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Two subtypes of thrombospondin (TSP-1 and TSP-2) have inhibitory roles in angiogenesis in vitro, although the biological significance of these TSP isoforms has not been determined in vivo. We examined TSP-1 and TSP-2 gene expression by reverse transcription polymerase chain reaction (RT-PCR) analysis in 61 colon cancers. Thirty-eight of these 61 colon cancers were positive for TSP-2 expression and showed hepatic metastasis at a significantly lower incidence than those without TSP-2 expression (P = 0.02). TSP-2 expression was significantly associated with M0 stage in these colon cancers (P = 0.03), whereas TSP-1 expression showed no apparent correlation with these factors. The colon cancer patients with TSP-2 expression showed a significantly low frequency of liver metastasis correlated with the cell-associated isoform of vascular endothelial growth factor (VEGF-189) (P = 0.0006). Vascularity was estimated by CD34 staining, and TSP-2(–)/VEGF-189(+) colon cancers showed significantly increased vessel counts and density in the stroma (P < 0.0001). TSP-2(–)/VEGF-189(+) colon cancer patients also showed significantly poorer prognosis compared with those with TSP-2(+) / VEGF-189(–) (P = 0.0014). These results suggest that colon cancer metastasis is critically determined by angiogenesis resulting from the balance between the angioinhibitory factor TSP-2 and angiogenic factor VEGF-189. © 1999 Cancer Research Campaign

Vascular endothelial growth factor (VEGF) is a well known factor that induces angiogenesis. Four isoforms, i.e. VEGF206, 189, 165, and 121, have been identified. We examined the isoform patterns of VEGF mRNA using reverse transcription polymerase chain reaction (RT-PCR) analysis in 61 colon cancers. All the colon cancers examined expressed VEGF121. The isoform patterns were classified into three groups: type 1, VEGF121; type 2, VEGF121 + VEGF165; type 3, VEGF121 + VEGF165 + VEGF189. Three of the 61 colon cancers examined showed type 1 expression, 26 showed type 2 expression and 32 showed the type 3 pattern. The patients with liver metastases showed the type 3 isoform expression pattern at a significantly higher incidence (12 of 16, 75%) than those without liver metastasis (20 of 45, 44%) (P=0.036). The type 3 isoform pattern was significantly associated with M1 stage (P=0.019). The patients with colon cancer and the type 3 isoform pattern showed significantly poor prognosis (P < 0.01, Cox-Mantel). The colon cancers with the type 3 pattern showed a significantly higher involvement of veins (P=0.006). These observations suggest that the aberrant type 3 expression pattern of VEGF189 mRNA isoforms is correlated with liver metastasis, M stage, and poor prognosis in colon cancer. Images Figure 2 Figure 3

This article outlines the role of 16α-[(18)F]fluoro-17β-oestradiol ((18)F-FES) positron emission tomography (PET) combined with 2-[(18)F]fluoro-2-deoxy-D-glucose ((18)F-FDG) in patients with oestrogen-related tumours for evaluating tumour phenotype. (18)F-FES-PET combined with (18)F-FDG is helpful in characterising the distinct phenotypic features of oestrogen-related tumours; that is, inter- and intrapatient tumour heterogeneity, which indicates its great potential as a determinant of individualised treatment and a prognostic predictor for patients with oestrogen-related tumours.

In spite of the much evidence for the beneficial effects of probiotics, their anti-obesity effects have not been well examined. We evaluated the effects of the probiotic Lactobacillus gasseri SBT2055 (LG2055) on abdominal adiposity, body weight and other body measures in adults with obese tendencies.We conducted a multicenter, double-blind, randomized, placebo-controlled intervention trial. Subjects (n=87) with higher body mass index (BMI) (24.2-30.7 kg/m(2)) and abdominal visceral fat area (81.2-178.5 cm(2)) were randomly assigned to receive either fermented milk (FM) containing LG2055 (active FM; n=43) or FM without LG2055 (control FM; n=44), and were asked to consume 200 g/day of FM for 12 weeks. Abdominal fat area was determined by computed tomography.In the active FM group, abdominal visceral and subcutaneous fat areas significantly (P0.01) decreased from baseline by an average of 4.6% (mean (confidence interval): -5.8 (-10.0, -1.7) cm(2)) and 3.3% (-7.4 (-11.6, -3.1) cm(2)), respectively. Body weight and other measures also decreased significantly (P0.001) as follows: body weight, 1.4% (-1.1 (-1.5, -0.7) kg); BMI, 1.5% (-0.4 (-0.5, -0.2) kg/m(2)); waist, 1.8% (-1.7 (-2.1, -1.4) cm); hip, 1.5% (-1.5 (-1.8, -1.1) cm). In the control group, by contrast, none of these parameters decreased significantly. High-molecular weight adiponectin in serum increased significantly (P0.01) in the active and control groups by 12.7% (0.17 (0.07, 0.26) microg/ml) and 13.6% (0.23 (0.07, 0.38) microg/ml), respectively.The probiotic LG2055 showed lowering effects on abdominal adiposity, body weight and other measures, suggesting its beneficial influence on metabolic disorders.

