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Biomedical subjects

C Hill

Publications and source records attributed to C Hill.

At least 19 recordsLinked to original sources

Plasmid involvement in the formation of a spontaneous bacteriophage insensitive mutant of Lactococcus lactis.

Lactococcus lactis subsp. lactis biovar. diacetylactis DPC721 is a spontaneous bacteriophage insensitive mutant of strain DPC220, isolated after challenge with an industrial bacteriophage, phi D1. Plasmid analysis demonstrated that the bacteriophage insensitivity was associated with the absence of two native DPC220 plasmids (pAH82 and pAH33), and the presence of a novel plasmid (pAH90) in DPC721. The plasmids were transferred by conjugative mobilization to a plasmid free background where it was confirmed by restriction mapping that pAH90 is a co-integrate formed by the precise recombination of pAH82 and pAH33. The resistance phenotype encoded by pAH90 was also active against two bacteriophage homologous for the plasmid-free strain. Plasmid pAH90 was shown to encode at least two independent resistance mechanisms, including an adsorption-inhibition mechanism and a restriction and modification system. The adsorption-inhibition mechanism encoded by the co-integrate plasmid was specific for one of the phage used in this study.

Bacteriophages

Multidiagnostic evaluation of prolactin response to haloperidol challenge in schizophrenia: maximal blunting in Kraepelinian patients.

We have previously reported that prolactin (PRL) responses to haloperidol 0.5 mg IV were blunted in subjects characterized by several diagnostic systems of schizophrenia compared to controls (Keks et al 1990). However, an attempt to find a diagnostic system most different from controls was unsuccessful due to inherent difficulties in the statistical analysis of multidiagnostic data. In this paper we present new methodologies. A test for differences in dependent correlations demonstrated that most of the variance in stimulated PRL was accounted for by Kraepelinian, and least by Schneiderian and M. Bleulerian, schizophrenias (p < 0.001). The main symptomatic difference between nonKraepelinian and Kraepelinian patients was the presence of association disturbance and feelings of passivity. Patients with both symptoms had a lower stimulated PRL than controls. Further findings and possible implications are discussed.

Adult

Familial clustering of cardiovascular disease in patients with insulin-dependent diabetes and nephropathy.

BACKGROUND: Patients who have insulin-dependent diabetes mellitus and nephropathy have an excess of cardiovascular disease. Familial factors may in part account for this phenomenon. METHODS: We identified 61 white patients under 65 years of age with insulin-dependent diabetes who had nephropathy, and then matched them with 61 diabetic patients without nephropathy. We determined the prevalence of cardiovascular disease in the parents of these patients with use of information obtained from death certificates or from the World Health Organization questionnaire for cardiovascular disease. RESULTS: The rates of ascertainment of information were 96 percent (n = 117) for the parents of diabetic patients with nephropathy and 95 percent (n = 116) for the parents of patients without nephropathy. Cardiovascular disease was more often a direct cause of death among the parents of diabetic patients with nephropathy (40 percent vs. 22 percent, P less than 0.03), and the combined morbidity and mortality from cardiovascular disease in this group was greater than that in the parents of diabetic patients without nephropathy (31 percent vs. 14 percent, P less than 0.01). The age-adjusted and sex-adjusted relative risk of cardiovascular disease in this group of parents was 2.9 (95 percent confidence interval, 1.5 to 5.5; P less than 0.001). Moreover, a paternal history of cardiovascular disease was associated with a significantly increased risk of nephropathy in the diabetic patient after the analysis was adjusted for age, sex, and duration of diabetes (odds ratio, 3.2; 95 percent confidence interval, 1.3 to 7.9; P less than 0.01). Among the diabetic patients with nephropathy, those who had had a cardiovascular event were much more likely to have a family history of cardiovascular disease (odds ratio, 6.2; 95 percent confidence interval, 2.0 to 19.0; P less than 0.005) than those who had not had such an event. CONCLUSIONS: Among patients with insulin-dependent diabetes, a parental history of cardiovascular disease is significantly associated with the development of nephropathy and, among those with nephropathy, increases the likelihood of cardiovascular disease.

Adolescent

Dopamine uptake by platelets from subjects with schizophrenia: a correlation with the delusional state of the patient.

The uptake of 3H-dopamine by platelets from patients with a number of psychiatric disorders has been compared with that by platelets from normal volunteers. Overall, 3H-dopamine uptake by platelet-rich plasma (PRP) from 25 schizophrenic subjects did not differ from 3H-dopamine uptake by PRP from 22 nonschizophrenic patients and 61 normal volunteers. In the schizophrenic group, however, there was an increased spread of results with seven values falling outside the range of results observed in the control group. Furthermore, of the patients rated, only for the schizophrenic patients was there an inverse correlation between 3H-dopamine uptake by platelets and the rating for delusions on the Scale for the Assessment of Positive Symptoms. Thus, 3H-dopamine uptake by platelet seems, in some way, to be linked to be delusional state of the patient. Further study of 3H-dopamine uptake by platelets is warranted in a larger and more diverse group of patients to determine the significance of altered dopamine uptake by platelets from some schizophrenic subjects and the correlation between platelet 3H-dopamine uptake and the delusional state of these subjects.

