Drug repositioning of antipsychotic drugs for cisplatin-induced pica behavior in mice.

We aimed to clarify whether various antipsychotics ameliorate cisplatin-induced pica behavior in mice using a drug repositioning approach. Mice were administered cisplatin (12.5 mg/kg, i.p.) with or without olanzapine (1 mg/kg, i.p.), asenapine (4 mg/kg, i.p.), mirtazapine (5 mg/kg, i.p.) or standard three-drug antiemetics (granisetron [0.5 mg/kg, i.p.], fosaprepitant [25 mg/kg, i.p.], and dexamethasone [3 mg/kg, i.p.]). Kaolin, food, and water intake, and spontaneous motor activity on the day before and seven consecutive days after the cisplatin administration were measured using a telemetry system. At the primary endpoint, kaolin intake was significantly higher at day three in the cisplatin group than in the pre-treatment and saline groups ( p < 0.05). Additionally, kaolin intake was not significantly higher in cisplatin with olanzapine, asenapine, and mirtazapine groups for seven days than in the pre-treatment group. At the secondary endpoint, cisplatin decreased the food and water intake, and spontaneous motor activity in a time-dependent manner. Three antipsychotics failed to improve the cisplatin-induced decrease in food and water intake, and spontaneous motor activity. The findings suggest that prophylactic administration of antipsychotics besides olanzapine may improve cisplatin-induced nausea and vomiting in a delayed phase and de-escalate standard 3-drug antiemetics.

Increased circulating interleukin-12 (IL-12) p40 in pulmonary sarcoidosis.

In sarcoidosis, a T helper 1 (Th1) response is an essential event and the up-regulation of interleukin-12 (IL-12) has been detected in affected disease sites. In order to investigate the clinical usefulness of circulating IL-12, we measured the serum concentrations of IL-12 by ELISA and performed immunohistochemistry using specific MoAbs for IL-12 in the lungs and scalene lymph nodes of patients with sarcoidosis. The serum concentration of IL-12 p40 was detectable in all 45 patients with pulmonary sarcoidosis and 18 normal controls, whereas that of IL-12 p70 was undetectable. The serum concentrations of IL-12 p40 in pulmonary sarcoidosis were significantly higher than those of the normal controls, especially in cases with abnormal intrathoracic findings detected by chest roentogenogram. The serum concentrations of interferon-gamma (IFN-gamma) also increased compared with those of normal controls and there was a significant positive correlation between the serum concentrations of IL-12 p40 and IFN-gamma. Furthermore, serum angiotensin-converting enzyme (ACE) and lysozyme, which are known to be useful markers for disease activity in sarcoidosis, correlated well with the serum concentrations of IL-12 p40. The positive 67Ga scan group (for lung field) had significantly elevated serum IL-12 p40 levels compared with those of the negative group. No bioactivity of IL-12 p70 was detected in three sarcoid cases sera by using the IL-12 responsive cell line. Finally, the immunohistochemical approach revealed that IL-12 p40 was expressed in the epithelioid cells and macrophages of sarcoid lungs and lymph nodes. We concluded that the production of IL-12 p40 was far greater in the sera and we have demonstrated this to be a useful clinical marker for disease activity and the Th1 response in pulmonary sarcoidosis.

IL-12 and IL-18 are increased and stimulate IFN-gamma production in sarcoid lungs.