To evaluate the clinical significance of reverse redistribution (RR) of resting 201Tl single photon emission computed tomography (SPECT) in patients with vasospastic angina (VSA), we performed left ventriculography, coronary angiography and resting 201Tl-SPECT in 22 patients with VSA. Left ventriculography showed abnormal wall motion in 17 of 22 patients (77%) and 37 of 154 segments. Thirty-one of these 37 segments (84%) were within the area perfused by coronary arteries showing acetylcholine-induced vasospasm. On 201Tl images, abnormal findings were observed in 11 of 22 patients (50%), and among them, 7 patients (32%) had RR. Seven of 37 segments (19%) having abnormal regional wall motion had RR of 201TI, and in 6 of these 7 segments (86%), accumulation of 123I-BMIPP was found to be reduced. We conclude that repetitive brief myocardial ischemia may cause myocardial injuries in patients with VSA, and that the presence of RR of 201Tl indicates the presence of myocardial injury in these patients.

BACKGROUND AND PURPOSE: Chronic hypoperfusion may cause ischemic insult in the deep white matter. The magnetization transfer phenomenon is associated with the amount and constitution of myelin. The purpose of this study was to assess the usefulness of the magnetization transfer ratio (MTR) for detecting vasculometabolic abnormalities on positron emission tomography (PET) studies in patients with unilateral severe stenosis of the internal carotid artery (ICA). METHODS: MTR maps and PET data—including regional cerebral blood flow (rCBF), regional cerebral metabolic rate of oxygen (rCMRO(2)), and regional oxygen extraction fraction (rOEF)—were investigated in 13 patients with unilateral severe stenosis of the ICA. The same regions of interest were selected in the white matter both on MTR maps and PET scans. The areas were classified into three groups based on MTR values (group 0, MTR >47.22%; group 1, MTR = 45.77% to 47.22%; group 2, MTR

Recently, cases of collecting duct carcinoma have been reported which were thought to have arisen from the renal collecting ducts or distal tubuli. We present here a rare case of collecting duct carcinoma mixed with common (conventional) renal cell carcinoma. A 51-year-old man underwent right nephrectomy under the diagnosis of renal tumor. Histochemically, markers for the collecting ducts/distal tubuli, such as peanut agglutinin (PNA) and soybean agglutinin (SBA), were identified in the collecting duct carcinoma as well as on several luminar surfaces of the common renal cell carcinoma. Based on the results of histological, histochemical and chromosomal examinations, we speculated on the histogenesis of this collecting duct carcinoma.

Interleukin 10 (IL-10) is an immuno-suppressive cytokine produced by T-lymphocytes, and a regulatory molecule for angiogenesis in various cancers. We examined IL-10 gene expression in 53 colon cancer patients who underwent surgical resection. IL-10 gene expression was correlated with TSP1 and TSP2 gene expression (P=0.0049, P=0.0285). Colon cancer with IL-10 gene expression (19/53) showed significantly decreased venous involvement (P=0.0433). The mean vessel counts in the colon cancers with IL-10 gene expression were significantly lower than those without IL-10 gene expression (P

Normative ethyl cysteinate dimer (ECD) SPECT data must be available to successfully apply ECD SPECT to clinical studies. The purpose of this study was to determine ECD SPECT scan patterns of healthy adults.Forty-eight healthy volunteers (22 men, 26 women; age range, 22-95 y; mean age, 47.6 +/- 19.2 y) underwent high-resolution ECD SPECT. For visual analysis of regional brain ECD uptake, we used a scale of +3 to -3, in which +3 and -3 indicated highest ECD uptake and deficit, respectively. For quantitative analysis, we measured the region-to-cerebellum ratio (R/CE) and the region-to-cerebral cortex ratio (R/CO) for 17 regions (13 cortical, 3 subcortical, and 1 cerebellar).On visual analysis, no subject had a score of -3. All subjects had a score of -2 for the hippocampus and a score of +3 for the medial occipital cortex, except for 2 subjects who had a score of +3 for the striatum and thalamus. A frontal eye field and posterior parieto-occipital junction were identified in 60% of subjects with a score of +1 and 79% of subjects with a score of +2. On quantitative analysis, a significant regional variation (ANOVA, P0.0001) was seen in R/CE, ranging from 0.709 (hippocampus) to 1.26 (medial occipital cortex). However, regional right-to-left differences and intersubject variability of R/CE were small (asymmetry index, 3.6% +/- 0.8%; coefficient variation, 6.6% +/- 0.7%). R/CE declined significantly with age in 6 regions, including the anterior and posterior cingulate cortex, superior prefrontal and parietal cortex, striatum, and hippocampus (1.0%-2.0% per decade, P0.05), whereas R/CO in the cerebellum increased significantly with age (1.0% per decade, P0.05).Although regional ECD brain perfusion patterns vary significantly, including variability caused by the age-related effect, intersubject variability is small. Recognition of these normal patterns is important for clinical interpretation of ECD SPECT studies.

