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The administration of corticosteroids induced apoptosis of thymocytes in vivo. Among various adhesion molecules examined, vascular cell adhesion molecule-1 (VCAM-1, CD106) was shown to be strongly expressed in these apoptotic cells. Flow cytometric analysis also showed the expression of VCAM-1 in apoptotic thymocytes. An RT-PCR study demonstrated the expression of VCAM-1 mRNA in thymocytes. Splenic lymphocytes and other lymphoid cell lines also expressed VCAM-1 during the process of apoptosis. VCAM-1 mRNA expression was also observed in RT-PCR performed on these cell lines.

The feasibility and safety of left-sided biliary drainage with ultrasound (US) guidance were studied prospectively.From July 1987 to July 1996, 208 consecutive patients underwent US-guided biliary drainage; all were evaluated for left-sided drainage. Drainage procedure was begun with puncture of the hepatic duct branch of the lateral segment of the left lobe when the branch was well visualized with US; otherwise, a right-sided approach was used. When the hepatic duct branch diameter was greater than 3 mm, puncture was performed with an 18-gauge needle; smaller branches were punctured with 21-gauge needles.In 147 (71%) patients, the left hepatic duct branch was well visualized with US, and the branch diameter was greater than 3 mm. In these patients, left-sided drainage with use of an 18-gauge needle was successful. In 26 (12%) patients, the left hepatic duct branch diameter was less than 3 mm, and drainage was initiated with a 21-gauge needle. In six (23%) of these 26 patients, left-sided drainage was unsuccessful, but five of these patients underwent successful US-guided drainage from the right hepatic duct branch. Two patients died of septic shock within 72 hours of completed drainage. Three patients experienced severe hemobilia.US-guided left-sided biliary drainage is a highly successful and safe method when the left hepatic duct branch diameter is greater than 3 mm.

Lipase G, a partial glycerides eliminating enzyme produced by Penicillium camembertii, was subjected to safety evaluation studies to establish its safety when used as a processing aid in the food industry. The toxicological studies on the enzyme included a 90-day gavage study with rats, a mutagenicity study using bacteria, and a pathogenicity study using mice. The no-adverse-effect level from the 90-day gavage toxicity study was 2000 mg/kg body weight/day for rats. There was no evidence of mutagenic potential. The micro-organism was evaluated for pathogenicity using mice and classified as a non-pathogen. Results indicate that the production and use of lipase G may be regarded as safe for the enzyme production worker and the consumer.

Several reports have shown expression of cyclooxygenase-2 (COX-2) in malignant skin tumors. COX-2 has also recently been reported as a marker of malignant melanoma (MM).Our aim was to investigate whether there is a difference in the immunohistochemical expression of COX-2 between malignant and benign melanocytic lesions of the skin.We selected 40 archival cases of MM including 10 cases of superficial spreading melanoma, 10 of lentigo maligna melanoma, 10 of nodular melanoma, and 10 of acral lentiginous melanoma. For comparison, we also selected 35 benign melanocytic lesions, which included 15 nonatypical nevi and 10 atypical nevi. The remaining 10 cases were Spitz nevi. COX-2 immunohistochemical staining was performed, and intensities were assessed quantitatively.The MM group and the benign melanocytic nevi group showed a highly statistically significant difference in the intensity of COX-2 expression (P0.0001). Staining intensity in the dermal component of MM cases also showed a tendency to increase with increasing tumor depth. By contrast, the intensity of the dermal component in the melanocytic nevi group decreased with increasing depth as the nevus cells matured from type A to type C cells. No statistical difference was noted between the MM and Spitz nevi cases (P = 0.20).Malignant melanoma shows stronger immunohistochemical expression of COX-2 than benign melanocytic nevi. Although COX-2 cannot be used alone to differentiate MM from melanocytic nevi, it may serve as an aid in the differential diagnosis of melanocytic skin lesions.

An 11-year-old male Rough collie was submitted with paraparesis, but did not respond to medical treatment. Clinical signs worsened and the dog displayed paralysis, inability to stand and loss of voluntary bladder control, whereupon magnetic resonance imaging (MRI) was performed. No significant abnormalities were identified from MRI, blood tests, cerebrospinal fluid tests or radiography. After MRI, the dog developed dyspnoea and died. Autopsy and subsequent histopathological examination led to a diagnosis of degenerative myelopathy.

