Association of incompleteness of the anterior part of the circle of Willis with the occurrence of lacunes in the basal ganglia.

BACKGROUND AND PURPOSE: This study investigated whether incompleteness of the anterior part of the circle of Willis affects the occurrence of lacunes in the basal ganglia. METHODS: One thousand and seventy-seven healthy individuals examined by magnetic resonance (MR) imaging and MR angiography were divided into eight subgroups according to our new classification. RESULTS: Logistic regression analysis demonstrated that healthy individuals with incompleteness of the anterior circle of Willis had significantly higher frequency of lacunes [odds ratio (OR): 2.121, 95% confidence interval (CI): 1.477-3.108; or OR: 2.46, 95% CI: 1.377-4.384 in cases without or with fetal type posterior communicating artery, respectively] and higher numbers of lacunes (P < 0.001 or P < 0.001 in cases without or with fetal type posterior communicating artery, respectively) compared to patients with complete circle of Willis. CONCLUSIONS: Incompleteness of the anterior part of the circle of Willis significantly affected the occurrence of lacunes.

Thoracic chordoma: review and role of FDG-PET.

Chordoma is an uncommon primary bone tumor and the thoracic spine is the least common of all sites for a chordoma. It may recur despite slow-growing nature. Precise literature review will be performed and possible use of fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) for detection of both primary and recurrent diagnosis will be discussed. This article presents the case of a 73-year-old male patient who complained of back pain. Magnetic resonance (MR) imaging, computed tomography (CT) and FDG-PET demonstrated thoracic lesion and biopsy revealed chordoma. The patient was operated on and histological findings showed the tumor was chondroid chordoma. He suffered recurrence after 7 months by FDG-PET. He received 6,000 rads radiation therapy and is neurological free but, suffered backache 15 months after initial diagnosis. Only 12 cases including this case were reported precisely and this is the first report of FDG-PET for both initial and recurrent diagnosis of chordoma.

Ossification of the ligamentum flavum of the cervical spine.

AIM: Ossification of ligamentum flavum (OLF) mainly occurs in the thoracic spine, and rarely in the cervical spine. To clarify its etiology; the features of OLF in the cervical spine were reviewed in 50 reported cases. METHODS: Age, sex, location of OLF, classification of OLF, radiographic findings, computed tomography (CT) findings, magnetic resonance imaging findings, association of ossification of the posterior longitudinal ligament (OPLL), association of OLF in other spinal regions, and association of diffuse idiopathic skeletal hyperostosis (DISH) were analyzed in 23 detailed cases. RESULTS: Association of OPLL was observed in 7 of 20 cases and 4 of these 7 OPLL cases were at C2-4. Association of OLF in other spinal regions was recognized in 7 of 15 cases. DISH was also present in 3 of 7 cases. Local kyphosis was recognized in 10 of 12 cases by radiography. CT showed facet hypertrophy in 13 of 15 cases and lamina hypertrophy in 14 of 16 cases. Patients with OLF at C2-4 had high rates of local kyphosis and association of hyperostotic state, suggesting both local factors and systemic hyperostotic factors are involved in the formation of OLF of the upper cervical spine. CONCLUSION: Local factors may be strongly related to the formation of OLF of the middle or lower cervical spine.

Risk factors for the association of intracranial and aortic aneurysms.

This study investigated the association of intracranial aneurysms and abdominal aortic aneurysms to elucidate the incidence and independent risk factors for this association. Ultrasonography of the abdominal aorta was performed in 181 patients with 224 intracranial aneurysms. Six patients had suffered subarachnoid haemorrhage and the others had chronic disease or no symptoms. Magnetic resonance angiography was performed for confirmation if abdominal aortic aneurysm was identified by ultrasonography. Thirteen patients (7.2%) with 23 intracranial aneurysms had abdominal aortic aneurysms. Univariate analysis demonstrated that age (p < 0.01), size of intracranial aneurysms (p < 0.001), male sex (p < 0.01), multiplicity of intracranial aneurysms (p < 0.001), history of cerebrovascular diseases (p < 0.05), and current smoking (p < 0.0001) were significantly different between patients with and without this association. Multiple logistic analysis indicated that age (odds ratio [OR] 1.27, 95% confidence interval 1.08-1.48, p < 0.01), multiplicity (OR 22.1, 95% confidence interval 1.83-266.3, p = 0.01), size of intracranial aneurysms (OR 1.30, 95% confidence interval 1.10-0.54, p < 0.01), and current smoking (OR 33.3, 95% confidence interval 2.43-456.7, p = 0.01) were independent risk factors for the association. Patients with intracranial aneurysms who are older males with multiple or large intracranial aneurysms, and current smokers should be examined for abdominal aortic aneurysms using ultrasonography.

