Endosonographic features of Brunner's gland hamartomas which were subsequently resected endoscopically.

BACKGROUND AND STUDY AIMS: Brunner's gland hamartomas are uncommon duodenal submucosal tumors. We aim to describe their morphological characteristics, with particular attention to the endosonographic features. PATIENTS AND METHODS: We reviewed the radiological, endoscopic, endosonographic, and histological findings from six Brunner's gland hamartomas which were completely removed by endoscopic resection. RESULTS: The lesions appeared as broad-based, sessile, or pedunculated submucosal tumors, measuring 0.7 to 2 cm in maximal diameter. Three lesions contained tiny dimple-like depressions on the surface; in one lesion these were only recognized following the use of an endoscopic dye-spraying technique. All the lesions could be safely removed by endoscopic resection after endosonographic confirmation of the layer origin within the submucosa. The internal echo structure of the tumors appeared to be solid echogenic in two, simple cystic in two, and multicystic in the remaining two lesions. In three lesions with an indistinct boundary, some stromal proliferation and solid Brunner's glands were recognized in an area extending from the mucosa to the submucosa. These endosonographic features corresponded to histological findings comprising stromal proliferation and various degrees of solid and cystic glandular Brunner's glands. CONCLUSIONS: Brunner's gland hamartoma is characterized endosonographically by a heterogeneous solid and/or cystic mass within the submucosa.

Long-term follow-up of interferon-treated chronic hepatitis C and serum hepatic fibrosis markers.

BACKGROUND/AIMS: We investigated the clinical application of serum fibrosis markers in a long-term follow-up of patients with chronic hepatitis C treated with interferon-alpha. METHODOLOGY: This study included 52 patients treated with interferon-alpha (total: 480 MU) for 6 months. They each underwent liver biopsy before and after treatment. Twenty-eight patients who underwent liver biopsy less than 2 years after treatment were classified as group 1, and 24 patients as group 2. The two groups were subdivided into HCV RNA-negative responders and HCV RNA-positive nonresponders. Liver specimens were estimated using grading and staging scores. Serum hyaluronan, PIIIP, and type IV collagen levels were measured before and after treatment. RESULTS: In the responders of groups 1 and 2, grading score after treatment was significantly decreased compared with that before treatment. Staging score after treatment was significantly improved only in the responders of group 2. In the responders of group 2, serum hyaluronan level was significantly decreased compared with that before treatment. In group 2, the grading score was significantly correlated with serum PIIIP and type IV collagen levels, and the staging score was significantly correlated with only serum hyaluronan level. CONCLUSIONS: These findings indicate that the serum PIIIP and type IV collagen levels reflect the activity, and serum hyaluronan reflects the degree of fibrosis in liver specimens of HCV RNA-negative patients in a long-term follow-up of patients after interferon-alpha treatment.

[A case of bilateral synchronous renal cell carcinoma treated with left partial nephrectomy and laparoscopic right nephrectomy].

We describe a case of bilateral synchronous renal cell carcinoma. A 70-year-old female was admitted to our department because of further examination for bilateral renal masses. Computed tomographic scanning and ultrasound examinations revealed bilateral solid enhanced renal masses, and bilateral renal cell carcinomas were suspected. First, partial left nephrectomy was performed. On the 21th day after the first operation, we confirmed the recovery of the left kidney, and performed right nephrectomy laparoscopically. The histopathological diagnosis revealed bilateral renal cell carcinomas. The patient is alive with no metastatic lesions and no recurrence at 16 months after the operations.

An evaluation of Bosniak's radiological classification of cystic renal masses.

OBJECTIVE: To determine the clinical usefulness of Bosniak's classification of cystic renal masses, the differentiation of which remains difficult despite significant advances in diagnostic imaging. PATIENTS AND METHODS: The computed tomography (CT) findings of all histopathologically examined cystic renal masses diagnosed at our institution were analysed retrospectively; 35 patients with cystic renal masses were treated between 1986 and 1998. Tissues surgically removed were examined pathologically and the final diagnosis compared with the preoperative CT category of Bosniak's classification. RESULTS: The histopathological examined showed cystic renal cell carcinoma in 21 patients, a benign renal cyst in 12, haemangiosarcoma in one and transitional cell carcinoma in one. Most of the 35 masses (26, 74%) were found incidentally during evaluation for an unrelated disease or a routine health check. All 11 masses of Bosniak category I were benign and one category II mass was malignant. All 10 masses of category III and 12 of category IV were malignant. CONCLUSIONS: Bosniak's classification is useful for differentiating category I, III and IV cystic renal masses. There were too few samples to allow meaningful conclusions to be drawn for category II renal masses. It is critical to differentiate between complicated cysts of category II and III because of the major implications for prognosis and clinical management.

