Search PubMed⌕ Search

Biomedical subjects

T Williams

Publications and source records attributed to T Williams.

At least 55 records · Page 3Linked to original sources

BHRF1 is highly conserved in primate virus analogues of Epstein-Barr virus.

The Epstein-Barr virus (EBV) protein BHRF1 (BamHI rightward reading frame 1) was the first viral member of the Bcl-2 family of apoptosis-regulating proteins described. In vitro studies imply that BHRF1 is dispensable for virus-induced cellular transformation and virus replication. However, in contrast to several essential viral genes that show divergence outwith their functional domains, sequence data from a wide range of EBV isolates show there is striking conservation of the BHRF1 gene. Contrary to the in vitro studies, the high degree of conservation hints at a more important role for BHRF1. Analogous viruses are endemic in each of the higher primate species. Whilst their genome organisation is colinear, limited sequence analysis indicates that the viruses have diverged significantly and that only important functional domains of proteins are likely to be conserved. We have isolated the BHRF1 equivalents from the viruses which infect chimpanzees (Herpesvirus pan) and baboons (Herpesvirus papio) and find that they are highly homologous in both species, strengthening the hypothesis that BHRF1 plays a significant, evolutionarily conserved function in vivo and that changes to the protein are not well tolerated.

Amino Acid Sequence↗

Static compliance of the respiratory system in healthy infants.

We recorded static deflation pressure-volume (PV) curves from near TLC to FRC in 49 healthy, sedated, spontaneously breathing infants of 1 to 104 wk of age. Respiratory activity was transiently inhibited by inflating the respiratory system several times to a volume at an airway pressure of 30 cm H2O (V30). Passive deflation from V30 to FRC was then interrupted by multiple brief occlusions at the airway opening, in order to measure static recoil pressures. The expired volume from V30 to FRC was defined as V30E. Compliance of the respiratory system (Crs) was calculated as the slope of the linear portion of the PV curve from 5 to 15 cm H2O. Crs and V30E increased with increasing body length (p < 0.001). After adjustment for body length, males had greater Crs values than did females (p < 0.01). V30E was smaller in female infants (p < 0.05) and in infants whose mothers smoked during pregnancy (p < 0.04). Specific compliance (Crs/V30E) declined with increasing age (p < 0.01), but there were no differences related to sex or maternal smoking. We conclude that static deflation PV curves can be recorded in the age range from 1 to 104 wk, and that maternal smoking may produce hypoplastic lungs.

Child, Preschool↗

A prospective study using the Monroe Dyscontrol Scale as a measure of impulsivity in referrals to a forensic psychiatry service.

Many people referred to a forensic psychiatry service will have displayed impulsive aggression. There are few validated tests to allow a quantitative measurement of such behaviour. The Monroe Dyscontrol Scale (MDS) arose from work that recognized certain symptoms in people who had impulsive aggression, the so-called 'episodic dyscontrol syndrome'. This study uses the MDS in two groups of people who were referred to a forensic psychiatry service. One was a group of 'mentally disordered' in-patients, and the other comprised consecutive referrals to the service. The groups were compared and certain features noted. The most interesting feature was that a family history of epilepsy was common, and associated with high scores on the MDS. The value of the MDS, and the importance of a family history of epilepsy, are discussed.

Adult↗

Patient satisfaction with store-and-forward teledermatology.

We assessed patient satisfaction with a nurse-led store-and-forward teledermatology service in Manchester. A teledermatology nurse obtained the patient's history, took digital photographs of the patient's skin lesion and then sent the information to a hospital dermatologist, who responded with management advice the following week. Of 141 patients who attended their teledermatology appointment, 123 (50 male, 73 female) completed the study questionnaire (87%). The average age of respondents was 42 years (SD 17, range 18-90 years). Ninety-three per cent reported that they were happy with the teleconsultation while 86% reported that it was more convenient than going to the outpatient clinic. Forty per cent agreed that they would feel more comfortable seeing the dermatologist in person while only 58% were comfortable with not speaking to the dermatologist about their skin condition. The absence of interaction with the dermatologist and the delay in receiving management advice may have contributed to the somewhat low satisfaction rates.

Adolescent↗

Environmental sensitivities: prevalence of major symptoms in a referral center: the Nova Scotia Environmental Sensitivities Research Center Study.