Tumor regression induced by intratumor administration of adenovirus vector expressing CD40 ligand and naive dendritic cells.

We have previously shown that in vivo genetic modification of tumors with an adenovirus (Ad) vector engineered to express CD40 ligand (AdmCD40L) induces tumor-specific CTLs and suppresses tumor growth in vivo. In the present study, we investigate the hypothesis that this treatment can be made more efficient with 10(2)-fold less Ad vector by also administering bone marrow-generated dendritic cells (DCs) to the tumor. Using AdmCD40L and the number of DCs that alone had no effect on tumor growth, the data show that the growth of CT26 (colon adenocarcinoma; H-2d) and B16 (melanoma; H-2b) murine s.c. tumors is significantly suppressed by direct administration of DCs into s.c. established tumors that had been pretreated with AdmCD40L 2 days previously. The antitumor effect produced by the combination therapy AdmCD40L + DCs correlated with in vivo priming of tumor-specific CTLs. The antitumor cell-mediated immunity was transferable to naive mice by spleen cells from AdmCD40L + DC-treated animals. The interactions between CD40L and CD40 within treated tumors were critical because tumor suppression was abrogated by coadministration to the tumors of neutralizing monoclonal antibody against CD40L along with the DCs. Finally, in vivo depletion and knockout mice experiments demonstrated that tumor regression produced by this combination therapy depends on CD8+ T cells, but not on CD4+ T cells. These findings should be useful in designing strategies for use of DCs and AdmCD40L in cancer immunotherapy.

Immunological detection of glycated proteins in normal and streptozotocin-induced diabetic rats using anti hexitol-lysine IgG.

A polyclonal antibody specific for the Amadori compound, a product of an early stage of the Maillard reaction, was raised in rabbits by immunization with hexitol-lysine (1-glucitol-lysine or 1-mannitol-lysine) coupled with various carrier proteins. The affinity purified antibody has a high titre and preferentially recognizes the glucose adduct, in the presence of sodium borohydride, as judged on enzyme-linked immunosorbent assay as well as immunoblot analysis. The glycated proteins (Amadori products) in various tissues of normal and streptozotocin-induced diabetic rats were examined by immunoblot analysis. In diabetic conditions, kidney, liver, lens, brain and lung proteins are more susceptible to glycation than other tissue proteins. Heart, spleen, adrenal gland and muscle proteins exhibit similar extents of glycation in both normal and diabetic conditions. This is the first demonstration of a specific antibody against the Amadori compound being raised with a synthetic compound, and of the tissue distribution of glycated proteins in normal and diabetic conditions. The antibody was very useful for in vitro and in vivo experiments on the Maillard reaction.

Effects of exercise stress and cold stress on glutathione and gamma-glutamyltransferase in rat liver.

Effects of acute and chronic stress (exercise and cold) on glutathione and gamma-glutamyltransferase (gamma GT) in the rat liver were investigated. Such stress, except for in the case of acute exercise, had no definite influence on the glutathione level. On the other hand, gamma GT activity in both the extramicrosomal and microsomal fractions varied substantially, suggesting that acute exercise increases the release ability of the microsomal membrane of the rat liver, and that swimming training and long-term cold exposure stabilize the membrane. Immunoreactive gamma GT, however, did not always correlate with the enzyme activity, especially in the extramicrosomal fraction. Cross-adaptation appeared to exist between swimming training and chronic cold exposure.

Dynein- and microtubule-mediated translocation of adenovirus serotype 5 occurs after endosomal lysis.

