Radioimaging of human glioma xenografts with 123I labeled monoclonal antibody G-22 against glioma-associated antigen

Summary Monoclonal antibody (MCA) G-22 is directed against a human glioma-associated surface antigen. Its availability for the radioimmunodetection of human glioma was analyzed by utilizing the xenografts in athymic mice. Nude mice with subcutaneous grafts of U251-MG or U251-SP glioma received intravenous administration of ¹²³I or ¹³¹I labeled F(ab)2 fragment or whole immunoglobulin. Results of radioimaging revealed that ¹²³I-labeled antibody was better than the ¹³¹I-labeled. It was also noted that administration of ¹²³I-labeled F(ab)2 fragment of G-22 MCA enabled the imaging of human glioma xenografts weighing 80–650 mg after 48 hours. When biodistribution of ¹²³I MCA was compared between G-22 and control antibodies, the percentages of dose/g in tumors were 5.228–1.799 at 30 hours and 4.112–1.132 at 48 hours with G-22 and they were 4.164–1.248 and 0.314–0.142 with control. The tumor/blood ratio until 72 hours after injection was constantly above 1 with G-22 and less than 1 with control antibody. These results indicate the potential usefulness of G-22 MCA for the radioimmunodetection of human gliomas.     

Changes of nitric oxide synthase activity and free methylarginines contents in regenerating rat liver after partial hepatectomy

In the present study, liver regeneration rate (%) was increased up to 70% 3 days after partial hepatectomy (PH). Nitric oxide synthase (NOS) activity in liver tissue as well as serum nitrite/nitrate content had no timed response, revealing no significant difference between shamoperated and partially hepatectomized rat liver. Contents of free methylarginines in liver tissue were increased biphasically in a time-dependent manner after PH. However, those in serum did not exhibit the same patterns as in liver. Taken together, the results suggest that N^G-monomethyl-L-arginine (MMA) and N^G, N^G-dimethylarginine (DMA) play a role in inhibiting nitric oxide (NO) synthesis in regenerating rat liver because the increase of their contents was synchronized with NOS expression.     

Negative developed tension in rapidly shortening whole frog muscles

Summary High speed isovelocity shortening using a servo-controlled lever was performed on isolated whole frog sartorius muscles at long lengths to ensure substantial passive tension. The tension records of unstimulated control experiments were subtracted from the tension records of fully-tetanized experiments on the same muscles to yield the developed tension exerted by the contractile proteins alone. There are several main results: (1) the positive developed tension had the same relation with shortening speed observed by other researchers in single fibres with no passive tension present; (2) negative developed tension was always measured at velocities of shortening above V _max where V _max (typically 1.5 muscle-lengths s^-1 at 2° C) is defined as the velocity of shortening observed to yield zero developed tension; (3) negative developed tension was roughly asymptotic to –0.05 T _o where T _o is the developed isometric tetanic tension for the muscle length at which the developed tension was measured during steady shortening; (4) negative developed tension diminished in magnitude at velocities of shortening above approximately 2.5 V _max; (5) a 10° C increase in temperature from 2° C to 12° C had no significant effect on the shape of the normalized force-velocity curve (%T _o versus %V _max), but did increase V _max by a factor of 2.6 in agreement with the results of previous studies measuring V _max in the absence of passive tension; (6) addition of curare in the saline bath did not affect the results.     

True histiocytic lymphoma of the esophagus in an HIV-positive patient: an ultrastructural study

A 56-year-old white woman, seropositive for human immunodeficiency virus for 18 months without signs of acquired immunodeficiency syndrome, presented with retrosternal pain and progressive dysphagia secondary to an exophytic esophageal mass. Biopsies of the tumor showed a malignant neoplasm composed of pleomorphic, noncohesive cells growing in a diffuse, sheet-like fashion. Immunohistochemically, tumor cells were nonreactive with epithelial, lymphoid, neural, and monocyte/macrophage markers. Despite the noncontributory immunohistochemical findings, ultrastructural study of the tumor cells revealed convincing histiocytic features. Individual cells possessed long, slender filopodial projections, prominent Golgi apparatus, residual bodies, rare lysosomes, and prelysosomes. Immunoglobulin heavy chain and T-cell receptor gamma gene rearrangement studies detected no evidence of a clonal gene rearrangement. The patient responded poorly to chemotherapy and died 5 months after her initial symptom of dysphagia.     

