Influence of micrometastasis on N stage in gastric cancer and clinical application.

In order to evaluate the real extent of lymph node metastasis (LNM) in gastric cancer, an immunohistochemical (IHC) analysis was performed. We examined 11173 lymph nodes removed from 355 patients with all stages of gastric carcinoma. Tissue preparations were stained with cytokeratin 18, monoclonal antibody against cytokeratin. Micrometastases were found in 2.5% of the lymph nodes and in 31.3% of patients. The incidence of the patients with LNM increased to 9.1% in T(1m) (n = 99), 31.6% in T(1sm) (n = 95, 23.1% in sm1, 34.8% in sm2), 66.7% in T2 (n = 108, 48.8% in mp, 76.5% in ss), 88.1% in T3 (n = 42), and 90.9% in T4 (n = 11) lesions. Upstage was identified in 8.5% of patients: 6.7% in T1 (4.0% in m, 7.7% in sm1, 10.1% in sm2), 14.8% in T2 (20% in mp, 11.8% in ss), 2.4% in T3, and 0% in T4. Factors related to LNM were: tumor size and lymphatic invasion in mucosal lesions; only lymphatic invasion in submucosal lesions; size and depth of tumor, and lymphatic invasion in T2 lesions. In conclusion, the incidence of micrometastasis in regional lymph nodes was higher than we imagined in T1 lesions, more than D1 lymphadenectomy for sm1 and selected cases of mucosal cancer, and D2 lymphadenectomy for sm2 are necessary.

Antitumor effect of bcl-2 antisense phosphorothioate oligodeoxynucleotides on human renal-cell carcinoma cells in vitro and in mice.

BACKGROUND AND PURPOSE: Programmed cell death is a genetically regulated pathway that is altered in many cancers. This process is, in part, regulated by the bcl-2 oncogene. Antisense oligodeoxynucleotides (ODNs) targeted to specific oncogenes have been used with some therapeutic success in animal models of leukemia and melanoma cells and human Hodgkin's lymphoma. We evaluated the effects of antisense ODNs targeted to the bcl-2 oncogene on the proliferation of human renal-cell carcinoma (RCC) cells in vitro and on the growth of human RCC xenografts in BALBc nude (nu/nu) mice. MATERIALS AND METHODS: Expression bcl-2 mRNA in five RCC cell lines (ACHN, Caki-1, RCZ, RCW, and OS-RC-2) was analyzed by reverse transcriptase-polymerase chain reaction. The effects of phosphorothioated ODNs containing human bcl-2 sense and bcl-2 antisense sequences that were transfected with Lipofectin on the proliferation and viability of cultures of established human RCC cell lines were determined by MTS assay. The expression of Bcl-2 protein in ACHN tumor cells following antisense bcl-2 (AS2) ODN treatment was evaluated by Western blot analysis, and the extent of apoptosis in these cells was determined by fluorescence-activated cell sorter (FACS) analysis. The antitumor activity in ACHN xenografts in nu/nu mice was monitored by measuring differences in tumor weight in treated and control mice. RESULTS: Expression of bcl-2 mRNA was detected in all five RCC lines. Treatment with antisense bcl-2 ODNs inhibited the growth of all tested RCC cells and decreased Bcl-2 protein expression in ACHN cells. The AS2 antisense ODN complementary to the coding region of bcl-2 mRNA showed a superior antiproliferative effect compared with AS1 ODN complementary to the translation initiation region. Inhibition by antisense bcl-2 ODNs of ACHN cells was dose dependent. The FACS analysis revealed that growth inhibition was associated with the induction of programmed cell death. In vivo, AS2 ODN antitumor activity was noted in locally injected groups. CONCLUSIONS: Treatment of human RCC with antisense ODNs targeted to bcl-2 inhibits growth and is associated with the induction of programmed cell death. These results suggest therapeutic use of antisense bcl2 in the treatment of RCC.

[Anthropometric study on normal human auricle in Japan].