Although the phenomenon of environmental sensitivities (ES) has no clear etiology nor well-accepted pathophysiology, affected individuals experience symptoms that cause varying levels of dysfunction. Through a dedicated, government-funded research and treatment center, a detailed questionnaire covering 217 symptoms in 13 systems was mailed in 1997-1998 to 812 individuals referred to the center by physicians. A total of 385 (47%) questionnaires were returned, and data were analyzed on 351 individuals. Participants tended to be women (80%), middle-aged individuals (37% age 40-49 years), and those in higher educational groups (28% completed university), but there was wide variation in demographic variables. General symptoms such as difficulty concentrating, fatigue, forgetfulness, and irritability dominated the overall prevalence of symptoms since the start of their illness. Those related to irritation such as sneezing, itchy or burning eyes, and hoarseness or loss of voice were more common after exposure to environmental irritants. Ranking of symptoms using severity scores was consistent between men and women. Overall scores were higher in women, in participants who were separated or divorced, and in low-income groups. The type and consistency of symptoms experienced after exposure to triggering substances may not fit a purely psychogenic theory.

Adolescent↗

Chemical typing of amyloid protein contained in formalin-fixed paraffin-embedded biopsy specimens.

The human amyloidoses represent a heterogeneous group of disorders characterized by the deposition of fibrillar protein in vital organs. Given the fact that at least 20 different molecules can form fibrils, the unambiguous identification of the type of amyloid deposited is critical to the correct diagnosis and treatment of patients with these disorders. Heretofore, this information has been inferred from particular clinical features of the disease, ancillary laboratory tests, and results of immunohistochemical analyses. However, to establish unequivocally the kind of protein that is deposited as amyloid, it is necessary to determine its chemical composition through amino acid sequencing or mass spectroscopy of material extracted from fibrillar deposits. We have developed a micromethod whereby such studies can be performed readily using sections of formalin-fixed, paraffin-embedded biopsy specimens. The ability to identify precisely the nature of the tissue deposits has diagnostic, therapeutic, and prognostic implications for patients with amyloid-associated disorders.

Amino Acid Sequence↗

Rhodopsin-mediated blue-light damage to the rat retina: effect of photoreversal of bleaching.

PURPOSE: Acute white-light damage to rods depends on the amount of rhodopsin available for bleaching during light exposure. Bleached rhodopsin is metabolically regenerated through the visual cycle involving the pigment epithelium, or photochemically by deep blue light through photoreversal of bleaching. Because photoreversal is faster than metabolic regeneration of rhodopsin by several orders of magnitude, the photon catch capacity of the retina is significantly augmented during blue-light illumination, which may explain the greater susceptibility of the retina to blue light than to green light. However, blue light can also affect function of several blue-light-absorbing enzymes that may lead to the induction of retinal damage. Therefore, this study was conducted to test whether rhodopsin and its bleaching intermediates play a role in blue-light-induced retinal degeneration. METHODS: Eyes of anesthetized rats and mice that did or did not contain rhodopsin were exposed to green (550 +/- 10 nm) or deep blue (403 +/- 10 nm) light for up to 2 hours. Rats with nearly rhodopsinless retinas were obtained by bleaching rhodopsin in animals with inhibited metabolic rhodopsin regeneration-that is, under halothane anesthesia. In addition, Rpe65(-/-) mice that are completely without rhodopsin were used to test the susceptibility to blue-light damage of a rodent retina completely devoid of the visual pigment. Effects of illumination on photoreceptor morphology were assessed 24 hours or 10 days thereafter by morphologic and biochemical methods. RESULTS: Exposure to blue light resulted in severe retinal damage and activation of the transcription factor AP-1 in rats. In contrast, green light had no effect. When rhodopsin was almost completely bleached by short-term green-light exposure while metabolic regeneration (but not photoreversal) was prevented by halothane anesthesia, blue-light exposure induced distinct lesions in rat retinas. When both metabolic rhodopsin regeneration and photoreversal of bleaching were almost completely inhibited, blue-light exposure caused only very moderate lesions. When mice without rhodopsin were exposed to blue light, no damage occurred, in contrast to wild-type control mice. CONCLUSIONS: Short time exposure to blue light has deleterious effects on retinal morphology. Because damage was observed only in the presence of the visual pigment, blue-light-induced retinal degeneration is rhodopsin mediated. Absorption of blue light by other proteins is not sufficient to induce light damage. Photoreversal of bleaching, which occurs only in blue but not in green light, increases the photon-catch capacity of the retina and may thus account for the difference in the damage potential between blue and green light.

Animals↗

The mechanisms of parasite clearance after antimalarial treatment of Plasmodium falciparum malaria.