Sarcoidosis is a systemic chronic granulomatous disease of unknown cause. Recent investigations revealed that the cytokine profile in inflamed lesions of sarcoidosis is Th1 dominant. To obtain better immunopathologic understanding of sarcoidosis, we examined the expression of IL-12 and IL-18 and their roles in IFN-gamma production in pulmonary sarcoidosis. Sarcoid cases had significantly elevated levels of IL-12 (p40 and p70) and IL-18 in bronchoalveolar lavage (BAL) fluids compared with healthy subjects. IL-12 p70 and IL-18 were immunohistochemically expressed in the epithelioid cells and giant cells of sarcoid granulomas. Significant induction of IFN-gamma, IL-12 p70, and IL-18 was observed from sarcoid BAL fluid cells with LPS stimulation, whereas LPS tended to induce only IL-12 p70 in BAL fluid cells from healthy subjects. Sarcoid cases had significantly greater IFN-gamma induction with LPS stimulation than healthy subjects did. IL-18 mRNA expression was observed in freshly isolated sarcoid BAL fluid cells as well as in LPS-stimulated sarcoid BAL fluid cells, but IFN-gamma and IL-12 mRNA expression was observed only in LPS-stimulated BAL fluid cells. Treatment with anti-IL-12- and anti-IL-18-neutralizing Abs significantly inhibited IFN-gamma production from LPS-stimulated BAL fluid cells of sarcoid cases. Coadministration of rIL-12 or rIL-18 induced greater IFN-gamma production in sarcoid BAL fluid cells than in normal BAL fluid cells. We concluded that bioactive IL-12 and IL-18 were produced in sarcoid BAL fluid cells and synergistically induced IFN-gamma production, indicating important cytokines in the Th1 response of sarcoidosis.

Purification and characterization of a O-methyltransferase capable of methylating 2-hydroxy-3-alkylpyrazine from Vitis vinifera L. (cv. Cabernet Sauvignon).

An S-adenosyl-L-methionine-dependent O-methyltransferase capable of methylating 2-hydroxy-3-alkylpyrazine (HP) was purified 7,300-fold to apparent homogeneity with an 8.2% overall recovery from Vitis vinifera L. (cv. Cabernet Sauvignon) through a purification procedure including column chromatography on DEAE-Sepharose FF, Ether-5PW, hydroxyapatite, G2000SW(XL), and DEAE-5PW. The relative molecular mass of the native enzyme estimated on gel permeation chromatography was 85 kDa, and the subunit molecular mass was estimated to be 41 kDa on SDS-polyacrylamide gel electrophoresis. The enzyme also methylates caffeic acid. The Vmax for IBHP and caffeic acid were 0.73 and 175 pkatals/mg, respectively, and the respective Km for IBHP and caffeic acid were 0.30 and 0.032 mm. The optimum pH for IBHP (8.5) was different from that for caffeic acid (7.5).

Association of Clara cell 10-kDa protein, spontaneous regression and sarcoidosis.

Sarcoidosis is a systemic granulomatous disorder with a high rate of spontaneous regression. Clara cell 10-kDa protein (CC10), the predominant product of nonciliated bronchiolar epithelial cells, is a potent immunoregulatory and anti-inflammatory agent. CC10 levels were measured in sera and bronchoalveolar lavage (BAL) fluids from 31 sarcoidosis patients (nine progressive disease and 22 regressive disease) and their relevance to spontaneous regression investigated. The inhibitory effects of recombinant CC10 on interferon gamma (IFN-gamma) production were examined using lipopolysaccharide (LPS)-stimulated sarcoid BAL fluid cells, and the blocking effects of monoclonal antibody TY-5, directed against CC10, on CC10 function were also tested. Serum and BAL fluid CC10 levels in the regressive disease group were significantly higher than those in the progressive disease group (serum, p<0.05; BAL fluid, p<0.005) and healthy subjects (serum, p<0.0001; BAL fluid, p<0.005). CC10 inhibited, in part, IFN-gamma production from LPS-stimulated sarcoid BAL fluid cells (CC10 inhibition: 1,000 ng x mL(-1), 30%; 100 ng x mL(-1), 14%). TY-5 restored IFN-gamma production by blocking CC10 function. Sarcoidosis patients with regressive disease showed increased Clara cell 10-kDa protein levels in their sera and bronchoalveolar lavage fluids. Clara cell 10-kDa protein may be a regulator of the inflammatory process in sarcoidosis.

The prognosis of pulmonary sarcoidosis in Finland and Hokkaido, Japan. A comparative five-year study of biopsy-proven cases.