Intracellular mediators of exocytosis were investigated using isolated mouse pancreatic acini permeabilized with the bacterial toxin streptolysin O (SLO). Permeabilization was demonstrated by fluorescent staining with ethidium bromide and fluorescein diacetate and release of cytoplasmic lactate dehydrogenase. When SLO-permeabilized acini were incubated at 37 degrees C in Ca2(+)-EGTA buffers containing MgATP, amylase secretion was Ca2+ dependent with an EC50 of 0.40 microM Ca2+ and a maximally effective Ca2+ concentration of 1 microM. Maximal amylase secretion was 330% of that in Ca2(+)-free buffer (basal). The nonhydrolyzable GTP analogue guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S; 30 microM) increased the maximal secretion to 451% of basal in the presence of 1 microM Ca2+ and decreased the EC50 to 0.14 microM Ca2+. Removal of ATP plus addition of antimycin A and 2-deoxy-D-glucose inhibited Ca2(+)-dependent, GTP gamma S-enhanced amylase secretion by 56%. The phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA; 1 microM) also enhanced maximal secretion to 450% of basal and decreased the EC50 to 0.18 microM Ca2+. Enhancement of amylase secretion by submaximal concentrations of GTP gamma S or TPA was inhibited by the protein kinase C inhibitor staurosporine. These results suggest that Ca2+ stimulation of amylase secretion is potentiated by activation of protein kinase C. However, the enhancement of secretion by GTP gamma S and TPA was additive at their maximally effective concentrations, suggesting that another G protein(s) maybe involved in the terminal steps of exocytosis.

In only a very limited number of cultured cell lines, epidermal growth factor (EGF), a potent mitogen for many kinds of cells, was shown to activate STAT1 (signal transducer and activator of transcription 1) protein, which can transmit signals that cause cell growth arrest and apoptosis. The purpose of this work is to elucidate the physiologic and/or pathological significance of this EGF-STAT1 pathway.A series of cultured cell lines that had been established from surgical specimens of esophageal squamous cell carcinoma was studied for the existence of the EGF-STAT1 pathway. Normal esophageal squamous epithelial cells either explanted from non-neoplastic portions of surgically removed human esophageal tissue or in bovine esophageal epithelium in situ were examined as well.EGF treatment leads to a strong growth arrest in three of the 30 esophageal squamous cell carcinoma cell lines. STAT1 was found to be activated by EGF in the three cell lines but not in the others. EGF can also activate STAT1 in cultured normal esophageal squamous epithelial cells. STAT1 is at the activated state in the basal cell layer of the bovine esophageal epithelium. Notably, patients who had harbored the cancer cells with the EGF-STAT1 pathway had a dramatically better prognosis.The EGF-STAT1 pathway may be intrinsic to esophageal epithelial lineage of cells and is lost in a considerable fraction of the carcinomas. This loss appears to cause a significantly more malignant clinical course. These findings may point out a critical step in the progression of esophageal cancer and could lead to the development of useful clinical applications.

This case report describes a follow up investigation of a patient with impaired word discrimination due to mitochondrial encephalopathy with lactic acidosis and stroke-like syndrome (MELAS) using proton magnetic resonance spectroscopy ((1)H MRS) and auditory evoked magnetic fields (AEFs). The initial (1)H MRS showed no N-acetyl aspartate (NAA) and marked accumulation of lactate (Lac) in the stroke-like lesion of MELAS, which was silent in neural activity according to AEFs. The follow up investigations, however, demonstrated that NAA reappeared, that the formerly increased Lac signal was significantly reduced, and that the magnitude of AEFs of the lesion was markedly increased. Metabolic and functional changes in (1)H MRS and AEFs reflected the neurological recovery very well. The stroke-like lesion was shown, using AEFs and (1)H MRS, to be able to function properly, although brain tissue of the lesion initially had severe damage due to mitochondrial dysfunction.

We immunohistologically investigated 76 cases of primary colorectal cancer and 13 cases of adenoma to clarify the relationship of MHC class II expression with the grade of differentiation, the density of tumor-infiltrating lymphocytes, and the incidence of metastasis to lymph nodes. MHC class II expression was mostly negative in normal colonic epithelium. In contrast, 32 out of 76 cases (42%) of cancer and five out of 13 cases (38%) of adenoma were positive for MHC class II. MHC class II expression was higher in well-differentiated than in poorly differentiated adenocarcinoma. The density of infiltrating lymphocytes was higher in cancer than in the normal mucosa, and higher in MHC class II-positive tissues than in negative lesions. The incidences of lymphatic invasion and cancer metastasis to lymph nodes were definitely higher in MHC class II-negative cancers than in MHC class II-positive cancers. MHC class II was rarely expressed in metastatic cancer cells of lymph nodes. These results indicated that the loss of MHC class II is correlated with the incidence of metastasis to regional lymph nodes.

Fasting breath nitrous oxide (N2O) concentration was determined in relation to pH, nitrate (NO3-) and nitrite (NO2-) concentrations in gastric juice, and Helicobacter pylori infection in 86 successive patients. N2O was measured with an infrared-photoacoustic analyzer. NO3- and NO2- were measured using the Griess reaction. Fasting breath N2O concentration in controls (87 +/- 21 ppb) was not significantly different from that in patients with gastric ulcer or other gastric lesions. Breath N2O was significantly correlated with gastric NO3- (P0.01) and was higher in patients with elevated gastric NO2- (246 +/- 87 ppb) than in patients without NO2- (75 +/- 13 ppb). Breath N2O did not differ significantly between subjects who were positive or negative for H. pylori. In conclusion, fasting breath N2O concentration is in some manner related to intragastric NO3- and NO2- concentrations. The possible use of measuring breath N2O as predictors of cancer needs further research.