Adult

Detection of Mycobacterium leprae and the potential for monitoring antileprosy drug therapy directly from skin biopsies by PCR.

An improved protocol for PCR analysis of Mycobacterium leprae-infected tissues, based on enzymatic lysis, has been developed and used to demonstrate the feasibility of using PCR for detecting M. leprae in routine skin biopsies taken from leprosy patients throughout the clinical spectrum. Of 92 multibacillary patients tested, 99% were PCR-positive using gel electrophoresis or DNA hybridization to detect the amplified product. Similar analysis of paucibacillary patients, in which only one of 27 biopsies had demonstrable AFB microscopically, gave a positivity rate of 74%. No PCR signals were demonstrated from skin biopsies from seven patients with non-leprosy dermatoses and one AIDS patient with a disseminated atypical mycobacteriosis. Evaluation of leprosy patients with antileprosy drug therapy prior to biopsy demonstrated that PCR signals were either greatly diminished or absent after 2 months of continuous antibiotic therapy. PCR was also able to detect the presence of M. leprae in tissues of patients receiving antibacterial therapy when patients were suspected of harbouring drug-resistant M. leprae.

Anti-Bacterial Agents

Epidemiological evidence for a common mechanism for neuroblastoma and differentiated thyroid tumour.

Because genetic predisposition probably plays an important role in the aetiology of most of childhood cancers, studies of second primaries occurring after these cancers may be particularly informative about possible common genetic mechanisms in both of these cancers. We have studied the incidence of thyroid tumours occurring after cancer in childhood in a cohort of 592 children treated before 1970. Among these children, six later developed a thyroid carcinoma, and 18 developed a thyroid adenoma. Radiation doses received to the thyroid by each of the irradiated children have been estimated using individual radiotherapeutic technical records. Thyroid carcinomas and thyroid adenomas were five times more frequent after irradiation for neuroblastoma than after irradiation for any other first cancer. This ratio did not depend on sex, nor on time elapsed since irradiation, nor on dose of radiation received for the thyroid gland. This result suggests that there is a common mechanism for the occurrence of neuroblastoma and of differentiated thyroid tumour.

Adenoma

Symptomatic response to antipsychotics differs between recent onset and recurrent chronic schizophrenic patients.

The symptomatic response to standard antipsychotic treatment was assessed over the first 4 weeks of hospitalisation in 39 patients with DSM-III schizophrenia, active phase, using the Brief Psychiatric Rating Scale (BPRS). While highly significant improvement was noted overall, 36% of patients either did not improve or worsened. Furthermore there was no diminution in the withdrawal-retardation factor of the BPRS. Patients experiencing their first admission to hospital, all with recent-onset illness, were then compared with patients who presented with a recurrence and had illness of at least 3 years duration. Despite similarities in overall response, withdrawal-retardation scores did not diminish in recent-onset patients, in contrast to multiple admissions who demonstrated significant improvement. These findings suggest greater responsiveness of negative symptoms to treatment in patients with longstanding illness, and possibly a poorer prognosis in first admission patients with deficit manifestations.

Acute Disease

[Let's stop using packet-years as expression of tobacco consumption].

It has become standard practice to describe the consumption of cigarettes by the number of "pack-years" obtained by multiplying number of packs per day by number of years. This leads conveniently to a single number summarising the overall tobacco consumption of an individual. Unfortunately, this summary is not relevant to the study of the effect of tobacco on health since it assumes identical effects of dose and duration, when the effect of duration is much larger than the effect of dose. If tobacco consumption must be summarised by a single number, the relevant figure is the duration of exposure to tobacco, ignoring the dose.

Bronchial Neoplasms

Prevalence of eating disorders in three Cambridge general practices: hidden and conspicuous morbidity.

The aims of this study were to investigate the prevalence of anorexia nervosa, bulimia nervosa and partial syndromes in women general practice attenders to establish the relative proportions of 'conspicuous' and 'hidden' morbidity. A consecutive series of 540 women patients aged 16-35 years attending their family doctor were screened using a specially devised questionnaire, the weight and dietary practices survey. A total of 115 patients were selected for further assessment and of these 101 patients were interviewed using a standardized diagnostic interview for DSM III-R eating disorders. The prevalence of anorexia nervosa was 0.2% (one case), of bulimia nervosa 1.5% (eight cases) and of partial syndrome bulimia nervosa 5.4% (29 cases). Half of the cases of bulimia nervosa had not been identified by the general practitioner and two of these patients had been referred to specialists for treatment of secondary complications of the eating disorder. Hidden cases of bulimia nervosa or partial syndromes are relatively common in general practice. Certain key questions could be used by general practitioners in order to identify women with eating disorders.