BACKGROUND AND AIM OF THE STUDY: The frequency and clinical picture of sarcoidosis are different in Finland and Hokkaido, Japan. The aim of this study was to compare the normalisation rate of chest radiographic changes in patients with biopsy-proven sarcoidosis. METHOD: The chest radiographs of 437 Finnish and 457 Japanese patients were used and, for the purpose of this study, double-checked in order to make sure that the interpretations were identical. On a yearly basis the radiographs were classified as normalised, improved, unchanged or deteriorated. RESULTS: Normalisation of chest radiographs occurred in 73% of the Japanese and 40% of the Finnish patients. The difference between the two series was significant (p < 0.001). Gender, young age, presence or absence of symptoms or extrapulmonary lesions at diagnosis or treatment with corticosteroids did not influence the difference between the two series. Of the 191 Finnish and 309 Japanese patients with initial stage I disease a normal chest radiograph was obtained in 47% of the Finnish and 76% of the Japanese patients (p < 0.001), despite the fact that the Finnish series included patients with erythema nodosum, who had a 59% normalisation rate. Of the 186 Finnish and 125 Japanese patients with initial stage II disease, normalisation of the chest radiographs was seen in 36% of the Finnish and in 73% of the Japanese patients (p < 0.001). No difference in normalisation rate was seen between stage III patients. CONCLUSION: The prognosis of pulmonary sarcoidosis in Japanese patients in Hokkaido is significantly better than that in Finland defined as normalisation rate of the chest radiographs.

[Sarcoidosis associated with lupus pernio and acute pulmonary cavitation].

Lupus pernio, an uncommon skin condition due to sarcoidosis in Japan, is a chronically persistent, violaceous skin lesion primarily involving the nose, cheek, ears, and fingers. It has often been associated with chronic fibrotic non-resolving pulmonary sarcoidosis. We reported a case of sarcoidosis associated with lupus pernio and primary pulmonary cavitation as a rare manifestation in the lung. A 44-year-old man visited our hospital in January 1986 because of a 3-year history of swollen and violaceous cheeks (lupus pernio) and an 8-year history of erythema in both upper and lower limbs. The biopsy specimen obtained from the skin lesion revealed epithelioid cell granulomas without any evidence of Mycobacterium or fungal growth. Serum ACE (45.4 U/ml) was elevated. Chest X-ray films and computed tomographic (CT) scans showed bilateral hilar lymphadenopathy, nodules, multiple small opacities, and reticulo-linear opacities. Gallium scintigraphy demonstrated abnormal uptake in the mediastinal and hilar lymph nodes and lung fields. The patient had not received corticosteroids. Chest X-ray films and CT scans in July 1989 showed increased opacities and cavitation. Because pyogenic bacteria and acid-fast bacilli were not detected by repeated sputum examinations or bronchial washing, we concluded that the cavitary lesions were manifestations of primary pulmonary cavitation due to sarcoidosis. Prednisolone (40 mg daily) was prescribed and the dosage was gradually tapered. The lung lesions gradually resolved and have not recurred.

The efficacy, safety and pharmacokinetics of intravenous ciprofloxacin in patients with lower respiratory tract infections.

The efficacy and safety of intravenous ciprofloxacin 200 mg every 8 or 12 h and 300 mg every 12 h in treatment lasting 3-14 days were investigated in patients with lower respiratory tract bacterial infections. Patients presented with pneumonia, bronchiectasis with infection, previous pulmonary tuberculosis with infection and diffuse panbronchiolitis. Clinical efficacy was seen in six of eight patients, with apparent recovery in terms of chest radiographs, fever reduction and laboratory findings. Pharmacokinetic analysis in one patient treated with intravenous ciprofloxacin 300 mg showed that at 0.5 h after the first dose, ciprofloxacin serum and sputum concentrations were equivalent (2.45 micrograms/ml and 2.25 micrograms/ml, respectively). Adverse events were recorded in only two patients and involved a slight elevation in liver function tests and eosinophilia. This study indicates that intravenous ciprofloxacin is useful in the treatment of lower respiratory tract infections.

Measurement of serum monocyte chemoattractant protein-1 and its clinical application for estimating the activity of granuloma formation in sarcoidosis.