Modified viruses are used as gene transfer vectors because of their ability to transfer genetic material efficiently to the nucleus of a target cell. To better understand intracellular translocation of adenovirus serotype 5 (Ad), fluorophores were covalently conjugated to Ad capsids, and movement of fluorescent Ad within the cytoplasm was observed during the first hour of infection of a human lung epithelial carcinoma cell line (A549). Ad translocation was characterized with respect to its ability to achieve nuclear envelope localization as well as directed movement in the cytoplasm. Whereas Ad achieved efficient nuclear localization 60 min after infection of A549 cells under control conditions, depolymerization of the microtubule cytoskeleton by addition of 25 microM nocodazole reversibly inhibited development of nuclear localization. In contrast, depolymerization of microfilaments by addition of 1 microM cytochalasin D had no effect on nuclear localization. Direct video observation of Ad motility showed that nocodazole, but not cytochalasin D, caused a reversible decrease in rapid linear translocations of Ad in the cytoplasm of A549 cells. Microinjection of function-blocking antibodies against the microtubule-dependent motor protein, cytoplasmic dynein, but not kinesin, blocked nuclear localization of Ad, consistent with net minus end-directed motility indicated by accumulation of Ad at mitotic spindles. Fluorescence ratio imaging revealed a neutral pH in the environment of translocating Ad, leading to a model in which the interaction of Ad with an intact microtubule cytoskeleton and functional cytoplasmic dynein occurs after escape from endosomes and is a necessary prerequisite to nuclear localization of adenovirus serotype 5.

Specific detections of the early process of the glycation reaction by fructose and glucose in diabetic rat lens.

The glycation reaction by fructose, as well as that by glucose, in control and diabetic rat lens was analyzed by using antibodies which specifically recognize adducts of lysine with fructose and with glucose. Levels of fructose adducts in diabetic rat lens were 2.5 times that of the control, and correlated with sorbitol levels. This was mainly due to enhanced glycation of beta- and gamma-crystallins by fructose under diabetic conditions. These data suggest that glycation by fructose may also play a role in cataract formation under conditions of diabetes and aging.

Comparison of continuous and intermittent bolus infusions of metoclopramide during 5-day continuous intravenous infusion with cisplatin.

In order to decide the administration method of metoclopramide for prevention or control of chemotherapy-induced nausea and vomiting in multidrug chemotherapy, with cisplatin 5-day continuous intravenous infusion (25 mg/m2/day) for patients with advanced lung cancer, a randomised crossover study of intermittent bolus infusion (1 mg/kg, 30 min, every 8 h, day 1-5) and continuous infusion (3 mg/kg/24 h, 120 h) of metoclopramide was performed. Both regimens included methylprednisolone and diphenhydramine given concurrently. The acute and delayed antiemetic effects were examined. 21 cases could be evaluated. There were 6 and 10 cases (P = 0.048), respectively, of no nausea and no vomiting; 14 and 18 cases (P = 0.048), respectively, of no vomiting; and vomiting episodes were seen 27 and 9 times, respectively (P = 0.042). Thus, metoclopramide continuous infusion was significantly superior in antiemetic effect compared to bolus infusion. Neither method had any serious side-effects and both were safe.

An immunohistochemical study of thymic epithelial tumors. I. Epithelial component.

Twenty-four cases of thymic epithelial tumors, including 18 cases of thymoma, five cases of squamous cell carcinoma, and one case of undifferentiated carcinoma, were studied immunohistochemically using monoclonal antibody Leu-7 (HNK-1) and antikeratin antibody. Seven cases of non-neoplastic thymic tissues were also studied. Leu-7 antibody stained epithelial cells in the outer cortex of the normal thymus, and antikeratin antibody stained thymic epithelial cells in both cortex and medulla of the normal thymus. Seventeen thymomas and one undifferentiated carcinoma were focally or diffusely stained with Leu-7, some showing cortical and medullary differentiation as seen in the normal thymus. On the other hand, none of the five squamous cell carcinomas were stained with Leu-7. All thymomas stained for keratin in varying degrees, and all squamous cell carcinomas were diffusely and strongly stained with antikeratin antibody. It is concluded that normal thymic epithelial cells showed zonal differentiation, and neoplastic cells were considered to retain these characteristics to some extent; i.e., thymomas had the same phenotype of epithelial cells of the cortex, especially the outer cortex of the thymus in some instances (Leu-7-positive, keratin-positive) and of both cortex and medulla (mixture of Leu-7-positive and -negative cells) with organoid arrangement in other instances, and thymic squamous cell carcinoma had the same phenotype as epithelial cells in the thymic medulla (Leu-7-negative, keratin-positive).

