Search PubMed⌕ Search

Biomedical subjects

J Hilton

Publications and source records attributed to J Hilton.

At least 109 records · Page 6Linked to original sources
PubMed1986

Is Entamoeba histolytica in homosexual men a pathogen?

Entamoeba histolytica (EH) in homosexual men is generally considered to be pathogenic. To test this hypothesis, the generally accepted features of invasion (haematophagous trophozoites in faeces; high-titre serum antibody; moderate to severe acute inflammatory change; and presence of EH in the mucosa on rectal biopsy) and the zymodeme pattern of cultured trophozoites were assessed in twenty-three EH excretors and eleven control homosexual men. No trophozoites or antibody to EH were found in either group. When other pathogens were excluded, no patient in either group had severe, acute histopathological proctitis. Moderately severe change was seen in 38% of EH excretors and 18% of controls (not significant). All the zymodemes were non-pathogenic. Successful eradication of EH did not result in even a trend towards normalisation of the moderate inflammatory histopathology. There are, therefore, no data here to suggest that EH is a pathogen in homosexual men.

Adult↗
PubMed1986

Blood flow to experimental renal tumors.

Radiolabeled microsphere techniques were used to measure renal blood flow (RBF) in rabbit kidneys with 14- to 16-day-old experimentally induced renal tumors. VX-2 carcinoma cells (25 microliters) harvested from carrier animal intramuscular tumors were injected supraselectively into an intralobar artery using fluoroscopically guided transcatheter techniques. Within 2 to 3 weeks, all animals developed localized 10 to 25 mm diameter renal tumors. Renal blood flow was calculated after left ventricular injection of 113Sn-labeled 15 mu diameter microspheres. Blood flow (ml/minute) in tumor-bearing kidneys (26.91 +/- 1.86) was significantly lower (P = less than .05) than in normal controls (49.79 +/- 7.71). The tumor-bearing kidneys were also significantly larger (15.21 +/- 1.27 gm) than control animal kidneys (10.89 +/- 0.071 gm). Analysis of the tumor kidneys showed flow (ml/minute/g) in the tumor-containing sections (1.82 +/- 0.15) and in the actual tumor tissue (0.62 +/- 0.07) to be significantly lower (P = less than .05) than (1) in the nontumor portions of the same kidneys (2.58 +/- 0.28), and (2) in the tumor animals' contralateral nontumor-bearing kidneys (3.22 +/- 0.16), and (3) in normal control animal kidneys (4.54 +/- 0.29). The reduced flow in tumor-bearing kidneys was not an artifact due to arteriovenous shunting, as demonstrated by 99mTc-microsphere studies in four additional tumor-bearing animals. This study has shown that blood flow to the tumor is extremely low compared with nontumor-containing ipsilateral, contralateral, and normal control renal tissue. These results provide important information relative to possible experimental therapeutic research involving embolization or pharmacologic manipulation of the blood supply to potentiate intra-arterial chemotherapy.

Animals↗
PubMed1986

DNA conformation of Chinese hamster V79 cells and sensitivity to ionizing radiation.

Chinese hamster V79 cells grown for 20 h in suspension culture form small clusters of cells (spheroids) which are more resistant to killing by ionizing radiation than V79 cells grown as monolayers. This resistance appears to be due to the greater capacity of cells grown in contact to repair radiation damage. Attempts to relate this "contact effect" to differences in DNA susceptibility or DNA repair capacity have provided conflicting results. Two techniques, alkaline sucrose gradient sedimentation and alkaline elution, show no difference in the amounts of radiation-induced DNA single-strand breakage or its repair between suspension or monolayer cells. However, using the alkali-unwinding assay, the rate of DNA unwinding is much slower for suspension cells than for monolayer cells. Interestingly, a decrease in salt concentration or in pH of the unwinding solution eliminates these differences in DNA unwinding kinetics. A fourth assay, sedimentation of nucleoids on neutral sucrose gradients, also shows a significant decrease in radiation damage produced in suspension compared to monolayer cultures. It is believed that this assay measures differences in DNA conformation (supercoiling) as well as differences in DNA strand breakage. We conclude from these four assays that the same number of DNA strand breaks/Gy is produced in monolayer and spheroid cells. However, changes in DNA conformation or packaging occur when cells are grown as spheroids, and these changes are responsible for reducing DNA damage by ionizing radiation.

Animals↗
PubMed1985

Morphological and biochemical aspects of monofunctional phosphoramide mustard teratogenicity in rat embryos cultured in vitro.

