18, and 24 months after RP. Chronological erectile function and testosterone levels were then evaluated. SPL was shortest 10 days after RP in both the NADT (-) and NADT (+) groups and gradually recovered in length thereafter. SPL in the NADT (-) group was significantly longer than that in the NADT (+) group before RP. However, no significant differences in SPLs were found between both groups 6 months after RP. Although all subjects in the NADT (+) group had testosterone levels of <50 ng/dL before RP, such levels increased after RP. Before RP, the NADT (-) group was found to have significantly better erectile function than the NADT (+) group. However, differences in erectile function between the NADT (-) and NADT (+) groups after RP were not significant. This report is the first to show that among patients with prostate cancer, those who underwent NADT had greater PL recovery after RP than those who did not. Data regarding PL recovery after NADT and RP obtained in this study could be useful for patients with prostate cancer who plan to undergo such procedures.

Effects of testosterone replacement therapy on metabolic syndrome among Japanese hypogonadal men: A subanalysis of a prospective randomised controlled trial (EARTH study).

We investigated the effects of testosterone replacement therapy (TRT) on metabolic factors among hypogonadal men with a metabolic syndrome. From the study population of the EARTH study, which was a randomised controlled study in Japan, 65 hypogonadal patients with a metabolic syndrome, comprising the TRT group (n = 32) and controls (n = 33), were included in this study analysis. The TRT group was administered 250 mg of testosterone enanthate as an intramuscular injection every 4 weeks for 12 months. Waist circumference, body mass index, body fat volume and blood pressure were measured in all patients at baseline and at 12 months. In addition, blood biochemical data, including total cholesterol, triglyceride (TG), HDL cholesterol, fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) levels, were also evaluated. Changes in these categories from baseline to 12 months were compared between the TRT and control groups, with significant differences observed in waist circumference, body fat percentage, FPG, TG and HbA1c levels. No significant differences were observed in other parameters. TRT for 1 year was associated with improvements in some metabolic factors among Japanese men with hypogonadism and metabolic syndrome.

Segregation of TRAF6-mediated signaling pathways clarifies its role in osteoclastogenesis.

Signals emanating from the receptor for interleukin-1 (IL-1), lipopolysaccharide (LPS) or osteoclast differentiation factor/receptor activator of NF kappa B ligand (ODF/RANKL) stimulate transcription factors AP-1 through mitogen-activated protein kinase (MAPK) activation and NF kappa B through I kappa B kinase (IKK) activation. These kinases are thought to be activated by tumor necrosis factor receptor-associated factor 6 (TRAF6). However, molecular mechanisms by which TRAF6 activates various downstream kinases remain to be elucidated. We identified functional domains of TRAF6 under physiological conditions established by appropriate expression of TRAF6 mutants in TRAF6-deficient cells. In IL-1 and LPS signaling pathways, the RING finger and first zinc finger domains are not required for NF kappa B activation but are required for full activation of MAPK. However, IL-1 and LPS signals utilize distinct regions within the zinc finger domains of TRAF6 to activate NF kappa B. Furthermore, the RING finger domain is not required for differentiation of splenocytes to multinuclear osteoclasts, but is essential for osteoclast maturation. Thus, TRAF6 plays essential roles in both the differentiation and maturation of osteoclasts by activating various kinases via its multiple domains.

Ecological risk-benefit analysis of a wetland development based on risk assessment using "expected loss of biodiversity".

Ecological risk from the development of a wetland is assessed quantitatively by means of a new risk measure, expected loss of biodiversity (ELB). ELB is defined as the weighted sum of the increments in the probabilities of extinction of the species living in the wetland due to its loss. The weighting for a particular species is calculated according to the length of the branch on the phylogenetic tree that will be lost if the species becomes extinct. The length of the branch on the phylogenetic tree is regarded as reflecting the extent of contribution of the species to the taxonomic diversity of the world of living things. The increments in the probabilities of extinction are calculated by a simulation used for making the Red List for vascular plants in Japan. The resulting ELB for the loss of Nakaikemi wetland is 9,200 years. This result is combined with the economic costs for conservation of the wetland to produce a value for the indicator of the "cost per unit of biodiversity saved." Depending on the scenario, the value is 13,000 yen per year-ELB or 110,000 to 420,000 yen per year-ELB (1 US dollar = 110 yen in 1999).

[Successful immunosuppressive therapy for a patient with hypoplastic myelodysplastic syndrome].

