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Biomedical subjects

J Bell

Publications and source records attributed to J Bell.

At least 145 records · Page 8Linked to original sources
PubMed1997

Second primary cancers after cancers of the colon and rectum in New South Wales, Australia, 1972-1991.

Data from the New South Wales Central Cancer Registry for the period 1972-1991 were examined to determine the risk of second primary cancers after an initial invasive cancer of the colon (ICD-9 153) or rectum (ICD-9 154). The expected numbers of cancers were obtained by assuming that subjects experienced the same cancer incidence as prevailed in the corresponding general population and by applying sex-, age-, and calendar-specific rates to the appropriate person-years at risk. The relative risk (RR) of a second primary cancer was taken to be the ratio of observed:expected numbers of second cancers. After colon cancer, there was an excess of cancers of the small intestine in both sexes (RRs of 4.5 and 4.4); prostate (RR = 1.4) and kidney (RR = 1.8) in men; and breast (RR = 1.3), body of uterus (RR = 1.9), ovary (RR = 2.8), and thyroid (RR = 2.7) in women. Lung cancer occurred less frequently in men than expected (RR = 0.7). After rectal cancer, men had increased risks of cancers of the colon (RR = 1.5) and prostate (RR = 1.3) and a reduced risk of pancreatic cancer (RR = 0.3). A reciprocal relationship of increased risk was seen between cancers of the proximal (but not the distal) colon and rectum. Shared luminal risk factors for proximal colon cancer and rectal cancer and three syndromes of hereditary predisposition to colon cancer seem to be the major contributors to second primary cancers in patients with an initial colon cancer. Sources of bias have been considered.

Age Factors↗
PubMed1997

[Neuronal apoptosis in the central and peripheral nervous system in HIV infection].

Apart from the unique changes characteristic of "HIV encephalitis", the productive infection of central nervous system by HIV, which predominantly involves the white matter and basal ganglia, evidence is accumulating that the cerebral cortex may also be affected in AIDS patients. Neuronal loss, suspected at microscopic examination, has been demonstrated by a number of morphometric studies. However, the cause and mechanism of neuronal damage in HIV infection, are still unclear. In an attempt to look for an apoptotic process at the origin of neuronal loss in AIDS, we examined samples of frontal cortex, temporal cortex and basal ganglia from 12 patients who died from AIDS and 4 asymptomatic HIV-positive cases using in situ end labelling to demonstrate characteristic DNA fragmentation. These were compared with 5 asymptomatic seronegative controls, and 2 seronegative patients with Alzheimer's disease. We demonstrated neuronal apoptosis in all AIDS cases and in the Alzheimer's cases. Positive in situ end labelling was usually associated with morphological changes suggestive of neuronal apoptosis. Semiquantitative assessment of the density of apoptotic neurons showed that neuronal apoptosis was more severe in atrophic brains. In contrast, no correlation was found between the density of apoptotic neurons and the presence of HIV-encephalitis or a history of cognitive disorder. Only occasional apoptotic neurons were found in one asymptomatic, HIV-positive case. Apoptosis was never observed in asymptomatic seronegative cases. We also looked for apoptotic neurons in spinal ganglia of 20 AIDS cases, 5 of whom had a terminal sensory distal neuropathy, and 10 seronegative controls devoid of neuropathy. Apoptotic neurons were found in 6 of the AIDS patients and in none of the seronegative controls. However, no correlation was found between the severity of neuronal apoptosis in the spinal root ganglia and the presence of absence of a terminal distal sensory neuropathy. Experimental studies tend to support our in vivo findings. HIV-infection of primary cultures of human embryonic central nervous system induced frequent apoptosis of neurons. No apoptotic cell was identified in non infected control cultures.

AIDS Dementia Complex↗
PubMed1996

Susceptibility to human papillomavirus-associated cervical intra-epithelial neoplasia is determined by specific HLA DR-DQ alleles.

