Characterization of gamma-glutamyltranspeptidase from human pancreatic cancer

To elucidate the specific changes of pancreatic gamma-glutamyl-transpeptidase (gamma-GTP) associated with malignant transformation, some properties of gamma-GTP purified from pancreatic cancer were compared with those of gamma-GTPs from normal pancreas and other tissues. Four of five pancreatic cancer gamma-GTPs showed distinctly slower electrophoretic mobility than normal pancreatic enzymes. Isoelectric points of pancreatic cancer gamma-GTPs varied in each case, but they were all higher than those of normal pancreatic enzymes. This difference in isoelectric points of gamma-GTPs between cancerous tissue and normal tissue was reduced by neuraminidase treatment. Lectin affinity chromatography revealed two of five pancreatic cancer gamma-GTPs with a greater affinity to concanavalin A (Con A) than normal pancreas gamma-GTPs. Four of five pancreatic cancer gamma-GTPs had a greater affinity to Lens culinaris agglutinin (LCA) than normal pancreas gamma-GTPs. Normal pancreas gamma-GTPs had little affinity to Phaseolus vulgaris erythroagglutinating (E-PHA), but two of five pancreatic cancer gamma-GTPs had an apparent affinity to E-PHA and one of them had a slight affinity to E-PHA. These results indicate that the transformational changes of pancreatic cancer gamma-GTP are mainly induced in the sugar chains of the enzyme molecule, resulting in lower content of sialic acid and higher content of fucose and bisecting GlcNAc residue (the beta-N-acetylglucosamine residue linked at the C-4 of the beta-mannosyl residue of the trimannosyl core of the asparagine-linked sugar chain) as compared with the normal pancreatic enzyme.     

Studies on hyperthermia by the use of a thermosensitizing drug

Hyperthermic treatment using ACNU combined with a thermosensitizing drug, methylglyoxal-bis-guanylhydrazone (MGBG), was studied in human gastric cancer xenotransplanted into nude mice. In order to increase the intra-cellular MGBG content, intraperitoneal injection of alpha-difluoromethylornithine(DFMO) 1000 mg/kg was performed twice with an interval of 6 hours and 50 mg/kg of MGBG was given at the time of the second administration of DFMO. After 6 hours of MGBG administration, ACNU 20 mg/kg was given intraperitoneally and, subsequently a 23-minute hyperthermia was carried out in a water bath at 43.5 degrees C. After 48 hours a second hyperthermia was performed by the same method. Tumor weight was estimated using Battelle's Columbus Institute protocol and the inoculated tumors, which were extirpated 60 minutes after 3H-thymidine injection at a prescribed interval after cessation of hyperthermia, were assayed biochemically for the determination of DNA biosynthesis. In mice given ACNU, DFMO, MGBG plus heat, considerably superior results were obtained. Although the DFMO plus MGBG group was inferior in antitumor activity to the ACNU only or heat only group, the DFMO, MGBG plus heat group showed much the same antitumor effects, compared to the ACNU plus heat group. These data suggest that the thermosensitizing efficacy of MGBG may be applicable for clinical use.     

Analytical studies of both initial symptoms and clinical symptoms and signs of different etiologies of chronic pancreatitis: an approach by using odds ratios]