We encountered a patient with hypoplastic myelodysplastic syndrome (MDS) who responded to immunosuppressive therapy including antithymocyte globulin and cyclosporin A (CsA). A 13-year-old girl was referred to our hospital because of pancytopenia. Bone marrow smears disclosed extreme hypocellularity without cellular atypism. A diagnosis of aplastic anemia was made, and immunosuppressive therapy consisting of ATG, CsA, granulocytecolony-stimulating factor (G-CSF), methylprednisolone, and danazol was started. A month later dysplastic cells appeared in the bone marrow. The karyotype of pretreatment bone marrow cells was 46, XX, del (13) (q12; q14). Therefore, the final diagnosis was hypoplastic MDS. CsA and danazol were continued. The patient became transfusion-independent 1 month later and dysplastic cells disappeared from bone marrow 3 months later. The chromosomal abnormality also became undetectable 6 months after the initiation of treatment. These findings indicated that immunosuppressive therapy is beneficial for patients with hypoplastic MDS.

Membrane type 1-matrix metalloproteinase is involved in the formation of hepatocyte growth factor/scatter factor-induced branching tubules in madin-darby canine kidney epithelial cells.

Matrix metalloproteinases (MMPs) are believed to be involved in morphogenesis. Association of MMPs in a model of kidney tubulogenesis was studied using Madin-Darby canine kidney (MDCK) epithelial cells in an in vitro morphogenetic system. MDCK cells form branching tubules in three-dimensional collagen gel matrix in the presence of hepatocyte growth factor (HGF). The addition of specific MMP inhibitor BB-94 and tissue inhibitor MMP (TIMP)-2 but not TIMP-1 to such collagen gel cultures reduced the formation of branching tubules induced by HGF. The induction of membrane-type 1-matrix metalloproteinase (MT1-MMP) mRNA expression was observed in MDCK cells cultured in the collagen gel. Stable expression of MT1-MMP antisense RNA interfered with the tubule formation of MDCK cells induced by HGF-collagen gel culture. These observations implicate MT1-MMP in kidney tubulogenesis and TIMP-2-specific inhibition suggests a direct role of MT1-MMP rather than a gelatinase A-mediated effect.

Transformation of epithelial Madin-Darby canine kidney cells with p60(v-src) induces expression of membrane-type 1 matrix metalloproteinase and invasiveness.

Membrane-type 1 matrix metalloproteinase (MT1-MMP) is expressed both in carcinoma cells and in surrounding stromal fibroblasts. MT1-MMP localizes to the surface of tumor cells and is thought to play an important role in tumor invasion. To analyze the mechanism of MT1-MMP gene expression in epithelial tumor cells, the dog kidney epithelial cell line Madin-Darby canine kidney (MDCK) was transformed by oncogenes, including v-src, and expression of MT1-MMP was examined. Transformation of MDCK cells with v-src resulted in loss of cell-to-cell contacts and morphological change. Expression of MT1-MMP in v-src-transformed cells was identified by Northern and Western blotting. Gelatin zymography analysis showed that progelatinase A in the culture medium was processed from latent to activated form by MDCK cells transformed with v-src. The MDCK cells transformed by v-src were tumorigenic in the subcutis (ectopic) and kidney (orthotopic) of nude mice and spontaneously metastasized to the lung after orthotopic implantation. These results suggest that MT1-MMP induced by v-src transformation may promote invasiveness of transformed cells.

Chemotherapy of metastatic testicular germ cell tumors: relationship of histologic response to size reduction and changes in tumor markers.

BACKGROUND: Although testicular germ cell tumor is one of the most curable cancers, approximately 20% of advanced cases remain incurable. In this study we investigate factors that may predict a poor response to standard chemotherapeutic regimens and thus allow earlier initiation of more aggressive measures. METHODS: We analyzed the records of 19 patients with metastatic testicular germ cell tumors (8 seminomas and 11 nonseminomas). Sixteen patients underwent surgical exploration for residual tumors following chemotherapy, and the histological findings on the resulting specimens were correlated with reductions in tumor size observed on computed tomography and with changes in tumor marker levels. RESULTS: Complete necrosis was obtained in 10 of 12 lesions that shrank by at least 80%, while continued existence of teratoma or cancer was confirmed in 9 of 11 lesions with smaller size reductions. An initial human chorionic gonadotropin-beta subunit (HCG-beta) level more than 100 times the upper limit of normal appeared to predict poor histological response (teratoma/cancer) to chemotherapy. Slow fall (prolonged half-life) of tumor markers during chemotherapy also correlated with poor histological response. CONCLUSION: Factors which predict poor histological response of tumors to chemotherapy include size reduction less than 80%, initial HCG-beta levels more than 100 times the upper limit of normal, and prolonged half-life of tumor markers (placental alkaline phosphatase, alpha-fetoprotein and HCG-beta).

Alteration of midkine expression associated with chemically-induced differentiation in human neuroblastoma cells.