BACKGROUND AND AIM OF THE WORK: The role of monocyte chemoattractant protein-1 (MCP-1) in bronchoalveolar lavage fluids from sarcoidosis patients was previously reported. To study the role of MCP-1, we evaluated the serum MCP-1 and its clinical significance in sarcoidosis. METHODS: The serum MCP-1 level was measured in 47 patients with sarcoidosis and 10 normal healthy controls with the use of an enzyme-linked immunosorbent assay. The localization and mRNA expression of MCP-1 in sarcoid lymph nodes were evaluated by an immunohistochemical method using an anti-MCP-1 monoclonal antibody and an in situ hybridization technique to determine the cellular source(s) of MCP-1. RESULTS: Serum MCP-1 levels were significantly elevated in the sarcoidosis patients compared with the healthy controls (698.3 +/- 101.9 vs. less than 39 pg/ml, p < 0.001). A comparison of the patients' serum MCP-1 levels among standard radiographic stages revealed that the serum MCP-1 was significantly higher in early stages: stage 0 vs. III, and stage I vs. II. In addition, the serum MCP-1 levels were significantly correlated with the serum angiotensin converting enzyme levels (r = 0.539, p = 0.0006). MCP-1 expression was detected in macrophages peripheral to the epithelioid granuloma in sarcoid lymph nodes, by both immunohistochemistry and in situ hybridization. CONCLUSIONS: These data suggest that MCP-1 may be expressed by the macrophages in the granuloma throughout the body, and that the measurement of serum MCP-1 levels may have clinical value as an indicator in estimating the activity of granuloma formation throughout the body in sarcoidosis.

[Fulminant Mycoplasma pneumoniae pneumonia resulting in respiratory failure and a prolonged pulmonary lesion].

A previously healthy 26-year-old woman presented with a fever and coughing on October 1, 1995. Despite treatment with beta-lactam antibiotics at another hospital, she had a high fever, coughing, and dyspnea. A chest roentgenogram showed diffuse infiltrates in both lung fields. On October 9, she was transferred to our hospital. On admission, a chest X-ray film showed marked diffusely infiltrates in both lung fields and a effusion in the left lung. Arterial blood gas analysis after inhalation of 4 liters per minute of oxygen via a nasal cannula revealed a PaO2 of 39.0 torr. Despite treatment with various antibiotics, including minocyclin and gamma-globulin, her respiratory condition rapidly deteriorated. She was mechanically ventilated by with intermittent mandatory ventilation and positive end-experiatory pressure, and received antibiotics and methylprednisolone pulse therapy. He chest X-ray and arterial blood gase findings, gradually improved. The passive hemagglutination titer for Mycoplasma rose from 1:4 on October 9, to 1:2,560 on the 14th hospital day. Acute respiratory failure due to Mycoplasma pneumoniae pneumonia was diagnosed. A chest X-ray film obtained 2 months after admission showed linear-reticular shadows in both lung fields and pulmonary-function tests revealed abnormally low vital capacity and diffusing capacity. Examination of a specimen obtained by transbronchial lung biopsy revealed focal intraalveolar exudate with fibrin and macrophages. Very mild interstitial thickening was also noted. The lymphocyte stimulation responses to PPD, PHA, and Con A were low early in the illness and became normal after recovery. Several reports have said that an enhanced pulmonary cellular immune response may be responsible for the development of severe Mycoplasma pneumoniae, resulting in a temporary decrease in the cell-mediated immune response. This case supports that hypothesis. We believe that in severe cases, steroid therapy including pulse therapy should be started as soon as possible.

Immunoreactive MUC1 expression at the deepest invasive portion correlates with prognosis of colorectal cancer.