OBJECTIVE: Japanese people are physically larger and live longer than in the past. In light of these changes, we studied anthropometric auricular morphology in Japanese people in all age groups. METHODS: Subjects were 1,958 healthy Japanese people with no ear disease, 966 males aged 0-94 years and 992 females aged 0-99 years. They were classified at 5-year intervals into 18 age groups, and each group consisted of 50-72 persons. Bilateral size of auricles (ear length, ear width, length of ear attachment, auricular cartilage length, and auricular lobe length) were measured in the usual manner. All measurements were made with calipers by a single observer. RESULTS: Larger values were obtained in males than in females in almost all age groups. Rapid growth was observed until late teenage, and significant growth continued thereafter until advanced age. Auricular size was found to be greater than that in Japanese people in the past. CONCLUSIONS: In addition to changes in auricular size believed attributable to growth until late teenage, age-associated changes appear to continue during adulthood.

[Three-dimensional architecture of the intrinsic tongue muscles using a modified alkaline maceration method].

The three-dimensional architecture of the intrinsic tongue muscle fibers using the anterior part of the rabbit tongue was studied by scanning electron microscopy with a modified chemical-maceration method. The tongue tissues fixed with 10% formalin solution were treated with 1% OsO4 solution at 5 minutes for hardening of the specimen surface. Subsequently, they were immersed in 6N-NaOH solution for 30 minutes at 60 degrees C for the removal of connective tissues followed by dissection of muscle fibers under a binocular microscope to clarify the structure of the intrinsic tongue muscles. The specimens were treated with tannic acid and OsO4 (conductive staining method; Murakami, 1974), and observed with a SEM. Muscular fiber bundles of the transverse and vertical muscles of the tongue changed their direction at the alignment on the sites where the bundles enter the longitudinal muscles from the innermost surface to form monolayers of muscular bundles extending anteroposteriorly. These muscular bundles formed tunnel-like structures each of which covered a longitudinal muscle bundle. It was considered that these tunnel-like structures support the contraction of the longitudinal muscles as the "muscular sheath".

[Chest radiograph of atypical pneumonia: comparison among Chlamydia pneumoniae. Pneumonia, ornithosis, and Mycoplasma pneumoniae pneumonia].

No report has been found comparing Chlamydia pneumoniae (C. pneumoniae) pneumonia radiographically with other atypical pneumonias, Chlamydia psittaci (C. psittaci) pneumonia and Mycoplasma pneumoniae (M. pneumoniae) pneumonia. We described the chest radiographs of three kinds of pneumonia cases: 46 cases of C. pneumoniae pneumonia, 39 cases of C. psittaci pneumonia, and 131 cases of M. pneumoniae pneumonia. Radiographic shadows were categorized into main shadows and sub-shadows. The main shadows are classified from the viewpoint of the characteristics; air space consolidation(AS), ground-glass opacity(GG), reticular shadow(RS), bronchopneumonia(BP), and small nodular shadows (SN). The size, the site, and the number of the main shadows were also analyzed. In comparison among the three pneumonias, BP was the most frequent in M. pneumoniae pneumonia (0.40/case). AS predominated in C. pneumoniae pneumonia (0.67/case), and GG in C. psittaci pneumonia (0.62/case). The number of main shadows was equal, about 1.4/case in three pneumonias. Large shadows were less frequent in M. pneumoniae pneumonia than C. pneumoniae pneumonia (p = 0.02) and C. psittaci pneumonia (p = 0.01). Main shadows were more frequent in the outer zone in M. pneumoniae pneumonia than C. psittaci pneumonia (p = 0.01), and in the middle zone in C. psittaci pneumonia than in M. pneumoniae pneumonia (p = 0.02). Cases with bilateral main shadows were less common in M. pneumoniae pneumonia (9%) than C. pneumoniae pneumonia(33%, p = 0.001) and C. psittaci pneumonia(30%, p = 0.005). Thickening of bronchovascular bundles as a sub-shadow was most frequently noted in M. pneumoniae pneumonia. Some differences among the three atypical pneumonias were seen in the chest radiograph. However, no specific findings of C. pneumoniae pneumonia were shown radiographically in this study.

[Portal and pulmonary hypertension in a patient with MCTD].