Human papillomaviruses (HPV) play a causative role in the aetiology of cervical intra-epithelial neoplasia (CIN) and cervical cancer. Human leukocyte antigens (HLA) are important in the regulation of immune response to foreign antigens. The role of genetic variation at the HLA class II loci (DR and DQ) in CIN (HPV 16, 18, 31 and 33 typed) was investigated by PCR DNA amplification and oligonucleotide probe typing of cervical smears from British Caucasian patients (n = 176) and controls (n = 416). The alleles of the DQB1*03, DRB1*04 and DRB1*11 loci were strongly associated with susceptibility to CIN. Specifically, the haplotypes DRB1*0401-DQB1*0301 and DRB1*1101-DQB1*0301 were significant and indicated susceptibility. The DQB1*03 locus was more contributory to this association than the DRB1 loci. A weak protective effect was shown for the haplotype DRB1*0101-DQB1*0501. Positive correlation was also observed for HPV-positive CIN, suggesting that specific HLA class II alleles may be important in determining the immune response to HPV antigens and the risk for CIN after HPV infection. Our results should help in the rational design of vaccines against HPV.

Alleles↗
PubMed1996

Clonal populations of CD4+ and CD8+ T cells in patients with multiple myeloma and paraproteinemia.

Patients with paraproteinemia have abnormalities in their T-cell subsets including inversion of the CD4:CD8 ratio and increased expression of activation markers. Recently, distortions in T-cell receptor (TCR) TCRAV and TCRBV gene segment expression have been reported, although the significance of these observations is unclear given the finding of clonal populations of CD8+ T cells in healthy elderly individuals. We have used an extensive range of TCR V-region-specific monoclonal antibodies to assess TCRAV and TCRBV expression in patients with myeloma and paraproteinemia. TCR sequence analysis was used to assess the clonality of expansions and 3-color fluorescence-activated cell sorting analysis determined the phenotype of the expanded populations. The patients show novel oligoclonal expansions within the CD4+ subset and show an increased frequency of CD8+ expansions. Oligoclonal CD4+ T cells belong to the rare CD4+CD28- T-cell subset, a phenotype associated with granular morphology. CD45RA and CD11b are expressed on many of the CD8 T-cell expansions. Comparison of T-cell receptor sequences from two T-cell clones in one patient suggests a possible role for a common peptide antigen in the generation of the expansions. Further work is needed to identify the relevance of such T cells to the B-cell proliferation.

Aged↗
PubMed1996

Disease in children infected with HIV in Abidjan, Côte d'Ivoire.

OBJECTIVE: To document the range of disease in African children infected with HIV. DESIGN: Necropsy results in consecutive children aged 1 month or more who were HIV positive and in children who were HIV negative for comparison; IgA western blots on serum samples from children under 2 years of age who were positive for HIV-1 to test the validity of routine HIV serology. SETTING: Largest hospital in Abidjan, Côte d'Ivoire. SUBJECTS: 78 children who were HIV positive and 77 children who were HIV negative on whom a necropsy was performed; their median ages at death were 18 and 21 months respectively. 36 HIV positive children and 29 HIV negative children were 1-14 months old; 42 HIV positive and 48 HIV negative children were > or = 15 months old. MAIN OUTCOME MEASURES: Cause of death and prevalence of diseases confirmed pathologically. RESULTS: Respiratory tract infections were more common in HIV positive than in HIV negative children (73 (94%) v 52 (68%); P < 0.05), and were aetiologically heterogeneous. Pneumocystis carinii pneumonia was found in 11 out of 36 (31%) HIV positive children aged < 15 months, but in no HIV negative children. Among older children measles was more common in HIV positive children (8/42 (19%) v 2/48 (4%); P < 0.06). Pyogenic meningitis was present in similar proportions of HIV positive and HIV negative children aged < 15 months (7/36 (19%) and 7/29 (24%)). In HIV positive children tuberculosis (1/78), lymphocytic interstitial pneumonitis (1/78), and HIV encephalitis (2/78) were rare. CONCLUSIONS: There is greater overlap between diseases associated with HIV infection and other common health problems in African children than there is in adults. Compared with adults, HIV positive children had a high prevalence of P carinii pneumonia and a low prevalence of tuberculosis. Measles, but not malaria, was associated with HIV infection.

AIDS Dementia Complex↗
PubMed1996

Isolation, characterization, and properties of a trypsin-chymotrypsin inhibitor from amaranth seeds.