This study sought to examine the relationship between MUC1 expression at the deepest invasive portion, invasive/metastatic potential, and prognosis of colorectal cancer in relation to cellular proliferation. MUC1 expression was detected immunohistochemically using KL-6 antibody (anti-MUC1 monoclonal antibody) in 100 surgically resected specimens of advanced colorectal cancer. Distinct staining of the luminal surfaces, defined as positive immunoreactive (IR)-MUC1 expression, was seen in more than 30% of the tumor cells at the deepest invasive portion. The proliferating cell nuclear antigen labeling index (PCNA-LI) was also examined in the same areas. IR-MUC1 expression was detected in 71 (71%) of 100 lesions. Lesions with lymphatic or venous invasion showed a significantly higher incidence of IR-MUC1 expression than those without lymphatic or venous invasion (80 vs. 42% and 82 vs. 61%, respectively). Lesions with lymph node metastasis showed a significantly higher incidence of IR-MUC1 expression than those without lymph node metastasis (88 vs. 53%). Lesions with liver metastasis showed a significantly higher incidence of IR-MUC1 expression than those without liver metastasis (92 vs. 59%). Dukes' stage was also significantly correlated with IR-MUC1 expression. The incidence of IR-MUC1 expression did not significantly differ with regard to histologic subclassification and depth of invasion. There was no significant correlation between IR-MUC1 expression and the PCNA-LI. IR-MUC1 expression at the deepest invasive portion revealed a significant correlation with prognosis; furthermore, in patients with better differentiated lesions, in those with lesions confined to muscularis propria or subserosa (subadventitial) invasion, in those with Dukes' B and C, or in those undergoing curative resection, IR-MUC1 expression significantly correlated with prognosis. Patients with high PCNA-LI lesions showed a significantly poorer prognosis than those with low PCNA-LI lesions. Only in patients undergoing curative resection, patients with IR-MUC1-positive and high PCNA-LI lesions showed a significantly poorer prognosis than those with IR-MUC1-negative and low PCNA-LI lesions. The significant risk factors in the order of poorer prognosis in patients undergoing curative resection by the multivariate analysis were the histologic grade (moderately-poorly, poorly or mucinous adenocarcinomas), IR-MUC1 expression, and lymph node metastasis. These results indicate that IR-MUC1 expression is an important predictor of the metastatic potential and the prognosis of colorectal cancer, independent of histologic grade, depth of invasion or cellular proliferative activity. Combined analysis of IR-MUC1 and histologic grade, and combined expression of IR-MUC1 and PCNA at the deepest invasive portion are especially useful in predicting colorectal cancer prognosis.

Seroprevalence of anti-Borrelia antibodies among patients with confirmed sarcoidosis in a region of Japan where Lyme borreliosis is endemic.

BACKGROUND: Sarcoidosis is a multisystemic granulomatous disease of unknown etiology, while Lyme borreliosis is a multisystemic disorder caused by Borrelia burgdorferi. The purpose of this study is to evaluate the relationship between sarcoidosis and Lyme borreliosis in a region of Japan where Lyme borreliosis is endemic. METHODS: We determined the seroprevalence of anti-Borrelia burgdorferi antibodies as well as antibodies three Japanese Borrelia strains by enzyme-linked immunosorbent assay and dotblot assay using purified Borrelia-specific proteins in 46 patients with confirmed sarcoidosis and 150 controls (50 disease controls and 100 healthy controls) in Hokkaido, the affected region. RESULTS: Fifteen patients with sarcoidosis (32.6%) tested positive for Borrelia spirochete in both assays, compared with two disease controls (4.0%) and two healthy controls (2.0%). The seroprevalence of anti-Borrelia antibodies in patients with sarcoidosis was much higher in the affected region than in the region in our previous study were Lyme borreliosis is non-endemic. CONCLUSION: In a region where Lyme borreliosis is endemic, Borrelia infection may be partially associated with sarcoidosis.

An anatomical study of the junction of the orbital septum and the levator aponeurosis in Orientals.

The anatomical relationships of the orbital septum and levator aponeurosis has been studied in 40 eyelids subjected to blepharoplasty and corrective ptosis surgery by dissection in 10 cadavers and in histological sections. The orbital septum originates from the arcus marginalis of the frontal bone and consists of two layers. The whitish outer (superficial) layer, containing vertically running vessels, descends just inside the orbicularis oculi muscle to interdigitate with the levator aponeurosis with loose connective tissue, then disperses inferiorly. The inner (deep) layer follows the superficial one initially, then reflects at the levator aponeurosis and continues posteriorly with the levator sheath. We reconfirmed Whitnall's original description that the levator sheath thickens to form the superior transverse ligament runs continuously inferiorly anterior to the levator aponeurosis and forms the inner layer of the orbital septum. This detailed anatomical analysis should assist in performing upper eyelid surgery such as the Oriental double fold operation or levator resection.

[Thymic carcinoma associated with pulmonary sarcoidosis].

