Systemic chemotherapy using cisplatin plus 5-fluorouracil for inoperable gallbladder cancer

We report a case of advanced gallbladder cancer in a 37-year-old man who presented in June 1993 with malignant obstructive jaundice. After percutaneous transhepatic biliary drainage and several diagnostic imaging examinations, the patient underwent laparotomy under a diagnosis of extremely advanced gallbladder cancer involving the confluence of the hepatic ducts. The tumor, however, was judged to be unresectable because of its massive spread into the liver along Glisson's sheath, and because of histologically proven peritoneal dissemination. After exploratory laparotomy, one course of anticancer chemotherapy (cisplatin, 100 mg/body IV, on day 1, and 5-fluorouracil, 1000 mg/body, on days 1–5, by continuous infusion) was administered and the completely obstructed hepatic duct was dramatically re-canalized. Four courses of chemotherapy were administered over a 16-month period until jaundice recurred. For these 16 months, the patient's quality of life was well maintained without biliary drainage. He died of increased peritoneal dissemination approximately 2 years after the first course of anticancer chemotherapy.     

Changes in the volume and histology of retractile testes in prepubertal boys

Testicular development was studied in prepubertal boys with retractile testes. Testicular volume, the diameter of the seminiferous tubules and the number of spermatogonia in the tubules were decreased in cases of unilateral retractile testis, when compared with values for the contralateral normally descended testis. On the other hand, in patients with a unilateral retractile testis and contralateral inguinal testis, there was no difference in the developmental parameters between the two testes. These results suggest that the retractile testis has developmental failures characteristic of a cryptorchid testis and therefore requires orchiopexy.     

Effect of myasthenic IgG on degradation of junctional acetylcholine receptor

We investigated the effect of the lgG from patients with myasthenia gravis (MG) on the degradation of normal rat junctional acetylcholine receptor (AChR) labeled with ¹²⁵l-α-bungarotoxin (BuTx) and calculated the degradation rate (DR). The DR for the lgG from these patients was significantly higher than that from healthy volunteers and patients with other autoimmune diseases. For MG, DR was significantly correlated with the severity of the disease but not with anti-AChR antibody titer. DR was accelerated by lgG from patients with generalized MG whose antibody titers were in the normal range and by lgG from patients with ocular MG. These results indicate that measurement of the DR of junctional AChR in normal rats is more closely correlated with the severity of the disease than is measurement of anti-AChR antibody and that the former is a sensitive and confirmatory method for evaluating MG. © 1993 John Wiley & Sons, Inc.     

Small round and spindle cell sarcoma with neuronal differentiation and oncocyte-like features of the thoracic wall: A case report with histological,immunohistochemical and ultrastructural examinations

A case of small round and spindle cell sarcoma with neuronal differentiation and oncocyte-like features is presented. The tumor was encountered in a 32 year old Japanese woman with an initial presentation of palpable tumor in the left lateral region of the thorax. The resected tumor was a partially well encapsulated whitish medullary one and consisted of small round and spindle tumor cells, together with so-called rhabdoid cells in the small round cell area. Although pseudorosettes were often observed, true rosette formation could not be detected anywhere. Ultrastructurally, despite a histologic variety of tumor cells, most tumor cells possessed numerous mitochondria, some of which occasionally contained abnormal filamentous or crystalloid structures. Various amounts of microfilaments were present in most tumor cells and microtubules were present in a few. A minority of small round cells possessed a small number of neurosecretory granules, especially in short cytoplasmic processes. A positive immunoreaction for neuron specific enolase was found by immunohistochemical examination in several small round tumor cells and for neurofilaments in lesser numbers. Despite the lack of S-100 protein, MB2 was detected in both small round and spindle cells. On the basis of these findings, the tumor of the present case corresponds to malignant peripheral nerve sheath tumor with neuronal differentiation and oncocytic features.     

Galectin-3 expression in follicular tumours: an immunohistochemical study of its use as a marker of follicular carcinoma

AIMS: Galectin-3, a member of the beta-galactoside binding family of lectins, has been regarded as a useful tool for discriminating malignant tumours from benign nodules of the thyroid, including the distinction between follicular carcinoma and adenoma. However, there are follicular tumours with unclear vascular or capsular invasion, which makes diagnosis more difficult. In this study, we investigated the relationship between galectin-3 expression and the degree of vascular or capsular invasion of follicular tumours. METHODS: We immunohistochemically investigated galectin-3 expression in 260 cases of follicular tumour with various degrees of vascular or capsular invasion classified into four categories. RESULTS: The galectin-3 expression level significantly increased with the degree of vascular or capsular invasion (p<0.0001). However, its diagnostic value for follicular carcinoma was not high because the sensitivity and specificity were 68.7% and 57.5%, respectively. CONCLUSIONS: Our findings suggest that galectin-3 plays a role in the transformation of follicular tumours from benign to malignant; however, when diagnosing follicular tumours, the presence of this protein should not be required for diagnosing malignant transformation in all cases. Therefore, we must conclude that galectin-3 should only be considered an adjuvant marker for follicular carcinoma.     

