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Biomedical subjects

J C Lin

Publications and source records attributed to J C Lin.

At least 271 records · Page 15Linked to original sources

Histopathological and biochemical analyses of transplantable renal adenocarcinoma in rats induced by N-ethyl-N-hydroxyethylnitrosamine.

Transplantable renal adenocarcinoma can be readily induced in Wistar strain male rats by initiation with N-ethyl-N-hydroxy-ethylnitrosamine followed by promotion with beta-cyclodextrin. The transplantability rates of the tumors by s.c. inoculation in newborn rats were 33 and 50%, respectively, for tumors of the first and second passages, and 100% for both third and fourth passages. The transplantability rates were affected by route of inoculation; rates of 50 and 100% were observed for s.c. and i.p. inoculations, respectively. The growth rate of tumors induced by i.p. inoculation was 3-fold higher than that induced by s.c. injection. Macroscopically, most of the tumors grew in the s.c. tissue of inoculation sites. However, invasive growth of tumors in spleen, liver, stomach, peritoneum, and intestine were seen in 50% of the animals inoculated i.p.; metastatic cancers to lung were seen in 16%. Histologically, the tumors were well-differentiated adenocarcinomas composed of uniform cells resembling kidney tubular cells and appeared to be derived from normal kidney tissues. A 5-fold decrease in gamma-glutamyl transferase activity in tumor tissues was found as compared with that of nontumorous kidney tissues. Electrophoretic analysis of cellular proteins in polyacrylamide gels revealed that tumor tissues exhibited five new polypeptides with molecular weights of 81,000, 64,000, 59,000, 50,000, and 36,000 which were either lacking or undetectable in the nontumourous area and control kidney. In addition, protein banding patterns of transplantable renal tumor appeared to be more heterogeneous than those of primary kidney tumor.

Adenocarcinoma↗

Microwave enhancement of membrane conductance: effects of EDTA, caffeine and tetracaine.

Effects of tetracaine and caffeine on snail neurons were studied. They displayed depolarization and an increase of membrane conductance. In addition, tetracaine diminished membrane time constant whereas caffeine augmented hyperpolarizing after-potential. It was also shown that tetracaine blocks the caffeine effect. Microwave irradiation of snail neurons enhanced membrane conductance. This effect was not observed in neurons treated with tetracaine or injected with EDTA. Analysis of these results points to intracellular free calcium as a possible trigger of snail neuron microwave response.

Animals↗

Hydrogen peroxide contrast echocardiography.

Several agents are used as echocardiographic contrast agents, but their unreliability discourages routine clinical use. Studies from the early 1960s suggest that dilute hydrogen peroxide (H2O2) is a safe intravascular agent. Its use was evaluated in contrast echocardiography. To obtain dense opacification reliably, H2O2 (3%) was passed through a sterile 0.2 micron Millipore filter and diluted with heparinized saline solution to make a 0.1 to 0.2% solution. A drop of blood was withdrawn from an indwelling peripheral venous needle into a syringe containing 0.5 to 2.0 ml of the dilute H2O2 and the contents injected. Studies in dogs, normal adults and 36 patients with noncyanotic congenital and acquired cardiac disorders produced dense opacification with no complications. In vitro mixture of H2O2 (0.3%) with leukocyte-poor blood or plasma produced only a few microbubbles, while addition to whole blood or buffy coat produced many, suggesting a role for leukocyte peroxidase. H2O2 contrast echocardiography is simple, inexpensive, and reliably provides dense, sustained opacification. This study and previous studies suggest that intravenous injection of 0.2% H2O2 can be done safely. Great caution should be exercised in patients with severe pulmonary hypertension or large right-to-left shunts because little clinical experience with H2O2 is available.

Animals↗

Epstein-Barr virus: inhibition of replication by three new drugs.

Epstein-Barr virus (EBV) is the cause of infectious mononucleosis and is associated with three human malignancies. Acyclovir [9-(2-hydroxyethoxymethyl)guanine], the first clinically useful drug effective against replication of EBV, is without effect against latent or persistent EBV infection. Three nucleoside analogs, E-5-(2-bromovinyl)-2'-deoxyuridine, 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine, and 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-methyluracil are potent inhibitors of EBV replication in vitro. Moreover, in contrast to the reversibility of viral inhibition by Acyclovir, these three drugs have prolonged effects in suppressing viral replication even after the drugs are removed from persistently infected cell cultures.