Sialyl Le(a) antigen (CA19-9), a member of a family of high molecular weight glycoproteins, was originally described as a gastrointestinal- and pancreatic-specific tumor marker. Recent studies have demonstrated that sialyl Lea is a ligand for E-selectin and may play an important role in tumor metastasis. However, expression patterns of sialyl Le(a) have not yet been established in human gallbladder carcinomas. In this study, we examined sialyl Le(a) expression in human gallbladder adenocarcinoma and its clinicopathological significance. Sialyl Le(a) immunoreactivity was detected not only in cancer cells (cytoplasmic type; 68.5%, 37/54) but also in cancer stroma (stromal type; 46.3%, 24/54). According to TNM classification, stromal sialyl Le(a) expression was detected in 60. 0% (24/40) and 7.1% (1/14) of the T2-4 and T1 cancers, respectively (p

The major neuropathological feature in Parkinson's disease (PD) is severe degeneration of the dopamine (DA) neurons in the substantia nigra. Dopamine transporter (DAT) is an important protein in the regulation of DA neurotransmission. It has been reported that PD patients show a loss of DAT in striatum. We report here the findings of single photon emission computed tomography (SPECT) of the DAT with 2 beta-carboxymethoxy-3 beta-(4[123I]iodophenyl)tropane ([123I] beta-CIT) to investigate striatal DAT in 10 patients with PD, one patient with vascular parkinsonism (VP), and one patient with dystonia syndrome. Patients were evaluated using the Webster rating scale. Specific/nondisplaceable striatal binding ratio (V3") was obtained in each case. In PD patients, the uptake of [123I] beta-CIT was reduced, especially in the tail of putamen compared with caudate nucleus. Even in the early stage of PD, the uptake of beta-CIT was reduced not only in the severely affected side, but also in the mildly disturbed side of the brain. Putamen caudate ratio was generally low in PD patients. In VP patient, the uptake was reduced, but putamen caudate ratio was not decreased. V3" values showed significant correlation with the severity of clinical symptoms such as self-care, facies, posture, gait, speech, and Hoehn-Yahr's stage. On the other hand, V3" values were not significantly correlated with the degree of tremor, seborrhea, and duration of the illness. In conclusion, we found that SPECT of the [123I] beta-CIT is a useful method for the diagnosis in the patients presenting parkinsonism, and for the clinico-physiological estimation of parkinsonian symptoms such as self-care, facies, posture, gait, and speech.

Thrombospondin-1 (TSP1) is an extracellular matrix glycoproteins that affecting cell adhesion, motility and growth. Based on its effects on tumors, TSP1 is thought to be a potential regulator of tumor growth and metastasis. In this study, we clarified TSP1 immunoreactivity in human esophageal squamous cell carcinoma and its clinicopathological significance. TSP1 immunoreactivity was detected mainly in the cancer stroma and was observed infrequently in cancer cells. According to the TNM classification, 70.6% (12/17) of the T3 esophageal cancers were TSP1-positive, while only 26.9% (7/26) of the Tis and T1 cancers showed TSP1 expression. Lymph node metastasis and venous involvement was frequently found in the TSP1-positive cases (71.4% and 80.0%, respectively) of esophageal squamous cell carcinoma (p0.001). This observation suggested that TSP1 expression plays an important role in cancer cell growth and metastasis of human esophageal squamous cell carcinomas, and that stromal TSP1 immunoreactivity is a good predictor of venous involvement and lymph node metastasis.

Carcinoembryonic antigen (CEA) is a good marker of colorectal cancer. Recent studies have demonstrated that CEA may function as a metastatic potentiator by different pathways; i.e., modulation of immune responses, facilitation of intercellular adhesion and cellular migration. However, expression patterns of CEA have not yet been established in human gallbladder carcinomas. In this study, we examined CEA expression in human gallbladder adenocarcinomas and its clinicopathological significance. CEA immunoreactivity was detected not only in the cancer cells (cytoplasmic type: 63.0%, 34/54) but also in the cancer stroma (stromal type: 29.6%, 16/54). According to TNM classification, 75.0% (30/40) of T2-4 gallbladder cancers showed cytoplasmic CEA, while 28.6% (4/14) of the T1 cancers were cytoplasmic CEA-positive (p

Multidrug resistance-associated protein (MRP) is one of the major factors responsible for non-P-glycoprotein (Pgp)-mediated multidrug resistance of human tumour cells. In this study, we examined MRP and aberrant p53 expression in 54 colorectal cancers (CRC), 35 carcinoma in adenomas (CIA) and 40 adenomatous polyps by immunohistochemical procedures. 38 of 54 (70%) CRCs, 16 of 35 (46%) CIAs and 3 of 40 (8%) adenomatous polyps were MRP positive (chi 2 test, P0.0001). 36/54 (67%) CRCs, 10/35 (29%) CIAs and 0/40 adenomatous polyps were p53 positive. 30 of the 36 p53-positive CRCs were also MRP positive and 8/10 CIAs were both p53 and MRP positive. MRP overexpression correlated with aberrant p53 accumulation in CRCs and CIAs (chi 2 test, P= or 0.01). Coexpression of MRP and p53 in the same cells was confirmed in the CRCs and CIAs by double staining procedures. These results suggested that MRP overexpression is related to aberrant p53 expression in CRC.