A trypsin-chymotrypsin inhibitor was isolated from the seeds of amaranth--a highly nutritious protein source. The purification of the inhibitor (AmI) was carried out by affinity chromatography on trypsin-Sepharose and by HPLC. AmI is a single-chain protein of 8 kD, as determined by electrophoresis on SDS-polyacrylamide gels and by gel exclusion on Sephadex G-50 column. It is stable at neutral and alkaline pH and is relatively thermostable. AmI inhibits trypsin and chymotrypsin from the digestive system of insects such as Tribolium castaneum and Locusta migratoria, supporting the hypothesis that inhibitors may have evolved as defense mechanisms of seeds against insects. AmI lost its inhibitory activities when submitted to limited proteolysis with trypsin, while limited proteolysis with chymotrypsin had almost no effect. The partial amino acid sequence of 45 amino acids from the amino terminus of AmI differs significantly from the known sequences of legume-seed and cereal-grain protease inhibitor families. Differences in the chemistry at the inhibitory site(s) and in the amino acid sequence of AmI in comparison to that of other cereal and legume inhibitors suggest that AmI is a member of a new family of serine protease inhibitors. AmI was found to inhibit the anchorage-independent growth of MCF-7 breast cancer cells, suggesting that AmI may have anticarcinogenic activity.

Amino Acid Sequence↗
PubMed1996

Differential release of prostaglandins by organ cultures of human fetal trachea and lung.

Human fetal lung at 16-19 weeks gestation has a partially differentiated epithelium, and in organ culture, distal airsacs dilate and the epithelium autodifferentiates to type I and II pneumatocytes, processes regulated by endogenous prostaglandin PGE2. Human fetal trachea, at the same gestation, has a terminally differentiated mucociliary epithelium but after 4-6 d in organ culture, develops squamous metaplasia. Tracheal cultures restricted to 3 d have normal phase-contrast and light microscopy appearances and immunohistochemical reactivities (epithelium: cytokeratin 7,8,18; glutathione S-transferase pi-isozyme; epithelial membrane antigen and mesenchyme; desmin; vimentin). In human fetal trachea organ cultures, the predominant prostaglandins released are 6-keto-PGF1 alpha, PGF2 alpha, and PGE2, a pattern similar to that previously described for human adult trachea and lung. In fetal lung cultures, 13,14-dihydro-15-keto-PGF2 alpha is the major prostaglandin released with lesser amounts of 13,14-dihydro-15-keto-PFG2 alpha,PGF2 alpha,PGE2, and 6-keto-PGF1 alpha. Human fetal lung in vitro has the competence to self-differentiate, as early as 12 weeks gestation and presence of high levels in fetal lung of the inactive metabolite 13,14-dihydro-15-keto-PGE2 relative to PGE2 suggests that active prostaglandin catabolism may be one of the mechanisms to retard this stage of maturation in vivo by limiting PGE2 availability. Surprisingly, the profile of prostaglandins released from fetal lung organ culture does not change to that of a mature lung with terminal differentiation of the epithelium, and this may indicate differences in the expression of key prostaglandin-metabolizing enzymes in developing human fetal lung in culture and with in utero ontogeny.

Animals↗
PubMed1996

Disk diffusion interpretive criteria for fusidic acid susceptibility testing of staphylococci by the National Committee for Clinical Laboratory Standards method.

Fusidic acid is used in many countries for the treatment of multiresistant staphylococcal infection, especially multiresistant Staphylococcus aureus infection (MRSA). We collected consecutive fusidic acid-resistant isolates of staphylococci from the routine laboratory over several years, and compared these strains with fusidic acid-susceptible staphylococci to establish interpretive criteria for disk diffusion testing by National Committee for Clinical Laboratory Standards (NCCLS) methods. The minimum inhibitory concentrations (MICs) and zone diameters for strains of S. aureus (n = 102), including MRSA, S. saprophyticus (n = 20) and other coagulase-negative staphylococci (n = 115) were determined by NCCLS agar dilution and disk diffusion tests using a 2.5-micrograms disk of fusidic acid. MICs were bimodally distributed. No isolates had MICs of 0.5 or 1 microgram/ml; thus, we chose these values to define strains of intermediate susceptibility. The error-rate-bounded method was used to determine interpretive zone diameters for disk testing. Interpretive zone diameter criteria were found to be: susceptible > or = 22 mm, intermediate 18-21 mm, and resistant < or = 17 mm. All S. saprophyticus were intrinsically resistant to fusidic acid (MIC > or = 2 micrograms/ml).