A 42-year-old woman with mixed connective tissue disease (MCTD) died due to the rupture of esophageal varices. The autopsy revealed fresh thrombi in the main trunk of the portal vein. Microscopic examination disclosed wide-spread periportal fibrosis and stenosis of peripheral portal veins without remodeling of hepatic lobular architecture, which was compatible to idiopathic portal hypertension (IPH). Anti-phospholipid antibody was negative. Accordingly it is likely that portal vein thrombosis developed secondary to IPH. In the literature 6 (37.5%) of 16 collagen vascular disease patients with IPH died, and three of them were due to rupture of esophageal varices. Therefore IPH should be considered to be one of the most important complications affecting its grave prognosis in patients with collagen vascular disease. The patient also had had pulmonary hypertension (PH) when the diagnosis of portal hypertension was made. In the literature we found 5 collagen vascular disease patients with both PH and IPH like this case. The most outstanding common clinical feature among these 6 patients was Raynaud's phenomenon associated with positive anti-RNP antibody. Moreover 5 of 6 cases including this case simultaneously developed both PH and IPH. The clinical course of these patients suggests there may be a common pathogenetic factor for these two lesions. A possible candidate involved in the pathogenesis of PH and IPH may be endothelin, one of the vasoactive substances, since its receptor is said to be expressed abundantly in pulmonary and portal vasculatures. However, further investigation is necessary to elucidate the mechanism of PH and IPH in collagen vascular diseases.

Sickness absence due to mental disorders in Japanese workforce.

This study was conducted to elucidate sickness absence due to mental disorders in Japanese companies. Data on sickness absence taken for seven consecutive days or more at eight companies (total number of employees: 44,816) was used for the analysis. Diagnosis of mental disorders was based on medical certificates prepared by physicians. The frequency of absence due to all diseases and mental disorders was 3.0% and 0.3%, respectively. The proportion of frequency absence due to mental disorders compared to that for all diseases was 9.4%. Figures for absence prevalence were almost the same as those for frequency absence. The average length of absence due to mental disorders and non-mental disorders was 119.5 days and 47.3 days, respectively. Rate of absence days due to mental disorders compared to that for all diseases was 21.0%. Percent of sickness absenteeism was 0.4%. In one company, the proportion of frequency absence and rate of absence days due to mental disorders compared to those for all diseases had an increasing tendency over the last six years.

[Method of preventing hepatic artery occlusion during continuous intrahepatic arterial infusion chemotherapy of 5-FU].

A randomized clinical trial of combined use of steroids, which have a vascular endothelium-protecting action, was performed to develop a method to prevent hepatic artery occlusion during continuous intrahepatic arterial infusion chemotherapy with 5-FU. The steroid used was dexamethasone palmitate (Limethason), which has a high rate of uptake by endothelial cells. The 24 patients with advanced colorectal cancer were divided into 2 groups randomly and both were treated with 5-FU 250 mg/day by continuous hepatic arterial infusion for three weeks. The weekly dose was 5-FU 7 V (1,750 mg) adjusted to 50 ml with physiological saline in Group A and 5-FU 7 V (1,750 mg) adjusted to 50 ml with Limethason 1 A (4.0 mg of dexamethasone palmitate) in Group B. The reservoir was replaced every week. No changes in the mixture (appearance, pH, granule diameter, dexamethasone palmitate content) were observed up to one week. Hepatic arterial stenosis was observed in 8 cases in Group A (67%), but was not observed in any of the cases in Group B. The above results indicated that Limethason has a preventive effect against hepatic artery occlusion.

[N-3 polyunsaturated fatty acids in surgical nutrition].

Recent surgical nutrition includes the management of mediator to induce the stress response and immune function. N-3 polyunsaturated fatty acid (n-3 PUFA) were reported to increase the survival rate, and to improve the nutritional and immune status of septic or burned animals. N-3 PUFA also inhibited the proliferation and metastasis of cancer, and improved the cancer cachexia. N-3 PUFA decreased the production of cytokine and eicosanoid originated from n-6 PUFA, and reduced the inflammatory and stress response. Cell-mediated immunity was suppressed with the reduction of cytokine. But in the stressed state, N-3 PUFA ameliorated the stress induced immunosuppression. Alteration of transcription of cytokine mRNA, changes of membrane fluidity, and reduced expression of adhesion molecule were proposed to interpret these effects. In conclusion, n-3 PUFA can be applied for the surgical patients, especially for the critically ill patients.