Acyclovir↗

Noninvasive recognition of the parchment right ventricle (Uhl's anomaly arrhythmogenic right ventricular dysplasia) syndrome.

The case of a 53-year-old man with right heart failure, selective enlargement of the right-sided cardiac chambers, and recurrent sustained ventricular tachycardia is presented. Echocardiographic, radionuclide ventriculographic, and angiographic studies were typical of the right ventricular abnormalities in Uhl's anomaly; electrocardiographic and electrophysiologic findings were those of arrhythmogenic right ventricular dysplasia. Features of this unusual cause of cardiac failure and ventricular arrhythmias in the adult are reviewed, and compared to previous reports of both Uhl's anomaly and arrhythmogenic right ventricular dysplasia. We postulate that these two syndromes are manifestations of a single, presumably congenital, pathophysiologic process--the "parchment right ventricle" syndrome.

Echocardiography↗

Unique spectrum of activity of 9-[(1,3-dihydroxy-2-propoxy)methyl]-guanine against herpesviruses in vitro and its mode of action against herpes simplex virus type 1.

A guanosine analog, 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (DHPG), was found to inhibit herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2, cytomegalovirus, and Epstein-Barr virus replication by greater than 50% at concentrations that do not inhibit cell growth in culture. The potency of the drug against all of these viruses is greater than that of 9-[(2-hydroxyethoxy)methyl]guanine (acyclovir). DHPG was active against HSV-1 growth during the early phase of virus replication and had no activity when added at a later time after infection. Its antiviral activity was irreversible. Thymidine partially neutralized its action. The anti-HSV-1 activity of DHPG was dependent on the induction and the properties of virus-induced thymidine kinase. Virus variants that induced altered virus thymidine kinase and became resistant to acyclovir were still as sensitive to DHPG as the parental virus. DHPG is active against five different HSV variants with induced altered DNA polymerase and resistance to acyclovir.

Acyclovir↗

Enhancement of replication of Epstein-Barr virus DNA in human lymphoblastoid cell lines by N-methyl-N'-nitro-N-nitrosoguanidine.

N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) is a potent carcinogen that alkylates nucleic acids. Interaction of MNNG with human lymphoblastoid cell lines carrying Epstein-Barr virus (EBV) was studied. Treatment of virus-producing cells (P3HR-1) with MNNG resulted in an approximately 3-fold increase in EBV genome copies per cell as determined by cRNA--DNA hybridization. This effect was not observed in a non-virus-producer line (Raji). Dose-response studies indicated that the optimum concentration was between 0.5 micrograms and 2 micrograms/ml. This same dose range was most effective in inhibiting cell proliferation both of P3HR-1 and Raji cells. Concomitant treatment of P3HR-1 cells with MNNG and 12-O-tetradecanoylphorbol-13-acetate gave an additive increase to 9-fold of the number of EBV genome copies per cell. Pretreatment of Raji cells with MNNG followed by superinfection with P3HR-1 virus resulted in a 35% enhancement of EBV DNA replication as analyzed by density centrifugation. In contrast, Raji cells superinfected with MNNG-treated EBV showed a marked reduction in EBV DNA replication which indicates that the lesions produced in the viral genome by the drug interferred with the infectious potential of the virus.

Burkitt Lymphoma↗

Acyclovir and Epstein-Barr virus infection.

Acyclovir (ACV) has an ED50 of 0.3 microM against EBV replication in vitro. Based on these and other data we carried out a pilot, double-blind, placebo-controlled trial of ACV for treatment of infectious mononucleosis. Only patients with relatively severe illness requiring hospital management were enrolled. Ten subjects with proven infectious mononucleosis received placebo and 10 ACV. The drug was administered intravenously at 8-hourly intervals in a total daily dosage of 1500 mg/m2 for 5 days. Preliminary analyses of the results indicate that the drug interrupted virus excretion in the oropharynx transiently but had no effect on ability to generate lymphocytic lines from peripheral blood. Symptoms and signs unaffected by ACV were splenomegaly, lymphadenopathy, lethargy, fever and pharyngitis. There was significantly more rapid regain of weight in the ACV-treated group. On the basis of these results we have instituted an out-patient trial of orally administered ACV in patients with less severe illness earlier in its course. We have also begun in-vitro tests of other drugs that might prove to be effective against Epstein-Barr virus infection, and have shown that 9-1 (1,3-dihydroxy-2-propoxymethyl)guanine (BW759) has an ED50 of 0.05 microM.