Midkine (MK), a neurotrophic polypeptide of which expression is developmentally regulated in embryogenesis, is expressed in malignant tumor tissues including neuroblastoma (NB). A retinoic acid analogue, E5166, and dibutyryl cyclic AMP (dbcAMP) are known to induce differentiation in NB cells. This study showed that MK mRNA expression increased in association with differentiation by E5166, but not by dbcAMP in SK-N-SH and KP-N-RTBM1 human NB cell lines. We concluded that MK could be an important factor in differentiation of NB cells, and further, that there could be at least two pathways in differentiation of NB cells at molecular mechanism.

Enhanced tumorigenic and metastatic potential of an androgen-sensitive human prostate cancer cell line, LNCaP, by intratesticular inoculation in SCID mice.

To establish a prostate cancer model expressing prostate-specific antigen (PSA) with metastatic potential, LNCaP or PC-3 cells were inoculated into the testis of SCID mice, resulting in a 100% rate of tumor formation. A significant increase in serum PSA was found in mice with LNCaP xenografts. Circulating tumor cells and micrometastases to organs such as lung, liver, spleen, and omentum were detected for both cell lines by PCR of the human beta-globin gene. Lymph node metastases occurred more frequently with PC-3 than LNCaP cells. This is the first report showing stable growth of LNCaP cells in mice with metastases to the regional lymph nodes. This model of prostate cancer should help to assess treatment strategies targeting PSA.

MAGE-1 and MAGE-3 or -6 expression in neuroblastoma-related pediatric solid tumors.

MAGE-1 and MAGE-3 or -6 are genes encoding melanoma-rejection antigens recognized by cytotoxic T lymphocytes in an HLA-A1 restriction manner. MAGE-1 and MAGE-3 or -6 were expressed in 5/14 (36%) and 6/14 (43%) neuroblastoma (NB) cell lines, and in 20/41 (49%) and 24/41 (59%) clinical NB-related tumors, respectively. Additionally, they were also expressed in pediatric tumors of other types such as rhabdomyosarcoma and Wilms' tumor. MAGE-1 expression at a functional level in tumor cells was confirmed by the cytotoxicity assay using MAGE-1-specific tumor-infiltrating lymphocytes (TIL). In clinical NB-related tumors, MAGE-3 or -6 expression demonstrated an inverse correlation to clinical stage. Furthermore, although the sample number was small, the incidence of MAGE-1 and/or MAGE-3 or -6 expression was significantly correlated to the absence of metastasis and a more favorable clinical outcome (p < 0.05). These results may suggest that NB cells silent for the expression of MAGE genes escape from the host anti-tumor immune response and consequently retain a growth advantage. Finally, NB-related tumors could be reliable candidates for immunotherapy targeted towards MAGE gene products.

Effects of antidepressants on thyroid stimulating hormone release in rats under ether stress.

We found inhibitory effects of antidepressants (clomipramine, maprotyline, mianserin and zimelidine) and 5-hydroxytryptophan (5-HTP) on thyroid stimulating hormone (TSH) release induced by ether stress in freely moving rats. We confirmed that ether stress suppressed the plasma TSH levels after 30 min. We then injected intravenously 250 ng thyrotropin releasing hormone (TRH), 0.1 mg/kg clomipramine, 2.5 mg/kg maprotyline, 2.5 mg/kg mianserin, 0.5 mg/kg zimelidine and 25 mg/kg 5-HTP simultaneously. These materials blocked the influences on plasma TSH levels by the ether stress. Serotonergic antidepressants (clomipramine, zimelidine) and 5-HTP (precursor of serotonin) had a higher potency against the ether stress. These results suggest that antagonizing effects against the ether stress may involve the serotonergic system in the pituitary gland.

Clinical symptoms and regional cerebral blood flow in schizophrenia.

This study examined the relationship between clinical symptoms and regional cerebral blood flow (rCBF) in schizophrenic patients using single photon emission computed tomography (SPECT). The subjects were 26 medicated schizophrenic patients diagnosed according to DSM-III-R criteria. Clinical symptoms were assessed using the Scale for the Assessment of Negative Symptoms (SANS), selected items for the Positive and Negative Syndrome Scale (PANSS), and the scale for Schneider's first rank symptoms. Resting rCBF was measured using N-isopropyl-p-[I-123] iodoamphetamine (I-123 IMP) SPECT, and relative rCBF distribution was evaluated in nine regions of interest in each hemisphere. Factor analysis of symptom ratings indicated four separate syndromes: psychomotor poverty, alienation (hallucination and disturbance of the self), delusion, and disorganization. Stepwise multiple regression analysis showed the psychomotor poverty syndrome to be correlated with decreased rCBF in bilateral superior frontal areas and increased rCBF in the left thalamus and right basal ganglia. The disorganization syndrome was correlated with increased rCBF in bilateral anterior cingulates and decreased rCBF in bilateral middle frontal areas. The alienation syndrome was shown related to increased rCBF in the right inferior frontal area and parietal area. Dysfunction in distinctive neural networks involving various prefrontal areas would thus appear to underlie these syndromes in schizophrenia.