Analysis of Host Cells Associated with the Spv-Mediated Increased Intracellular Growth Rate of Salmonella typhimurium in Mice

The 90-kb virulence plasmid of Salmonella typhimurium encodes five spv genes which increase the growth rate of the bacteria within host cells within the first week of systemic infection of mice (P. A. Gulig and T. J. Doyle, Infect. Immun. 61:504–511, 1993). The presently described study was aimed at identifying the host cells associated with Spv-mediated virulence by manipulating the mouse host and the salmonellae. To test the effects of T cells and B cells on the Spv phenotype, salmonellae were orally inoculated into nude and SCID BALB/c mice. Relative to normal BALB/c mice, nude and SCID BALB/c mice were unaffected for splenic infection with either the Spv⁺ or Spv⁻ S. typhimurium strains at 5 days postinoculation. When mice were pretreated with cyclophosphamide to induce granulocytopenia, there was a variable increase in total salmonella infection, but the relative splenic CFU of Spv⁺ versus Spv⁻ S. typhimurium was not changed after oral inoculation. In contrast, depletion of macrophages from mice by treatment with cyclophosphamide plus liposomes containing dichloromethylene diphosphate resulted in equivalent virulence of Spv⁺ and Spv⁻ salmonellae. To examine if the spv genes affected the growth of salmonellae in nonphagocytic cells, an invA::aphT mutation was transduced into Spv⁺ and Spv⁻ S. typhimurium strains. InvA⁻ Spv⁺ salmonellae were not significantly affected for splenic infection after subcutaneous inoculation compared with the wild-type strain, and InvA⁻ Spv⁻ salmonellae were only slightly attenuated relative to InvA⁺ Spv⁻ salmonellae. Invasion-defective salmonellae still exhibited the Spv phenotype. Therefore, infection of nonphagocytes is not involved with the Spv virulence function. Taken together, these data demonstrate that macrophages are essential for suppressing the infection by Spv⁻ S. typhimurium, by serving as the primary host cell for Spv-mediated intracellular replication and possibly by inhibiting the replication of salmonellae within other macrophages.     

Lon,a stress-induced ATP-dependent protease,is critically important for systemic Salmonella enterica serovar typhimurium infection of mice

Studies on the pathogenesis of Salmonella enterica serovar Typhimurium infections in mice have revealed the presence of two prominent virulence characteristics-the invasion of the nonphagocytic cells to penetrate the intestinal epithelium and the proliferation within host phagocytic cells to cause a systemic spread and the colonization of host organs. We have recently demonstrated that the ATP-dependent Lon protease of S. enterica serovar Typhimurium negatively regulates the efficiency of invasion of epithelial cells and the expression of invasion genes (A. Takaya et al., J. Bacteriol. 184:224-232, 2002). This study was performed to reveal the contribution of the Lon protease to the virulence of S. enterica serovar Typhimurium in mice. Determination of 50% lethal doses for the lon disruption mutant and wild-type strain revealed that the mutant was highly attenuated when administered either orally or intraperitoneally to BALB/c mice. The mutant was also found to be able to reach extraintestinal sites but unable to proliferate efficiently within the spleen and cause lethal systemic disease of mice. Macrophage survival assays revealed that the lon disruption mutant could not survive or proliferate within murine macrophages. In addition, the mutant showed extremely increased susceptibility to hydrogen peroxide, which contributes to the bactericidal capacity of phagocytes. The mutant also showed increased sensitivity to acidic conditions. Taken together, the impaired ability of the lon disruption mutant to survive and grow in macrophages could be due to the enhanced susceptibility to the oxygen-dependent killing mechanism associated with respiratory burst and the low phagosomal pH. These results suggest that the Lon protease is essentially involved in the systemic infection of mice with S. enterica serovar Typhimurium, which can be fatal. Of further interest is the finding that the lon disruption mutant persists in the BALB/c mice for long periods without causing an overwhelming systemic infection.