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Biomedical subjects

M A Johnson

Publications and source records attributed to M A Johnson.

At least 199 records · Page 11Linked to original sources
PubMed1997

Comparison of CO2 laser, electrocautery, and scalpel incisions on acute-phase reactants in rat skin.

Lasers and electrocautery devices have been applied as an alternative to the scalpel because of better hemostasis and lymphatic sealing. However, previous studies have demonstrated conflicting data regarding the effects of these modalities on the inflammatory response, the first reaction by tissue during wound healing. The purpose of this study is to quantitate inflammatory responses in rat skin following laser, electrocautery, and scalpel injury by measuring T-kininogen (T-KGN), a major acute-phase protein in the rat and its endogenous substrate, cathepsin B, an important inflammatory mediator. Full-thickness wounds (6 cm) were created on the dorsum of Sprague Dawley rats by using a laser, electrocautery, or scalpel. Tissue samples were harvested at 1 hour to 21 days after injury. T-KGN levels were radioimmunoassayed; cathepsin B activity was assayed by using a synthetic substrate Z-Arg-Arg-MCA. Data were analyzed by analysis of variance. T-KGN levels peaked at 3 days for all modalities, although the laser group was statistically (P < or = 0.01) higher at 1, 3, and 7 days after injury. In contrast, cathepsin B activity was significantly (P < or = 0.01) lower at 3 days in the laser group. CO2 laser ablation incites a greater inflammatory response than electrocautery or scalpel injuries. High levels of T-KGN may provide protection from proteolytic damage associated with cathepsins.

Animals↗
PubMed1997

A new mtDNA mutation showing accumulation with time and restriction to skeletal muscle.

We have identified a new mutation in mtDNA, involving tRNALeu(CUN) in a patient manifesting an isolated skeletal myopathy. This heteroplasmic A-->G transition at position 12320 affects the T psi C loop at a conserved site and was not found in 120 controls. Analysis of cultured fibroblasts, white blood cells/platelets, and skeletal muscle showed that only skeletal muscle contained the mutation and that only this tissue demonstrated a biochemical defect of respiratory-chain activity. In a series of four muscle-biopsy specimens taken over a 12-year period, there was a gradual increase, from 70% to 90%, in the overall level of mutation, as well as a marked clinical deterioration. Single-fiber PCR confirmed that the proportion of mutant mtDNA was highest in cytochrome c oxidase-negative fibers. This study, which reports a mutation involving tRNALeu(CUN), demonstrates clearly that mtDNA point mutations can accumulate over time and may be restricted in their tissue distribution. Furthermore, clinical deterioration seemed to follow the increase in the level of mutation, although, interestingly, the appearance of fibers deficient in respiratory-chain activity showed a lag period.

Base Sequence↗
PubMed1997

Repeat HIV testers at a London same-day testing clinic.

OBJECTIVE: To compare the characteristics of repeat HIV testers with first-time testers in a National Health Service HIV testing clinic in London. SUBJECTS AND METHODS: A self-administered questionnaire was distributed to clinic attenders between September 1995 and January 1996. The sample was stratified by gender and sexual orientation. Repeat and first-time testers were compared with respect to recent sexual risk behaviour, reasons for taking the HIV test, condom use, knowledge of sex partner's HIV status, and sociodemographic and psychosocial variables. RESULTS: Of 965 clinic attenders surveyed, 404 (41.9%) reported at least one previous HIV test outside the window period and were classified as repeat testers: homosexual men, 62.5% (178 out of 285); heterosexual men, 35.1% (126 out of 359); heterosexual women, 31.2% (100 out of 321). Among homosexual men, repeat testers were more likely to report the following: two or more partners in the previous 6 months for both unprotected anal sex (25.8 versus 9.3%; P < 0.01) and unprotected oral sex (53.9 versus 37.4%; P < 0.01); ever having had a sexually transmitted disease (STD) other than HIV (49.4 versus 29.0%; P < 0.01); taking the present test "as part of a regular health check' (48.9 versus 28.0%; P < 0.01); and knowing others who had tested for or been infected with HIV. Repeat testing heterosexual men were more likely to report the following: two or more partners in the previous 6 months for unprotected vaginal sex (42.9 versus 30.9%; P < 0.05) and unprotected oral sex (41.3 versus 25.3%; P < 0.01); ever having had an STD other than HIV (31.7 versus 20.6%; P < 0.05); taking the present test "as part of a regular health check' (36.5 versus 26.2%; P < 0.05); and knowing others who had tested for or been infected with HIV. For heterosexual women, repeat testers were more likely to report ever having had an STD other than HIV (25.0 versus 14.5%; P < 0.05), and knowing others who had tested for or been infected with HIV. CONCLUSIONS: Repeat testing was associated with high-risk sexual behaviour, a previous STD, knowledge of others who have tested for or been infected with HIV, and seeking the test as part of a regular health check. Factors contributing to repeat testing are multi-faceted and vary between groups of different sexual orientation. Use of the impact of knowledge of others infected by HIV and the experience of contracting an STD other than HIV may guide the development of HIV counselling interventions aimed at reducing sexual risk behaviour.