Is CIS of the ureter responsible for skipped lymph node metastasis? A case report.

A case of skipped lesion of lymph node metastasis of left ureteral tumour with concurrent carcinoma in situ in the affected ureter is presented. Postoperatively, lymph node metastasis was de novo detected in the left retrocrural and renal hilar regions on CT scan, although only the obturator lymph node was histologically metastatic among the regional lymph nodes completely dissected. The possible explanations of this rare metastatic mode are discussed.

Differential alpha-smooth muscle actin expression in a gastric epithelioid leiomyosarcoma in a 14 year old girl.

Leiomyosarcoma in childhood is very rare. This report describes the immunohistochemical study of a gastric epithelioid leiomyosarcoma in a 14 year old girl. Microscopically, the tumor showed two distinct histological patterns within the same tumor: small epithelioid cells forming a lobular pattern and spindle-shaped cells forming interlacing fascicles, but no distinct border divided the two types of cells. Immunohistochemically, vimentin was positive in all tumor cells; alpha-smooth muscle actin, however, was negative in small epithelioid cells and positive in spindle-shaped cells. The data revealed that the tumor had components showing two stages of morphological and biochemical differentiation. This case indicates that leiomyosarcomas might lose smooth muscle actin during malignant transformation; or, alternatively, they might arise from a primitive type of smooth muscle cell and some of them could spontaneously differentiate into mature smooth muscle cells, expressing this actin.

Scanning eye movements in schizophrenic patients. Relationship to clinical symptoms and regional cerebral blood flow using 123I-IMP SPECT.

Eye movements during the Benton Visual Retention Test were examined using an eye-mark recorder in 32 schizophrenic patients and 32 normal controls. The patients had significantly fewer eye fixations, longer mean duration of fixation and shorter length of mean scan path than the controls. In the patients, these eye movement parameters were significantly correlated with the negative symptom score but not with the positive symptom score on the Positive and Negative Syndrome Scale. These parameters had a significant correlation with the composite score on the Scale for the Assessment of Negative Symptoms (SANS). In particular, they were highly correlated with avolition-apathy and affective flattening or blunting scores on SANS subscales. Thus, examination of scanning eye movements seemed to be a good objective index of negative symptoms. Secondly, regional cerebral blood flow (rCBF) was examined using N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) and single photon emission computer tomography in 17 of 32 patients. With regard to the relationship between the eye movement parameters and rCBF, the mean duration of fixation was negatively correlated with 123I-IMP uptake in the left superior frontal area and left basal ganglia. The mean length of the scan path was correlated with uptake in the left superior frontal area. These findings suggest that the characteristic eye movements of schizophrenic patients are likely to be related with dysfunction of the frontal-basal ganglia neural circuit.

["Saving-effect" of stimulating pulses at low-frequency limbic kindling in cats].

To assess the development of kindling effect induced with low frequency electrical stimulations, we stimulated the lateral amygdala (AM group, 5 cats) and the dorsal hippocampus (HP group, 5 cats) bipolarly, once a day, with 2 mA base to peak, biphasic 1 msec square-wave pulses. In each stimulation we measured the longest inter-pulse interval required for the provocation of epileptic afterdischarge (AD), defined as the pulse-interval threshold; and the number of stimulating pulses required for the provocation of AD at this pulse-interval, defined as the pulse-number threshold. The observed behavioral seizures were classified into 6 stages in both the AM and HP group according to the conventional classification. In the AM group, an increase of the pulse-interval threshold and a decrease of the pulse-number threshold were observed during the kindling process. At the completion of kindling, a generalized convulsion was provoked with 1,200-1,600 msec pulse-intervals, and with 8-12 stimulating pulses. In the HP group an increase of the pulse-interval threshold and a decrease of the pulse-number threshold were observed in the early seizure stages, but not so significantly as the AM group. In the late seizure stages, a decrease of the pulse-interval threshold and an increase of the pulse-number threshold were observed. The observed behavioral stage of seizures in the two groups were similar to that of the conventional high-frequency kindling.(ABSTRACT TRUNCATED AT 250 WORDS)

Serial changes of the susceptibility of epileptogenic focus during hippocampal kindling induced with low-frequency electrical stimulation in cats.

Cats were stimulated in the dorsal hippocampus with low-frequency square wave pulses. All subjects were kindled until generalized convulsion occurred. In the early stage of the kindling process, an increase in the interpulse interval and a decrease in the number of stimulating pulses required for the provocation of epileptic afterdischarge were observed, but in the late stage a decrease in the former and an increase in the latter were observed. It appears from these data that completion of hippocampal kindling is accompanied by a decrease in excitability at the site of stimulation subsequent to an increase in the same.