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Biomedical subjects

H Thompson

Publications and source records attributed to H Thompson.

At least 19 recordsLinked to original sources

Physical map and organization of Arabidopsis thaliana chromosome 4.

A physical map of Arabidopsis thaliana chromosome 4 was constructed in yeast artificial chromosome clones and used to analyze the organization of the chromosome. Mapping of the nucleolar organizing region and the centromere integrated the physical and cytogenetic maps. Detailed comparison of physical with genetic distances showed that the frequency of recombination varied substantially, with relative hot and cold spots occurring along the whole chromosome. Eight repeated DNA sequence families were found in a complex arrangement across the centromeric region and nowhere else on the chromosome.

Arabidopsis

Dissociation of the genotoxic and growth inhibitory effects of selenium.

The effects of forms of selenium compounds that enter the cellular selenium metabolic pathway at different points were investigated in a mouse mammary carcinoma cell line. The goal of these experiments was to determine if the genotoxicity of selenium, defined as its ability to induce DNA single-strand breaks, could be dissociated from activities proposed to account for its cancer inhibitory activity. The results demonstrated that growth inhibition, measured as inhibition of cell proliferation and induction of cell death, was induced by all the forms of selenium evaluated. However, sodium selenite and sodium selenide, which are metabolized predominantly to hydrogen selenide, caused the rapid induction of DNA single-strand breaks as an early event that preceded growth inhibition. Interestingly methylselenocyanate and Se-methylselenocysteine, which are initially metabolized predominantly to methylselenol, induced growth inhibition in the absence of DNA single-strand breakage. Differences in the time course of selenium retention, in the occurrence of membrane damage, and in the induction of morphological changes by selenite versus methylselenocyanate were noted. Collectively, these data indicate that different pathways affecting cell proliferation and cell death are induced depending on whether selenium undergoes metabolism predominantly to hydrogen selenide or to methylselenol.

Animals

A cluster of cases of feline dysautonomia (Key-Gaskell syndrome) in a closed colony of cats.

Twenty-five cases of feline dysautonomia (Key-Gaskell syndrome) occurred in a closed cat colony over a period of three weeks. The clinical and pathological signs were sufficiently similar to those reported during the 1982-1986 outbreak to establish a positive diagnosis. The special epidemiological and environmental circumstances of the outbreak provide a new insight into the cause(s) of the syndrome.

Animals

Comparison of isolates of canine parvovirus by restriction enzyme analysis, and vaccine efficacy against field strains.

Canine parvovirus isolates from clinical cases of enteritis were obtained from the United Kingdom, Germany and the USA and differentiated by restriction enzyme analysis into three groups, namely CPV2, CPV2a and CPV2b. The three groups were readily identified by their HphI restriction profile. CPV2 was not prevalent in cases of canine parvovirus disease after 1986. Only two CPV2 strains (original type) were found among 110 strains isolated after 1980. In Europe the frequency of isolation of the CPV2a and CPV2b field strains was similar whereas in the USA the CPV2b strain predominated. Dogs inoculated with a vaccine strain were resistant to infection after challenge with UK isolates of CPV2a and CPV2b.

Animals

Cellular and metabolic effects of triphenylselenonium chloride in a mammary cell culture model.

Triphenylselenonium chloride, a novel synthetic organic selenium compound in which selenium is bonded to three unsubstituted benzene rings, possesses significant chemopreventive activity against chemically-induced mammary carcinogenesis. The effects of triphenylselenonium chloride on a mammary tumor cell line (MOD) were compared to selenite, a reference compound in selenium chemoprevention research. It was observed that triphenylselenonium chloride treatment exerted a cytostatic effect in the absence of membrane damage or DNA strand breaks. The observed cytostasis was associated with a selenium concentration-dependent inhibition of cell proliferation, measured by [3H]thymidine incorporation into DNA, and delayed cell cycle progression. In contrast, selenite treatment rapidly induced DNA damage and cell death. These marked differences were observed across the same levels of cellular selenium. In addition, triphenylselenonium chloride treatment increased glucose consumption and lactate production, indicating an effect of the compound on cellular energy metabolism. Collectively these observations demonstrate that the toxic activities associated with selenite treatment do not occur when cells are treated with triphenylselenonium chloride. This compound represents a new type of selenium compound that exerts significant cellular effects through mechanisms distinct from those induced by selenite.

Animals

Vaginal cysts causing tenesmus in a bitch.

An eight-year-old female border collie was referred with a two-month history of faecal tenesmus. Ultrasonography and radiology identified fluid-filled masses in the cranial vagina. The fluid was drained from the vaginal cysts via an episiotomy and the clinical signs resolved. Histological examination confirmed that the cysts were of urogenital origin. This is believed to be the first report of vaginal cysts causing faecal tenesmus in the dog.