A 54-year-old man who worked as a farmer was admitted to the hospital in August 1989 because of bilateral hilar adenopathy that was detected during a mass screening. Laboratory examination showed a high serum lysozyme level and the PPD skin test was negative. Examination of a specimen obtained by transbronchial lung biopsy revealed non-caseous epithelioid cell granuloma. Sarcoidosis was diagnosed. The patient was not treated, and the bilateral hilar adenopathy had lessened by 1992. The patient was readmitted to our hospital because of right hilar and upper mediastinal enlargement seen on a chest radiograph in April 1994. Computed tomography and magnet resonance imaging disclosed an anterior mediastinal tumor in contact with the right upper lobe, the left inominate vein, and the pericardium. Bronchoscopy showed no abnormality in the right upper-lobe bronchus. Examination of a specimen obtained from the B3b bronchus showed no evidence of malignant cells. Examination of a tumor specimen obtained by transdermal biopsy showed squamous cell carcinoma. After the patient underwent combination chemotherapy, the tumor ws resected, along with the right upper lobe, the left inominate vein, and the pericardium, which were difficult to separate from the tumor. Postoperative pathological examination showed that squamous cell carcinoma was intermingled with normal thymus tissue. We believe that squamous cell carcinoma originated in the thymus. Non-caseous epithelioid cell granulomas were also found in the resected right upper lobe and in a mediastinal lymph node. The patient was discharged after post-operative irradiation of the mediastinum. Thymic carcinoma is rare, and sarcoidosis in a patient with thymic carcinoma is very rare. T lymphocytes are very important in the pathogenesis of sarcoidosis, and the thymus is involved in the growth and differentiation of T lymphocytes. The occurrence of these two diseases in one patient is interesting, but the relationship is not clear.

Single carcinoma cells at the deepest invasive portion correlate with metastatic potential of advanced colorectal carcinoma.

The clinical significance of detecting single carcinoma cells (SC) at the deepest invasive portion of a tumor in terms of metastatic potential and prognosis was examined in 57 patients with surgically resected advanced colorectal carcinoma. SC were detected using an immunohistochemical stain for cytokeratin in these sections. The deepest invasive portions of tumors were subclassified by histology into three grades as follows: well-differentiated (W), moderately-well differentiated (Mw; a type that more closely resembles the W tumor), and moderately-poorly differentiated (Mp; more closely resembling poorly differentiated tumor). SC detection was defined positive if more than three single cancer cells with clear cytoplasmic expression of cytokeratin was seen distinct from carcinoma glands and tumor sheets in mid-power (x100) field. SC were detected in 51 (89%) of the 57 carcinomas. There were 5 W or Mw (W/Mw) tumors without SC, 34 W/Mw tumors with SC, 1 Mp tumor without SC, and 17 Mp tumors with SC. W/Mw tumors with SC had a significantly higher (p<0.01) incidence of lymph node metastasis than W/Mw tumors without SC. There was no lesion with lymph node or liver metastasis of W/Mw tumors without SC. SC detection, when combined with histologic subclassification at the deepest invasive portion of a tumor, correlated with prognosis. These results indicate that a combination of the tumor histologic subclassification and SC detection at the deepest invasive portion is a useful predictor of metastatic potential and prognosis in advanced colorectal carcinoma.

The mode of presentation of sarcoidosis in Finland and Hokkaido, Japan. A comparative analysis of 571 Finnish and 686 Japanese patients.

We compared the clinical picture of sarcoidosis in patients diagnosed at Mjölbolsta hospital in Finland in 1955-1987 with those diagnosed in Sapporo in 1964-1988. The female:male ratios showed a slight female predominance. The mean age (SD) at diagnosis was 41.5 (13.0) years at Mjölbolsta and 30.0 (15.4) years in Sapporo. In both series, half of the patients had been detected at mass x-ray surveys. The presenting symptoms varied considerably among the symptomatic patients. At Mjölbolsta hospital, 189 patients (33%) had cough, 21% fever, 21% general malaise, 18% dyspnoea, 18% erythema nodosum, 16% joint pain and only 27 patients (5%) had eye symptoms. In Sapporo, 245 patients (41%) had eye symptoms, 18 (4%) had enlarged peripheral lymph nodes, 14 (3%) had cough, 10 (2%) had fever. Erythema nodosum did not occur as a presenting symptom in Sapporo. The chest radiographs showed bilateral hilar lymphadenopathy (BHL, stage I) in 48% of the Mjölbolsta patients and in 57% of the Sapporo patients. Stage II lesions were seen in 39% and 20%, and stage III lesions in 12% and 5% respectively. Only 1% had a normal chest radiograph at Mjölbolsta hospital as compared with 18% in Sapporo. The Sapporo patients were more obstructive but the proportion of smokers was also higher. No difference in diffusion capacity was seen.