Studies were conducted to determine how malaria parasites are cleared from the blood after antimalarial treatment. Neither artesunate nor quinine decreased parasitized red cell deformability or increased antibody binding. In acute falciparum malaria, ring-infected erythrocyte surface antigen (RESA) was observed in erythrocytes without malaria parasites (RESA-red blood cell [RBC]), indicating prior parasitization. In uncomplicated malaria, RESA-RBC numbers increased significantly (P=.002) within 24 h of starting artesunate but rose much more slowly (7 days) after quinine treatment. In severe malaria, RESA-RBC increased significantly (P=. 001) within hours of starting artesunate but not with quinine treatment (P=.43). RESA-RBCs were not produced after drug treatment of malaria parasite cultures in vitro. Rapid malaria parasite clearance after treatment with artemisinin derivatives results mainly from the extraction of drug-affected parasites from host erythrocytes-presumably by the spleen. This explains why the fall in hematocrit after treatment of hyperparasitemia is often less than that predicted from loss of parasitized cells.

Animals↗

Behavioral treatment of PTSD in a perpetrator of manslaughter: a single case study.

Studies of posttraumatic stress disorder (PTSD) have predominantly focused on victims of trauma. Some studies have examined the after-effects of a person's own violent actions in combat or police situations. However, there is a sparsity of literature examining the development of PTSD in convicted perpetrators of violent crime, and there is no literature concerning the treatment of PTSD in such perpetrators. This single-case study presents the outcome of behavioral treatment in one case in which the patient had PTSD consequential to being a perpetrator of manslaughter. The theoretical implications of this case are briefly discussed.

Female↗

An epizootic of patent iridescent virus disease in multiple species of blackflies in Chiapas, Mexico.

Simulium blackfly larvae (Diptera: Simuliidae) were collected from rivers and streams at 500-1500 m a.s.l. in Chiapas State of southern Mexico. Among 45 sites surveyed over an area of 2300 km2 (around 15 degrees 15'N 92 degrees 20'W), some Simulium larvae from three sites were opalescent violet-blue, interpreted as patent infection with invertebrate iridescent virus (IIV). Dissection confirmed the presence of putative Iridovirus particles, 130nm diameter, but no IIV isolates were obtained from homogenates injected into Galleria mellonella (L) larvae (Lepidoptera: Pyralidae). All Simulium with patent IIV infection died before metamorphosis, whereas approximately 60% of asymptomatic Simulium survived to adulthood in the laboratory. During 1997, standard monthly samples from two parallel rivers 42-50 km north-west of Tapachula comprised the following species proportions (and rates of patent IIV infection): 41.8% (47%) Simulium mexicanum Bellardi complex, 31.3% (31.4%) S. rubicundum Knab, 10.1% (13.1%) S. paynei, 6.5% (2.9%) S. callidum (Dyar & Shannon), 6.3% (5.1%) S. ochraceum Walker complex, 3.1% (0.7%) S. downsi Vargas et al., 0.7% S. samboni Jennings and 0.2% S. metallicum Bellardi complex, showing a strong correlation between blackfly abundance and the prevalence of patent infection. An epizootic of IIV in January and February (infection rates 41-100%) was followed by absence of larvae (March-August) until the end of the rainy season, when numbers collected on nylon strings rose to approximately 1/cm with patent IIV infection rates of 0-12.5% during September-December. Further investigations are underway to isolate this IIV and assess its potential usefulness for biological control of Simulium pests and vectors of onchocerciasis.

Animals↗

Armadillo exposure and Hansen's disease: an epidemiologic survey in southern Texas.

BACKGROUND: Naturally occurring leprosy has been demonstrated in wild nine-banded armadillos (Dasypus novemcinctus ). This suggests a possible mode of transmission of human leprosy in regions where armadillo contact is prevalent. OBJECTIVE: Our purpose was to study the possible relationship between armadillo exposure and Hansen's disease. METHOD: One hundred one patients (67 men, 34 women) with established Hansen's disease seen in the Hansen's Disease Clinic in Houston, Texas, were questioned about their exposure to armadillos. These patients were divided into two groups: Asian (n = 32) and non-Asian (n = 69). RESULTS: Seventy-one percent of the non-Asian patients surveyed reported either direct or indirect armadillo exposure. None of the Asian patients reported armadillo exposure (P <.001). Of the non-Asian patients, 75.4% had lepromatous disease versus 50.0% of the Asian patients (P <.001). The average age at diagnosis for the non-Asian group with Hansen's disease in this study was 51 versus 38 years for the Asian group (P <.001). CONCLUSION: Although it is yet to be determined whether direct transmission from the armadillo to human occurs, it is likely based on the high incidence of armadillo exposure in non-Asian patients with Hansen's disease in our study population that this animal acts as a reservoir for human disease. However, the Asian patients reporting no known armadillo exposure likely obtained the disease from person-to-person contact in their respective countries of origin where Hansen's disease has a much higher prevalence.