[Subcutaneous sarcoidosis of the extremities].

A 65-year-old man was referred to our hospital due to abnormal chest roentgenograms showing bilateral hilar enlargement with diffuse micronodular opacities. He presented with uveitis and elevated serum ACE and tested negative for tuberculin response. Transbronchial lung biopsies as well as bronchoalveolar lavage were performed and yielded a diagnosis of sarcoidosis. Several months later, the patient showed multiple subcutaneous nodules around the knee joints and elbow joints with exacerbation of intrapulmonary lesions. A skin biopsy revealed multiple foci of typical non-caseating epithelioid cell granulomata. These pulmonary and subcutaneous lesions rapidly resolved in response to the systemic administration of corticosteroids. Subcutaneous sarcoidosis may be a subacute variant of sarcoidosis associated with systemic involvement.

Integrin alpha6beta1 plays a significant role in the attachment of hepatoma cells to laminin.

BACKGROUND/AIMS: Tumor invasion and metastasis consist of a series of complex events. During this process, the ability of tumor cells to adhere to laminin, a major component of basement membranes, is required at various steps. The expression of laminin-binding integrins and the extent of tumor metastasis and progression appear to be related. In hepatocellular carcinoma, increased expression of laminin-binding integrins is observed. However, little is known concerning the possible functional interactions between laminin-binding integrins and laminin. Therefore, we investigated the participation of laminin-binding integrins in the attachment of hepatoma cells to laminin. METHODS: Human hepatoma cell lines (KIM-1, KYN-1, 2) were used. We investigated the expression of integrin alpha1, alpha2, alpha3, alpha6, beta1, and beta4 subunits on hepatoma cells by immunocytochemical and flow cytometric analysis. Participation of these integrin subunits in the attachment of hepatoma cells to laminin was evaluated by an inhibition of cell adhesion assay. RESULTS: Integrin alpha1, alpha2, alpha3, alpha6 and beta1 subunits were expressed at the marginal areas of hepatoma cells, while the integrin beta4 subunit was scarcely detected. Laminin promoted the attachment of hepatoma cells in a dose-dependent manner. Although anti-integrin alpha1, alpha2, beta3 and beta4 subunit antibodies did not inhibit cell attachment to laminin, anti-integrin alpha6 and beta1 subunit antibodies inhibited the attachment by 50% or more. CONCLUSIONS: These findings indicate that integrin alpha6beta1 is very important in the attachment of hepatoma cells to laminin, suggesting the participation of this integrin in metastasis and invasion of hepatoma cells.

[Change in prevalence of allergic diseases in primary school children in Fukuoka City for the last fifteen years].

We have been investigating the yearly change of prevalence rate of childhood allergic diseases using same method and in same region in five primary schools in Fukuoka City for the last fifteen years. From 1981 to 1995, revised ATS-DLD questionnaire had been administered yearly to the first graders of primary school children (6-7 yrs). The total number of subjects for fifteen years were 8000. The average number of children in each year was 533. 1. The cumulative prevalence of bronchial asthma statistically increased from 5.7% (average of 1981 to 1983) to 7.7% (1993 to 1995). It was 1.7 times higher on boys. 2. The cumulative prevalence of atopic dermatitis did not change yearly and its average was 36.3%. The boys/girls ratio was 1.2. Remission rate of atopic dermatitis statistically increased from 14.3% (average of 1987 and 1988) to 19.6% (1994 and 1995). 3. The cumulative prevalence of allergic rhinitis did not change yearly and its average was 17.6%. It was 1.5 times higher on boys. 4. The cumulative prevalence of allergic conjunctivitis statistically increased from 8.4% (average of 1987 and 1988) to 11.1% (1994 and 1995).

[Long-term effects of bicycle-ergometry training on exercise endurance and dyspnea in patients with chronic pulmonary emphysema].