To re-do coronary artery bypass grafting (CABG), we employed the descending branch of the lateral femoral circumflex artery (LFCA) as a free arterial graft. Early postoperative angiography demonstrated that the graft was patent with a sufficient flow. The descending branch of the LFCA can be recommended as a possible arterial graft for re-do CABG.

Vascular endothelial growth factor (VEGF) has five isoforms (VEGF206, 189, 165, 145 and 121). Increased VEGF expression in renal cell carcinoma (RCC) is associated with angiogenesis, but, it is not apparent which isoform is involved in this effect. We examined the isoform patterns of VEGF by reverse transcription-polymerase chain reaction (RT-PCR) in 47 RCCs. All showed increased VEGF expression as compared with extraneoplastic renal tissue. Four of the 47 RCCs showed VEGF121 alone, 10 showed VEGF121 + 165, and 33 showed the VEGF121 + 165 + 189 pattern. Patients with pathological stage pT3-4 RCC showed the VEGF121 + 165 + 189 isoform pattern at a significantly higher incidence (10/10, 100%) than those with pT0-2 (23/37, 62%) (P < 0.022). The VEGF121 + 165 + 189 isoform pattern was also significantly associated with high vessel counts and density (P = 0.0002, Mann-Whitney U test). These observations suggested that the VEGF189 mRNA isoform is closely associated with angiogenesis and results in the growth of RCC.

If activation of the p53 gene is involved in the progression or metastasis of colon cancer, it may affect the angiogenic phenotype in vivo. To verify this hypothesis, we studied the correlation between p53 accumulation and expression of thrombospondin-1 (TSP1) in colon cancer specimens. Levels of TSP1 gene expression were estimated by Northern blotting in 65 colon cancers. Accumulation of p53 and the distribution of TSP1 protein were evaluated immunohistochemically. Various levels of TSP1 gene expression were seen in colon cancers, while p53 accumulation was confirmed in 42 of the 65 colon cancers. The level of TSP1 gene expression demonstrated a significant inverse correlation with p53 accumulation in colon cancer. Colon cancer cells expressed TSP1 protein and p53 accumulation reciprocally in the same nests. These results suggest that alterations in the tumour suppressor gene p53 may inhibit TSP1 expression in colon cancer.

We describe the clinical features and results of cardiac catheterization, PET ([13N]ammonia, 18F-fluorodeoxyglucose (FDG)) and SPECT [123I-labeled 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP)], in a patient with acute myocardial infarction successfully treated with intracoronary thrombolytic therapy. We compared the clinical and electrocardiographic changes with the myocardial glucose and fatty acid metabolism in stunned myocardium over a period of several months. The patient we studied illustrates the features of stunned myocardium. In the subacute phase, there was a concordant depression of myocardial [13N]ammonia and FDG uptake, and the metabolic abnormalities persisted even after regional wall motion at rest had returned to normal. The electrocardiographic recovery of deep negative T waves appeared to be related to the metabolic recovery in regions of stunned myocardium in this patient.

The association between the type of precipitating autoantibodies and occurrence of avascular necrosis of bone (AVN) was examined. We prospectively analyzed clinical and laboratory findings of our 113 patients with SLE. Seven of 113 (6%) patients developed AVN. Anti-Ro (SS-A) and anti-RNP antibodies coexisted in 3 of 7 AVN patients. The same combination of these two antibodies were observed in 1 without AVN. Antibodies to topoisomerase I were detected in 2 other patients with AVN but not in any of the patients without AVN. The coexistence of the former two or the presence of the latter one is rare in SLE. However, these (combination of) antibodies can be useful as a local ischemic marker predicting the development of AVN.

Cutaneous manifestations of systemic lupus erythematosus (SLE) in men have not been precisely investigated.The purpose of this study is to define the clinical features of SLE in men, focusing on skin lesions.The clinical and laboratory manifestations of 28 male and 111 female patients were compared.Widespread discoid lupus erythematosus (DLE) and papular and nodular mucinosis (PNM) were significantly more common in men than in women. Serum sex hormone levels were within the normal range in all make patients examined.This study suggests that gender differences exist in SLE and that male patients tend to present with atypical cutaneous manifestations.

