Biomedical subjects

S Holroyd

Publications and source records attributed to S Holroyd.

At least 19 recordsLinked to original sources

PubMed2002

The genome sequence of Schizosaccharomyces pombe.

We have sequenced and annotated the genome of fission yeast (Schizosaccharomyces pombe), which contains the smallest number of protein-coding genes yet recorded for a eukaryote: 4,824. The centromeres are between 35 and 110 kilobases (kb) and contain related repeats including a highly conserved 1.8-kb element. Regions upstream of genes are longer than in budding yeast (Saccharomyces cerevisiae), possibly reflecting more-extended control regions. Some 43% of the genes contain introns, of which there are 4,730. Fifty genes have significant similarity with human disease genes; half of these are cancer related. We identify highly conserved genes important for eukaryotic cell organization including those required for the cytoskeleton, compartmentation, cell-cycle control, proteolysis, protein phosphorylation and RNA splicing. These genes may have originated with the appearance of eukaryotic life. Few similarly conserved genes that are important for multicellular organization were identified, suggesting that the transition from prokaryotes to eukaryotes required more new genes than did the transition from unicellular to multicellular organization.

Base Sequence↗

PubMed2001

Complete genome sequence of a multiple drug resistant Salmonella enterica serovar Typhi CT18.

Salmonella enterica serovar Typhi (S. typhi) is the aetiological agent of typhoid fever, a serious invasive bacterial disease of humans with an annual global burden of approximately 16 million cases, leading to 600,000 fatalities. Many S. enterica serovars actively invade the mucosal surface of the intestine but are normally contained in healthy individuals by the local immune defence mechanisms. However, S. typhi has evolved the ability to spread to the deeper tissues of humans, including liver, spleen and bone marrow. Here we have sequenced the 4,809,037-base pair (bp) genome of a S. typhi (CT18) that is resistant to multiple drugs, revealing the presence of hundreds of insertions and deletions compared with the Escherichia coli genome, ranging in size from single genes to large islands. Notably, the genome sequence identifies over two hundred pseudogenes, several corresponding to genes that are known to contribute to virulence in Salmonella typhimurium. This genetic degradation may contribute to the human-restricted host range for S. typhi. CT18 harbours a 218,150-bp multiple-drug-resistance incH1 plasmid (pHCM1), and a 106,516-bp cryptic plasmid (pHCM2), which shows recent common ancestry with a virulence plasmid of Yersinia pestis.

Chromosome Mapping↗

PubMed2001

Genome sequence of Yersinia pestis, the causative agent of plague.

The Gram-negative bacterium Yersinia pestis is the causative agent of the systemic invasive infectious disease classically referred to as plague, and has been responsible for three human pandemics: the Justinian plague (sixth to eighth centuries), the Black Death (fourteenth to nineteenth centuries) and modern plague (nineteenth century to the present day). The recent identification of strains resistant to multiple drugs and the potential use of Y. pestis as an agent of biological warfare mean that plague still poses a threat to human health. Here we report the complete genome sequence of Y. pestis strain CO92, consisting of a 4.65-megabase (Mb) chromosome and three plasmids of 96.2 kilobases (kb), 70.3 kb and 9.6 kb. The genome is unusually rich in insertion sequences and displays anomalies in GC base-composition bias, indicating frequent intragenomic recombination. Many genes seem to have been acquired from other bacteria and viruses (including adhesins, secretion systems and insecticidal toxins). The genome contains around 150 pseudogenes, many of which are remnants of a redundant enteropathogenic lifestyle. The evidence of ongoing genome fluidity, expansion and decay suggests Y. pestis is a pathogen that has undergone large-scale genetic flux and provides a unique insight into the ways in which new and highly virulent pathogens evolve.

Animals↗

PubMed2001

Massive gene decay in the leprosy bacillus.