Adult↗
PubMed1997

Health and dietary characteristics of supplement users in an elderly population.

The purpose of this study was to investigate the association of health and dietary characteristics with the use of vitamin and mineral supplements in community-dwelling, cognitively intact elders aged in their 60s (n = 89), 80s (n = 92), and 100s (n = 76) who resided in Georgia in the southeastern United States. Elders who were physically active (p = 0.008), had stomach problems (p = 0.042), or used arthritis medication (p = 0.015) were more likely to take a nutritional supplement than elders without these characteristics. Physically active elders were more likely to take calcium (p = 0.004), vitamin E (p = 0.022), and vitamin C (p = 0.046) than non-physically active elders. Compared to non-users, supplement users were also more likely to comply with nutritional health seeking behaviors such as avoiding too much salt, fat, cholesterol, sugar, caffeine, and eating enough fiber, vitamins and minerals from food or supplements, and calcium in foods or supplements. The observation that the use of certain vitamin or mineral supplements is associated with dietary fat intakes, dietary protein intakes, and patterns of alcohol, decaffeinated coffee, and tea consumption suggests that supplement use is one of a cluster of health behaviors. Thus, it may be important that future investigations concerning the impact of supplement use on diseases, such as heart disease or cancer, control for the effects of dietary patterns and physical activity.

Aged↗
PubMed1997

Mitochondrial involvement in the ageing process. Facts and controversies.

Mitochondria are believed to be involved in human ageing. Whilst it is clear that various mitochondrial DNA mutations do accumulate in human tissues with age, whether or not they interfere with respiratory chain function is uncertain. We question the results of previous studies which have measured respiratory chain function in human skeletal muscle with age. Whilst cytochrome c oxidase deficient fibres are a real finding in skeletal muscle, the contribution of mitochondrial DNA mutations to human ageing is still controversial. Our results show for mitochondria to be involved in ageing then it must be through a more subtle mechanism than a global decline in respiratory chain function.

Aging↗
PubMed1997

HIV-1 dynamics after transient antiretroviral therapy: implications for pathogenesis and clinical management.

Simple models of CD4 lymphocyte interactions with human immunodeficiency virus (HIV) lead to the hypothesis that progression of HIV infection involves an increase in viral replicative capacity, due either to changes in the virus or in the host environment, or both. In order to consider how changes in plasma virus load after transient, potent antiretroviral therapy can be used to test the above hypothesis--a simple mathematical model that encompasses the processes of (1) arrival of new CD4 lymphocytes, (2) death/removal of these cells by HIV-independent mechanisms, (3) infection of susceptible CD4 lymphocytes by HIV, and (4) death/removal of infected cells was investigated. This showed that the in vivo rate of increase in plasma virus load immediately after transient therapy provides a measure of the viral replicative capacity. Thus, the hypothesis that progression of HIV infection involves an increase in viral replicative capacity can be tested by measuring this viral growth rate in patients with high CD4 counts and in patients with low CD4 counts. Studies should thus investigate dynamics of changes in virus levels after stopping antiretroviral therapy and, in particular, measure rates of increase in virus in patients at high and low CD4 counts. In practice, such data may assist in therapeutic management of patients with HIV infection.