Effects of a newly developed fat emulsion containing eicosapentaenoic acid and docosahexaenoic acid on fatty acid profiles in rats.

A new fat emulsion of symmetrical triacylglycerols, containing only eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was developed. The effects of this preparation on serum and liver fatty acid composition were investigated. Male Sprague-Dawley rats were fed a fat-free oral diet for 2 wk and were then divided into two groups. Seven rats were infused for 7 d with 1 mL of the new fat emulsion, which accounted for 1% of total caloric intake. The other 7 rats received saline. Both groups of rats received a fat-free diet during the infusion. EPA and DHA decreased to one third to one fifth of normal value after 2 wk on a fat-free diet. EPA and DHA of serum and liver remained at a low level in the control group throughout the study. But in the rats administered with the new fat emulsion, EPA and DHA increased rapidly and exceeded normal values in both serum and liver after 7 d of infusion. Decreased arachidonic acid with increased 20:3n-9 resulted in the rise of the triene/tetraene (T/T) ratio to greater than 0.4, indicating an n-6 essential fatty acid deficiency in the control rats. In the group administered the new fat emulsion, however, 20:3n-9 and total content of monounsaturated fatty acids decreased significantly, and the T/T ratio was less than than 0.4 in both serum and liver. In conclusion, the intravenous use of a newly developed fat emulsion containing EPA and DHA is useful in improving the EPA and DHA status of serum and liver without any harmful effects. Beneficial effects are expected in the modulation of inflammatory and stress response.

A new pseudo-peptide of Arg-Gly-Asp (RGD) with inhibitory effect on tumor metastasis and enzymatic degradation of extracellular matrix.

A series of pseudo-peptide analogs of the Arg-Gly-Asp (RGD) sequence of fibronectin have been synthesized, and their anti-metastatic effects in mice and inhibitory effects on tumor cell invasion in vitro have been examined. The partially modified retro pseudo-peptide of RGD, Rrev-COCH2CO-D (FC-63), was more effective in inhibiting tumor metastasis than the original RGDS peptide. Replacement of the malonyl moiety of FC-63 with a carboxyethylene linkage (Rrev-COCH2CH2-D, FC-303 ) achieved more potent inhibition of lung metastasis of melanoma cells than FC-63. Among the analogs, FC-336, a p-xylylendiamine derivative having two FC-303 moieties, showed the most potent inhibitory effect on experimental lung metastasis produced by i.v. co-injection with B16-BL6 melanoma or colon 26 M3.1 cells in a dose-dependent manner. Multiple administrations of FC-336 after tumor inoculation also showed efficient therapeutic potency against spontaneous lung metastasis of B16-BL6 melanoma in mice. Furthermore, FC-336 effectively inhibited the invasion, migration and adhesion of tumor cells in vitro, but its inhibitory effects were not more than those of RGDS peptide. Zymography analysis revealed that FC-336 inhibited the degradation of gelatin substrate by matrix metalloproteinases (MMPs) produced by tumor cells, while the RGDS peptide did not affect the enzymatic degradation. These findings indicate that the pseudo-peptides of the RGD sequence, possessing the inhibitory property of the degradation by MMPs differently from original RGD-containing peptides, may be advantageous and useful in preventing tumor metastasis.

FP-21399 blocks HIV envelope protein-mediated membrane fusion and concentrates in lymph nodes.