A 52-year-old man with a 4-year history of rheumatoid arthritis, and who had an episode of suspected BOOP in early 1994, was admitted to our hospital because of cough and fever. A chest X-ray film on admission showed small patchy infiltrates, and a computed tomographic (CT) scan showed centrilobular nodules and patchy infiltrates with thickened broncho-vascular bundles in both lungs. Transbronchial and thoracoscopic lung biopsies disclosed the coexistence of interstitial pneumonia with BOOP pattern, follicular bronchiolitis, and diffuse panbronchiolitis-like purulent and obliterative bronchiolitis. Due to findings of chronic sinusitis, the patient was treated with erythromycin for 8 weeks, and the abnormal CT shadows regressed. This was an interesting case of various pulmonary lesions associated with rheumatoid arthritis, and successfully treated with erythromycin.

The catalytic activity of type II phospholipase A2 (PLA2) in blood has been reported to increase in acute pancreatitis and to reflect the severity of pancreatitis. In this study, we evaluated the effects of a new inhibitor of type II PLA2, S5920/LY315920Na, on trypsin-taurocholate-induced pancreatitis in rats. Hemorrhagic pancreatitis was induced by an infusion of a mixture of trypsin and taurocholate into the pancreatic duct. S5920/LY315920Na was administered subcutaneously at 0 h and 3 h after the induction of pancreatitis. Survival rates for 24 h in rats treated with 0.1 and 1 mg/kg of S5920/LY315920Na were significantly higher than that in untreated rats (71 and 86% vs. 14%). Serum levels of amylase and lipase in rats treated with 1 mg/kg of S5920/LY315920Na were significantly lower than those in untreated rats (amylase, 6,903 vs. 32,516 U/L; and lipase, 514 vs. 6,710 U/L) at the time of death or 24 h after the induction of pancreatitis. Plasma levels of S5920/LY315920Na were enough to inhibit catalytic activity of PLA2 in plasma for 9 h. A new inhibitor of type II PLA2, S5920/LY315920Na, inhibited catalytic activity of PLA2 and improved the survival rate in experimental hemorrhagic pancreatitis in rats.

A 40-year-old man with glycogen storage disease type 1a (von Gierke disease, GSD1a) developed hepatocellular carcinoma (HCC). Cold single-strand conformation polymorphism (SSCP) with 12% glycerol identified the G727T mutation in the glucose-6-phosphatase (G6Pase) gene, which has been reported to be the most common mutation in Japanese GSD1a patients. This case report is the first documentation of HCC in a case with G727T mutation. Given the prevalence of HCC in GSD1a with various germline mutations, analysis is needed to confirm that the germline mutation in this case is really related to hepatocarcinogenesis. DNA analysis of the family pedigree of this case, revealed three individuals with GSD1a and seven heterozygous carriers of the G727T mutation. As the diagnosis of GSD1a in this family was made only after these three patients reached adulthood, DNA diagnosis may help early identification of GSD1a patients and prevention of the progression of the disease. This DNA-based diagnosis permits prenatal diagnosis in at-risk patients and may facilitate screening and counselling of patients clinically suspected of having this disease.

To clarify the clinicopathologic features of neuroendocrine carcinomas (NECs) of the stomach, we reviewed 56 cases of surgically treated gastric carcinomas with a solid growth or with areas containing patterns characteristic for neuroendocrine (NE) tumors.Of the 56 cases reviewed, we selected 33 cases of NEC based both on histologic patterns common to NE tumors and on histochemical/immunohistochemical results.The average age of patients with NEC was 69.8 years (range, 44-92 years). The majority of patients were men (male-female ratio, 23:10). The most frequently affected site was the upper third (46%) of the stomach. Grossly, 9 cases of NEC were fungating and 24 were ulcerated. As compared with 23 patients with non-NEC tumors, the patients with NECs had a worse prognosis. Histologically, NECs had a variety of histologic patterns, including solid, organoid, trabecular, pseudoglandular, spindle cell, and rosettelike. Based on both cell size and morphologic features, we subdivided NECs into 2 variants, namely, small cell NEC and large cell NEC. Our series included 12 cases of small cell NEC and 21 cases of large cell NEC.Compared with small cell NECs, large cell NECs had a higher mitotic count, larger polygonal cells, a lower nuclear-cytoplasmic ratio, coarser nuclear chromatin, and more frequent conspicuous nucleoli. Large cell NEC was an aggressive tumor with a very poor prognosis (median survival time, 15.2 months; 1-year survival rate, 58%), which approached that for small cell NEC.

A 45-year-old male presented with sudden onset of severe headache. Computed tomography and magnetic resonance imaging demonstrated an irregularly enhanced suprasellar mass with intratumoral and subarachnoid hemorrhage. The mass was removed in two operations. Histological examination of the tumor revealed pilocytic astrocytoma. The relatively rich vascularity and perivascular tumor cell proliferation observed in this benign lesion were probably the causes of this extremely rare association.