Anti-HIV Agents↗
PubMed1996

Will we ever know when to treat HIV infection?

Confidence in the efficacy of using antiretroviral drugs to treat HIV infection has grown in the past year as a result of the prolonged survival of those randomly allocated to receive an additional drug in comparative controlled trials. HIV remains, however, the only serious infectious disease for which antimicrobial treatment is deliberately delayed. This is because infected subjects can often be symptomless for more than a decade in the absence of any treatment, and results from trials with the nucleoside analogue reverse transcriptase inhibitor zidovudine have failed to show any evidence for extended survival in those beginning treatment early compared with those who deferred treatment. The new confidence in currently available treatments, and in the prospects for new ones, inevitably leads to renewed questioning of the current strategy of waiting for signs of immune deficiency before electing to intervene. A new randomised controlled trial comparing strategies of early and deferred treatment is required to assess whether the time has come for intervention immediately after HIV has been diagnosed.

Antiviral Agents↗
PubMed1996

Safety and efficacy of lamivudine-zidovudine combination therapy in zidovudine-experienced patients. A randomized controlled comparison with zidovudine monotherapy. Lamivudine European HIV Working Group.

OBJECTIVE: To compare the safety and efficacy of 2 doses of lamivudine given in combination with zidovudine with continued zidovudine monotherapy. DESIGN: Double-blind, randomized, multicenter, comparative trial of 223 patients treated for 24 weeks. SETTING: Patients from 32 hospitals in Europe were enrolled throughout a 1-year period. PATIENTS: Adult human immunodeficiency virus type 1 (HIV-1)-positive, zidovudine-experienced ( > or = 24 weeks prior zidovudine) patients with CD4+ cell counts between 0.10 and 0.40 x 10(9)/L (100-400 cells/microL). INTERVENTION: Patients received either 200 mg of zidovudine every 8 hours, 150 mg of lamivudine every 12 hours plus zidovudine, or 300 mg of lamivudine every 12 hours plus zidovudine for 24 weeks. All patients were then allowed to receive zidovudine and open-label lamivudine combination therapy. Twelve patients withdrew because of adverse events during the 24-week treatment period. MAIN OUTCOME MEASURES: Efficacy was measured by evaluating immunological and viral load changes, and safety was assessed by evaluating clinical manifestations and laboratory indexes of toxic effects. RESULTS: Patients receiving low- or high-dose combination therapy had greater treatment effects compared with patients receiving continued zidovudine monotherapy during the first 24 weeks as documented by changes in CD4+ cell counts (+0.04 vs +0.03 vs -0.02 x 10(9)/L, respectively; P < .001); log10 HIV-1 RNA as measured by the Roche assay (-0.96 vs -0.77 vs +0.07 copies/mL, respectively; P < .001) or log10 HIV-1 RNA measured by the quantitative nucleic acid sequence-based amplification assay (-0.59 vs -1.06 vs -0.02 copies/mL, respectively; P < .011); and immune-complex dissociated (ICD) p24 antigen (-74% vs -68% vs +27%, respectively; P < .001). There were no statistically significant differences in viral measurements, in CD4+ cell counts, or in safety profile between the groups receiving 2 doses of lamivudine in combination with zidovudine. The effects on CD4+ cell counts and ICD p24 antigen were sustained throughout 48 weeks for patients continuing combination therapy. Patients switching to combination therapy at week 24 showed improvement. CONCLUSION: In zidovudine-experienced HIV-1-infected patients, combination treatment with lamivudine and zidovudine is well tolerated and provides greater and more sustained increases in CD4+ cell counts and decreases in viral load than continued zidovudine monotherapy.