Leprosy, a chronic human neurological disease, results from infection with the obligate intracellular pathogen Mycobacterium leprae, a close relative of the tubercle bacillus. Mycobacterium leprae has the longest doubling time of all known bacteria and has thwarted every effort at culture in the laboratory. Comparing the 3.27-megabase (Mb) genome sequence of an armadillo-derived Indian isolate of the leprosy bacillus with that of Mycobacterium tuberculosis (4.41 Mb) provides clear explanations for these properties and reveals an extreme case of reductive evolution. Less than half of the genome contains functional genes but pseudogenes, with intact counterparts in M. tuberculosis, abound. Genome downsizing and the current mosaic arrangement appear to have resulted from extensive recombination events between dispersed repetitive sequences. Gene deletion and decay have eliminated many important metabolic activities including siderophore production, part of the oxidative and most of the microaerophilic and anaerobic respiratory chains, and numerous catabolic systems and their regulatory circuits.

Animals↗

PubMed2001

Prospective study of hallucinations and delusions in Parkinson's disease.

OBJECTIVE: This study was undertaken to determine the prevalence of hallucinations and delusions in Parkinson's disease, to describe such symptoms phenomenologically, and possibly to determine factors associated with their development. In addition, the role of the visual system in relation to visual hallucinations was examined. METHOD: 102 consecutive patients diagnosed with strictly defined Parkinson's disease were examined for the presence of hallucinations and delusions and assessed for visual acuity, cognition, depression using the geriatric depression scale, disease severity as measured by the UPDRS, and other clinical variables. RESULTS: Of 102 consecutive patients, 29.4% (n=30) had hallucinations or delusions, four (3.9%) were determined to be psychotic due solely to delirium and were excluded from further analysis. Of the 98 remaining patients, 26.5% (n=26) had visual hallucinations. Among these, one patient also had delusions, two had auditory hallucinations, and one had gustatory hallucinations. Visual hallucinations were significantly associated with worse visual acuity, lower cognitive score, higher depression score, and worse disease severity. Hallucinations were not associated with history of psychiatric disease, dose or duration of levodopa or other antiparkinsonian medication treatment, or duration of illness. CONCLUSIONS: Visual hallucinations are common symptoms in Parkinson's disease and are most likely of multifactorial origin. Although higher doses of levodopa are known to be related clinically to hallucinations in individual patients, the results suggest that several underlying characteristics of patients with Parkinson's disease (disease severity, dementia, depression, worse visual acuity) may be more important determinants of which patients experience hallucinations. The data also provide preliminary evidence that abnormality of the visual system may be related to visual hallucinations in Parkinson's disease, as has been found in other disorders with visual hallucinations.

Aged↗

PubMed2000

Complete DNA sequence of a serogroup A strain of Neisseria meningitidis Z2491.

Neisseria meningitidis causes bacterial meningitis and is therefore responsible for considerable morbidity and mortality in both the developed and the developing world. Meningococci are opportunistic pathogens that colonize the nasopharynges and oropharynges of asymptomatic carriers. For reasons that are still mostly unknown, they occasionally gain access to the blood, and subsequently to the cerebrospinal fluid, to cause septicaemia and meningitis. N. meningitidis strains are divided into a number of serogroups on the basis of the immunochemistry of their capsular polysaccharides; serogroup A strains are responsible for major epidemics and pandemics of meningococcal disease, and therefore most of the morbidity and mortality associated with this disease. Here we have determined the complete genome sequence of a serogroup A strain of Neisseria meningitidis, Z2491. The sequence is 2,184,406 base pairs in length, with an overall G+C content of 51.8%, and contains 2,121 predicted coding sequences. The most notable feature of the genome is the presence of many hundreds of repetitive elements, ranging from short repeats, positioned either singly or in large multiple arrays, to insertion sequences and gene duplications of one kilobase or more. Many of these repeats appear to be involved in genome fluidity and antigenic variation in this important human pathogen.

Antigenic Variation↗

PubMed2000

The genome sequence of the food-borne pathogen Campylobacter jejuni reveals hypervariable sequences.