Expression of vimentin in surgically resected adenocarcinomas and large cell carcinomas of lung.

The expression of vimentin in pulmonary carcinomas was studied in 285 cases of surgically resected lung cancer from our hospital files. Formalin fixed, paraffin-embedded sections were studied by immunoreactive staining techniques using two monoclonal antibodies against vimentin. Cases demonstrating vimentin positivity by the avidin-biotin-peroxidase method included 11 of 129 adenocarcinomas studied (8.5%), and 15 of 61 large cell carcinomas studied (24.6%). Vimentin expression was not seen in any of the 51 squamous cell carcinomas or 35 small cell carcinomas in our series. The positive cases of adenocarcinoma were in moderately and poorly differentiated cancers. Four of the eight giant cell carcinomas (50%) demonstrated vimentin expression. All cases that exhibited vimentin positivity were studied for cytokeratin expression. Coexpression of vimentin and cytokeratin was demonstrated not only within the same tumor but also within the same cells in some cases stained by double antibody technique, including both adenocarcinomas and large cell carcinomas. Similar immunoreactive methods were also applied to sections from human lung cancer transplants grown in the nude mouse. Of 28 tumors studied, four of 11 adenocarcinomas (36%) and all 4 large cell carcinomas demonstrated coexpression of vimentin and cytokeratin, while none of the five squamous cell carcinomas or eight small cell carcinomas expressed vimentin.

Adjuvant chemotherapy for completely resected stage III non-small-cell lung cancer. Results of a randomized prospective study. The Japan Clinical Oncology Group.

Two hundred nine patients with completely resected stage III non-small-cell lung cancer were randomized to receive postoperative cisplatin and vindesine chemotherapy or no further treatment. Before randomization, patients were stratified by the histologic characteristics of their tumors (squamous versus nonsquamous cell carcinoma). Prognostic variables such as histology, performance status, extent of operation, and tumor and nodal status of the eligible patients in chemotherapy (n = 90) and control groups (n = 91) were equally distributed. There was no statistically significant difference in disease-free and overall survival between the two groups. The 3-year disease-free survivals of the chemotherapy and control groups were 37% and 42%, respectively. The median survival times (5-year survival) were 31 months (35%) in the chemotherapy group and 37 months (41%) in the control group. These was no different pattern in the first site of recurrence (local versus systemic) between the two groups. This study failed to demonstrate the therapeutic benefits of postoperative cisplatin and vindesine chemotherapy.

Immune reactivity in primary carcinoma of the lung and its relation to prognosis.

Detailed studies of immune reactivity were performed in 154 patients with primary lung cancer, 20 patients with benign thoracic lesions, and 109 healthy persons. Reactions to the 2,4-dinitrochlorobenzene (DNCB) skin test were postive in 73 per cent of patients with lung cancer and all (100 per cent) of the patients with benign disease (p less than 0.05). The incidence of DNCB reactions was 78 per cent for Stage I and II cancers (37 patinets), 73 per cent for resectable Stage III cancer (22 patients), and 66 per cent in patients with unresectable or inoperable Stage III cancer. DNCB reactivity showed a relationship to primary histology. The incidence of DNCB positive reactions was 80 per cent in patients with epidermold carcinoma versus 57 per cent in patients with adenocarcinoma, 64 per cent in patients with oat cell cancer, and 80 per cent in patients with terminal bronchiolar carcinoma. In vitro immune studeis correlated best with stage of disease. These included the absolute lymphocyte count and absolute T cell count and lymphoxyte stimulation witalen A (Com A). These values were in the normal range in patients with Stage I cancer but were significantly depressed in patients with Stage III cancer. Svrvival curves were plotted in patients with Stage III disease according to the responses to three immune parameters: DNCB, absolute lymphocyte count, and PHS stimulation. Although patients with normal reactions generally had better survival rates, PHA responses showed the most significant correlation to survival. These tests support the usefulness of immune testing as an additional parameter of assessing biological risk in patients with primary lung cancer.

Tandem single-step construction of chiral hexahydrophenanthrenes: a concise route to (+)-ferruginol.