Adult↗
PubMed1996

Differential expression of perforin in muscle-infiltrating T cells in polymyositis and dermatomyositis.

Polymyositis (PM) and dermatomyositis (DM) are the prototypical inflammatory diseases of skeletal muscle. In PM, CD8+ T cells invade and destroy muscle fibers, whereas humoral effector mechanisms prevail in DM. We studied the expression of the cytotoxic mediator perforin in inflammatory cells in PM and DM muscle by semiquantitative PCR, immunohistochemistry and confocal laser microscopy. Similar levels of perforin mRNA were expressed in PM and DM, and abundant perforin-expressing CD3+CD8+ and CD3+ CD4+ T cells were observed in both diseases. However, there was a striking difference in the intracellular localization of perforin. In DM, perforin was distributed randomly in the cytoplasm of the inflammatory T cells. In contrast, 43% of the CD8+ T cells that contacted a muscle fiber in PM showed perforin located vectorially towards the target muscle fiber. The results suggest (a) that the random distribution of perforin in the cytoplasm of muscle-infiltrating T cells observed in DM reflects nonspecific activation, and (b) that the vectorial orientation observed only in PM reflects the specific recognition via the T cell receptor of an antigen on the muscle fiber surface, pointing to a perforin- and secretion-dependent mechanism of muscle fiber injury.

Base Sequence↗
PubMed1996

Normal respiratory chain function in patients with low-tension glaucoma.

OBJECTIVE: To test the hypothesis that low-tension glaucoma has a pathogenesis similar to Leber's hereditary optic neuropathy and results from a defect in the mitochondrial respiratory chain. METHODS: Mitochondrial fractions were prepared from skeletal muscle samples collected from eight subjects with low-tension glaucoma. Their oxidative metabolism was compared with that of age- and sex-matched controls. Skeletal muscle DNA prepared from the subjects with glaucoma was also screened for the 3,460, 11,778, and 14,484 mitochondrial DNA mutations that are associated with Leber's hereditary optic neuropathy. RESULTS: No subject with low-tension glaucoma had a defect in respiratory chain activity or one of three mitochondrial DNA mutations that are commonly associated with Leber's hereditary optic neuropathy. CONCLUSION: Although these results do not exclude the possibility that low-tension glaucoma is caused by an organ-specific defect of mitochondrial function, we have excluded a systemic defect of the mitochondrial respiratory chain.

Adult↗
PubMed1996

Genomic location and nucleotide sequence of a porcine adenovirus penton base gene.

The putative penton base gene of a porcine adenovirus serotype 3 (PAV3) has been identified, cloned and sequenced. The genomic location of the PAV3 penton base was deduced by probing a Southern blot with a polymerase chain reaction generated product containing the human adenovirus type 2 (HAV2) penton base gene. Sequencing revealed an open reading frame (ORF) of 1527 nucleotides coding for a polypeptide of 509 amino acids. However, cDNA analysis indicated an acceptor splice site one nucleotide upstream of the second ATG in the ORF. This produced an ORF of 1452 nucleotides coding for a polypeptide of 484 amino acids with a calculated molecular weight of 54.5 kDa. Comparison with the HAV2 penton base amino acid sequence revealed the putative PAV3 penton base homologue to be 87 amino acids shorter with an overall amino acid homology of approximately 65%. Comparison with the penton base proteins of other HAV types revealed a region between amino acid positions 283 and 379 with no similarity.

Adenoviridae↗
PubMed1996

Effects of physical activity and age on mitochondrial function.