Anti-Bacterial Agents↗
PubMed1996

Extra-articular features of benign joint hypermobility syndrome.

To define the phenotype of patients with benign joint hypermobility syndrome (BJHS), we studied 58 consecutive patients (mean age 37 yr) presenting to a rheumatology clinic and 30 controls. Patients underwent rheumatological and ophthalmic examination, hypermobility scoring, echocardiography, measurement of bone mineral density (BMD), and skin thickness, elasticity and light transmissibility. The median hypermobility score was 5/9 Beighton and 31/56 Contompasis. Eighteen (31%) patients complained of significant arthralgia. Six (10%) patients and two (7%) controls had mitral valve prolapse (MVP) (chi(2) = 0.27, P = NS). Neither MVP nor aortic diameters showed a correlation with hypermobility score. There was no significant reduction in BMD. There was a significant correlation between hypermobility and light transmissibility of the skin (r = 0.71, P < 0.0001 Contompasis; r = 0.47, P < 0.05 Beighton) and skin stretchiness (r = 0.49, P < 0.05 Contompasis; r = 0.39, P < 0.05 Beighton). On ophthalmic examination, 14 (41%) patients had upper eyelid laxity. Thus, patients with BJHS do not have an increased prevalence of significant cardiac, bone, skin or eye abnormalities, helping differentiate BJHS from other more serious hereditary disorders of connective tissue.

Adolescent↗
PubMed1996

Cross-screening: a new method to assemble clones rapidly and unambiguously into contigs.

We have developed a new procedure that relies on an array of cross-hybridization tests to order a set of random clones into a contig. The method, called cross-screening, uses each clone as a target and its end sequences as probes, in a matrix of reciprocal cross-hybridization tests performed on a single blot. The relationships among the clones are determined rapidly from the pairwise tests, allowing clone order to be determined directly. We have applied this technique to DNAs from a set of overlapping lambda clones from Drosophila chromosome 4. The location and orientation of each clone derived from the cross-screening data was that expected from the map assembled from overlapping restriction sites and chromosomal walking. The procedure provided additional information on a previously unknown, internally repeated DNA sequence. To demonstrate the general utility of the procedure, we have applied it to a previously described clone set within a contig in region 22q12 of human chromosome 22. The correct relative position and orientation of these clones were derived from the cross-screening data without knowledge of, or reference to, any nucleotide sequence or restriction site analysis of the DNA concerned. The cross-screening procedure is fast, economical, and robust and allows clone overlaps to be determined efficiently, with minimal interference from repeated DNA sequences. This new procedure is specifically designed for small groups of overlapping clones (tens to hundreds) and should facilitate the ordering of subclone libraries derived from small chromosomes or the large cloned inserts carried in YAC, BAC, and P1 vectors.

Animals↗
PubMed1996

Differences in patterns of care of prostate cancer, New South Wales, 1991.

BACKGROUND: In this time of uncertainty about the benefits of earlier diagnosis for prostate cancer and the optimal choice of treatment in various clinical scenarios, we addressed the hypothesis that two groups in the population, namely country dwellers and migrants from non-English-speaking countries, were less likely to be offered new methods of diagnosis and treatment for prostate cancer. METHODS: Incident cases of prostate cancer in 1991 were identified through the population-based New South Wales Central Cancer Registry. For 73% of eligible cases information relating to diagnosis, staging and treatment was abstracted onto a checklist from clinical records in urologists' consulting rooms and in public hospitals. RESULTS: Transrectal ultrasound and prostatic biopsy were used for diagnosis significantly more often in urban than in rural cases while the reverse was true for transurethral resection of the prostate. Intravenous pyelography, ultrasound (other than transrectal) and bone scans were performed for staging more frequently in urban than rural cases. Rural cases were more likely to be treated with anti-androgens than urban cases and less likely to be given luteinizing-hormone releasing hormone (LH-RH) agonists. The pattern of use of various diagnostic and staging procedures for 1991 rural cases resembled that for urban men diagnosed with prostate cancer in 1986 rather than that for 1991 urban cases. CONCLUSIONS: At least in part, these urban-rural differences could be explained by the fact that some patients in the country would have been treated by general surgeons rather than urologists. The patterns of care for non-English-speaking migrants resembled those for the Australian-born and for English-speaking migrants.