We conducted the statistical analysis of both initial symptoms and clinical symptoms and signs of different etiologies of chronic pancreatitis by using odds ratios which was one of the techniques of evidence-based medicine. The official report published by The Research Group of Intractable Pancreatic Diseases sponsored by the Welfare Ministry of Japan in 1986 was available as the data source of the present study. Nine items of initial symptoms and 25 items of 28 clinical symptoms and signs were compared in 4 different etiologies of the disease which were alcoholic, biliary, idiopatic and nonalcoholic (both biliary and idiopatic). In initial symptoms, 1.5 items were significantly more observed in alcoholic pancreatitis than in nonalcoholic, biliary and idioatic pancreatitis, 4 of which (abdominal pain, back pain, poor appetite and loss of body weight) were common items as might be related closely to the alcohol intake, 2. only one item of jaundice was significantly more observed in biliary pancreatitis than in alcoholic and idiopatic pancreatitis, 3.3 items of poor appetite, diarrhea and abdominal mass were more frequently observed in idiopatic pancreatitis than in biliary pancreatitis. In clinical symptoms and signs, 1. almost all items (21 to 24) were significantly more observed in alcoholic pancreatitis than in the other etiologies of the disease, and seemed to be related directly or indirectly to alcohol intake, 2.3 or 4 items which were related closely to gallstone and acute cholecystitis were significantly more observed in biliary pancreatitis than the other two etiologies of the disease, and 3.4 items consisting of diarrhea, loss of body weight, and pancreatic swelling were more frequently observed in idiopathic pancreatitis than in biliary pancreatitis.     

Managing subdural fluid collection in infants

INTRODUCTION: The authors classify infantile subdural fluid collection (SFC) into four chronological stages: (I) SFC with arachnoid tear, (II) SFC with inner membrane, (III) SFC with inner and outer membrane, and (IV) subdural hematoma, and discuss the appropriate treatment for each stage. CONCLUSIONS: Fontanel tapping can be used for every stage of SFC, but it is best indicated for stage II. Massive bleeding seldom occurs with punctures made with a small needle. Continuous external drainage is indicated for stages II and III. Although the risk of bleeding decreases even in stage III, this method involves a risk of infection. Burr hole irrigation is usually indicated for stage IV. Implantation of an Ommaya reservoir and endoscopic observation of the SFC cavity along with burr hole irrigation are very useful. A subduroperitoneal shunt cannot be recommended for the treatment of SFC in most cases.     

Lichen Planus and Sjögren-type Sicca Syndrome in a Patient with Chronic Hepatitis C

We report a 54-year-old Japanese male with lichen planus and Sjögren-type sicca syndrome, accompanied by the latent complication of chronic hepatitis C. The patient first showed erythematous and erosive lesions with white irregular striae in the buccal mucous membrane, and blepharitis and hyperemia of conjunctiva in his eyes. He later had two small erosions on the glans penis, and flat-topped violaceous papules on the dorsa manus and nape. A biopsy specimen of the lower lip lesion demonstrated a lichenoid tissue reaction at the basement membrane zone, and lymphocytic focal accumulations in the salivary glands. Immunohistochemical study of this specimen revealed CD45RO⁺ (T) cells associated with the expression of HLA-DR antigens predominantly in both the lichenoid tissue reaction and the lymphocytic sialadenitis. Objective keratoconjunctivitis sicca was confirmed by the Schirmer and Rose-Bengal tests. Anti-DNA antibody was positive; however anti-SS-A, and anti-SS-B antibodies were negative. Increased levels of transaminase enzymes, TTT, ZTT, and IgG were observed in first laboratory examinations; thereafter, anti-hepatitis C virus (HCV) antibodies and HCV-RNA were detected. The high serum amylase level, in which salivary amylase predominated, was normalized by etretinate therapy in parallel with the clinical improvement of the oral LP lesions. Our case is considered to support the hypothesis that an etiologic association may be present among lichen planus, Sjögren's syndrome, and chronic hepatitis C.     

Influences of menopause and oophorectomy on sex steroids secretion and metacarpal bone mineral content

The effects of menopause and oophorectomy (OPX) upon blood levels of sex steroid and bone mineral content were studied in age- and body size-matched postmenopausal subjects (n = 55), OPX subjects (n = 42) and premenopausal controls (n = 35). Blood levels of 17-OH-pregnenolone, 17-OH-progesterone and androstenedione were significantly lower in the OPX group than in the other two groups. For DHEA, DHEA-sulfate and testosterone, there were no significant intergroup differences. The blood level of estrone was the lowest in the OPX group, followed by the postmenopausal group (p less than 0.05). For estradiol, there was no difference between the two groups and its blood level was lower in these groups than in the controls. For LH and FSH, there were no differences between the former two groups, but blood levels were significantly high in these groups (p less than 0.01). Microdensitometric indices such as GS min and sigma GS/D were all low in postmenopausal and OPX groups in comparison with the controls (p less than 0.01). There were no considerable differences in these indices between the former groups. In conclusion, ovarian interstitial cells are still functioning and secrete androgens in short interval of three years after menopause, as known from higher blood levels of androgens and converted estrone in the postmenopausal group than in the OPX group. However, there was no significant difference between these two groups with regard to metacarpal bone mineral content.     