It has been proposed that ageing results from the accumulation of mitochondrial DNA mutations with age which interfere with respiratory chain ATP production. Insufficient ATP production impairs cell function, and tissue dysfunction ensues, leading to morbidity, decline and eventually death. Supporting this theory, mitochondrial DNA mutations accumulate with age and respiratory chain function declines dramatically in human skeletal muscle. However, the extent of decline in respiratory chain function is greater (50%) than anticipated from the low levels of mitochondrial DNA mutations (< 1%) observed in aged muscle. We hypothesized that an age-related reduction in physical activity could be an important factor in this decline and thus studied the influence of chronological age on muscle mitochondria in subjects matched for levels of physical activity. In this carefully selected group, there was little correlation between oxidative metabolism and age. However, several parameters of respiratory chain function did correlate with markers of physical activity (activity score and handgrip strength). Our results suggest that reduced physical activity is a major contribution to the decline in mitochondrial oxidations during ageing. Physical activity ameliorates and may even mask mitochondrial 'ageing' in muscle.

Adult↗
PubMed1996

The distribution of immunocompetent cells in the genital tract of HIV-positive women.

OBJECTIVE: To study the distribution of immunocompetent cells in the female lower genital tract and to determine whether it is altered in HIV infection. METHODS: Colposcopically directed cervical biopsies were taken in the premenstrual phase of 10 HIV-positive women with sexually acquired infection, and matched HIV-negative controls. Peripheral blood was collected from the HIV-infected group for immune studies. Histological, immunohistochemical and double immunofluorescence techniques were applied to the biopsies to reveal immunocompetent cell distribution. Comparisons were made between the immune cell populations in the cervix in the HIV-positive and negative groups, and between the cervix and peripheral blood in the HIV-positive group. RESULTS: Cervical biopsies from HIV-positive women had significantly reduced Langerhans and plasma cell counts in the submucosa, but increased T lymphocyte counts compared with the HIV-negative group. There was an increase in CD8+ lymphocyte numbers in cervical biopsies of HIV-positive women, causing an inversion of the CD4/CD8 ratio. The majority of these CD8+ cells were 'memory' (CD45RO+) cells, with reduced proportions expressing perforin (cytoplasmic cytolytic granules) and TIA-1 (cytolytic granule-associated protein). Natural killer (CD57) cell markers were not detected. The levels of CD8+ cells expressing Bcl-2 (a gene product inhibiting cell apoptosis) in HIV-positive women with relatively high peripheral CD4 lymphocyte cell counts was higher than in HIV-negative women, but these levels fell with declining CD4 lymphocyte counts (< 300 x 10(6)/1). The reduction in CD4/CD8 ratio in the cervix occurred even with relatively high peripheral CD4 counts. CONCLUSIONS: HIV disease is associated with alterations in the proportions of immunocompetent cells in the cervix. There is an increase in CD8+ T-lymphocytes and evidence of reduced cytolytic capacity; thus, CD8+ cells may lack the ability to respond to viral infection. Reduction in Langerhans' and plasma cells may reflect loss of signals from CD4+ T cells. These findings may, in part, explain why HIV-infected women are susceptible to recurrent fungal and viral infections, even when peripheral immune function is intact. Further studies of immune cell function are urgently required to further elucidate these findings.

Adult↗
PubMed1996

Increased numbers of primed activated CD8+CD38+CD45RO+ T cells predict the decline of CD4+ T cells in HIV-1-infected patients.

OBJECTIVE: To look for surrogate markers in HIV-1 infection that can predict the decline of CD4+ T cells. METHODS: Multiparameter flow cytometric analyses of CD8+ lymphocytes were performed. These cells were investigated for their expression of the activation marker CD38+ within the naive (CD45RA+) and primed (CD45RO+) subsets. Serial CD4 counts were plotted for each patient and the straight line that best fitted was obtained using least squares regression. Differences in rate of decline were tested using analysis of variance, after each patient was weighted by the reciprocal of the variance. RESULTS: Baseline levels of percentages of CD8+CD38+ T lymphocytes predict the CD4 decline in HIV-1-infected patients. Within the CD8+ subset, the primed CD8+CD38+CD45RO+ population was responsible for this prediction. Conversely, the naive CD8+CD38+CD45RA+ population was not predictive. Patients who initially showed a percentage of CD8+CD38+ T lymphocytes above the median (> 25%) had a more marked decline in CD4+ T cells when compared to individuals with percentages of CD8+CD38+ T lymphocytes below the median value (79.3 and 21.2 x 10(6)/l mean CD4 cell decline per year, respectively). Similarly, percentages of CD8+CD38+CD45RO+ T cells above the median value (> 7%) were also associated with a more rapid decline (69.4 and 14.2 x 10(6)/l mean CD4+ cell decline per year). These results were statistically significant after adjustment for the baseline CD4 count and beta 2-microglobulin levels. CONCLUSIONS: Percentages of activated CD8+ cells expressing CD38+ can predict the rate of decline (slope) of the CD4+ T cells. This resides in the CD45RO+ primed population. An early prediction of the CD4+ slope will allow the clinician to target treatment to those patients that are most likely to benefit.