Exercise reconditioning has long been considered an essential component of the pulmonary rehabilitation regime. To investigate the long-term effects of exercise training on exercise endurance and dyspnea in patients with chronic pulmonary emphysema (CPE), we developed a supervised exercise program using bicycle ergometers. Nineteen patients (mean age: 67) with moderate to severe airflow limitation (average FEV1/FVC, 39.8%) were enrolled in a predominantly outpatient rehabilitation program. After their lactate thresholds were measured by an incremental symptom-limited maximum test, patients engaged in exercise training 15 to 30 minutes per day in an arbitrary frequency and at a work rate at or below their lactate threshold (average: 20.1 w). No significant improvements were observed in resting pulmonary function, blood gas, nutrition, or systemic muscle volume. After long-term exercise training (average period: 33 months; average frequency: 6.5 times per month, individually), the patients demonstrated significantly improved exercise endurance and relief of their dyspnea during exercise. These findings provide a physiologic rationale for long-term exercise training by patients with CPE.

Analysis of environmental carcinogens associated with the incidence of lung cancer.

It is presumed that carcinogens present in human lungs contribute to the incidence of lung cancer. Most of the carcinogens are inhaled in lung alveoli with particulate matter through the respiratory tract. On the basis of chemical analysis of 256 lung specimens with carcinomas resected in the period 1991 1996, the concentration of 1-nitropyrene (1-NP) was 19.7+/-10.5 pg/g of dry weight, and that of the dinitropyrenes (DNP) was 3.50+/-0.14-6.26+/-1.76. In addition, 2-nitrofluoranthene (NF) and 3-NF were detected at a higher level of 38.6+/-17.2 and 39.1+/-14.2, respectively, pg/g of dry weight. Concentrations of benzo[a]pyrene, benzo[e]pyrene, benzo[k]fluoranthene and benzo[ghi]perylene in 37 specimens collected in the period 1991 1996, were in the range of 138+/-82-399+/-220 pg/g of dry weight. No difference was found in the concentration of chemicals deposited in lung specimens from patients with lung cancer and tuberculosis as a control. By following the prognosis of 112 patients with carcinomas, we found that the deposition of 1-NP, 1,3-DNP, and 3-NF in lung tissues influenced their 5-year-survival after determination of chemicals. Lung specimens were divided into two groups of higher and lower chemical concentrations at the levels of 18 pg/g for 1-NP, 15 for 1,3-DNP, and 35 for 3-NF, and the findings were statistically analyzed by adjusting for age, gender, smoking status and cell type. The 5-year-survival of patients was markedly lower in the higher concentration group than the lower group.

Biological monitoring of metabolites of sarin and its by-products in human urine samples.

More than 20,000 passengers of Tokyo underground trains were intoxicated with warfare toxic chemicals. Most of the patients examined had marked miosis and decreased serum cholinesterase activity. Transient increase of serum CPK activity after 3 days of the exposure was the another sign. We intensively analyzed the metabolites in the urine of 4 patients. The following analytic results indicated the exposure to sarin as well as contaminated compounds such as diisopropyl methylphosphonate (DIMP), ethyl methylphosphonate fluoridate (EMPF, or ethylsarin), diethyl methylphosphonate (DEMP), and ethyl isopropyl methylphosphonate (EIMP). (1) Isopropanol (IPA) and ethanol (EtOH) were detected of large quantities in the urine samples, and were thought to be derived from sarin and the sarin counterpart, EMPF, DIMP, DEMP and EIMP. (2) Monoalkyl methylphosphonic acids (isopropyl methylphosphonic acid (IMPA) and ethyl methylphosphonic acid (EMPA) also were excreted in large amounts with taking the similar excretion pattern of IPA and EtOH. (3) The metabolite only derived from sarin and ethylsarin is F anions whose integral output in the urine was less than the equimolar level of the excreted (IMPA + EMPA + IPA + EtOH). (4) Other corroborative findings were low lethality: of more than 5,510 patients treated, 11 were acutely dead. (5) Nine exposed males had higher sister chromatid exchange (SCE) rate (5.00 +/- 1.48/cell) than the control (3.81 +/- 0.697/cell), because dialkyl methylphosphonates seemed to have alkylating activity and producing DNA adducts. The SCE rate also increased after the in vitro exposure of lymphocytes to dialkyl methylphosphonates.