We describe a patient who presented with hypoxemia and diffuse bilateral pulmonary infiltrates. The diagnosis of eosinophilic pneumonia was confirmed by bronchoalveolar lavage and transbronchial lung biopsy. The remarkable characteristic was reappearance of the symptoms on the patient's return home, suggesting the existence of etiologic agents in his house. An environmental survey of the patient's house yielded Alternaria alternata. A high titer of anti-A. alternata antibody (IgG) was detected in his serum, and the inhalation bronchoprovocation test with A. alternata antigen was positive. This case indicates that A. alternata is a probable cause of eosinophilic pneumonia.

To improve the diagnostic accuracy of computed tomography (CT)-guided biopsy of small lung nodules.The usefulness of fine-needle core biopsy combined with immediate frozen-section diagnosis by pathologists was prospectively studied. Forty-six biopsies of small lung nodules (less than 3 cm in greatest diameter) were performed under CT guidance in 46 patients with 31 malignant and 15 benign processes. Initial biopsy was always attempted with a 20 or 21G histological needle; tissue samples were sent to the pathology department immediately after biopsy for pathologic diagnosis of the frozen sections.In 41 of 46 lesions (89.1%), sufficient material was obtained for diagnosis, permitting a correct final diagnosis. For malignancy, the sensitivity was 100%, whereas 81.8% of the benign lesions were diagnosed as specifically benign. Pneumothorax occurred in 41.3%.Histological diagnosis using frozen sections is a useful adjunct for CT-guided biopsy of the chest.

We resected 158 cases of hepatocellular carcinoma (HCC), including 20 (12.6%) cases of large HCC. These 20 cases were divided into group 1 (curative resection, n = 9) and group 2 (noncurative resection, n = 11). The clinicopathologic features and long-term survival of the cases were evaluated. In groups 1 and 2, portal vein invasion (Vp+) was noted in 44.4% and 63.3%, intrahepatic metastasis (IM+) in 77.8% and 100%, absence of a fibrous capsule (Fc-) in 55.6% and 63.6%, and stage III or IV in 77.8% and 100%, respectively. The DNA ploidy pattern was aneuploid in 44.4% of group 1 and 100% of group 2. In group 1, the 1-, 3-, and 5-year cumulative survival rates were 75%, 62.5%, and 62.5%, respectively (the longest survivor is alive after 11 years 1 month). Five cases survived more than 3 years in group 1, and all were Vp(-) and nonaneuploid. On the other hand, in group 2, the 1-year survival rate was only 33.3%; none survived more than 2 years. These results suggest that even patients with large HCC have a favorable long-term prognosis if their clinicopathologic factors are Vp(-) and nonaneuploid, and if curative resection can be performed.

A 75-year-old man had for many years taken the commercially sold medicine PABRON-S whenever he caught a cold. He caught a cold and took the drug six days before admission. When PABRON-S was not available, he took PABRON-GOLD and experienced dyspnea the next day. A roentgenogram at another hospital revealed bilateral diffuse lung shadows. He was referred to our hospital. A thoracic CT scan showed bilateral interstitial shadows. Bronchoalveolar lavage fluid contained inflammatory cells including neutrophils and lymphocytes. Examination of a transbronchial lung biopsy specimen showed infiltration of mononuclear cells into the thick alveolar wall and interstitum. A drug lymphocyte stimulation test with PABRON-GOLD was positive. Based on these findings, we believe that this patient had drug-induced pneumonitis caused by PABRON-GOLD. He was treated with a steroid hormone and his symptoms resolved immediately, the abnormal roentgenographic shadows remained longer.

We report four cases of acute pneumonitis due either to interferon, or a herbal drug, "Sho-saiko-to", or both in combination, in patients with chronic active hepatitis, focusing on its pathogenesis and response to prednisolone therapy. These cases shared common clinical features: fever, dry cough, dyspnoea, hypoxaemia, diffuse infiltrates both on chest radiography and chest computed tomography, restrictive pulmonary functional impairment, and alveolitis on examination of transbronchial lung biopsy, all of which suggest acute interstitial pneumonia. Furthermore, lymphocytosis was observed in association with the dominant CD8+ T-cell subset in bronchoalveolar lavage fluid. A lymphocyte stimulation test using peripheral blood was positive to interferon in one case and to Sho-saiko-to in another. All patients responded to oral prednisolone therapy. Peripheral soluble interleukin-2 receptor levels decreased in parallel with improvement in the clinical course. All patients were free of symptoms with a follow-up of 1-3 yrs. We conclude that interferon- and/or Sho-saiko-to-induced acute pneumonitis may be due to allergic-immunological mechanisms rather than toxicity, and that peripheral levels of soluble interleukin-2 receptor appear to be good markers of disease activity.