Successful endoscopic therapy of superficial esophageal cancer on varices in a patient with alcoholic liver cirrhosis

A case of successful endoscopic therapy of superficial esophageal cancer on varices in a patient with alcoholic liver cirrhosis is reported. A slightly depressed superficial cancer (type 0‐IIc) occupied half the inner surface of the middle esophagus. Endoscopic ultrasonography revealed esophageal varices and periesophageal collaterals, but no perforating veins connecting the varices and collaterals were observed where the cancer was located. The esophageal cancer could not be detected even with a 20 MHz microprobe. The tortuous esophageal varices in the lower esophagus were endoscopically ligated to reduce blood flow just below the cancer and 10 mL polidocanol solution was endoscopically injected to induce sclerosis of the varices. After these procedures, the mucosal cancer was endoscopically resected without any severe complications and residual cancer was eliminated by cauterization using a heater probe. Histopathological examination revealed that poorly differentiated squamous cell carcinoma invaded into the lamina propria mucosae but not into the vessels or the lymphatic system. Three years after treatment, the patient showed no signs of local recurrence of cancer. It is considered that the endoscopic techniques used in this patient constitute a valuable and minimally invasive treatment for superficial esophageal cancer on varices.     

Effects of Rho-kinase inactivation on eosinophilia and hyper-reactivity in murine airways by allergen challenges

BACKGROUND: A small GTPase, Rho, and its target molecule, Rho-kinase, play an important role in the cell functions, including contractility, chemotaxis, adhesion, and migration. It is generally considered that eosinophilic inflammation and hyper-reactivity to methacholine in airways are fundamental to the pathophysiology of bronchial asthma. OBJECTIVE: This study was designed to determine whether the Rho/Rho-kinase pathways are involved in the eosinophil recruitment and airway hyper-reactivity. We investigated inhibitory effects of fasudil, a specific inhibitor of Rho-kinase, on acute allergic inflammation in mice. METHODS: BALB/c mice were sensitized and challenged with ovalbumin (OVA). OVA-challenged mice were treated orally with fasudil (3, 10, 30 mg/kg) or saline before each OVA challenge. Total cell counts, differential cell counts, cytokines, and chemokines levels were measured in bronchoalveolar lavage (BAL), and lungs were examined histologically. Moreover, respiratory resistance in response to methacholine was measured. RESULTS: When fasudil was administrated to OVA-challenged mice, increased cell numbers of total cells and eosinophils were significantly attenuated in a dose-dependent manner. However, inflammatory cells other than eosinophils were not affected by fasudil. Fasudil caused a dose-dependent inhibition in increased levels of IL-5, IL-13, and eotaxin in BAL fluid by OVA challenges. Histological analysis of the airways revealed that both infiltration of inflammatory cells and goblet cell hyperplasia were significantly suppressed in fasudil treatment. Furthermore, fasudil significantly suppressed the augmented responsiveness to methacholine induced by OVA challenges. CONCLUSION: Oral administration of fasudil inhibits eosinophil recruitment, goblet cell hyperplasia and airway hyper-reactivity by allergen challenges. These effects of this agent may be mediated by suppressing a chemokine and cytokines related to the pathophysiology of bronchial asthma such as eotaxin, IL-5, and IL-13. Our findings provide evidence that inhibition of the Rho/Rho-kinase pathway may be beneficial for bronchial asthma.