Independent association of antibodies against human papillomavirus type 16 and E7 proteins with cervical cancer

The E4 open reading frame (ORF) of human papillomaviruses (HPVs) is transcribed in abundant mRNAs encoding an fusion gene during the productive infection, and the HPV 16 E7 ORF encodes an oncoprotein detectable in the cell lines derived from cervical carcinoma. We examined 421 human sera, which included 108 samples from the patients with cervical carcinoma, for the presence of IgG antibodies against the HPV 16 E4 and E7 proteins by enzyme-linked immunosorbent assay. Bacterially expressed fusion protein lac- and nonfusion protein E7 were purified and used as antigens. All of the 22 serum samples positive for anti-E7 antibody and the 11 out of 15 samples positive for anti- antibody were from the patients with cervical carcinoma, but only one sample was found to contain both anti- and anti-E7 antibodies. These findings show specific and independent association of these antibodies with cervical carcinoma.     

Treatment of tardive dyskinesia with ceruletide

1. Seven patients with TD were treated with a single dose of ceruletide 0.8 microgram/kg i.m. 2. EMG and MV were recorded, and the average power spectrum was computed. 3. Effect of ceruletide on TD within 2 hr after injection was varied (3 cases: inhibitory, 2 cases: facilitatory, 2 cases: no effect). 4. Two patients with severe TD, who showed improvement after a single administration, received repeated administration of ceruletide (0.6 microgram/kg i.m.) and their TD symptoms were recorded on videotape for blind consensus ratings. In both patients ceruletide caused a marked decrease in severity of TD, and the effects lasted for several weeks. 5. The present findings might contribute to further understanding of the role of CCK in the brain and to the treatment of TD.     

Lack of modifying effects of atrazine and/or tamoxifen on thyroid carcinogenesis in rats pretreated with N-bis(2-hydroxypropyl)nitrosamine (DHPN)

The modifying effects of atrazine, and/or tamoxifen, on thyroid carcinogenesis were investigated in a rat two-stage carcinogenesis model following N-bis(2-hydroxypropyl)nitrosamine (DHPN) initiation. Five-week-old male F344 rats were given a single subcutaneous injection of DHPN (2800 mg/kg, body weight) or vehicle alone. Starting 1 week later, the animals were fed a diet supplemented with 0, 5, 50 or 500 ppm of atrazine, 500 ppm atrazine plus 5 ppm tamoxifen, or 5 ppm tamoxifen in the DHPN-treated groups, and 0 or 500 ppm of atrazine in the DHPN-untreated groups for 24 weeks. At autopsy major organs, including the thyroid, pituitary, liver, kidney, testis, epididymis, and brain, were collected and histopathologically examined. Body weights were significantly (P<0.05) decreased by the high doses of atrazine or tamoxifen, the effect being enhanced in combination. Relative thyroid weights were significantly increased (P<0.05) only in the tamoxifen-treated group and pituitary weights were elevated with 500 ppm atrazine plus tamoxifen (P<0.05). Relative liver weights were increased by the high dose of atrazine. However, the atrazine and/or tamoxifen treatments did not induce significant histopathological changes in the major organs, including the thyroid, nor cause significant changes in serum TSH levels. These results suggest that neither atrazine nor tamoxifen may promote thyroid carcinogenesis, alone as well as in combination.     

Detection of beta-lactamase-producing strains isolated from urinary tract and their drug susceptibility

A total of 518 bacterial strains isolated from the urine of patients with various urological diseases in our Urological Department between November, 1987 and February, 1989 were studied for their beta-lactamase production and susceptibility to various antimicrobial agents was determined. beta-lactamase activity was determined by the acidometry disc method. There were 241 gram-positive cocci, 276 of gram-negative rods and 1 Neisseria gonorrhoeae. Thirty-four percent of the gram positive and 76.3% of gram negative rods produced beta-lactamase. S. aureus (81.3%), S. epidermidis (65.1%) in gram-positive cocci, E. cloacae (100%), S. marcescens (100%), C. freundii (100%), P. aeruginosa (97.2%), P. Rettgeri (88.9%), E. gergoviae (85.7%), K. oxytoca (84.6%), M. morganii (81.8%) and E. coli (69.0%) in gram-negative rods produced beta-lactamase at a higher rate. beta-lactamase produced by gram-positive cocci was entirely penicillinase, and that produced by gram-negative rods only penicillinase in 4.0%, only cephalosporinase in 44.2% and both in 25.4%. In S. aureus and S. epidermidis, the isolated rate of strains resistant to ampicillin (p less than 0.01) and piperacillin (p less than 0.05) in the beta-lactamase producing strains was significantly higher than that in the beta-lactamase non-producing strains. In E. coli, the isolation rate of strains resistant to ampicillin and piperacillin in the penicillinase-producing strains was significantly higher than in the penicillinase non-producing strains (p less than 0.01). But both cephalosporinase-producing strains and beta-lactamase non-producing strains showed high susceptibility to cephalothin. These results suggest that the penicillinase might present a clinical problem in the treatment of urinary tract infections by S. aureus, S. epidermidis and E. coli.     