Fv-4 is a mouse gene that dominantly confers resistance to infection by ecotropic murine leukemia virus (MuLV). We demonstrated previously that the Fv-4 resistant (Fv-4r) gene product, Fv-4r env antigen, is released from Fv-4r-bearing BALB/c-Fv-4Wr (C4W) mouse-derived cells into serum in vivo and binds to cells expressing surface receptors for ecotropic MuLV, thereby protecting them from infection with Friend leukemia virus (FLV) by receptor interference. This unique resistance mechanism against retroviral infection might provide a possible therapeutic model system of human retroviral infection such as AIDS. To further investigate the Fv-4r gene action in vivo, we examined the distribution and character of Fv-4r env antigen in serum and systemic organs from C4W mice. The Fv-4r env antigen was immunohistochemically localized to the lympho-hematopoietic cells and exocrine glandular cells, such as those of the salivary gland and pancreas. Using immunoprecipitation followed by Western blotting, we determined two types of gp70-related Fv-4r env antigen in the serum of C4W mice, showing molecular weights of either 70-75 kDa and 80-85 kDa. When thymocytes from Fv-4 susceptible gene (Fv-4r)-bearing C3H mouse were mixed with C4W mouse serum, the 70-75k Da molecule of the C4W serum dominantly bound to C3H thymocytes and thus contributed to receptor interference function. Using immunoelectron microscopy, Fv-4r env antigen was mainly localized to the cell surface membrane of thymic lymphoid cells, while acinar cells of the salivary gland possessed Fv-4r env antigen in the endoplasmic reticulum (ER) as well as on the cell surface membrane. These data indicate that several glandular organs, as well as lymphohematopoietic organs of C4W mice, may contribute to the production of cell-free Fv-4r env antigen, resulting in protection of cells from infection with FLV by receptor interference.

A 74-year-old man presented with chest pain, dry cough, progressive respiratory distress and infiltrative lung shadow. Diagnosis of acute eosinophilic pneumonia was confirmed by histological examination as well as clinical features. On the 8th day post-admission, he developed progressive generalised muscle weakness that required mechanical ventilation. Clinical investigations revealed features concurring with the accepted diagnostic criteria for Guillain-Barré syndrome. Although precise aetiologies for the disorders suffered by this case were unknown, a common cause of allergic nature was speculated. This is the first report of acute eosinophilic pneumonia accompanied by Guillain-Barré syndrome.

A 73-year-old man had complained of painful swelling in the upper and lower extremities for several months before detection of small cell lung carcinoma. A bone scan showed abnormal symmetrical accumulations in the extremities, but periosteal proliferation was not demonstrated by X-ray. When a complete remission was obtained by chemoradiotherapy, the joint manifestation also subsided completely. In almost all reported cases, hypertrophic pulmonary osteoarthropathy was observed in all patients with non-small cell lung carcinoma. To our knowledge, this is the first case report of hypertrophic pulmonary osteoarthropathy associated with small cell lung carcinoma published in the English literature.

A 75-year-old man with multiple myeloma presented with fever and respiratory symptoms. A chest roentgenogram showed interstitial shadows and transbronchial lung biopsy revealed diffuse infiltration of amyloid in the alveolar walls. Analysis of bronchoalveolar lavage fluid showed the presence of an IgA-lambda paraprotein, and the IgA/albumin ratio was similar to that in serum. However, plasma cells could not be detected in the cells obtained by lavage. We know of no previous case in Japan in which bronchoalveolar lavage fluid was examined in a case of diffuse alveolar septal amyloidosis.

alpha 2-macroglobulin-trypsin complexlike substance (MTLS) was determined in plasma of pancreatic and nonpancreatic diseases using a two-step enzyme immunoassay to study the diagnostic and pathophysiological significance of MTLS. Plasma levels of MTLS in acute pancreatitis (mean +/- SD = 265.6 +/- 346.2 ng/ ml, n = 9), calcified chronic pancreatitis (128.6 +/- 257.4, n = 13), and noncalcified chronic pancreatitis (13.5 +/- 12.5, n = 10) were significantly higher than that in controls (3.6 +/- 1.8, n = 81). In other diseases such as gastric cancer, hepatoma, diabetes mellitus, and gallstones, MTLS values were not different from those of control. Plasma MTLS values showed low correlation with serum trypsin, elastase 1, pancreatic amylase, lipase, and pancreatic secretory trypsin inhibitor (PSTI). The elevation of plasma MTLS values in acute pancreatitis suggests that plasma MTLS levels reflect that protease is inappropriately activated in pancreatic acinar cell and released into the circulation and that the determination of MTLS can be useful for diagnosis and pathophysiology of acute pancreatitis and chronic pancreatitis.