Day 10 rat embryos were exposed in vitro to a monofunctional analog of phosphoramide mustard (MPM) at concentrations of 25 to 200 micrograms/ml (144 to 1,156 X 10(-6) M). After a 24-hour exposure, embryos exhibited a dose-dependent decrease in growth parameters (crown-rump length, number of somites, and protein content) as well as incidence of malformations. Abnormal embryos were characterized by hypoplasia of the prosencephalon as well as hypoplasia of the mandibular arches, tail, and limb buds. Histological analysis revealed abnormal levels of necrotic cells, particularly in the neuroepithelium and surrounding mesenchyme. In all respects embryos exposed to MPM could not be distinguished from embryos exposed to phosphoramide mustard. We also determined using mouse L1210 cells that at the maximum nonlethal concentration used in our embryo exposure experiments, MPM did not cause DNA cross-linking but did cause single-strand DNA breaks. Phosphoramide mustard, at concentrations teratogenic to embryos in vitro, did produce DNA cross-linking. Taken together, our results indicate that although cyclophosphamide (CP)-induced DNA cross-linking may play a role in CP teratogenesis, DNA cross-linking is not an absolute requirement.

Animals↗
PubMed1985

Effect of intraperitoneal 32% dextran 70 on blood coagulation and serum electrolytes.

The most promising intraperitoneal agent for preventing adhesion formation is 32% dextran 70. To investigate its effect on blood coagulation and serum electrolytes, 22 women who required surgery for infertility were studied. No significant difference was seen in prothrombin time, partial thromboplastin time, platelet count or red-blood-cell indices between the dextran group (n = 12) and the control group (n = 10) on day 0 (before surgery) and postoperative days 1 and 3. In both groups the decrease in hematocrit and a proportionate decrease in serum albumin 24 hours after the operation suggested hemodilution. There was no further decrease in hematocrit on postoperative day 3. The dextran had no effect on serum electrolytes. These results suggest that intraperitoneal 32% dextran 70 does not impair blood coagulation and is not associated with an electrolyte inbalance.

Adult↗
PubMed1984

Deoxyribonucleic acid crosslinking by 4-hydroperoxycyclophosphamide in cyclophosphamide-sensitive and -resistant L1210 cells.

4-Hydroperoxycyclophosphamide, a synthetic, activated form of cyclophosphamide, has been used to study DNA crosslinking in L1210 cell lines sensitive and resistant to cyclophosphamide. The time course of crosslink appearance and the proportion of inter-strand to DNA-protein crosslinks support the belief that phosphoramide mustard is the ultimate alkylating agent derived from cyclophosphamide. Cell survival and DNA crosslinking studies with a cyclophosphamide-resistant L1210 cell line indicate that resistance is associated with a failure of 4-hydroperoxycyclophosphamide to produce DNA crosslinks. The ability to reverse this situation by exposure of resistant cells to disulfiram points to a role of aldehyde dehydrogenase in this mechanism of cyclophosphamide resistance.

Aldehyde Dehydrogenase↗
PubMed1984

Upper genital tract abnormalities and pregnancy outcome in diethylstilbestrol-exposed progeny.

Previous studies have suggested that there is an association between genital tract abnormalities and pregnancy outcome in women exposed to diethylstilbestrol (DES) in utero. In a collaborative study, 676 DES-exposed women had hysterosalpingographic examinations, and the findings were related to the outcome of pregnancy in 327 of these women. The findings revealed that (1) there is a considerable variation of frequency of different types of upper genital tract anomalies in women from different sources and with different motivations for enrollment in the study, (2) the presence of structural cervical changes and vaginal epithelial changes are markers for the likelihood of abnormalities in the uterine fundus, (3) women with upper genital tract abnormalities have increased odds for poor pregnancy outcome as compared to women with normal hysterosalpingographic findings, and (4) although some abnormalities were most often or consistently associated with poor pregnancy outcome, no specific changes could be related to specific types of pregnancy outcomes.

Abortion, Spontaneous↗
PubMed1984

Role of aldehyde dehydrogenase in cyclophosphamide-resistant L1210 leukemia.

A cyclophosphamide-resistant L1210 cell line has been shown to have unusually high aldehyde dehydrogenase activity. The sensitivity of this cell line to 4-methylcyclophosphamide and phosphoramide mustard in vivo and corresponding sensitivities in vitro indicate that 4-hydroxycyclophosphamide and/or aldophosphamide is the form in which cyclophosphamide reaches these tumor cells in mice and that intracellular aldehyde dehydrogenase activity is an important determinant of cyclophosphamide sensitivity in these leukemia cell lines.