Immunogenicity of the whole antigen and glycoprotein I of varicella-zoster virus (VZV) and the VZV skin test antigen.

Specific cellular immunity against the whole antigen and glycoprotein I (gp I) of varicella-zoster virus (VZV) and the skin test antigen were determined for 13 healthy immune adults to compare the immunogenicity of these antigens using a lymphoproliferative assay. The stimulation index values (mean +/- s.d.) were 16.4 +/- 11.2 against the whole VZV antigen, 4.2 +/- 2.9 against the VZV skin test antigen and 1.1 +/- 0.5 against gp I. The immunogenicity of the skin test antigen, which mainly contains gp III and gp IV, appears to be more favorable than that of gp I alone, but to be weaker than that of the whole VZV antigen.

[Clinical analysis on the course and prognosis of patients with Crohn's disease].

We analyzed 66 cases (47 males and 19 females) of Crohn's disease at Hiroshima University hospital from September 1975 to October 1994 to clarify the course and prognosis of Crohn's disease. The age at onset was 21.1 +/- 7.3 years old (mean +/- SD), terms between onset and diagnosis were 21.5 +/- 33.0 months (mean +/- SD) and observation period was 65.5 +/- 44.6 months (mean +/- SD). Sites of lesion were 18 ileum, 41 ileocolon and 7 colon. Thirty-one cases, 20 cases of which had intestinal obstruction, underwent surgical operation (12 ileum types, 18 ileocolic types, 1 colon type). The cumulative probability of surgery at one, five and ten years after onset of symptoms were 12.1%, 28.8% and 56.9%, respectively. As for cumulative probability of surgical operation at one, five and ten years after diagnosis were 25.8%, 36.7% and 74.4%, respectively. Results of the cumulative probability of surgery by anatomical involvement indicated that the ileum type had a statistically significantly higher risk than other types. In each analysis compliance to nutritional therapy was also an important prognostic factor. Overall, our results indicated that the site of lesion and the compliance to nutritional therapy were important factors which have an effect on the course and prognosis of Crohn's disease patients.

[Clinicopathologic evaluation on colorectal laterally spreading tumor (LST)].

Clinicopathologic characteristics of 92 colorectal laterally spreading tumors (LST) endoscopically or surgically resected were examined. Lesions were macroscopically classified into two categories according to their surface structure :(1) granular type (G type, 47 lesions), (2) flat type (F type, 45 lesions). The size (maximum diameter) of G type lesions was 24.7 +/- 11.3 mm (Mean +/- SD) and that of F type lesions was 14.2 +/- 7.4 mm. The size of G type lesions was significantly larger than that of F type lesions (p < 0.01). Among G type lesions, cancerous lesion was present in 2 (25.0%) of 8 lesions 10-14 mm in diameter, 2 (22.2%) of 9 lesions 15-19 mm in diameter and 19 (63.3%) of 30 lesions more than 20mm in diameter. Regarding F type lesions, cancerous lesion was present in 15 (46.9%) of 32 lesions 10-14 mm in diameter, 4 (80.0%) of 5 lesions 15-19 mm in diameter and 8 (100%) of 8 lesions more than 20mm in diameter. The incidence of carcinoma in F type lesions was higher than that in G type lesions irrespective of size. F type lesions with carcinoma showed a trend toward a higher frequency of submucosal invasion and F type lesions with adenoma revealed tendency of showing severe atypia in comparison with G type lesions. The adenomatous component of LST showed a tubulo-villous architecture in 13 (28.3%) of 46 G type lesions, however none of F type lesions had a tubulo-villous component. These results indicated that clinicopathologic characteristics of F type are obviously different from G type. Furthermore, F type had a higher malignant potential than G type and is thought to have a more important role as a precursor of colorectal carcinoma than G type.