A 70-year-old man with a 10-year history of seal engraving presented with exertional dyspnea and dry coughing. Chest roentgenograms showed an interstitial shadow and bilateral progressively enlarging bullae. Open lung biopsy led to the diagnosis of idiopathic interstitial pneumonia (Type B). The size of bullae usually does not change, so cases such as this are rare because the bullae continued to expand subacutely. Persistent stimulation by the inhaled A1 and Si may have played a role in the pathogenesis of this condition.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a novel hypothalamic peptide, structurally related to vasoactive intestinal peptide (VIP). Our previous study in conscious dogs revealed that PACAP stimulated exocrine pancreatic secretion in a manner different from VIP. The objectives of this study were to characterize the effects of PACAP on amylase secretion and intracellular cAMP production in guinea pig pancreatic acini and to compare them with those of VIP and secretin. PACAP38 and PACAP27 (10(-10)-10(-8)M) stimulated amylase secretion from pancreatic acini in a concentration-related manner. The order of potency for amylase secretion was PACAP27 = VIPPACAP38. The maximally stimulated amylase secretion by PACAP27 was not enhanced by VIP or secretin, but was synergistically increased by cholecystokinin and A23187. PACAP38 and PACAP27 (10(-2)-10(-7)M) increased intracellular cAMP levels in a concentration-related manner. The potency for cAMP production was PACAP38 = PACAP27 = VIP. These results suggest that PACAP38 and PACAP27, like VIP, directly stimulate amylase secretion from guinea pig pancreatic acini through alterations in cellular cAMP levels.

Bone marrow transplantation experiments were conducted in mice in order to develop an experimental bone marrow transplantation therapy model, with which to investigate possible means to cure retrovirus-infected hosts with bone marrow or stem cells from virus-resistant donors. In one experiment, lethally irradiated Friend leukemia virus (FLV)-sensitive C3H/He (C3H; Fv-2s, Fv-4s, Rfv-1s, Rfv-2s Rfv-3s) mice were transplanted with (i) bone marrow cells from FLV-resistant BALB/c-Fv-4Wr (C4W; Fv-2s, Fv-4r, Rfv-1s, Rfv-2s, Rfv-3s) mice (C4W --C3H) or (ii) a mixture of bone marrow cells from C4W and C3H mice (C4W + C3H --C3H). They were then inoculated with FLV 3-4 months later and leukemia development was examined. The results indicated that C4W --C3H chimeras were completely resistant to FLV-induced leukemogenesis and that C4W + C3H --C3H mixed chimeras that contained as low as 30% C4W-derived cells, or as high as 70% C3H-derived cells, did not develop leukemias. In another experiment, bone marrow cells from C57BL/6 (B6; Fv-2r, Fv-4s, Rfv-1r, Rfv-2r, Rfv-3r) or C4W donors were grated to FLV-sensitive DBA/2 mice (DBA; Fv-2s, Fv-4s, Rfv-1s, Rfv-2s, Rfv-3s) that had been infected with FLV 6 days earlier (DBA-FLV). The results indicated that most, if not all, FLV-infected DBA mice which received bone marrow transplantation from B6 donors developed B6-derived leukemias, although the survival time of these mice was dramatically prolonged as compared to that of untreated DBA-FLV mice. In contrast, bone marrow transplantation from Fv-4r-bearing C4W donors successfully rescued FLV-infected DBA mice from leukemic deaths. Thus, the bone marrow transplantation therapy against retroviral infection of hemopoietic cells was shown to be feasible, provided that donor cells carry a resistant allele that functions via receptor blockade as in the case of Fv-4r, but less effective when the roles of the resistant alleles partially interfered with the virus replication, leukemic transformation and/or cycling of target cells as suggested for Fv-2r gene action, or to resist virus infection by immunological means as are known for Rfv-1r, Rfv-2r and Rfv-3r genes which are also carried by B6-strain mice. Implication of these findings on the somatic gene therapy against retrovirus infection diseases in man are discussed.

An 82-year-old man was admitted for evaluation of dry cough and low grade fever. A chest roentgenogram obtained on admission revealed an abnormal mass shadow at the left hilus. Trans-bronchial lung biopsy was used to make a diagnosis of small cell lung cancer. This tumor regressed spontaneously.

Clinicopathological features of surgically-treated peripheral T1 adenocarcinoma of the lung were compared between 30 females and 26 males, and the following sex differences were observed; 1) Females were younger than males, 2) There was a higher percentage of smokers among males, 3) The acinar histologic subtype was less frequently found in females, 4) Well differentiated tumors were more frequently found in females, 5) K-ras gene mutations were observed only in males, 6) Prognosis was slightly better in females. As to other factors such as N-factor, tumor ploidy or central fibrosis, there was no statistical difference between the two groups. Although we were not able to explain the causes for the above sex differences, it was speculated that smoking was mainly responsible for them.

A 73-year-old man was admitted to Toyama Red Cross Hospital, because of productive cough and right flank pain. His chest X-ray film and computed tomography (CT) showed pleural effusion and a mass shadow in the right lung area. On CT vessels and bronchi were seen curving toward the mass (comet tail sign), suggesting rounded atelectasis. Transthoracic lung biopsy under CT and echo guidance revealed suppurative pleuritis. MRI also showed the comet tail sign. Moreover, in the lesion, curling hypointense lines were observed on various slices. We describe how MRI facilitates the diagnosis of rounded atelectasis.