Campylobacter jejuni, from the delta-epsilon group of proteobacteria, is a microaerophilic, Gram-negative, flagellate, spiral bacterium-properties it shares with the related gastric pathogen Helicobacter pylori. It is the leading cause of bacterial food-borne diarrhoeal disease throughout the world. In addition, infection with C. jejuni is the most frequent antecedent to a form of neuromuscular paralysis known as Guillain-Barré syndrome. Here we report the genome sequence of C. jejuni NCTC11168. C. jejuni has a circular chromosome of 1,641,481 base pairs (30.6% G+C) which is predicted to encode 1,654 proteins and 54 stable RNA species. The genome is unusual in that there are virtually no insertion sequences or phage-associated sequences and very few repeat sequences. One of the most striking findings in the genome was the presence of hypervariable sequences. These short homopolymeric runs of nucleotides were commonly found in genes encoding the biosynthesis or modification of surface structures, or in closely linked genes of unknown function. The apparently high rate of variation of these homopolymeric tracts may be important in the survival strategy of C. jejuni.

Amino Acid Sequence↗

PubMed2000

MRI findings differentiate between late-onset schizophrenia and late-life mood disorder.

OBJECTIVES: Compare MRI scans of patients with late-onset schizophrenia, late-life depression and late-life bipolar disorder to age- and gender-matched controls. MRI head scans of 14 patients in each diagnostic group and 21 patients in the normal control group were compared. Subjects were recruited from inpatient and outpatient services. MEASURES: The CERAD MRI rating algorithm was used to rate degree of atrophy. RESULTS: Patients with bipolar and unipolar disorder had greater left sylvian fissure and left and right temporal sulcal enlargement, and more bilateral cortical atrophy than normals. Patients with late-onset schizophrenia had larger right temporal horns and larger third ventricles. These findings validate the distinctions between late-life affective disorder and late-onset schizophrenia and mirror changes reported in younger individuals. They may reflect underlying structural and functional abnormalities found in neuropathologic and functional imaging studies.

Age of Onset↗

PubMed2000

Occipital atrophy is associated with visual hallucinations in Alzheimer's disease.

In this study of patients with Alzheimer's disease (AD), patients with visual hallucinations were compared with patients who did not have visual hallucinations to determine if selective occipital lobe atrophy is associated with visual hallucinations. Seven AD patients with visual hallucinations were matched by cognitive score to 7 AD patients without visual hallucinations and 3-D MRI images obtained. A ratio of measured occipital volumes to whole brain volumes was compared between the two groups. AD patients with visual hallucinations had a significantly smaller occipital/whole brain ratio than AD patients without visual hallucinations. These results suggest visual hallucinations in AD may be associated with neuropathology of the occipital lobe.

Aged↗

PubMed2000

In Reply.

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Journal Article↗

PubMed1999

The complete nucleotide sequence of chromosome 3 of Plasmodium falciparum.

Analysis of Plasmodium falciparum chromosome 3, and comparison with chromosome 2, highlights novel features of chromosome organization and gene structure. The sub-telomeric regions of chromosome 3 show a conserved order of features, including repetitive DNA sequences, members of multigene families involved in pathogenesis and antigenic variation, a number of conserved pseudogenes, and several genes of unknown function. A putative centromere has been identified that has a core region of about 2 kilobases with an extremely high (adenine + thymidine) composition and arrays of tandem repeats. We have predicted 215 protein-coding genes and two transfer RNA genes in the 1,060,106-base-pair chromosome sequence. The predicted protein-coding genes can be divided into three main classes: 52.6% are not spliced, 45.1% have a large exon with short additional 5' or 3' exons, and 2.3% have a multiple exon structure more typical of higher eukaryotes.

Animals↗

PubMed1999

Psychotropic drugs in acute intermittent porphyria.