Copper-62-pyruvaldehyde bis(N4-methylthiosemicarbazone) copper II (62Cu-PTSM) has been proposed as a generator-produced positron-emitting tracer for perfusion imaging. To evaluate the characteristics of 62Cu-PTSM as a cerebral perfusion tracer, brain PET images of 62Cu-PTSM were compared with cerebral blood flow (CBF).Following an intravenous injection of 62Cu-PTSM, a serial dynamic PET scan was performed for 10 min with arterial sampling in 10 subjects. CBF was measured by 15O-labeled water before the 62Cu-PTSM study.Dynamic PET scan with octanol-extracted arterial input function indicated the presence of significant back-diffusion of 62Cu-PTSM from the brain within 3 min after injection, followed by stable activity from 3 to 10 min. Comparison with 15O-water PET demonstrated less contrast between high- and low-flow regions in 62Cu-PTSM image and a nonlinear relationship of flow and 62Cu-PTSM uptake, which suggests the underestimation of CBF in high-flow regions due to the existence of back-diffusion.Although 62Cu-PTSM can be used widely for evaluation of brain perfusion with PET, kinetic analysis and correction may be needed to quantify regional CBF.

Loading therapy consisting of the ACNU regimen was instituted as postoperative anticancer chemotherapy for malignant gliomas. The efficacy rate of the regimen was 25% at a dose of 3 mg/kg. A high incidence of hematological changes, such as leukopenia (neutropenia) and thrombocytopenia, were observed after chemotherapy. The former could be prevented by the administration of G-CSF, but platelet infusions were necessary in some patients for amelioration of thrombocytopenia. Gastroenterological symptoms, such as nausea and vomiting, were also frequently noted. Granisetron (Kytril), which is a recently developed selective competitive inhibitor of the 5-HT3 receptor, was used for the treatment of these adverse effects, and was found to be clinically effective.

The purpose of this study was to observe the effects of folate and vitamin B12 on bronchial squamous metaplasia with cellular atypia, known to be a precancerous change, in heavy smokers. Cases of squamous metaplasia were recognized on sputum cytologic study. The location of bronchial lesions was identified by bronchofiberoscopy in all cases. The grade of cellular atypia was evaluated on the basis of histologic specimens. Thirty-eight patients with squamous metaplasia, including 21 patients receiving folate and vitamin B12 and 17 patients without any medication, were investigated prospectively for 1 year. Consecutive bronchofiberoscopic examinations were performed in each patient in 3 to 4 months after the first examination in order to evaluate the lesions. Grades of cellular atypia were examined by histologic specimens using a scoring system from 0 to 3. There was no significant difference in mean scores at entry in the medication group (1.7) and control group (1.4). The medication group showed significant decrease in mean scores (0.4) while the control group had no change in mean scores (1.2) at termination. Plasma levels in the medication group were significantly increased at termination of the study while those of the control group showed a slight decrease. The results show that the cellular atypia squamous metaplasia in heavy smokers can be reduced by administration of folate and vitamin B12.

We describe a 56-year-old woman with Stewart-Treves syndrome who had severe dyspnea from a pleural effusion caused by metastatic angiosarcoma in the right lung. Tumor-infiltrating lymphocytes (TIL) in the pleural effusion were cultured and expanded in vitro in the continuous presence of recombinant interleukin 2 with periodic stimulation by CD3 antibody. The expanded TIL were administered intrapleurally seven times at 1- to 4-week intervals in combination with intravenous infusion of recombinant interleukin 2. A panel of T-cell clones was also obtained from TIL. Immunotherapy dramatically improved the patient's dyspnea and pleural effusion. A CD4+ T-cell clone and a CD8+ T-cell clone established from TIL had specific cytotoxicity to the tumor cells.

Four patients with pontine gliomas were treated with radiation and intra-arterial chemotherapy using ACNU, cisplatin, and/or carboplatin. All underwent biopsy and were histologically proven to have gliomas. Even though three were benign histologically, all appeared malignant on neuroimaging. Two patients had complete remissions; the others had partial responses; three patients died, 36, 14, and 15 months after the primary diagnosis. One patient, now in complete remission, has been alive for 24 months. There was no neurotoxicity except for transient nausea and vomiting. Intra-arterial chemotherapy is effective against brain stem gliomas, producing remission with minimum side effects.

A case of solitary papilloma of the bronchus is described, and 15 other cases occurring in Japan are reviewed. A 57 year old asymptomatic male was referred to our hospital because many squamous metaplastic cells with moderate atypia were observed in sputum cytology, twice in 3 months. The chest X-ray showed no abnormal findings. Endoscopic examination revealed a polypoid tumour at the bifurcation of the right B6a and B6b. The tumour was removed completely by endoscopic biopsy, and histological findings showed squamous papilloma. There has been no evidence of recurrence for 3 yrs. We are not aware of a previously reported case of bronchial papilloma without symptoms or abnormal shadow on chest X-ray. Considering the fact that malignant change was reported in only one case in Japan, and that there is a possibility of cancer subsequently developing at another location in the lung which might also require resection, lobectomy should be avoided if the tumour can be removed completely through endoscopy. If the lesion is limited to a small area in the bronchus, conservative treatment such as photodynamic therapy and/or yttrium aluminium garnet (YAG) laser vaporization might be sufficient to obtain a complete cure.