Animals

KCl cotransport activity in light versus dense transferrin receptor-positive sickle reticulocytes.

A subset of sickle cells becomes K(+)-depleted and dehydrated before or soon after leaving the bone marrow. These young cells may be identified in blood as transferrin receptor-positive (TfR+) dense reticulocytes. KCl cotransport, which is normally active in young erythroid cells with a maximum at pH 6.8, is a candidate pathway for K+ depletion of sickle reticulocytes. In this investigation, KCl cotransport activity was evaluated in young, TfR+ cells which had become dense in vivo and in age-matched cells which had retained normal hydration. Sickle erythrocytes were first separated into three primary density fractions, with care taken to preserve the in vivo hydration state. After normalization of intracellular hemoglobin concentration with nystatin, the cells were incubated at 37 degrees C for 20 min at pH 6.8 and 7.4. Before and after incubation, each primary fraction was separated into four secondary density fractions. The percentage of TfR+ cells in each secondary fraction was measured and a density distribution for TfR+ cells was determined for each primary fraction before and after incubation. The density shift during incubation was a measure of KCl cotransport. TfR+ cells from the denser primary fractions II and III had significantly more density shift than TfR+ cells from the light fraction I. Although the shifts were larger at low pH, differences between primary fractions were also observed at pH 7.4. These data indicate that the cells which become dense quickly in vivo have more KCl cotransport activity than those which remain light in vivo, and support this pathway as a primary mechanism for dehydration of young sickle cells.

Anemia, Sickle Cell

The gut-brain peptide cyclo(His-Pro) is secreted in a pulsatile fashion in fasting humans.

Histidyl-proline diketopiperazine (CHP) is a cyclic dipeptide that is found in many animal tissues, most notably brain and gut. It has been found to have a variety of biologic actions and has been postulated to play a role in appetitive behavior and energy metabolism. This study was conducted in order to characterize the secretory pattern of CHP during a 24 h fast. Four subjects (2 obese and 2 lean) were studied during the latter 24 h of a 36 h fast. Blood was sampled every 10-15 min and assayed for CHP concentration using a specific radioimmunoassay. Analysis revealed that circulating CHP oscillates in humans and that diurnal variation occurred but only in the obese subjects.

Adult

Adenocarcinoma arising in an oesophageal colonic interposition graft.

This case report describes the rare complication of an adenocarcinoma developing in a colonic interposition graft 20 years following surgical resection of a postcricoid squamous carcinoma. A free jejunal graft was used for further oesophageal reconstruction following resection of the colonic graft.

Adenocarcinoma

Activity of triphenylselenonium chloride in mammary cancer prevention.

The present study was designed to evaluate the tolerance and cancer chemopreventive activity of triphenylselenonium chloride in female Sprague-Dawley rats. No information is available in the literature on the anticarcinogenic efficacy of a lipophilic cationic selenium compound as exemplified by the triphenylselenonium ion. A short-term preliminary study indicated that it was well tolerated via the dietary route. Supplementation at levels up to 200 p.p.m. Se did not produce any apparent adverse effect in the animals. In the dimethylbenzanthracene mammary cancer model, a level of 30 p.p.m. Se in the diet reduced the total tumor yield by approximately 70% when treatment was applied during either the initiation phase or the post-initiation phase. In the MNU mammary cancer model, the inhibitory response was expressed only during the post-initiation phase. These findings suggest that the triphenylselenonium ion may have multiple modes of action in suppressing the development of neoplasia. Tissue analysis confirmed that there was minimal accumulation of total selenium until the level of supplementation reached 100 p.p.m. Se or above. Our study therefore convincingly demonstrates that triphenylselenonium chloride fits the criteria of an effective and desirable anticancer agent with a distinct separation between the chemopreventive dose range and the toxic dose range.

9,10-Dimethyl-1,2-benzanthracene

Expression of p53 in early (T1) gastric carcinoma and precancerous adjacent mucosa.

Abnormalities of the tumour suppressor gene p53 have been shown in approximately 60% of advanced gastric adenocarcinomas and it has been suggested that the immunohistochemical finding of increased p53 expression is a prognostic marker in gastric cancer. No studies of early (T1) tumours have been reported. Over expression of p53 protein in 95 early gastric carcinomas and in adjacent mucosa was investigated using immunohistochemistry with antibody CM1. Thirty five per cent of the tumours were positive. The frequency of p53 positivity in tumours of tubular histological type (46%) was significantly higher than that in signet ring tumours (10%) (p = 0.006), and neoplasms that invaded deeply into the submucosa were more frequently positive (45%) than others (30%). Five of eight (62%) T1 tumours with lymph node metastases showed immunoreactive p53. In signet ring tumours, immunopositivity correlated with the frequency of DNA aneuploidy. p53 Over expression was also found in 15% of 26 examples of high grade dysplasia in mucosa adjacent to invasive tumours. No positivity was found in intestinal metaplasia or in normal mucosa. The findings show that immunocytochemically demonstrable over expression of p53 correlates with other morphological markers of aggressiveness in T1 gastric adenocarcinoma. The increasing frequency of p53 immunoreactivity in the sequence of high grade dysplasia-->early gastric cancer-->advanced gastric cancer supports the view that abnormalities of p53 are related to tumour progression in gastric carcinogenesis.