Adolescent

Trends in tobacco use in Europe.

Tobacco consumption in Europe can be estimated from several sources, including sales statistics and population surveys. The first source provides a reasonable estimate of total tobacco consumption, whereas the second gives estimates of the prevalence of smokers by sex and age. In 1950, daily cigarette consumption by adults in European countries varied between 1.7 in Portugal and 6.9 in Ireland, the corresponding US consumption being 8.9. In 1989, the variation was much smaller, ie, between 3.5 in the Netherlands and 10.1 in Greece. In the countries where consumption was high in 1950, maximum consumption was achieved around 1975, followed by stabilization or reduction. In other countries, where consumption was low in 1950, it is still increasing. In a 1987 European survey, the proportion of current smokers varied between 33% in Portugal and 46% in Denmark. Much of this difference comes from the low prevalence of smoking habits in the adult female population of southern Europe.

Europe

The bacteriophage resistance plasmid pTR2030 forms high-molecular-weight multimers in lactococci.

Lactococcus lactis ME2 can transfer a 46-kb plasmid, pTR2030, which encodes abortive phage infection (Hsp) and restriction/modification (R/M) activities. pTR2030 can be detected as a monomeric plasmid in transconjugants at low copy number, but not in ME2. pTR2030-specific probes were cloned and used to determine the location of the element in ME2. No homology was observed between these pTR2030-specific probes and the CsCl-purified plasmid content of ME2. However, probes specific for pTR2030 hybridized strongly to a high-molecular-weight moiety, and not to chromosomal DNA, in total DNA isolated by a gentle lysis procedure. The absence of junction fragments indicates that pTR2030 forms high-molecular-weight multimers in lactococci. A phage-sensitive derivative of ME2, L. lactis N1, is cured of pTR2030 and no longer possesses the high-molecular-weight species. When pTR2030 was reintroduced to N1 via conjugation, an ME2-like phage-insensitive phenotype was restored. pTR2030 could remain as a detectable monomeric plasmid in the N1 transconjugants or could revert to the high-molecular-weight structure.

Bacteriophages

Trends in cancer mortality, France 1950-1985.

Trends in mortality for main cancer sites in France between 1950 and 1985 are presented by sex. In the population aged 35-65, where long term trends can most reliably be assessed, an overall 1.1% mean annual increase is observed for males and a 0.6% mean annual decrease is observed for females. For males, this increase in total cancer mortality is mostly due to the sites associated with tobacco and alcohol. The important increase for lung cancer, and lesser increases for bladder, pancreas and kidney cancers are related to the increase in tobacco consumption from 4.7 g per adult per day in 1950 to 6.3 g in 1976. For cancer sites associated with alcohol and tobacco, namely oesophagus, pharynx, larynx, tongue and mouth, mortality is increasing similarly for males and for females, although these cancers are much less frequent among females. For females, the overall moderate decrease is mostly due to the decrease in cervix and stomach cancer mortality, uncompensated by the observed increase in breast cancer; there is no marked increase in lung cancer mortality for women, contrary to what is observed in other Western countries.

Adult

In vivo genetic exchange of a functional domain from a type II A methylase between lactococcal plasmid pTR2030 and a virulent bacteriophage.

The conjugative plasmid pTR2030 confers bacteriophage resistance to lactococci by two independent mechanisms, an abortive infection mechanism (Hsp+) and a restriction and modification system (R+/M+). pTR2030 transconjugants of lactococcal strains are used in the dairy industry to prolong the usefulness of mesophilic starter cultures. One bacteriophage which has emerged against a pTR2030 transconjugant is not susceptible to either of the two defense systems encoded by the plasmid. Phage nck202.50 (phi 50) is completely resistant to restriction by pTR2030. A region of homology between pTR2030 and phi 50 was subcloned, physically mapped, and sequenced. A region of 1,273 bp was identical in both plasmid and phage, suggesting that the fragment had recently been transferred between the two genomes. Sequence analysis confirmed that the transferred region encoded greater than 55% of the amino domain of the structural gene for a type II methylase designated LlaI. The LlaI gene is 1,869 bp in length and shows organizational similarities to the type II A methylase FokI. In addition to the amino domain, upstream sequences, possibly containing the expression signals, were present on the phage genome. The phage phi 50 fragment containing the methylase amino domain, designated LlaPI, when cloned onto the shuttle vector pSA3 was capable of modifying another phage genome in trans. This is the first report of the genetic exchange between a bacterium and a phage which confers a selective advantage on the phage. Definition of the LlaI system on pTR2030 provides the first evidence that type II systems contribute to restriction and modification phenotypes during host-dependent replication of phages in lactococci.

Amino Acid Sequence