ADP-ribosyl Cyclase↗
PubMed1996

Quantification of human herpesvirus 6 in immunocompetent persons and post-mortem tissues from AIDS patients by PCR.

A quantitative competitive PCR assay for human herpesvirus 6 (HHV-6) was developed. Firstly, viral burden was determined in the blood of 25 healthy persons. Using 1 microgram of DNA, the prevalence of HHV-6 was 36% (9/25). Eight persons had viral loads of < or = 32 HHV-6 genomes/microgram DNA. The viral burden in the ninth individual was 1.2 x 10(6) HHV-6 genome copies/microgram DNA, which remained constant over a period of 10 months. This demonstrates the persistence of a high HHV-6 load in the absence of apparent disease. Secondly, HHV-6 burden was determined in 100 post-mortem tissues from seven AIDS patients and three controls. For all tissues combined, there was a statistically significant higher median viral load in AIDS patients (56 copies/microgram DNA, range 0-43321) compared to controls (10 copies/microgram DNA, range 0-423) (P = 0.04). The precision and reproducibility of this assay will allow hypotheses concerning the pathogenic potential of HHV-6 to be tested quantitatively.

AIDS-Related Opportunistic Infections↗
PubMed1996

Screening for sexually transmitted diseases in an HIV testing clinic; uptake and prevalence.

OBJECTIVE: To estimate the prevalence of sexually transmitted diseases (STDs) and the acceptability of STD screening among people seeking an HIV antibody test in an established free standing HIV testing clinic. DESIGN: A 9 month period prevalence study conducted between August 1993 and April 1994. SETTING: The Same Day Testing Clinic (SDTC) for HIV antibodies at the Royal Free Hampstead NHS Trust Hospital, London. SUBJECTS: 242 males and 160 females attending the Same Day Testing Clinic. OUTCOME MEASURES: The prevalence of STDs including gonorrhoea, chlamydia, syphilis and hepatitis B and the percentage of clinic attenders accepting an STD screen. RESULTS: Of those invited to take part in the study 69% of the males (242/350) and 59% (160/269) of the females agreed to be screened although for a variety of reasons not everyone agreed to a full screen. Two cases of untreated syphilis, no cases of gonorrhoea and six cases of chlamydia were detected. Four people had active, previously undiagnosed herpes while three had genital warts. Evidence of previously unknown hepatitis B infection was found in 26 people. Despite a high level of previous contact with genitourinary medicine services, uptake of hepatitis B vaccination among those homosexual men eligible for immunisation was low (28%; 23/83). Nine (4%) of the males, but none of the females screened for STD were found to be HIV antibody positive. CONCLUSION: Among people seeking an HIV antibody test in an established free standing HIV testing clinic, the prevalence of acute STDs was low. However, evidence of previously undiagnosed hepatitis B infection was found in a number of subjects and uptake of vaccination among those most at risk had been low. While opportunistic screening for STD was acceptable to almost two thirds of HIV testing clinic attenders, a substantial minority nonetheless declined this offer. Selective STD screening could be offered to those people seeking an HIV test who report never having been screened before, as both cases of positive syphilis serology and all those of chlamydia were in people who had not previously been screened. All those at risk for hepatitis B infection should be encouraged to establish their infection status and be immunised where appropriate.

Ambulatory Care↗