Clinico-pathological study of xanthogranulomatous cholecystitis

Xanthogranulomatous cholecystitis (XGC) is an uncommon lesion which may form a tumor-like mass in inflamed gallbladders. In a review of 44 cases there were 40 associated with gallstones which had been incarcerated in the neck of the gallbladder, 10 with past histories of abdominal surgeries, 15 with diabetes mellitus, three with carcinomas in the neck of the gallbladder and four with carcinomas in the other organs. Radiologically the differential diagnosis of gallbladder cancer and XGC was difficult in several cases. Thirty five cases of XGC have been diagnosed as chronic cholecystitis and 7 have been mistaken for feature of XGC in the contrast enhancement CT that is, detection of an intramural low density mass with continuously enhanced internal membraneous layer of the gallbladder wall. In view of the clinico-pathological findings of XGC, the lesions appear to result from intramural extravasation of bile and subsequent xanthogranulomatous reaction under obstructive conditions in the neck of the gallbladder. We conclude that XGC is not an uncommon special type of cholecystitis but an accompanied lesion sometimes seen in a kind of cholecystitis.     

Ultrastructure of primary squamous cell carcinoma of the submandibular gland

Primary squamous cell carcinoma of the submandibular gland is a rare tumor. In this report, the histological and ultrastructural features of a case of primary squamous cell carcinoma arising in the left submandibular gland is presented. Light microscopically, the tumor consisted of well differentiated keratinizing squamous cell nests. Ultrastructurally, the tumor cells were oval or spindle-shaped, and several tumor cells had intracytoplasmic desmosome-like structures, resembling intercellular desmosomes. The majority of the tumor cells contained a large number of intermediate filaments (tonofilaments). Intercellular desmosomes were well developed. No secretory granules were found. These ultrastructural features may enable us to distinguish primary squamous cell carcinoma from mucoepidermoid carcinoma which is often misdiagnosed as squamous cell carcinoma.     

Metastatic Behavior and Tumorigenicity of a Human Melanoma Cell Line (MM-RU) after Injection into Nude Mice

The ability of the human amelanotic melanoma cell line MM-RU to produce experimental metastases and to grow tumors at subcutaneous inoculation sites in 4-week-old nude mice was examined. After i.v. inoculation of 10⁶ cells, all injected mice (n=21) developed consistent numbers of metastatic pulmonary colonies within 32 days. The coefficients of variation for the number of colonies were between 17%–23% in three independent experiments. Survival time after i.v. inoculation was 63 ± 7 days (mean ± SD) (n=20). Within 20 days, subcutaneous inoculation of 5 × 10⁶ cells resulted in tumor growths of 13 ± 3 mm (mean ± SD) at the inoculation sites in all nude mice (n=12). The MM-RU cell line seems to be a simple, fast vehicle for testing the effect of melanoma growth modulators on experimental pulmonary metastases as well as on subcutaneously growing melanoma.     

Development of new immunoradiometric assay for CA 125 antigen using two monoclonal antibodies produced by immunizing lung cancer cells

CA 125 is an antigen associated with non-mucinous epithelial ovarian cancer, which is defined by OC 125 antibody developed by immunizing ovarian cancer cells. We have produced two monoclonal antibodies, 130-22 and 145-9, by using the human lung adenocarcinoma cell line PC-9. Both 130-22 and 145-9 antibodies recognized CA 125 antigen. However, the binding sites seemed to be separate from those of OC 125. Testing by 9 immunoradiometric assays (IRMA), using different combinations of the 3 monoclonal antibodies 130-22, 145-9 and OC 125 demonstrated that the best standard curve for detecting CA 125 could be obtained by a "simultaneous sandwich" assay based on a mixture of 125I-labeled OC 125 and 130-22 or 145-9 coated beads. One-step IRMA, using 130-22 as a tracer and 145-9 as an immunoadsorbent, also showed good reproducibility and sensitivity for measuring CA 125. Antigens were detectable in the culture supernatants of PC-9 cells and 5 of 6 ovarian cancer and endometrial adenocarcinoma cells. These results indicate that one-step IRMA using 130-22 and 145-9 is useful for detecting CA 125 antigen.     

Effect of buthionine sulfoximine on orthophenylphenol-induced hepato- and nephrotoxic potential in male rats

A single oral administration of orthophenylphenol (OPP, 1400 mg/kg; about half the LD₅₀) to male Fischer 344 rats produced an elevation of serum transaminase activity 24 h later. Pretreatment with l-buthionine-S,R-sulfoximine (BSO, 900 mg/kg) in the OPP-treated rats potentiated the hepatic and renal damage which was accompanied by necrosis. Six hours after the administration of OPP (700 or 1400 mg/kg), hepatic and renal glutathione (GSH) levels decreased with increasing dosage. Hepatic GSH depletion with OPP was enhanced with BSO pretreatment and the recovery of GSH in both organs was slow in the high-dose OPP group. These results suggest that hepatic and renal damage is associated with a serious and prolonged GSH depletion. When either phenyl-p-benzoquinone (PBQ) or phenylhydroquinone (PHQ), which are intermediates of OPP, was administered orally to rats at 700 or 1400 mg/kg, the mortality with the high dose of PBQ was 75% at 24 h. The serum transaminase activity and UN level increased with the low dose of PBQ, accompanied by necrotic hepatocytes. The toxic effects of PHQ on kidney or liver were less than those on PBQ. These observations suggest that the liver and kidney may be target organs for toxic actions of a large dose of OPP and its intermediate, PBQ.Part of this work was presented at IInd International ISSX Meeting Xenobiotic Metabolism and Disposition, May 16–20, 1988, Kobe, Japan     