Delivery of Health Care↗
PubMed1996

Cervical cancer in New South Wales women: five-year survival, 1972 to 1991.

We analysed five-year relative survival of 6992 cases of cervical cancer incident between 1972 and 1991 in New South Wales (NSW) women, using data from the population-based state Cancer Registry. Follow-up was to 1992. Survival was determined by record linkage to death certificates. Relative survival was derived from absolute survival of cases with expected survival of age- and period-matched NSW women. Proportional hazard regression analysis was used for multivariate analysis. Relative survival at five years improved from 64 per cent in 1972-1976 to 72 per cent in 1987-1991, although the only significant increase occurred between 1972-1976 and 1977-1981 (64 to 70 per cent). Survival was better for the age groups 0-39 years (RR 0.51) and 40-49 years (RR 0.63) and worse for the elderly (> or = 65 years) (RR 1.47) than for the referent group (50-64 years). Excess mortality was much less for those with localised disease (referent group), than for those with regional spread (RR 3.47) or metastatic cancer (RR 10.5) at diagnosis. For the most recent period (1987-1991), relative five-year survival for localised disease was 82 per cent, for regional spread at diagnosis it was 49 per cent, and for metastatic cancer 21 per cent. When adjusted for confounding, excess mortality was significantly higher for adenocarcinoma (RR 1.16) than for squamous cell carcinoma. Five-year relative survival for cervical cancer in NSW women for the most recent period is similar to that in South Australia, and both compare favourably with international statistics. The lack of improvement of five-year survival for cervical cancer over 15 years since 1977-1981 reinforces the importance of prevention through regular screening by cytology.

Adenocarcinoma↗
PubMed1996

Neuropathology of early HIV-1 infection.

Early HIV-1 invasion of the central nervous system has been demonstrated by many cerebrospinal fluid studies; however, most HIV-1 carriers remain neurologically unimpaired during the so called "asymptomatic" period lasting from seroconversion to symptomatic AIDS. Therefore, neuropathological studies in the early pre-AIDS stages are very few, and the natural history of central nervous system changes in HIV-1 infection remains poorly understood. Examination of brains of asymptomatic HIV-1 positive individuals who died accidentally and of rare cases with acute fatal encephalopathy revealing HIV infection, and comparison with experimental simian immunodeficiency virus and feline immunodeficiency virus infections suggest that, invasion of the CNS by HIV-1 occurs at the time of primary infection and induces an immunological process in the central nervous system. This includes an inflammatory T-cell reaction with vasculitis and leptomeningitis, and immune activation of brain parenchyma with increased number of microglial cells, upregulation of major histocompatibility complex class II antigens and local production of cytokines. Myelin pallor and gliosis of the white matter are usually found and are likely to be the consequence of opening of the blood brain barrier due to vasculitis; direct damage to oligodendrocytes by cytokines may also interfere. These white matter changes may explain, at least partly, the early cerebral atrophy observed, by magnetic resonance imaging, in asymptomatic HIV-1 carriers. In contrast, cortical damage seems to be a late event in the course of HIV-1 infection. There is no significant neuronal loss at the early stages of the disease, no accompanying increase in glial fibrillary acid protein staining in the cortex, and only exceptional neuronal apoptosis. Although HIV-1 proviral DNA may be demonstrated in a number of brains, viral replication remains very low during the asymptomatic stage of HIV-1 infection. This makes it likely that, although opening of the blood brain barrier may facilitate viral entry into the brain, specific immune responses including both neutralising antibodies and cytotoxic T-lymphocytes, continuously inhibits viral replication at that stage.

Acquired Immunodeficiency Syndrome↗
PubMed1996

HLA class I associations of ankylosing spondylitis in the white population in the United Kingdom.