Acute intermittent porphyria is one of a group of metabolic diseases called the porphyrias that may lead to symptoms of the central nervous system during an acute exacerbation. Certain drugs such as barbiturates are known to precipitate attacks of acute intermittent porphyria, but unfortunately there is little information regarding the safety of many psychotropic drugs in this disorder, especially the newer antidepressants and atypical antipsychotics. We report a case of an elderly patient with acute intermittent porphyria who was treated with a variety of psychotropic agents for a severe depression with psychotic features. Although many of the agents did not improve the psychiatric status of the patient, all the drugs were tolerated without precipitating an episode of acute intermittent porphyria. To our knowledge, this is the first report of the safe use of sertraline, venlafaxine, olanzapine, risperidone, clozapine, buspirone, trazodone, lorazepam, and clonazepam in a patient with documented acute intermittent porphyria. Our report also supports the safety of trifluoperazine. Although response and sensitivity to drugs may vary greatly among patients with this disorder, clinicians may want to consider the possibility of the above drugs to treat psychiatric symptoms in patients with acute intermittent porphyria.

Antidepressive Agents↗

PubMed1999

Correlates of psychotic symptoms among elderly outpatients.

Psychotic symptoms presenting in late life can offer a diagnostic challenge to the clinician. In this study, 140 geriatric outpatients were prospectively examined for psychotic symptoms and assessed on a number of demographic and clinical variables. Cognition was assessed using the Mini-Mental State Exam. Psychiatric diagnoses were made by DSM-III-R criteria. Twenty-seven per cent (N = 38) had psychotic symptoms, delusions being the most common type. Patients with psychosis were significantly more likely to have a previous history of psychosis, to have a lower MMSE and to live in a nursing home. Four diagnoses accounted for 79.5% of all psychotic patients. In order of frequency, these were dementia, major depression, delirium and organic psychosis (organic hallucinosis, organic delusional disorder). Psychotic patients were significantly more likely to have a diagnosis of dementia, delirium or organic psychosis than non-psychotics, but depression was significantly more likely to occur in patients without psychosis. Although psychotic symptoms occur in a variety of illnesses, elderly patients with psychosis should be carefully evaluated for these disorders.

Aged↗

PubMed1998

Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence.

Countless millions of people have died from tuberculosis, a chronic infectious disease caused by the tubercle bacillus. The complete genome sequence of the best-characterized strain of Mycobacterium tuberculosis, H37Rv, has been determined and analysed in order to improve our understanding of the biology of this slow-growing pathogen and to help the conception of new prophylactic and therapeutic interventions. The genome comprises 4,411,529 base pairs, contains around 4,000 genes, and has a very high guanine + cytosine content that is reflected in the biased amino-acid content of the proteins. M. tuberculosis differs radically from other bacteria in that a very large portion of its coding capacity is devoted to the production of enzymes involved in lipogenesis and lipolysis, and to two new families of glycine-rich proteins with a repetitive structure that may represent a source of antigenic variation.

Chromosome Mapping↗

PubMed1997

Differences in geriatric psychiatry outpatients with early- vs late-onset depression.

This study assessed clinical and demographic differences between 74 geriatric psychiatry outpatients with early-onset vs late-onset depression. The following data were considered: age, gender, marital status, years of education, number of prescription medications and active medical diagnoses (including presence of various categories of medical disorder), presence of any comorbid dementia or other psychiatric disorder, age of depression onset, number of depressive episodes and MMSE score. Fifteen patients (20.3%) had an early onset of depression (before age 60 years) and 59 (79.7%) had a late onset of depression. Early-onset patients had significantly more episodes of depression than late-onset patients (4.2 vs 1.9, t = 4.74, p < 0.001). Patients with early-onset depression also had a higher mean number of prescribed medications (5.3 vs 3.5, t = 2.29, p = 0.025) and active medical disorders (4.6 vs 3.1, t = 2.89, p = 0.005). Specifically, early onset of depression was associated with an elevated prevalence of cardiac disease (53.3% vs 23.7%, chi 2 = 5.0, df = 1, p = 0.025), diabetes (46.7% vs 16.9%, chi 2 = 6.0, df = 1, p = 0.015), gastrointestinal disorder (40.0% vs 12.0%, chi 2 = 6.5, df = 1, p = 0.011) and arthritis (26.7% vs 6.8%, chi 2 = 4.9, df = 1, p = 0.027). These findings support previous reports that people with a history of depression experience greater medical morbidity than those without a history of depression. The study groups did not differ with respect to MMSE score or presence of a concurrent dementia disorder. These results were unexpected given previous studies that indicate greater cognitive impairment in late- vs early-onset depression. The potential contribution of increased vascular risk factors among the early-onset depression group may have partly contributed to the finding of no difference in cognition between groups in the present study.