Acyclovir↗

Activation of latent Epstein-Barr virus genomes: selective stimulation of synthesis of chromosomal proteins by a tumor promoter.

The tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) is a potent inducer of Epstein-Barr virus (EBV) gene expression. The optimal conditions for maximum activation of latent EBV genomes by TPA were determined. Although TPA is able to induce replication of EBV genomes in P3HR-1 cells in all phases of growth, the greatest increase in viral genome copies per cell (15-fold above the control level) occurred in nonproliferating cells as opposed to cells growing exponentially (6-fold above the control level). The synthesis of chromosomal proteins in nonproliferating cells under the conditions that induce maximum activation of latent virus genomes by TPA was studied. Selective stimulation in chromosomal protein synthesis accompanied the increase in EBV genomes in P3HR-1 cells despite an overall reduction in total cellular protein synthesis. Comparison of the chromosomal proteins from TPA-induced P3HR-1 cells and from superinfected Raji cells revealed comigrating chromosomal polypeptides of 145K, 140K, 135K, 110K, 85K, and 55K that are presumably EBV associated. The selective stimulation of synthesis of these chromosomal proteins in TPA-treated P3HR-1 cells was closely associated with the activation of latent EBV genomes.

Cell Division↗

Noise-modulated-microwave-induced response in snail neurons.

Helix aspersa neurons were irradiated with noise-amplitude-modulated microwaves (carrier frequency 2450 MHz, 20% AM, 0-20 kHz, specific absorption rate 6.8 and 14.4 mW/g). It was found that such an exposure caused an appearance of high frequency bursts and a rise in membrane resistance.

Action Potentials↗

Rat bladder isograft model for focal carcinoma.

A model for focal bladder carcinoma in rats was developed with the use of an isograft technique. Bladder tumors developed by carcinogen induction with FANFT or MNU were grafted to bladders of syngeneic rats. Ninety-six per cent (56 our of 58) of the grafts were taken and 83 per cent (34 out of 41) of the grafted tumors remained neoplastic. Most of the grafts from FANFT-induced tumor remained localized at the original site whereas many from the MNU-induced tumor spread beyond the original graft area. The model system may be useful for the evaluation of chemotherapeutic agents as well as for the studies of basic mechanisms of tumor growth and spreading.

Animals↗

Magnetic necklace: its therapeutic effectiveness on neck and shoulder pain.

The effect of the magnetic necklace on chronic neck and shoulder pain was studied on 101 volunteers, 46 males and 55 females. A double-blind method was applied on 4 divided groups (with pain vs without pain matched with magnetic vs nonmagnetic necklace). All the subjects wore the necklace 24 hours per day for 3 weeks. Subjective evaluation from the subjects with pain, either with magnetic or nonmagnetic treatment, was performed before and 3 weeks after the necklace treatment, and revealed a significant placebo effect in terms of decrease in intensity or frequency of pain. The objective tests with electrodiagnostic procedures were done before the treatment and at 3 weekly intervals. The proximal conduction time of the ulnar nerve was significantly reduced by magnetic treatment in the subjects without pain but was not changed in the subjects with pain. There was no significant change in the excitation threshold of the suprascapular nerve in all subjects. The possible mechanism of magnetic effects on pain and the prospect of magnetotherapy for pain relief in physical medicine are discussed.

Action Potentials↗

In vitro microwave effects on human neutrophil precursor cells (CFU-C).

Human marrow cells were irradiated with 2450-MHz CW microwaves in a fluid-filled waveguide irradiation system. Cell exposure was conducted by placing a marrow cell suspension in 20-microliter glass microcapillary tubes were positioned in the exposure chamber, and irradiated at power densities from 31 to 1,000 mW/cm2 (with corresponding specific absorption rates of 62 to 2,000 mW/g) for 15 minutes. The temperature of the sample was maintained at a fixed point. Sham-irradiated (SI) and microwave-irradiated (MWI) cells were cultured in a methylcellulose culture system for neutrophil colony proliferation. There was no reduction in neutrophil colony number on days 6-7 or 12-14 in cells exposed at 31 or 62 mW/cm2, but as the power density was increased to 1,000 mW/cm2, there was a reduction in colony number of MWI cells compared with SI cells. The microwave interaction with the human neutrophil colony-forming cells was apparently not related to temperature rise, or to the state of cells cycle, and was irreversible.

Bone Marrow↗