OBJECTIVE: To investigate the HLA class I associations of ankylosing spondylitis (AS) in the white population, with particular reference to HLA-B27 subtypes. METHODS: HLA-B27 and -B60 typing was performed in 284 white patients with AS. Allele frequencies of HLA-B27 and HLA-B60 from 5926 white bone marrow donors were used for comparison. HLA-B27 subtyping was performed by single strand conformation polymorphism (SSCP) in all HLA-B27 positive AS patients, and 154 HLA-B27 positive ethnically matched blood donors. RESULTS: The strong association of HLA-B27 and AS was confirmed (odds ratio (OR) 171, 95% confidence interval (CI) 135 to 218; p < 10(-99)). The association of HLA-B60 with AS was confirmed in HLA-B27 positive cases (OR 3.6, 95% CI 2.1 to 6.3; p < 5 x 10(-5)), and a similar association was demonstrated in HLA-B27 negative AS (OR 3.5, 95% CI 1.1 to 11.4; p < 0.05). No significant difference was observed in the frequencies of HLA-B27 allelic subtypes in patients and controls (HLA-B*2702, three of 172 patients v five of 154 controls; HLA-B*2705, 169 of 172 patients v 147 of 154 controls; HLA-B*2708, none of 172 patients v two of 154 controls), and no novel HLA-B27 alleles were detected. CONCLUSION: HLA-B27 and -B60 are associated with susceptibility to AS, but differences in HLA-B27 subtype do not affect susceptibility to AS in this white population.

Alleles↗
PubMed1996

Comparison of the efficacy of a demand oxygen delivery system with continuous low flow oxygen in subjects with stable COPD and severe oxygen desaturation on walking.

BACKGROUND: Provision of ambulatory oxygen using an intermittent pulsed flow regulated by a demand oxygen delivery system (DODS) greatly increases the limited supply time of standard portable gaseous cylinders. The efficacy of such a system has not previously been studied during submaximal exercise in subjects with severe chronic obstructive pulmonary disease (COPD) in whom desaturation is likely to be great and where usage is often most appropriate. METHODS: Fifteen subjects with severe COPD and oxygen desaturation underwent six minute walk tests performed in random order to compare the efficacy of a demand oxygen delivery system (DODS) with continuous flow oxygen. Walk distance, breathlessness, oxygen saturation, resting time, and recovery time (objective and subjective) were recorded and compared for each walk. RESULTS: Breathing continuous oxygen compared with baseline air breathing improved mean walk distance (295 m versus 271 m) and recovery time (47 seconds versus 112 seconds), whilst the lowest recorded saturation (81% versus 74%) and time desaturated below 90% (201 seconds versus 299 seconds) were reduced. When the DODS was compared with air breathing only the walk distance changed (283 m versus 271 m). A comparison of the DODS with continuous oxygen breathing showed the DODS to be less effective at oxygenating subjects with inferior lowest saturation (78% versus 81%), time spent below 90% (284 seconds versus 201 seconds), time to objective recovery (83 seconds versus 47 seconds), and walk distance (283 m versus 295 m). CONCLUSIONS: Neither of the delivery systems was able to prevent desaturation in these subjects. The use of continuous flow oxygen, however, was accompanied by improvements in oxygenation, walk distance, and recovery time compared with air breathing. The DODS produced only a small increase in walk distance without elevation of oxygen saturation, but was inferior to continuous flow oxygen in most of the measured variables when compared directly.

Administration, Inhalation↗
PubMed1996

A comparison of MRI and clinical examination of acute lateral ankle sprains.

Because of its excellent soft tissue contrast and ability to demonstrate soft tissue structures, magnetic resonance imaging is ideally suited to the evaluation of the soft tissues surrounding the ankle, including the lateral collateral ligaments. This study was undertaken to compare the clinical evaluation of 15 patients who suffered inversion injuries of the ankle with the results found on magnetic resonance imaging within 48 hours of the injury. Physical examination was found to be 100% accurate in the diagnosis of grade III ligament injuries but only 25% accurate in the diagnosis of grade II injuries. Clinicians most often underestimate the damage with a grade II ligament tear. Furthermore, other associated injuries, such as significant capsule ruptures and tendon damage, were often overlooked at physical examination.

Acute Disease↗