Twelve patients with supratentorial gliomas were treated with intra-arterial ACNU followed by intravenous maintenance chemotherapy. Six of the patients, treated from February 1987 through May 1989, received doses of 120-200 mg/m2 (high dose treatment group); six patients, treated from June 1989 through October 1990, received doses of 80-100 mg/m2 (low dose treatment group). The drug was given via the supraophthalmic portion of the internal carotid artery or vertebral artery at a rate of 10 mg/min. The response rate (CR + PR) on CT scan was 50% (3/6) in the high dose treatment group and 17% (1/6) in the low dose treatment group. Survival periods from first operation, however, did not differ between the high and low dose treatment groups. Bone marrow suppression was dose-related and reversible at these doses. Severe neurotoxicities (hemiparesis and aphasia) developed in the patients who received 200 mg/m2 of ACNU; in one case, this was irreversible. High dose intra-arterial ACNU chemotherapy is effective in reducing tumor size on CT scan but the prognosis is not improved. The dose limiting factor of intra-arterial nitrosourea is neurotoxicity, and doses of more than 200 mg/m2 are considered to be dangerous.

Using an endoscope we collected fasting gastric juice for estimation of gastric acid in subjects examined by upper gastrointestinal endoscopy. Subjects were 53 in- and out-patients (46 males and 7 females) at our hospital. Seventy-five gastric secretory studies were performed in this population before and after stimulation by tetragastrin, following the guidelines of The Japanese Society of Gastroenterology and using a specially devised endoscope of narrow caliber under direct vision. Acid in fasting gastric juice was correlated with basal acid output (BAO) and with maximal acid output (MAO). There was a statistically significant correlation between them. Thus, an estimation of gastric acid secretion can be obtained from the fasting gastric juice which we usually aspirate and discard during the routine endoscopic examination.

T and B cell functions were evaluated in eight patients with myelodysplastic syndrome (MDS). We studied the response to stimulation with phytohemagglutinin, concanavalin A, and anti-CD3 monoclonal antibody (OKT3 mAb), and found impairment of response in T cells from MDS patients in comparison with age-matched controls. The decreased proliferative response was not restored by combining normal T cells with monocytes from MDS patients, or by using T cells from MDS patients together with normal monocytes. Furthermore, proliferative responses in the autologous and allogenic mixed lymphocyte reactions were significantly decreased in MDS patients. B cells from MDS patients incorporated significantly less tritiated thymidine than B cells from controls when stimulated with Staphylococcus aureus Cowan I (SAC), and SAC stimulation failed to cause efficient immunoglobulin production by MDS B cells. However, T cells from MDS patients reacted normally when stimulated by phorbol myristate acetate plus a Ca2+ ionophore (ionomycin). Abnormal lymphocyte function may contribute to the failure of hematopoietic regulation and may thus play an important role in the pathogenesis of MDS. The finding that the addition of specific signals allowed the stimulation pathway to function may have important therapeutic implications.

This report evaluates the relevance of the ratio of the melanoma-associated ganglioside, GD3, and its precursor, GM3, to prognosis and management of Stage II disease. Tumor biopsy specimens from 42 melanoma patients were examined for the ratio and found that GD3 and GM3 constitute 80% of the total lipid bound sialic acids (LBSA) of melanoma. Although the ratio of GM3:GD3 in melanocytes, the progenitors of melanoma, is 19:1 (based on %LBSA), it ranged from 15:1 to 1:5 in tumor biopsy specimens. Patients are categorized into three groups based on their GM3:GD3 ratio (%LBSA) of tumor tissues as Group I (ratio ranged from 15:1 to 1.5:1) (10 of 42), Group II (1.4:1 to 1:1.4) (13 of 42), and Group III (1:1.5 to 1:5) (19 of 42). When the overall survival of patients from the onset of Stage II disease was evaluated among different groups, patients belonging to Group I survived significantly longer than patients of Group II (P = 0.02) and Group III (P = 0.01). Interestingly, Group III expressed immunogenic gangliosides (GD2, GM2, and O-AcGD3) better than the other groups and may benefit more from therapies targeted against these gangliosides antigens. The results of this study indicate that GM3:GD3 ratio is an unusual but well-defined biochemical criteria that may be useful for prognosis and therapeutic management of the disease. Therefore, we propose a routine analysis of the GM3:GD3 ratio of tumors excised after surgery. Screening the ratio is feasible since melanoma expresses a simple profile of gangliosides unlike other forms of cancer.