Adenocarcinoma

Polysulfone capillary fiber for intraocular drug delivery: in vitro and in vivo evaluations.

Studies were conducted to investigate the usefulness of polysulfone capillary fiber (PCF) as a drug delivery device for intraocular applications. Carboxyfluorescein (CF) was used as a model drug to prepare PCF-dye devices for both in vitro and in vivo kinetic studies. For the in vitro study, PCF-CF devices were incubated in 0.1 M phosphate buffer, pH 7.4 at 37 degrees C, and CF release was quantified at various times up to 5 weeks. In vitro results indicated a bi-phasic, sustained-release profile of CF from the PCF device for over 30 days. PCF-CF devices released 5% and 10% of their initial CF contents by the first and second day following incubation, respectively. By 10 days after incubation, approximately 50% of the dye content was released from the PCF-CF devices. The rate of dye release decreased thereafter, such that 65% and 90% of CF was released by 17 and 28 days after incubation, respectively. In a subsequent study, the in vivo kinetics of the PCF-CF device were determined in the rabbit eye. PCF-dye devices were prepared with the following CF formulations: 1) microsphere-incorporated CF; 2) lyophilized liposome-encapsulated CF; or 3) micronized CF powder. A PCF-dye device was implanted in the vitreous cavity, and fluorophotometry from the retina to the anterior chamber was performed at various times up to 45 days to quantify fluorescein level. At the conclusion of the study, eyes were enucleated and examined for histopathology. The time-course study showed fluorescein level for up to 45 days in the vitreous. The midvitreous concentration-time profile indicated a CF t1/2 of 10 and 30 days for the PCF-CF powder and PCF-CF liposome preparation, respectively. In contrast, the PCF device prepared with microsphere-incorporated CF showed fluorescein level with a t1/2 of less than one week in the vitreous. Histological examination of the eyes implanted with PCF or PCF-dye device showed no sign of ocular toxicity. Collectively, these results indicated that the PCF device is biocompatible and may be useful for the extended release of drugs in the posterior segment of the eye.

Analysis of Variance

Effects of cholinoceptor and 5-hydroxytryptamine3 receptor antagonism on erythromycin-induced canine intestinal motility disruption and emesis.

1. Erythromycin administration is associated with gastrointestinal problems, disturbed gastrointestinal motility and emesis. This study in the dog investigates the underlying mechanisms. 2. Intestinal myoelectrical activity and the occurrence and latency of emesis were recorded in eight conscious dogs. All drugs were administered intravenously. 3. Erythromycin (7 mg kg-1) increased contractions of the proximal small intestine, and caused emesis in all fasted dogs and in 5 dogs after food. Atropine (50 mg kg-1 min-1) and hexamethonium (10 mg kg-1 h-1) partially inhibited the GI motility effects but did not significantly reduce emesis. 4. Metoclopramide at a high dose (2 mg kg-1 h-1) reduced the incidence of emesis in the presence of increased intestinal motility, but a low dose (150 micrograms kg-1 h-1) was ineffective. 5. A 5-hydroxytryptamine3 (5-HT3) receptor antagonist, MDL 72222 (1 mg kg-1), reduced emesis when given alone and combined with metoclopramide (low dose). The 5-HT4 receptor agonist BRL24924 (Renzapride, 1 mg kg-1) had no effect on emesis either alone in combination with metoclopramide. 6. In conclusion, erythromycin-induced GI motility disturbances and emesis are not causally related. Whereas the increase in intestinal smooth muscle activity is possibly cholinergically mediated, emesis occurs at least in part via a 5-hydroxytryptaminergic mechanism, but does not involve the dopamine system.

Animals

Distemper encephalitis in pups after vaccination of the dam.

A five-year-old labrador bitch which had whelped 10 pups three days previously was given booster vaccination against distemper, adenovirus, parvovirus, parainfluenzavirus and leptospirosis. Eighteen days later, signs of central nervous system disease developed in some of the pups, five of which were ultimately euthanased. The cause of the nervous disease was found to be canine distemper, and serological studies showed that the infection was limited to some members of the litter, suggesting that the vaccinal rather than a field virus was more likely to have been responsible.

Animals