Similarities between the relaxations induced by vasoactive intestinal peptide and by stimulation of the non-adrenergic non-cholinergic neurons in the rat stomach

Summary The characteristics of the non-adrenergic, noncholinergic inhibitory response of the rat stomach fundus to transmural nerve stimulation were compared with the relaxation induced by vasoactive intestinal polypeptide (VIP). Treatment with -chymotrypsin (5 U/ml) or VIP antiserum (1:200) significantly reduced the relaxation induced by transmural nerve stimulation at 30 Hz, indicating that the possible transmitter in the non-adrenergic, non-cholinergic nerves is a peptide and may be VIP or a closely related peptide. VIP was able to relax, fully and dose-dependently, the stomach fundus that had previously been constricted by treatment with 10^–6 M serotonin, and the IC₅₀ value for VIP was 2.4 × 10^–9 M. VIP elevated levels of cyclic AMP in a dose-dependent manner and the EC₅₀ value was 2.8 × 10^–9 M in the presence of 10^–6 M atropine and 10^–6 M guanethidine. The stomach fundus was relaxed by transmural nerve stimulation (30 Hz, 50 mA) and transmural nerve stimulation also caused production of cyclic AMP in the rat stomach in the presence of atropine and guanethidine. The basal level of cyclic AMP in the stomach was 8.7 ± 0.26 pmole/mg protein. When transmural nerve stimulation was applied for 5 min, the contraction of the stomach, induced by 10^–6 M serotonin, was inhibited by 54% in the presence of atropine and guanethidine and the level of cyclic AMP was increased to 13.0 ± 0.73 pmol/mg protein. Apamin inhibited the transmural nerve stimulation-induced relaxation and shifted the dose-response curve for VIP to the right. These results suggest that one of the putative neurotransmitter from non-adrenergic, non-cholinergic nerves in the rat stomach is VIP and that VIP-induced relaxation may be mediated by the production of cyclic AMP and by the opening of apamin-sensitive K⁺-channels.Send offprint requests to K. Kamata at the above address     

Vascular endothelial growth factor overproduced by tumour cells acts predominantly as a potent angiogenic factor contributing to malignant progression

To elucidate the role of vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen, in tumour angiogenesis and malignant progression, an expression vector harboring human VEGF cDNA was stably transfected into three human cancer cell lines with poor VEGF productivity. Though their in vitro growth rate and intrinsic productivity of another angiogenic factor, basic fibroblast growth factor (bFGF), were not changed by transfection, those clones with higher VEGF production were endowed with tumorigenic and angiogenic potentials as follows: firstly, nontumorigenic, lung carcinoma QG90 cells having lower bFGF productivity acquired tumorigenicity as well as significant in vivo angiogenesis-inducing ability, secondly, tumorigenic colorectal carcinoma RPMI4788 cells having higher potency for bFGF production could form more vascularized solid tumour with faster growth rate and thirdly, oestrogen-dependent breast carcinoma MCF-7 cells, which did not produce detectable bFGF, acquired tumorigenicity even in the absence of oestrogen and the solid tumour growth rate was remarkably enhanced, accompanied with increased vascularization, in the presence of oestrogen. These results suggest that tumour progression closely depends on angiogenesis, and VEGF significantly contributes to malignant progression of a variety of tumour cells through its potent angiogenic activity, independent on the bFGF productivity of tumour cells.     

Morphometric difference in the human maxillary nerve fibers between dentulous and edentulous jaw subjects

This study was conducted to quantify the change in the number and size of myelinated nerve fibers of the maxillary nerve with tooth loss in humans. We carried out a morphometric analysis to compare the number and size of myelinated nerve fibers in the human maxillary nerve between four dentulous and four edentulous jaw cases. Our results indicated that the number of axons decreased by approximately 13,000 with tooth loss. The average size of axons remained unchanged, but there was a change in the fiber size distribution, namely the loss of a large number of small-sized axons was accompanied by the total disappearance of small number of large-sized axons.     

Protective Role of Nitric Oxide in Staphylococcus aureus Infection in Mice

This study was carried out to determine the role of nitric oxide (NO) in Staphylococcus aureus infection in mice. NO production in spleen cell cultures was induced by heat-killed S. aureus. Expression of mRNA of the inducible isoform of NO synthase (iNOS) was induced in the spleens and kidneys of S. aureus-infected mice. When mice were treated with monoclonal antibodies (MAbs) against tumor necrosis factor alpha (TNF-α) or gamma interferon (IFN-γ) before S. aureus infection, the induction of iNOS mRNA expression in the kidneys was inhibited. These MAbs also inhibited NO production in spleen cell cultures stimulated with heat-killed S. aureus. NO production in the spleen cell cultures and levels of urinary nitrate plus nitrite were suppressed by treatment with aminoguanidine (AG), a selective inhibitor of iNOS. The survival rates of AG-treated mice were significantly decreased by either lethal or sublethal S. aureus infections. However, an effect of AG administration on bacterial growth was not observed in the spleens and kidneys of mice during either type of infection. Production of TNF-α and IFN-γ was not affected by AG treatment in vitro and in vivo. These results suggest that NO plays an important role in protection from lethality by the infection, but the protective role of NO in host resistance against S. aureus infection was not proved. Moreover, our results show that TNF-α and IFN-γ regulate NO production while NO may not be involved in the regulation of the production of these cytokines during S. aureus infection.