Aldehyde Dehydrogenase↗
PubMed1983

The frequency of transcriptional and translational errors at nonsense codons in the lacZ gene of Escherichia coli.

Nonsense alleles in the lacZ gene of E. coli do not completely eliminate enzyme activity as errors during protein synthesis allow some chains to be completed. The relative contributions of transcriptional and translational errors to this leakiness were investigated by two methods: the introduction of rho- alleles into extreme-polar mutants and the kinetics of beta-galactosidase induction. Virtually all the errors appeared to be transcriptional in the case of two extreme-polar and one non-polar mutation. These alleles should prove useful for further in vivo investigations of RNA polymerase accuracy. With two other non-polar alleles, transcriptional mistakes were low and translational ones high. The frequency of RNA polymerase errors was context-dependent and varied for different nonsense codons in the same position and for the same codon in different positions. The reasons why some alleles showed no activity due to translational errors could not be clearly established. However, increasing the rates of ribosomal errors from one such allele with streptomycin raised the contribution of ribosomal errors to activity markedly and non-linearly. Translational mistakes may give rise to active enzyme only if the monomers are formed at a rate sufficient for effective aggregation to the normal tetramer.

Alleles↗
PubMed1983

Effect of plasma and carboxylesterase on the stability, mutagenicity, and DNA cross-linking activity of some direct-acting N-nitroso compounds.

The effects of mouse plasma, human plasma, and purified porcine liver carboxylesterase on nitrosourea, nitrosamide, and nitrosocarbamate chemical stability, mutagenicity, and DNA cross-linking activity were compared. These three classes of N-nitroso compounds are chemically similar but displayed different biological activities and were affected differently by plasma and carboxylesterase. Nitrosourea stability as well as mutagenicity and DNA cross-linking activity were affected negligibly by esterase or plasma. In contrast, nitrosamide and nitrosocarbamate stability, mutagenicity, and DNA cross-linking activity were rapidly decreased in the presence of plasma or carboxylesterase. For example, chemical half-lives were from 10- to 20-fold shorter for the nitrosamides and nitrosocarbamates in the presence of 5% mouse plasma. Similar decreases were seen for mutagenicity and DNA cross-linking activity. Preliminary studies indicated one active plasma component to be an enzyme, possibly an esterase. Additional factors such as sulfhydryls may also participate. Whereas some nitrosoureas are active antitumor agents, the lack of antitumor activity for analogous nitrosamides and nitrosocarbamates may reside predominantly in their rapid in vivo inactivation. These results may help to account for the high in vitro mutagenicity as compared with the low in vivo activities of nitrosamides and nitrosocarbamates.

Animals↗
PubMed1982

Comparison of culture and microscopy in the diagnosis of Gardnerella vaginalis infection.

A comparison was made between human blood agar containing amphotericin B, nalidixic acid and either gentamicin or colistin for the isolation of Gardnerella vaginalis from cases of non-specific vaginitis seen in a clinic for sexually transmitted diseases. The medium containing gentamicin was more inhibitory for non-Gardnerella species, but not sufficiently inhibitory to allow direct plating in the clinic without spreading for single colonies. The diffuse beta haemolysis produced by G vaginalis on human, but not on horse blood agar, proved very useful in differentiating it from other vaginal organisms and was not affected by the antibiotics used. This characteristic, together with Gram stain morphology, oxidase and catalase, provides a simple, reliable methods of identifying G vaginalis. Sixty women with symptoms of vaginitis, in whom no other pathogen was isolated, were examined by culture and microscopy. Gardnerella vaginalis was grown from 45 whereas only 31 had positive microscopy (clue cells or Gram-variable bacilli). There was no significant difference between the rate of isolation of G vaginalis in the group with positive microscopy (25/31) and that with negative microscopy (20/31).

Anti-Bacterial Agents↗
PubMed1982

Improved rabbit brain tumor model amenable to diagnostic radiographic procedures.

The VX2 carcinoma was used to create a rabbit brain tumor model. VX2 tumors were chemically dissociated and suspended in liquid medium. Twenty-five microliters of the tumor suspension containing 3 X 10(3), 3 X 10(4), or 3 X 10(5) viable tumor cells were injected through cranial burr holes 6 mm into the right frontoparietal lobes of 17 rabbits. Fifteen of these developed histologically documented nodular intraparenchymal tumors. Tumors were demonstrable with cerebral computed tomographic scans and by cerebral angiography. The feasibility of surgical resection of lesions using the fluorescein staining technique was also demonstrated. This animal brain tumor model is suitable for neuro-oncology research focusing on imaging and therapeutic techniques.

Animals↗