[Sarcoidosis presenting as a diffuse micronodular shadow on a chest radiograph].

A 36-year-old man was admitted to our hospital with chest-radiographic findings of diffuse ground-glass shadows in both lungs. A chest CT scan revealed disseminated micronodules with mediastinal lymphadenopathy. Histological examination of a transbronchial lung-biopsy specimen showed non-caseous epithelioid cell granulomata. Marked lymphocytosis and an abnormally high CD 4/CD 8 ratio was found in bronchoalveolar lavage fluid. These findings suggested a diagnosis of sarcoidosis despite the atypical radiographic findings.

A second p53-related protein, p73L, with high homology to p73.

The p53 protein, which regulates the rate of cell division and death, is the most frequently mutated tumor suppressor to be identified so far in human cancers. Recently, a gene with significant homology to p53, termed p73, has been identified in a chromosomal region that is implicated in the molecular pathogenesis of neuroblastoma. We have cloned a second human p53-related gene, termed p73L, which shows strong amino-acid similarity to p73. The p73L gene is mapped to human chromosome 3q27-28 using in situ hybridization technique. p73L encodes a protein of 586 amino acids and its putative DNA binding domain (DBD) has high identities to those of p53 (60.6%) and to p73 (87.8%). Northern blot analysis, which demonstrated that the expression profiles of p73L and p73 mRNAs are distinct in some tissues, implies that p73 and p73L may have separate, distinct roles in different tissues.

[Cough variant asthma among patients with chronic persistent cough and its clinical outcome].

Thirty-nine patients with chronic persistent cough continuing more than eight weeks were examined regarding to their airway responsiveness to methacholine challenge using the Astograph (TCK-6100H, Chest Corp. Japan). Of these, twenty-three individuals (59%) had airway hyperresponsiveness, leading to diagnose as having cough variant asthma (CVA). Patients with CVA had a higher percentage of eosinophils in peripheral blood and a lower forced expiratory volume in one second than those in non-CVA group. Furthermore, four patients (17%) developed the classic signs and symptoms of asthma, whereas 7 cases (30%) resolved their cough without further treatment and 12 cases (52%) continued to have CVA. These data suggested that a significant proportion of patients with chronic persistent cough had CVA and some of them may develop to classic wheezing asthma.

Urinalysis of body packers in Japan.

Urinalysis was performed on nine body packers/smugglers who were referred to the emergency room of a hospital near the New Tokyo International Airport between September 1994 and February 1996. This analysis had rarely been used on suspected body packers in Japan. Only one of the nine body packers was a female. Foreign bodies were detected in the gastrointestinal tracts of the body packers by plain x-ray photography or computerized tomography, and the suspected drugs were cocaine (five cases), heroin (two cases), opiate (one case), and marijuana (one case). The results of urinalysis and confessions of the smugglers corresponded well for the latter three drugs (four cases). In two of the suspicious cocaine cases, opiates were detected along with cocaine by urinalysis, and the metabolites were confirmed by gas chromatography-mass spectrometry. The urinary screening tests of another two suspicious cocaine cases were negative. Opiates (morphine and codeine), but no cocaine metabolites, were detected in the urine of the subject who confessed to smuggling in cocaine only. It may be inferred from these results that urinalysis on body packers is beneficial to both the patient (body packer) and the physician in preventing the disastrous outcome of drug intoxication. It can also be concluded that there is a need for the prompt establishment of a protocol that includes urinalysis upon admission to the hospital for the management of body packers in Japan.

Inhibitory effect of OPC-15161, a component of fungus Thielavia minor, on proliferation and extracellular matrix production of rat cultured hepatic stellate cells.