Age of Onset↗

PubMed1997

Substance use disorders in a geriatric psychiatry outpatient clinic: prevalence and epidemiologic characteristics.

This study was conducted to determine the prevalence of substance use disorders in a geriatric psychiatry outpatient clinic. The overall prevalence for any substance use disorder was 20% (N = 28). The prevalence of benzodiazepine dependence was 11.4% (N = 16); the prevalence of alcohol dependence was 8.6% (N = 12); and the prevalence of prescription narcotic dependence was 1.4% (N = 2). These findings suggest that substance use disorders in the geriatric psychiatry outpatient population exist to a significantly greater extent than previously reported. Descriptive statistics were used to characterize patients with benzodiazepine dependence, alcohol dependence, and no substance use disorder. These groups were compared on demographic and clinical variables using one-way analysis of variance (ANOVA) and chi-squared statistical techniques. Clinicians working in comparable outpatient settings may be in a better position to prevent, detect, and treat substance use disorders in their patients as a result of increased awareness of its epidemiologic characteristics in this population.

Aged↗

PubMed1997

A descriptive study of elderly community-dwelling alcoholic patients in the rural south.

Alcohol-related disorders, estimated to be more prevalent in the South, are associated with serious comorbid disorders, such as depression and suicide. In a rural outreach program, the authors examined patients with a diagnosis of alcoholism and compared them with nonalcoholic patients on various demographic and descriptive variables. Of 166 patients referred to the program, 35 (21.1%) had an alcohol-related disorder. Alcoholism was significantly associated with male gender and younger age, but nearly half of the alcoholic subjects were women. Alcoholism is associated with inappropriate health care utilization; alcohol-related disorders produced significantly more emergency room visits and somewhat more hospital admission; these patients were less likely to have a primary care physician. No patient was receiving treatment for alcoholism.

Activities of Daily Living↗

PubMed1997

Characteristics of persons utilizing a geriatric psychiatry outpatient clinic.

Mental-health service utilization among elderly people has been shown to be low relative to younger age groups. This study was done to determine the current proportion of elderly persons served in a university-affiliated psychiatry outpatient clinic, and to better characterize elderly patients who receive specialized mental-health care in this setting. The proportion of visits from elderly patients (aged 60 and over) was found to be 16%. Demographic and clinical characteristics of a sample of 140 consecutive geriatric patients evaluated at the clinic were obtained. The data revealed that the patients had a mean age of 74.7+/-7.5 (SD) years, and were mostly female (72.1%) and white (78.6%). Surprisingly, the age distribution was found to be bell shaped, with a small upper tail. The three most prevalent psychiatric diagnoses were depression (56.4%), dementia (35.7%), and substance use disorder (20%). Overall, 59.3% of geriatric patients had a history of prior psychiatric treatment. Females were significantly more likely than males to have a psychiatric history (69.3% vs. 33.3%, P = .0001). Among patients with a psychiatric history, females were more likely to have a current diagnosis of major depression (P = .0006), while males were more likely to have a current substance use disorder (P = .03). The prevalence of dementia increased with each successive decade above 60, while the occurrence of bipolar and adjustment disorders was confined to younger geriatric patients. Elderly patients receiving psychiatric treatment in the clinic thus formed a heterogeneous group. Gender, age, and presence of a psychiatric history were all associated with differences in prevalence and distribution of various mental disorders in this geriatric psychiatry outpatient clinic.

Age Distribution↗