We sent out a questionnaire to 47 patients of SLE and its similar diseases as to their past histories of chilblain. The results of the patients were compared to those of 141 cases of control. Although the percentage of cases who had revealed chilblain frequently (40.0%) and the age of chilblain onset (mean: 10.8 years old) in SLE group were not significantly different from those of control (28.4% and 12.4 years old, respectively), the chilblain which SLE patients developed had some characteristics compared to that of control, (1) higher incidence of chilblain episodes, (2) longer duration until cure, (3) more liability that chilblain leads to erosion or ulceration and (4) frequent occurrence of chilblain in the other seasons than winter. Especially SLE patients with the characteristic of (4) had higher association rates of Raynaud's phenomena, chilblain LE and livedo, suggesting disorder of peripheral circulation. It was also revealed that females are generally more liable to develop chilblain than males (females: 40.0%, males: 13.1%). Those results suggest some important relationship between chilblain and LE lesions. It is supposed that chilblain with the characteristics described above may possibly be transformed into LE lesions.

We investigated clinical features of our 22 male SLE patients with main respect to 11 articles of ARA criteria for diagnosis of SLE (1982). As for skin lesions, 14 cases (64%) manifested wide spread discoid lupus erythematosus as their first symptoms, however, rather rare lesions could be seen as follows: 3 cases with nodular cutaneous lupus mucinosis, 1 with vesiculobullous LE. As to visceral manifestations, renal involvements could be seen in 11 cases (50%), among which 6 showed nephrotic syndromes. In immunological examinations, 1 case revealed C4A deficiency. The clinical tendency of male SLE cases has not been settled by now, for the disease is uncommon in men. Each of our 22 cases manifested a variety of features respectively, indicating that rather atypical cases as SLE can be more often seen in males than females. In addition, many of our cases showed remarkable changes clinically during their courses, which suggests that we should follow them carefully from now.

We report a case presenting with 'flagellate' erythema which is a characteristic skin lesion of dermatomyositis seen in Japan. A possible pathological mechanism is proposed in comparison with the 'flagellate' erythema caused by bleomycin.

Experience with Radio Isotope Myelography is reported here. 169Yb-DTPA as a tracer was intrathecally injected at lumbar region in twenty three patients with various spinal cord lesions. The first scanning is perfomed after comfirming by gamma-camera that the tracer reaches to the lesion, the second and the third scannings are done according to the ascending rate of the tracer. (I) Normal scintimyelogram (A) In normal case, the shape of the Radio Isotope Myelogram well corresponds the shape of anatomical subarachnoid space. (B) In normal adult cases, the tracer comes up to the cisterna magna in 20-25 minutes after the lumbar injection. Therefore, the scintimyelographic diagnosis should be made not only by the shape but also by the ascending rapidity of the tracer. (II) Abnormal scintimyelogram Abnormal scintimyelograms could be summarized as following three categories. (A) "Delay": It means delay of the ascending of the tracer. Besides, "Transient delay" found in a case of Arnord-Chiari's malformation was proposed. (B) "Partial block": It meas a defect at the level of the lesion. This "Partial block" were observed in cases of spinal cord angioma, cervical spondylosis and spinal cord tumor etc. (C) "Complete block": It means the stagnation of the tracer below the lesion. To sum up, Rario Isotope Myelography, especially in partial block, can more easily and more sensitively represent the maximum extent of the spinal cord lesion than other myelographic study or angiographic one. On the other hand, we can not qualitatively diagnose about the lesions by its indistinct border.

A case of deep sylvian meningioma is reported which is unusual in the aspect that the initial symptoms were headache and vomiting due to intracerebral hemorrhage from meningioma. After evacuation of hematoma in the right temporal lobe and biopsy of the tumor, it was found to be meningothelial meningioma with psammoma bodies. Cerebral angiography showed characteristic findings of intrasylvian vascular tumor. Complete removal of this tumor was performed under microscopy, dissecting dense adhesion between the tumor and main branches of the middle cerebral artery. Consequently, the patient showed only slight impairment of fine movement of his left fingers. Deep sylvian meningioma designated by Cushing and Eisenhart is very rare. This case is the only one of deep sylvian meningioma in our whole series of 181 intracranial meningiomas and probably the twentieth case reported so far in the literature.

The reports of perangiographic rupture of intracranial aneurysm are very few, but the actual incidence is doubtless higher than reported. We could find only 49 cases in the literature, all of which were recognized by extravasation of contrast media. Three of our own cases are documented; in all of them cerebral angiography was carried out soon after subarachnoid hemorrhages. The danger of cerebral angiography in patients with a recently hemorrhaged intracranial aneurysm is stressed.