A component of fungus Thielavia minor, OPC-15161, has been shown to inhibit the proliferation and extracellular matrix production of extracellular matrix-producing mesangial cells in the kidney in vivo. In this study, we examined the effects of OPC-15161 on the proliferation and extracellular matrix production of rat cultured hepatic stellate cells (HSCs). To determine the effect of OPC-15161 on proliferation of HSCs, the cell number and the uptake of [3H]thymidine were investigated in the presence and absence of interleukin-1beta (IL-1beta). IL-1beta significantly increased the uptake of [3H]thymidine in the HSCs, and the addition of OPC-15161 inhibited the uptake in a dose-dependent manner. The cell number of HSCs was also increased by IL-1beta, which was inhibited by OPC-15161. Production of extracellular matrix by OPC-15161 was studied by the production of [3H]-hydroxyproline in the presence and absence of transforming growth factor-beta1 (TGF-beta1). TGF-beta1 significantly increased the production of [3H]-hydroxyproline in the cells, whereas the addition of OPC-15161 inhibited this effect dose dependently. We also investigated the effects of OPC-15161 on Ca2+ mobilization and measured D-myo-inositol 1,4,5-triphosphate (IP3) in the HSCs. IL-1beta induced the increase of intracellular Ca2+ and IP3 concentrations in the HSCs, which were decreased by OPC-15161. Based on these results, we conclude that OPC-1 5161 inhibited the proliferation and production of hydroxyproline in cultured rat HSCs, and thus, it may have a role in prevention of liver fibrosis in vivo.

The significance of colocalization of plasminogen activator inhibitor-1 and vitronectin in hepatic fibrosis.

BACKGROUND: We examined the relationships among vitronectin (VN), plasminogen activator inhibitor-1 (PAI-1), and transforming growth factor beta 1 (TGF-beta 1) in liver diseases to evaluate the presence of plasmin cascade in human hepatic fibrosis. METHODS: Blood and liver tissues were obtained from 57 patients with liver disease. Plasma VN, PAI-1 antigen, and PAI-1 activity levels were evaluated. Biopsied liver specimens were observed by light and electron microscopy after immunohistochemical staining. Morphometric analysis was performed on these specimens. RESULTS: Plasma VN and PAI-1 activity levels decreased significantly with the progression of hepatic fibrosis and were particularly marked in the liver cirrhosis group. Plasma PAI-1 antigen level increased significantly. The immunolocalization of the active form of TGF-beta became more intense with the progression of hepatic fibrosis, whereas that of the dual-stained positive areas of PAI-1 and VN (PAI-1.VN) decreased. There was a positive correlation between TGF-beta and PAI-1, whereas there was a negative correlation between TGF-beta and PAI-1.VN. Immunoelectron microscopy showed the localization of PAI-1-VN in the extracellular space around the sinusoidal cells or surface of aggregating platelets, TGF-beta mainly in Ito cells, and VN in hepatocytes near the focal necrotic area or fibrous septa. CONCLUSIONS: These findings suggest that VN and PAI-1 are related to the active form of TGF-beta and that it is possible that the plasmin cascade is present in the human liver.

Basic fibroblast growth factor regulates proliferation and motility of human hepatoma cells by an autocrine mechanism.

BACKGROUND/AIMS: Basic fibroblast growth factor has mitogenic and angiogenic properties. In this study, we aimed to evaluate the role of fibroblast growth factor in the development and progression of human hepatocellular carcinoma. METHODS: The expression of basic fibroblast growth factor, fibroblast growth factor receptor-1, and a receptor isoform was investigated by in situ hybridization, immunohistochemistry, reverse transcription-polymerase chain reaction, Western blot analysis and confocal laser-scanning microscopy. The influence of exogenous basic fibroblast growth factor on DNA synthesis and motility of human hepatoma cells were also evaluated. RESULTS: Basic fibroblast growth factor and fibroblast growth factor receptor-1 messenger RNAs were present mainly in tumor cells and less so in hepatocytes from noncancerous liver tissue. Immunoreactive products of basic fibroblast growth factor and fibroblast growth factor receptor-1 were observed in tumor cells. The isoform IIIc was expressed in hepatocellular carcinoma tissue and hepatoma cell lines. Exogenous basic fibroblast growth factor stimulated DNA synthesis and motility of hepatoma cells. The effect was more marked in poorly-differentiated hepatoma cells than in well-differentiated hepatoma cells. Fibroblast growth factor-1 expression on hepatoma cells was also more marked in poorly-differentiated hepatoma cells than in well-differentiated hepatoma cells. The stimulated motility on basic fibroblast growth factor was suppressed by an anti-fibroblast growth factor receptor-1 antibody. CONCLUSIONS: Basic fibroblast growth factor may play an important role in the development and progression of hepatocellular carcinoma via an autocrine mechanism involving fibroblast growth factor and its receptor.