Imaging features of pancreatoblastoma: a case report

We present a patient with pancreatoblastoma along with a discussion of various cross-sectional imaging features. The tumor was a large multilocular cystic mass with solid components in the left retroperitoneal space. There were fine internal echoes on ultrasonography, and the signal intensity was high on both T1- and T2-weighted MR images in most of the locules, suggesting the presence of hemorrhagic debris. Among the various retroperitoneal organs displaced by the tumor, only the pancreatic tail was inseparable from the mass, suggesting that the pancreatic tail was the origin of the tumor. Pancreatoblastoma should be included in the differential diagnosis when a large left upper quadrant mass with these imaging features is seen in infants and young children.     

Morphological investigation of the enteric nervous system in Hirschsprung's disease and hypoganglionosis using whole-mount colon preparation

BACKGROUND/PURPOSE: A suction rectal mucosal biopsy with positive staining for acetylcholinesterase is a useful test for diagnosis of Hirschsprung's disease (HD). However, hypoganglionosis has not been diagnosed by a rectal mucosal biopsy. The authors morphologically examined the enteric nervous systems in HD and hypoganglionosis patients using whole-mount preparations. METHODS: Six HD patients, two hypoganglionosis patients, and 10 with normally innervated colons were examined. Colonic specimens were incubated with the primary antibodies against protein gene product 9.5 (PGP 9.5) mixed with S-100b protein, tyrosine hydroxylase (TH), calcitonin gene-related peptide (CGRP), substance P (SP), and neurofilament protein 200 kDa (NFH). They were observed by histochemical technique using light-microscopy in whole-mount preparations. RESULTS: The aganglionic distal colon had thick nerve strands stained with PGP 9.5 mixed with S100 or NFH located in the layer between the longitudinal muscle and the circular one, and the submucosal layer. The nerve strands in the myenteric layer contained few CGRP- and SP-positive fibers and ran along the long axis of the intestine. Ganglion cells appeared along with those thick nerve strands in the transitional zone of HD. In hypoganglionosis, we found small myenteric ganglia with no thick nerve strands. CONCLUSIONS: The enteric nervous system in oligoganglionic segments of HD morphologically differed from the one in hypoganglionosis. A suction rectal mucosal biopsy would be of no use in the diagnosis of hypoganglionosis.     

Effects of bacterial endotoxin on the contraction and relaxation responses of the rabbit cavernous smooth muscles

PURPOSE: We evaluated effects of bacterial endotoxin during septicemia on contraction and relaxation responses of cavernous smooth muscles in rabbits. MATERIALS AND METHODS: We performed isometric tension studies with norepinephrine (NE), endothelium-dependent and endothelium-independent vasodilators, and nonadrenergic noncholinergic (NANC)-selective electrical field stimulation on the muscle strips of control and endotoxin (lipopolysaccharide; LPS)-treated rabbits. To determine reversibility of the LPS effects on the cavernous smooth muscle, the contraction and relaxation studies were repeated after resting the strips for 1 day at 4C. We also investigated the effect of the nonspecific nitric oxide synthase (NOS) inhibitor (NW-nitro-L-arginine methyl ester; L-NAME) and the selective immunologic NOS inhibitor (aminoguanidine) on reactivity of the strips to NE and acetylcholine. RESULTS: Contractile response to NE was significantly (p <0.01) reduced in the cavernous smooth muscles from the systemically and locally LPS-treated rabbits, compared with control group. Both aminoguanidine and L-NAME markedly improved the diminished contraction of the strips. Relaxation response to endothelium-dependent agonists (acetylcholine and bradykinin) was significantly (p <0.05) decreased in the LPS-treated groups, compared with the control group but not to endothelium-independent vasodilators (papaverine and verapamil) and NANC-selective electrical field stimulation. L-NAME completely inhibited the relaxation response to acetylcholine in the control and LPS-treated groups but aminoguanidine did not. The impaired contraction and relaxation of the strips was completely restored after resting for 1 day. CONCLUSIONS: Bacterial endotoxin may cause non-endothelial overproduction of NO and inhibition of endothelium-derived NO production, which may contribute to impairment of contraction and relaxation of rabbit cavernous smooth muscles.     