Nephrotoxicity of 5-(N-phenylcarboxamido)-2-thiobarbituric acid in the Fischer 344 rat

Summary In the present investigation, administration of a single i.p. dose of the anticancer drug merbarone [5-(N-phenylcarboxamido)-2-thiobarbituric acid] produced an acute and reversible decrease in renal function in female but not male Fischer 344 rats. The renal lesion in female rats was biochemically characterized as a decrease inp-aminohippuric acid accumulation by renal slices along with polyuria, glucosuria, proteinuria, and enzymuria. These functional changes were accompanied by histopathologic changes of focal tubular necrosis that was confined to the deep cortex and outer stripe of the outer medulla. The changes in these parameters were dose-dependent and were observed at doses as low as 0.2×MELD¹⁰ (12 mg/kg). This low merbarone dose increased urinary glucose and protein excretion by 26- and 9-fold, respectively, in the initial 16-h urine collection in female rats. This increase was accompanied by a 2- to 15-fold increase in the excretion ofN-acetyl--d-glucosaminidase (NAG), -glutamyl transpeptidase (-GTP), and lactate dehydrogenase (LDH) activities. No significant changes in renal function were observed in male rats apart from mild enzymuria after a high dose of merbarone (36 mg/kg). The drug did not increase urea nitrogen levels in male or female rats, reflecting the focal nature of this tubular lesion. Merbarone produced small elevations in serum transaminase activities [i. e., glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT)] at doses that produced marked alterations in renal function in female rats, suggesting only mild hepatotoxicity. The present study establishes the kidney as a possible dose-limiting target organ for merbarone toxicity.     

Human serum albumin incorporating synthetic heme: red blood cell substitute without hypertension by nitric oxide scavenging

The administration of extracellular, hemoglobin-based oxygen carriers often elicits an acute increase in blood pressure by vasoconstriction. This side effect is now recognized to be due to the depletion of nitric oxide (endothelial-derived relaxing factor) by the extravasuated hemoglobins. We have recently found that the administration of a recombinant human serum albumin (rHSA)-based oxygen carrier involving synthetic tetraphenyporphinatoiron(II) derivative (FeP) (rHSA-FeP) does not induce such hypertensive action, because of its low permeability through the vascular endothelium. The heart rate responses after the rHSA-FeP injection were also negligibly small. Visualization of the intestinal microcirculatory changes clearly revealed the widths of the venule and arteriole to be fairly constant. The entirely synthetic rHSA-FeP becomes a promising material as a new type of red blood cell substitute.     

A novel mutation in the FcgammaRIIIA gene (CD16) results in active natural killer cells lacking CD16

We report a novel mutation in FcgammaRIIIA (the transmembrane-form CD16) on natural killer (NK) cells in a patient with polyneuropathy. She had no history of recurrent infections. Her NK cells expressed no detectable CD16; however, her NK cytotoxic activity was normal, suggesting that CD16 expression and cytotoxic activity are independent of one another. Molecular analysis revealed a deletion of a single adenine base in exon 4 of CD16 at nucleotide 550. This deletion generates a STOP codon in an extra-cellular domain of the FcgammaRIIIA gene, thereby truncating the CD16 molecule. The patient's NK cells were not recognized by the anti-CD16 monoclonal antibodies 3G8 and Leu11c. Whether the development of her polyneuropathy is associated with this novel mutation is unclear.     

Compatibility in vitro of albumin-heme (O(2) carrier) with blood cell components

Recombinant human serum albumin including 2-[8-[N-(2-methylimidazolyl)]octanoyloxymethyl]-5,10,15,20-tetrakis(alpha,alpha,alpha,alpha-o-pivaloylamino)phenylporphinatoiron(II) (albumin-heme; rHSA-FeP) is a synthetic hemoprotein that has sufficient capability to reversibly bind and release O(2) under physiological conditions (pH 7.3, 37 degrees C) similar to hemoglobin and myoglobin. In order to use this albumin-based O(2) carrier as a new class of red blood cell substitutes, its compatibility with blood cell components carefully was investigated in vitro. After the addition of the rHSA-FeP solution into whole blood at 10, 20, and 44 vol %, the FeP concentration in the plasma phase remained constant for 6 h at 37 degrees C in each group, and no significant time dependence was observed in the numbers of red blood cells, white blood cells, or platelets. The microscopic observations clearly showed that the shapes of the red blood cells had not been deformed during the measurement period. With respect to the blood coagulation parameters (prothrombin time and activated partial thromboplastin time), the coexistence of rHSA-FeP had only a negligibly small influence. Also the blood compatibility under dynamic flow conditions was evaluated using a microchannel array flow analyzer. All these results suggest that the albumin-heme has no effect on the morphology of blood cell components in vitro.