Adolescent↗

Prevalence of HFE (hemochromatosis gene) mutations in unselected male patients with type 2 diabetes.

To assess the prevalence of mutations in the HFE (hemochromatosis) gene in unselected male patients with type 2 diabetes, we examined 220 white men without known diabetes and 220 age-matched white men with type 2 diabetes for mutations in the HFE gene. Nucleotide 845 (C282Y) and 187(H63D) alleles were amplified by polymerase chain reaction (PCR) with lymphocyte DNA. The PCR products were analyzed by restriction enzyme digestion. One of the 220 patients (0.45%) with diabetes was homozygous for the HFE 845A (C282Y) mutation and 25 (11.3%) were heterozygous for the same mutation, of whom 3 (1.3%) were compound heterozygotes also carrying the HFE 187G (H63D) mutation. These frequencies did not differ significantly from the control population without diabetes. There is no evidence that HFE mutations are found in excess in unselected male patients with type 2 diabetes, and there is no indication for a population-based search for an excess of these alleles in type 2 diabetes.

Adult↗

Magnetic resonance imaging to distinguish the type and severity of pediatric inflammatory bowel diseases.

BACKGROUND: The distinction between ulcerative colitis and Crohn's disease is important, because treatment options and clinical course may vary. Magnetic resonance imaging (MRI) allows noninvasive transmural assessment of the intestine and may facilitate differentiation of ulcerative colitis from Crohn's disease. The objective of this prospective study was to determine whether MRI differentiates Crohn's disease from ulcerative colitis in children as effectively as colonoscopy with mucosal biopsies. METHODS: Fifteen patients underwent colonoscopy with biopsies followed by abdominal MRI. The MRI diagnosis, determined by two radiologists independently completing a standardized form was compared with the gastroenterologic diagnosis. RESULTS: After colonoscopy and review of histology, Crohn's disease was diagnosed in nine patients, ulcerative colitis in five, and indeterminate colitis in one, who was excluded from study. Agreement of the MRI diagnosis with the gastroenterologic diagnosis was 4 of 4 (100%) for ulcerative colitis, 4 of 10 (40%) for Crohn's disease considering both radiologists, and 5 of 10 (50%) for Crohn's disease for each radiologist individually. Percentage of enhancement by MRI did not correlate with the severity of inflammation determined at endoscopy among the patients with Crohn's disease (r = -0.3, P = 0.366). There was agreement on severity of inflammation in three of four patients with ulcerative colitis. CONCLUSIONS: Current MRI interpretation of inflammatory bowel disease did not adequately recognize Crohn's disease in children. Therefore, colonoscopy with biopsy remains the most accurate tool for determining the type and severity of inflammatory bowel disease in children and adolescents.

Adolescent↗

Respiratory changes in vasovagal syncope.

INTRODUCTION: Respiratory changes accompany the cardiovascular changes during head-up, tilt test-induced vasovagal syncope. METHODS AND RESULTS: Using the 45-minute 60 degrees head-up Westminster protocol, 29 patients were studied (mean age 53.9+/-20.0 years; 19 females). Two groups resulted: tilt-induced vasovagal syncope positive and negative. The cardiorespiratory parameters blood pressure (BP), heart rate (HR), tidal volume, and minute volume were measured. Comparisons of the cardiorespiratory parameters were made within the positive group and negative group, and then between the two groups. There were 14 in the positive group and 15 in the negative group. Baseline measurements were normalized to 1.0. Comparing the late tilt periods between the positive and negative groups, there were differences in BP (P < 0.002), HR (P < 0.002), tidal volume (P < 0.05), and minute volume (P < 0.002). In the positive group comparing early with late intervals: BP 1.11+/-0.09 versus 0.49+/-0.17, P < 0.0001; HR 1.18+/-0.12 versus 0.85+/-0.35, P < 0.009; tidal volume 1.39+/-0.34 versus 2.17+/-1.00, P < 0.015; and minute volume 1.24+/-0.26 versus 3.3+/-2.03, P < 0.0025. There were no comparable cardiorespiratory changes in the negative group. CONCLUSION: There were significant differences in the respiratory and cardiovascular parameters measured between those who were positive and those who were negative for tilt-induced vasovagal syncope. Within the positive group, in addition to the falls in HR and BP, there were significant increases in minute volume and tidal volume during late tilt. This suggests that there may be a role for respiratory sensors in vasovagal syncope that may permit earlier and hence possibly more effective therapy for selected patients.

Adult↗