Involvement of endothelial nitric oxide synthase in the impaired endothelium-dependent relaxation of cavernous smooth muscle in hypercholesterolemic rabbit

The present study was designed to evaluate whether functional impairment and/or protein expression of constitutive nitric oxide synthase (cNOS; endothelial NOS [eNOS] and neuronal NOS[nNOS]) was involved in impairment of endothelium-dependent relaxation of cavernous smooth muscle in hypercholesterolemic rabbits. New Zealand White rabbits were randomly divided into control and experimental groups. The control group (n=20) received a regular diet, while the two experimental groups (n=20 for each) were fed a 2% cholesterol diet for 4 and 8 weeks, respectively. We conducted isometric tension studies with endothelium-dependent and endothelium-independent vasodilators with or without preincubation with L-arginine and nonadrenergic, noncholinergic (NANC)-selective electrical field stimulation on isolated strips of corpus cavernosum. Expression of cNOS (eNOS and nNOS) protein was assessed by Western blot analysis. cNOS activities in both cytosolic and particulate fractions were measured by determining the conversion of L-[U-14C] arginine to L-[U-14C] citrulline. Blood levels of cholesterol were significantly higher (P < 0.01) in the experimental groups than in the control group. The relaxation responses to endothelium-dependent agents (acetylcholine and adenosine 5'-diphosphate [ADP]) were significantly reduced (P < 0.05) in both experimental groups, regardless of their incubation with L-arginine, compared with the control group. However, no differences were found among the three groups in the relaxation response to endothelium-independent agents (papaverine and nitroprusside) and to NANC-selective electrical field stimulation. There was no difference in immunoreactive nNOS from cytosolic and particulate fractions between the cavernous tissues of the control and experimental groups. nNOS protein levels in the particulate fractions were markedly lower than in the cytosolic fractions. The particulate cNOS activity was significantly decreased (P < 0.05) in the experimental groups compared with the control group, while the cytosolic cNOS activity in the experimental groups was not different from that found in the control group. Therefore, it is concluded that functional impairment of eNOS, rather than of nNOS, may lead to impairment of cavernous smooth muscle relaxation in response to endothelium-mediated stimuli in hypercholesterolemic rabbits.     

Synthesis andin vitro antibacterial activity of quaternary ammonium cephalosporin derivatives bearing oxazolidinone moiety

Several oxazolidinones having amine moiety were prepared to form a quaternary ammonium salt with cephalosporin nucleus, and antibacterial activity of the quaternary ammonium cephalosporin derivatives bearing oxazolidinone moiety were examined particularly with expectation of dual activity. However, the cephalosporin-oxazolidinone compounds revealed rather weaker antibacterial activity in vitro than their parent oxazolidinone and cephalosporin without showing any characteristic activity as expected.     

Synthesis andin vitro antibacterial activity of C-3′ pyridinium cephalosporin derivatives

The quaternary ammonium cephalosporin derivatives were prepared with various pyridines substituted at the 3 or/and 4 position. Their in vitro antibacterial activities were determined and substituent effect on pyridine nucleus was studied. Preparation of substituted pyridines are also described.