The identification of fusin and other chemokine receptors as coreceptors for HIV-1 has renewed the interest in agents that may prevent viral entry. Polyanionic compounds such as dextran sulfate, curdian sulfate, and suramin act on the V3 loop of the viral envelope and may prevent its interaction with fusin. These agents show activity against a wide range of HIV-1 strains, but have undesirable circulating half-life, bioavailability, and toxicity. We have developed a small molecule inhibitor of HIV-1 that has several advantages over these other agents. FP-21399 is a novel compound of the bis(disulfonaphthalene) dimethoxybenzene class that blocks entry of HIV into CD4+ cells and blocks fusion of infected and noninfected CD4+ cells. This compound only weakly inhibits binding of CD4 and gp120, at concentrations much greater than are required to block viral entry. Furthermore, FP-21399 can block the interaction between gp120 and antibodies directed against the V3 loop, but does not block binding of antibodies directed against the V4 loop. Animal studies demonstrate that FP-21399 is concentrated in lymph nodes, making it a promising compound for anti-HIV therapy. In SCID mice reconstituted with human immune cells, maintenance of HIV-1 infection was blocked by a 5-day treatment with low doses of FP-21399, suggesting that lymph node accumulation may contribute to antiviral activity. Finally, attempts to generate drug-resistant virus in cell culture resulted in only weakly resistant variants with IC90 values that are much lower than concentrations of FP-21399 found in lymph nodes.

The CT findings of pulmonary sarcoidosis.

We analyzed the CT findings in 35 patients with pulmonary sarcoidosis. Twenty-seven patients had biopsy-proven sarcoidosis; in eight patients the diagnosis was made clinically. In all the 35 patients, 10-mm collimation scans were available. In seven patients, high-resolution CT was also obtained. Twenty-eight patients had lymphadenopathy associated with pulmonary infiltration, two patients had pulmonary infiltration without lymphadenpathy, five patients had lymphadenopathy alone. The most frequent parenchymal features on CT were small nodules (100%) and irregularly thickened bronchovascular bundle (90%). Other frequent CT findings were pleural or subpleural thickening (83%), septal lines (73%) and ground-glass attenuation (63%). In all cases, small nodules were associated with other lesions. The authors conclude that in patients with sarcoidosis, CT is a valuable technique to visualize the findings in the pulmonary parenchyma characteristic enough to allow confident diagnosis. While high-resolution CT is superior in the assessment of linear opacities and cysts, conventional CT is superior in demonstrating small nodular opacities. We believe that both should be combined in the examination of patients with sarcoidosis.

Inhibition of tumor invasion and metastasis by peptidic mimetics of Arg-Gly Asp (RGD) derived from the cell recognition site of fibronectin.

The partially modified retro- and retro-inverso peptides of the Arg-Gly Asp (RGD) sequence of fibronectin, in which the direction of the Arg residue is reversed and/or the chirality of the amino acid residue is inverted, i.e., mainly R(rev)-COCH2CO-D and DR(rev)-COCH2CO-D, have been synthesized to examine their antimetastatic effects in murine lung or liver metastasis models, as well as their inhibitory effect on tumor cell invasion in vitro. R(rev)-COCH2CO-D inhibited lung metastasis produced by i.v. coinjection with B16-BL6 melanoma more potently than did other pseudo-peptides or the original RGDS peptide. Rrev-COCH2CO-D also showed antimetastatic effects against several different types of tumor cells such as B16-BL6 melanoma, Colon26 M3.1 carcinoma, and L5178Y-ML25 lymphoma cells, in a dose-dependent manner, and multiple administrations had a therapeutic effect on spontaneous lung metastasis. The invasion of melanoma cells into reconstituted basement membrane Matrigel in vitro was suppressed by R(rev)-COCH2CO-D more effectively than by RGDS. These results indicate that the antimetastatic effect by R(rev)-COCH2CO-D was in part due to the inhibition of tumor invasion. The RGDS peptide decomposed when incubated with fresh plasma in vitro, whereas R(rev)-COCH2CO-D was not affected by this treatment. Thus, the reversion of the Arg-Gly linkage in the RGD sequence resulted in protease resistance leading to the retardation of the clearance of the peptide in vivo, and consequently augmented its antimetastatic and antiinvasive properties. Designed peptide analogues may provide various advantages and be useful for preventing cancer metastasis.

Antimetastatic activities of synthetic Arg-Gly-Asp-Ser (RGDS) and Arg-Leu-Asp-Ser (RLDS) peptide analogues and their inhibitory mechanisms.

