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.     

Optimal immobilization of penicillinase for lon-selective electrode

Penicillin sensor was prepared by immobilizing penicillinase (Pcase) on H⁺-selective carboxylated poly (vinyl chloride) (PVC-COOH) membrane or cellulose filter membrane. The immobilization techniques are as follows. Pcase was immobilized with GTH on H⁺-selective PVC-COOH membrane or some amount of BSA was dropped on that membrane. Another method to make immobilization is to mix type I Pcase with GTH and drop on a cellulose filter membrane. According to immobilization techniques, there were some differences in response properties of enzyme electrodes, however, all electrodes responded to Pcase-resistant penicillin derivatives. Pcase immobilized on cellulose filter membrane with H⁺-selective PVC membrane eletrode was more stable and more sensitive to penicillinase-resistant penicillin derivatives than any other immobilization techniques.     

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.     

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.     

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.     

Fucosidosis: four new mutations and a new polymorphism

Fucosidosis is a rare lysosomal storage disease due to a nearlycomplete deficiency of -L-fucosidase (EC 3.2.1.51 [EC] ). In thisstudy, all 8 exons of the -L-fucosidase structural gene (FUCA-1)were amplified by PCR methods, and the amplified products weresubcloned and sequenced. Five patient groups with fucosidosiswere selected according to their ethnic backgrounds and haplotypesfor RFLPs in FUCA-1. Four presumptive disease causing mutationswere detected: 1) A major deletion of DNA containing the lasttwo exons of FUCA-1 in two Algerian siblings. 2) A G to T mutationin exon 6 resulting in an in-frame termination codon (E375X)in eight Hispanic patients from Colorado and New Mexico. 3)A G to A mutation (G60D) in exon 1 in four Italian patientsand in three related French-American (Cajun) patients. ThisG60D mutation creates a unique site for Afl III. 4) A frameshiftmutation resulted from a two-base deletion in exon 2 (K151fs)in an Italian patient. This deletion obliterates a unique BstXIsite and creates a new BpmI site, and was found in only thispatient and in only one allele. The rationale for proposingthese defects as disease causing mutations includes pedigreeanalysis and the predicted consequences of each defect uponthe activity and the concentration of the enzyme. An A to Gtransition (Q281R) in exon 5 was found to be present in homozygousform in affected patients and also in normal subjects; it appearsto be a newly identified polymorphism. It causes a charge changeand may be responsible for the electrophoretic variant phenotypeof fucosidosis. This polymorphism is inherited concordant withthe RFLP PvuII—BglI haplotype 2 – 2, 2 – 2.The 4 new mutations identified here comprise 70% of allelesof the 25 fucosidosis patients in our study.     

Survey of attitudes among general practitioners regarding the introduction of a personal computer medical network system in community health care]

General practitioners (GPs) play an important part in community health care. Their opinion regarding introduction of a medical information network system using a personal computer and factors influencing the decision to introduce such a system were surveyed among 977 randomly sampled GPs. A response from 727 GPs was obtained. Based on a two stage selection method, 20 factors were selected as effective factors among the 73 factors surveyed, with the following results: (1) Responses to the question concerning the approval of system introduction were classified into three groups: "not necessary + too early to make a decision (DA)" (DA group), "approve (A)" (A group) and "undecided (UD)" (UD group). Each group had nearly equal numbers of respondees. (2) Significant effective factors were "experience with personal computers", "a desire to use a personal computer", "a desire to use a computer-diagnosis-system", "cost", and "a volition to operate a computer by himself". (3) The "A group" had high experience and affirmative opinions, while the "DA group" had low experience and negative opinions. The "UD group" also tended to respond with "do not know" regarding the factors. (4) Approval of system introduction requires providing basic knowledge on computers, opportunities for positive experience with computers, and practical examples of problem solutions in a general practitioner's work.