We reviewed 40 cases of intracranial ruptured aneurysm with intracerebral hematoma (An-ICH) and compared those with 177 cases of intracranial single ruptured aneurysm causing only subarachnoid hemorrhage (An-SAH). An-ICH accounted 11.6% of the intracranial aneurysm, ruptured at the mean age of 54 years, and occurred equally in both sexes. The localization of An-ICH was 50% in the middle cerebral artery (MC), 43% in the anterior cerebral artery (AC) and 8% in the internal carotid arterial region. Forty percent of An-ICH were treated conservatively and the outcome was very misery (no useful life and 94% was poor or dead). Sixty percent of An-ICH were treated surgically (neck-clipping and removal of the hematoma) and the outcome was poor (17% useful life and 46% poor and dead). Especially in MC aneurysm, operability was 85% and post-operative useful life was 12% and post-operative poor or dead was 53%. In AC aneurysm, operability was 35% and post-operative useful life was 33% and poor or dead was 33%. These miserable results raised a question of operative indication for An-ICH. The five clinical indices (decerebration, hypertension greater than or equal to 200 mmHg, Hunt-Hess grade V, anisocoria in AC, severe shift of midline structure on X-CT) were selected, because any patients who presented with even only one of them became fatal or vegetative state regardless of conservative or surgical treatment. Assuming them as the non-operative standards, operability decreased in 35% MC, 29% AC, useful life outcome came up to 20% MC, 40% AC, and misery outcome came down to 20% MC, 20% AC.(ABSTRACT TRUNCATED AT 250 WORDS)

Reviewing 223 cases of intracranial ruptured aneurysms including 46 cases of re-ruptured aneurysms, the following results were obtained. 1) The outcome of the re-rupture aneurysms was more miserable than that of the first rupture. Even low grade cases (Hunt and Hess 0-II) of re-rupture showed no better outcome than high grade cases (Hunt and Hess IV) of first rupture. 2) Re-rupture most often occurred on the 12th (11.6 +/- 6.7) day after the first attack of the subarachnoid hemorrhage. Re-rupture more often occurred in the vertebrobasilar system. In the internal carotid artery and its branches, aneurysms with daughter or bleb tended to rupture again. Aneurysms with daughter, regardless of these location, showed greater incidence of re-rupture than those without daughter. Also rupture often occurred in the cases of lower grade with less vasospasm and with the acute hydrocephalus. 3) It was suggested that the sequential changes of some factors of both the coagulating system and fibrinolytic system might forecast the vasospasm, infarction, re-rupture and prognosis of the patient of intracranial ruptured aneurysms. And therefore, in the cases in which re-rupture is likely, operation should be performed as early as possible, except in those showing diffuse vasospasm or clinical down hill course or in grade V.

A case of an empyema of cavum septi pellucidi and cavum Vergae is reported. A 60-year-old male was admitted because of fever, chill shivering, and slight conscious disturbance four days after head trauma. CT scan on admission showed cavum septi pellucidi and cavum Vergae. Lumbar puncture revealed whitish cloudy CSF containing 12256/3 WBC. So he was treated with antibiotics under the diagnosis of suppurative meningitis. Five days after administration of antibiotics high fever went down and consciousness was cleared. But about 10 days later his conscious level was lowered again. The follow up CT demonstrated remarkable expansion of cavum septi pellucidi and cavum Vergae with enhanced cavity wall. Empyema of the cavums was suspected and stereotaxic operation was performed. 10 ml of yellowish pus was aspirated. Post operative course was uneventful. CT scan of 15 days after operation revealed a marked decrease in size of the cavums, which almost completely disappeared three months later. Case similar to this was not found to be reported. The mechanism of formation of empyema of cavum septi pellucidi and cavum Vergae after meningitis in this case is discussed.

Surgical treatment of hemifacial spasm associated with tortuous vertebrobasilar system was reported. A patient was 63-year-old female, who first experienced mild and intermittent muscle twitching around her left eye twenty years prior to admission. Five years later, the twitching extended to all the facial muscles on the left side. She was treated with facial nerve block, which resulted in facial palsy for about one year. Because of recurrence of the hemifacial spasm, she was admitted to the Neurosurgical Department of Bokuto Municipal Hospital on October 12, 1977. Neurological examination revealed no abnormalities except for left hemifacial spasm with slight muscular weakness. Electromyogram showed severe twitching and synkinesis of all the muscles of facial expression. Vertebral angiogram on the left side disclosed pronounced elongation of the vertebral and basilar arteries, which extended into the left cerebellopontine angle. Compression of the facial nerve root exit zone at the brainstem by the vertebral artery was considered to be the cause of the hemifacial spasm. Suboccipital craniectomy was carried out on November 29, 1977. The vertebral artery extended into the cerebellopontine angle, and adhered to the facial nerve. After mobilization of the vertebral artery from the facial nerve, a small prosthesis of non-absorbable spongy material (Teflon felt) was interposed between the vertebral artery and brainstem. Postoperatively, the hemifacial spasm disappeared, but the facial palsy, which had been observed preoperatively probably due to previous facial nerve block and long-standing hemifacial spasm, remained. The function of the acoustic nerve was preserved. Recently vascular compression of the facial nerve root exit zone has been reported as a major cause of hemifacial spasm, but such abnormal vessels are rarely demonstrated angiographically.

Recurrence of an IC--PC aneurysm after a successful neck clipping (Heifetz' clip) is reported. This was caused by breaking of a clip blade at its proximal end. It is suggested that some structural weakness was present in the clip metal.