An efficient enantio- and diastereocontrolled construction of hydrophenanthrenes having either a quaternary or a tertiary benzylic stereogenic center has been developed by employing a tandem retro-aldol and intramolecular Friedel-Crafts alkylation sequence. Its application to a diastereocontrolled synthesis of an abietane diterpenoid (+)-ferruginol has also been demonstrated.

Effects of surfactant on the in vivo alveolar surface-to-volume ratio.

To investigate how pulmonary surfactant influences alveolar structure in vivo, we examined the alveolar surface area-to-lung volume (S/V) ratio of the lung parenchyma of a live dog by light-scattering stereology before and after saline lavage. We measured the backscattered light pattern produced by applying a laser beam to the pleural surface of a ventilated animal and obtained the S/V [equivalent to the inverse of the optical mean free path (lambda)]. After saline lavage, V at transpulmonary pressure (P) of 30 cmH2O (defined as total lung capacity) decreased by 11.1 +/- 3.1% (SD) and the P-V curve shifted to a lower V. The lambda-V curve was shifted to a higher lambda and to a lower V after saline lavage. S/V decreased after saline lavage (lambda increased by 38 +/- 27% on the deflation limb at a V of 80% of control total lung capacity). The alveolar surface tension increased after saline lavage, and the increase in surface tension was greater on inflation than on deflation. We conclude that depletion of pulmonary surfactant increases the alveolar surface tension in vivo, resulting in a decrease in S/V.

Alveolar surface area-to-lung volume ratio in oleic acid-induced pulmonary edema.

It is unknown how the in vivo alveolar surface area-to-volume ratio (S/V) changes in low-pressure pulmonary edema. Here, the S/V is the area of the air-tissue interface per unit total volume (air plus tissue). We hypothesized that in oleic acid (OA)-induced edema inactivation of the pulmonary surfactant may increase surface tension and decrease the S/V at any given lung volume. OA (0.04 mg/kg) was intravenously injected into dogs. We measured the in vivo S/V (equivalent to the inverse of optical mean free path by light-scattering stereology and the pressure-volume (PV) curve 60-90 min after OA administration. OA administration decreased the lung volume at each transpulmonary pressure and increased the wet-to-dry weight ratio. The S/V decreased after OA administration (optical mean free path increased). The air-filled PV curves shifted downward after OA, but the saline-filled PV curves after OA administration did not differ significantly from control saline-filled curves. The difference in transpulmonary pressure between air- and saline-filled PV curves (an index of the magnitude of surface tension) was increased in OA-induced pulmonary edema. This study suggests that in OA-induced pulmonary edema the alveolar surface tension increases and the S/V decreases, presumably due to inactivation of surfactant by serum leakage to alveoli.

Brain metastasis in resected lung cancer: value of intensive follow-up with computed tomography.

BACKGROUND: Brain metastases are a common mode of recurrence in resected lung cancer and are usually associated with an ominous outcome. METHODS: To assess the usefulness of follow-up using computed tomography of the brain for early detection and effective treatment of brain metastases, we prospectively studied 128 patients with completely resected non-small cell lung cancer. Follow-up computed tomographic scans were obtained every 2 to 6 months over 24 postoperative months in 69 patients and every 2 months for 6 postoperative months in 59. RESULTS: Brain metastases were discovered in 11 patients (8.6%), and 7 patients were neurologically asymptomatic when the metastases were diagnosed. Single metastasis was found in 5 patients and multiple metastases in 6. The maximal size of all but one lesion was less than 25 mm. The median survival time and 5-year survival rate in all 11 patients with brain metastases were 10 months and 24%, respectively. Furthermore, those in 7 asymptomatic patients were 25 months and 38%, respectively. CONCLUSIONS: We consider intensive follow-up with computed tomography to be worthwhile for early detection and effective treatment of brain metastases in patients with completely resected lung cancer.

Isolated incisional recurrence after curative resection for primary lung cancer.

We present a long-term survivor with isolated recurrent tumor in the incisional scar that developed 9 months after a curative resection for primary lung adenocarcinoma. She underwent an excision of the tumor followed by systemic chemotherapy, and is currently alive with no evidence of disease 69 months after the recurrence. Isolated incisional recurrence after complete resection of lung cancer is a rare phenomenon and may be curable using multimodal treatment.