We have investigated the inhibitory effect of the N-terminal modified Arg-Gly-Asp-Ser (RGDS) analogues, AcDRGDS and AcDRLDS, on tumor cell adhesion to the components of extracellular matrix and basement membrane, and also tested the antimetastatic effect of their conjugates with trimesic acid, Ar(DRGDS)3 and Ar(DRLDS)3. AcDRGDS significantly inhibited tumor cell adhesion to fibronectin, vitronectin and RGDS substrates, but not to CS1 substrate which is a ligand for the alpha 4 beta 1 tumor surface integrin receptor. In contrast, AcDRLDS variant peptide significantly inhibited tumor cell adhesion to laminin, in addition to RGDS-mediated adhesion to fibronectin and vitronectin. AcDRLDS also inhibited tumor cell adhesion to CS1 as well as the RGDS sequence within the fibronectin molecule in a concentration-dependent manner, although the inhibitory effect was less than that of the CS1 (EILDV) peptide. Ar(DRLDS)3 inhibited the laminin- and fibronectin-mediated invasion and migration of tumor cells, whereas Ar(DRGDS)3 selectively inhibited fibronectin-mediated invasion and migration. Ar(DRGDS)3 and Ar(DRLDS)3 were much more effective in inhibiting experimental lung or liver metastases of various types of murine and human tumors than the original RGDS-containing peptides or Ar(COONa)3. Multiple administrations of Ar(DRGDS)3 or Ar(DRLDS)3 potently inhibited spontaneous lung metastasis produced by intra-footpad injection of B16-BL6 cells without affecting the primary tumor size at the time of surgical excision, as compared with RGDS peptide or untreated control. Thus, Ar(DRGDS)3 and Ar(DRLDS)3 substantially increased the exhibiting any antimetastatic effect of the peptides without direct cytotoxicity.

Studies on the development of the articular part of the temporal bone with special reference to the postglenoid process.

The development and significance of the postglenoid process on the articular surface of the temporal bone were studied using 217 Indian skulls, which were divided by their level of tooth eruption into 6 developmental stages; preeruption period (Stage I), initial stage (m1 eruption) of the deciduous dentition period (Stage II), middle stage (m2 eruption) of the deciduous dentition period (Stage III), late state (eruption of 20 deciduous teeth) of the deciduous dentition period (Stage IV), mixed dentition period (Stage V), and permanent dentition period (Stage VI). Each skull was mounted on a Kraniophor in such a way that the auriculoorbital (Frankfurt) plane was positioned vertical to the horizontal plane and photographed at a focal distance of 40 cm. Using the Frankfurt plane as a base line, the vertical distances to the lowest point of the postglenoid process (a-A), to the deepest point of the mandibular fossa (b-B), and to the mid-point of the articular tubercle (c-C) were measured. The distances from various points of the mandibular fossa to the articular surface of the temporal bone were measured at the level of the Frankfurt plane. The results may be summarized as follows: The length of the postglenoid process as measured from the Frankfurt plane was 0.58 mm at Stage I and 0.75 mm at Stage II. It increased by 0.6-1.0 mm at each developmental stage. By Stage VI, it had increased to 3.85 mm (six- to seven-fold increase from the initial value). The anteroposterior width of the postglenoid process remained almost unchanged throughout the developmental stages. The growth of the articular structures of the temporal bone from the preeruption to deciduous dentition period increased 73% in the total anteroposterior dimension (5.22 mm) and 44% in the total vertical dimension (3.32 mm). The vertical dimension of the mandibular fossa began to rapidly increase following the eruption of the deciduous first molars.

Combination of anti-cell adhesive synthetic Arg-Gly-Asp-Ser analogue and anticancer drug doxorubicin heightens their original antimetastatic activities.