We reported a rare case of mediastinal cystic lymphangioma, which happened to be discovered on chest X-ray. CT density level of the mediastinal tumor was 20 HU and the tumor was homogeneous cystic lesion. Multilocularity of the cyst and the relationship to the adjacent inferior vena cava were clarified by pre-operative transesophageal and intraoperative ultrasonographic examination, and the tumor was successfully excised without mishap.

An atypical case of splenic lymphoma is presented. A large cystic mass lesion in the splenic area was found in an 80-year-old man. He was involved in a traffic accident, and subsequently the cyst ruptured. The histological diagnosis of malignant lymphoma was made at emergency splenectomy. No other lesions were identified, and there were no signs of tumor recurrence four months after the operation.

Nebulisation chemotherapy, a chemotherapeutic method for the treatment of lung cancer that involves the administration of anticancer agents through the inhalation of nebulised aerosols, has been found to be highly effective (Tatsumura et al., 1983a,b). We confirmed that 5-FU administered by this method accumulates in the trachea, bronchi and regional lymph nodes of patients treated before surgery, along with 5-FU metabolites, FUR and FUdR, indicating that 5-FU is directly incorporated and metabolised in the respiratory tract. Parallel result were obtained using mongrel dogs. The 5-FU levels in other organs, such as the heart and liver, were found to be extremely low. Only a trace of 5-FU was found in the serum of both the patients and the dogs. We further investigated the anti-tumour effect of this therapy in ten selected patients and observed a satisfactory anti-tumour response of 60.0%. These results, along with our previous finding that the retention time of isotope tracers inhaled as aerosol is considerably longer in tumour tissues than in normal parts (Tatsumura et al., 1983a) explain the high antitumour action of this therapy and the absence of adverse effects of administered 5-FU. Images Figure 1

Fifteen cases of small-size rectal carcinoid tumors (RCTs) were discovered among a total of 21,522 healthy teachers who received proctosigmoidoscopy. Adding another case seen in the outpatients, a total of 16 RCTs were clinicopathologically studied. The average age of the patients was 48.8 yr, and the incidence was predominantly among males. Prior to endoscopy, digital examination of the rectum revealed a palpable firm nodule in 13 patients. On endoscopy, RCTs were generally round, yellow-discolored polyps with a size less than 13 mm in diameter, covered by a normal-appearing mucosa. An erythematous change or depression was seen in three tumors. Histologically, they showed pure insular, trabecular, or mixed structures, and tumor cells were confined to the mucosa and/or submucosa in all cases. Immunohistochemically, RCTs never failed to show focal or diffuse positivities for chromogranin A and/or neuron-specific enolase. Pancreatic polypeptide was immunostained in 14 tumors to a varying degree. The tumors having been safely treated by endoscopic polypectomy and/or surgical excision, all of the patients are alive and clinically free of disease during the average observation period of 79 months.

A pulmonary tumorous shadow appeared and enlarged in a 25 years-old male patient undergoing intensive chemotherapy for tuberculosis. The chest X-rays taken on admission revealed effused pleura in the right lung and nodular shadows in the upper area of the right lung. After 40 days of using isoniazid (INH), rifampicin (RFP) and streptomycin (SM), a homogeneous opacity, not previously observed, appeared in the middle area of the right lung (S5). Microscopic examination of the tissues obtained during a transbronchial lung biopsy disclosed epithelioid cell granulomas with marked eosinophilic infiltration. The presence of eosinophilic infiltration due to the admission of antituberculosis agents was disregarded because no change was observed in the new granulomatous shadows during the drug challenge tests and the lymphocyte stimulation test to INH, RFP and SM was negative. Transient aggravation during the initial phase of chemotherapy for pulmonary tuberculosis, such as in this case, is suspected cause by some eosinophilic allergic-induced mechanisms, against bacillary components.

To clarify the clinical and histological features of polyps in the duodenal bulb (DB), we studied, clinicopathologically, a total of 263 patients (179 male, 84 female) with polyps in the DB. The patients were 13-86 yr of age (average age, 57.1 yr). On endoscopy, a semipedunculated or pedunculated polyp with a relatively large size was seen in 33 patients, and small polyps, either single or multiple, were incidentally discovered in 230 patients. Histological examination of the biopsied specimens from polyps revealed gastric tissue in 182 cases (69.2%), cyst formation in 51 (19.4%), and other miscellaneous lesions (tubular adenoma, Brunner's gland hyperplasia, etc.) in 30 (11.4%). With regard to the gastric tissue, a "full-thickness" or "incomplete" body-type mucosa was identified in 27 cases of polyps, and hyperplastic surface epithelium was recognized in 155. Forty cases of hyperplastic surface epithelium-type polyps were subclassified as "pyloric"-type mucosa, because pyloric gland-like components seen under the surface epithelium were identical to those of the gastric antrum. It was reconfirmed that small polyps with little or no clinical significance could be produced by various histological features.