A new compound containing the cell-adhesive Arg-Gly-Asp-Ser (RGDS) peptide was synthesized, i.e. tetrahydrofurantetracarboxylic acid (THFTCA)-RGDS conjugate [THFTCA- (RGDS)3, FC-243], and the inhibitory effect of FC-243 on lung metastasis of B16-BL6 melanoma in mice was examined in combination with or without the anticancer agent doxorubicin (DOX). FC-243 showed an inhibitory effect on lung metastasis of melanoma cells in a dose-dependent manner. A mixture of THFTCA and RGDS peptide or THFTCA alone did not show any inhibitory effect on experimental lung metastasis as compared with FC-243 on a molar basis. RGDS peptide, however, required a higher dose to obtain a sufficient antimetastatic effect. Intermittent IV administration of FC-243 after the inoculation of B16-BL6 cells caused significant inhibition of spontaneous lung metastasis as compared with multiple administration of RGDS or untreated control. The in vitro tumor invasion study showed that FC-243 as well as RGDS+THFTCA on a molar basis resulted in similar inhibition of the invasion of B16-BL6 cells into reconstituted basement membrane Matrigel. Combined treatment with FC-243 and DOX significantly inhibited lung metastasis of melanoma as compared with either treatment alone or the untreated control. Administrations of FC-243 and DOX in combination substantially prolonged the survival time of mice. These results demonstrate that combination therapy of the anti-cell adhesive FC-243 and the anticancer agent DOX, i.e. antiadhesion therapy and chemotherapy, is a new approach that offers enhanced inhibitory effects on tumor metastasis and invasion.

[Clinical significance of anti-cardiolipin antibody in patients with systemic lupus erythematosus (SLE)].

Anti-cardiolipin antibody (aCL) in SLE patients reacts with cardiolipin/beta 2-GP1 complex. In order to disclose clinical significance of aCL in patients with SLE, aCL was determined by newly-developed anti-CL.beta 2-GP1 kit [Yamasa] EIA in 58 patients with SLE and the relationship between clinical manifestation of SLE and the presence of aCL was examined. Anti-cardiolipin antibody was positive in 20 patients (34.5%). In 20 SLE patients with positive aCL, livedo reticularis in 7, retinal vein thrombosis in 3, thrombophlebitis in 3 and other vasculo-occlusive episodes were observed as a characteristic clinical features of positive aCL. In contrast, a SLE patient complicated by ileal perforation due to necrotizing angiitis had negative aCL. Other clinical and laboratory features associated with aCL include recurrent fetal loss and thrombocytopenia.

[Determination of urinary metabolites of organic solvents among chemical industry workers].

With the revision made to the Regulation on the Prevention of Organic Solvent Poisoning in June 30, 1989, analysis of urine must be made for metabolites as a part of the health examination of workers exposed to xylene, N,N-dimethylformamide, styrene, 1,1,1-trichloroethane, tetrachloroethylene, trichloroethylene, toluene, and n-hexane. In accordance with this Regulation, health examinations were conducted at eight factories of five chemical manufactures in 1990. This report presents the results obtained for 1,073 workers as compiled by the Committee of Industrial Health of the Japan Urea and Ammonium Sulfate Industry Association. 1) The results of data analysis have shown that workers whose urine was collected when they had been exposed to an imperceptible degree to organic solvent or who underwent urine collection during an unknown period of time after exposure numbered 615 or 57.3% of all the workers. 2) Workers whose urine was collected within about 5 hours after exposure numbered 458 (42.7%). The metabolite concentrations in these workers were significantly lower than the BEI values. 3) It may be concluded from the results that workers were exposed to organic solvents to an extremely small extent during organic solvent handling operations at chemical industry factories which maintain good control over toxic materials.

Ultrastructural study of rabbit buccal epithelial cells and intercellular junction by scanning and transmission electron microscopy.

We observed by scanning and transmission electron microscopy the ultrastructure on the upper and lower surfaces of buccal epithelial superficial layer cells and the arrangement of intercellular junction apparatuses. In the superficial layer cells of the rabbit buccal epithelium, microvillus-like processes were observed on the lower surface and microridges on the upper surface. The distal portion of the microvillus-like process on the lower cell surface formed a wedge-like structure. At the intermicroridge areas on the upper cell surface, wedge-like depressions were observed. These depressions were interdigitated with the wedge-like structures of the microvillus-like processes. From the observation of the serial ultrathin sections, most interdigitation sites have two demosomes per microvillus-like process (89.5%). The desmosomes were located in the distal portion of the microvillus-like processes (99.3%). The wedge-like structures of the microvillus-like processes and wedge-like depressions on the inter-microridge areas seem to increase the junctional surface and enhance cell cohesion against external forces from various directions.