Inhibitory effect of loxiglumide (D,L-4-(3, 4-dichlorobenzoylamino)-5-(N-3-methoxypropyl-pentylamino)-5- oxo-pentanoic acid, CAS 107097-80-3) on exocrine pancreatic secretion was compared between intraduodenal and intravenous administration. Doubling doses of intravenous cholecystokinin octapeptide (CCK-8) resulted in a dose-dependent increase of pancreatic secretion from 50 to 400 ng/kg/h. Both intraduodenal and intravenous loxiglumide of 5 and 10 mg/kg/h produced a dose-dependent inhibition of the pancreatic protein secretion to all doses of CCK-8. Cumulative increment of pancreatic protein output was inhibited by 79% and 77% at 10 mg/kg/h of intraduodenal and intravenous loxiglumide, respectively. Extents of the inhibition were similar to each other between the two routes of loxiglumide infusion. However, plasma levels of loxiglumide after intraduodenal administration were about half of those observed after intravenous administration of the corresponding dose, although plasma CCK levels were not different. Intraduodenal loxiglumide is as effective as intravenous loxiglumide in inhibitory potency on pancreatic secretion. Therefore, possible therapeutic indications of oral loxiglumide could be expected.

A 77-year-old man was scheduled for Love's method to correct lumbar disc herniation. He had fracture of maxilla and mandibula during World War II. Physical examination and laboratory data revealed no abnormalities. Anesthesia was induced with oxygen, nitrous oxide and halothane. Following administration of succinylcholine, an attempt was made to insert a tracheal tube (from 8.5mm to 5.5mm), but the tubes were met with an obstruction. The operation was cancelled because tumor-like nodules were seen in the trachea. Diagnosis of tracheobronchopathia osteoplastica was made afterwards following biopsy. The patient with this disease has a good prognosis. Artificial ventilation can be performed safely by choosing an appropriate method for airway maintenance.

Myelography was performed in 12 patients with juvenile muscular atrophy of unilateral upper extremity. Seven patients showed anterior shift of lower cervical dural canal in flexion (tight dural canal in flexion) (T group), however the other 5 patients did not show "tight dural canal in flexion" (NT group). Onset of illness and sex were not different between 2 groups. However, there was a tendency that the neurological signs and symptoms were more severe in the patients of T group than those of NT group. These results suggest that "right dural canal in flexion" can be one of mechanisms which exhibit the clinical symptoms of the juvenile muscular atrophy of unilateral upper extremity. However, there may be other etiological factors in the juvenile muscular atrophy of unilateral upper extremity.

Glycine receptor (GlyR) was expressed in Xenopus oocytes by injecting rat brain mRNA. Glycine (Gly)-elicited responses in the oocyte were measured by the voltage-clamping method. The following measurements were made to establish the relationship between Gly concentration and the current: 1) Gly-induced membrane current before desensitization, 2) Gly-induced membrane current after desensitization equilibrium, 3) fraction of the active form of the receptor after desensitization equilibrium, 4) rate of recovery of the desensitized receptors upon removal of Gly. These results were analyzed on the basis of the minimal model proposed for nicotinic acetylcholine and gamma-aminobutyric acid A receptor. The equilibrium and rate constants of the model were evaluated for GlyR. The effects of procaine and 13-L-hydroperoxylinoleic acid (LOOH) on GlyR were examined electrophysiologically. LOOH noncompetitively inhibited the receptor with the inhibition constant of 27 microM, while 1 mM procaine, a local anesthetic, did not inhibit GlyR at all.

Of 17 cases of small cell carcinoma of the stomach, three were early and 14 were advanced. Grossly, the tumors were mostly polypoid at the early stage, and as they advanced, deep ulcerations developed. Histologically, only one tumor was "oat cell type," and the other 16 were "intermediate cell type." With regard to tumor components, five were "pure" tumor, and 12 were "composite" admixing glandular and/or squamous differentiation. Argyrophil cells were seen in eight tumors. Immunohistochemically positive cells for chromogranin, neuron-specific enolase, and keratin were seen in 12, 10, and 7 tumors, respectively. Carcinoembryonic antigen was negative in the small cell component of most tumors as opposed to strong positivity in the glandular component. Electron-dense core granules were evident in seven of nine tumors examined. These findings suggest that histologic variety is quite characteristic of the small cell carcinomas of the stomach, and this type of carcinoma takes an aggressive clinical course like its counterparts in other organs.

A 65-year-old man was admitted to our hospital complaining of productive cough, dyspnea and stridor. Chest X-ray disclosed overinflation with micronodular infiltrates. Blood examination showed mild eosinophilia and IgE elevation. Pulmonary function test disclosed severe airway obstruction and diffusion capacity impairment. Although clinical improvement was achieved after bronchodilator therapy, laboratory abnormalities continued. Open lung biopsy demonstrated mononuclear cellular and eosinophilic infiltration at alveolar lumen and vessel walls without prominent fibrosis, which was compatible for prolonged eosinophilic pneumonia. From above findings, this case was thought as a prolonged eosinophilic pneumonia combined with pulmonary emphysema and bronchial asthma.