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Biomedical subjects

J J Turner

Publications and source records attributed to J J Turner.

At least 37 records · Page 2Linked to original sources

Epstein-Barr virus and HIV play no direct role in persistent generalized lymphadenopathy syndrome.

Persistent generalized lymphadenopathy (PGL) and polyclonal B cell activation are features of infection with HIV. Epstein-Barr virus (EBV) and HIV are known to activate B cells in vitro, but whether they are important B cell activators in patients infected with HIV is less clear. In this study, lymph node tissue was obtained from 10 patients with PGL and assessed for evidence of EBV and HIV gene sequences. DNA was extracted and specific viral gene sequences identified using the polymerase chain reaction (PCR). EBV sequences were difficult to detect in the PGL tissue, with a signal intensity similar to that of other benign and malignant lymphoid conditions not associated with EBV. HIV sequences were also rare in the PGL tissue, consistent with HIV infection of the small number of peripheral blood cells and nodal T cells likely to be present in such a sample. These findings suggest that the polyclonal B cell activation typical of HIV is not driven by direct EBV or HIV infection of B cells.

AIDS-Related Complex↗

Comparison of radial maze performance of rats after ibotenate and quisqualate lesions of the forebrain cholinergic projection system: effects of pharmacological challenge and changes in training regime.

Rats with ibotenic or quisqualic acid lesions to cholinergic projections showed similar significant increases in both short-term working and long-term reference memory errors in radial maze spatial (place) and nonspatial (cue) tasks, throughout a period of 10 weeks after lesioning. All types of error were dose-relatedly reduced to a similar extent in lesioned rats after treatment with nicotine and the beta-carboline ZK93426. Performance of controls was not affected by nicotine, but errors were increased with the higher doses of ZK93426. In contrast, amphetamine increased errors in both control and lesioned rats. With extensive training, lesioned rats improved to control level, but were more disrupted than controls by a break in testing, which reinstated high error rates to an equivalent extent in lesioned groups. Choline acetyltransferase (ChAT) activity showed a comparable degree of depletion in quisqualate and ibotenate lesioned groups to around 60% of control level in cortex and 75% in hippocampus. These results indicate that at volumes and concentrations that produced an equivalent degree of ChAT depletion, detrimental effects of ibotenate and quisqualate lesions on radial maze performance were very similar. The time course of improvement with over-training and impairment after a break in training were also comparable with both lesioning agents. Reduced errors following compounds acting directly (nicotine) or possibly indirectly (ZK 93426) to enhance cholinergic function, but not after amphetamine, suggested that damage to cholinergic neurons contributed to the behavioural deficits induced by both ibotenic and quisqualic acid.

Journal Article↗

Subtypes of Epstein-Barr virus in human immunodeficiency virus-associated non-Hodgkin lymphoma.

Biopsy samples obtained from 20 patients with human immunodeficiency virus (HIV)-associated non-Hodgkin lymphoma (NHL) were assessed for evidence of Epstein-Barr virus (EBV) and HIV sequences. DNA was extracted from formalin-fixed, paraffin-embedded NHL tissue and specific viral gene sequences were sought using the polymerase chain reaction (PCR). EBV sequences were found in 10 NHL samples (50%), with five tumors showing A-type and five B-type sequences. By serologic testing, 18 of 19 patients had antibodies to EBV, with 14 patients having antibodies to A-type EBV and 11 to B-type EBV. Serology confirmed the high prevalence of type B EBV in HIV-infected patients, but was not a reliable indicator of the EBV subtype present in the lymphomas. HIV sequences were present in biopsy tissue but at a level consistent with an origin from bystander HIV-infected cells. All 20 patients were negative by enzyme-linked immunosorbent assay for antibodies to human T-cell leukemia virus-type I. The high prevalence of type B EBV in these tumors is similar to the findings in endemic Burkitt's lymphoma, where 40% of the tumors have type B viral sequences. In normal populations, type B EBV is rarely found outside the nasopharynx. These studies support the hypothesis that EBV is an important cofactor in NHL in HIV-infected persons. The finding that B-type EBV is present in 25% of HIV-associated NHL suggests that this EBV subtype may be an important human pathogen with a wider geographic distribution than originally thought.

Antigens, Viral↗

The formation of free radicals by cardiac myocytes under oxidative stress and the effects of electron-donating drugs.

The interaction of myoglobin with H2O2 leads via a two-electron oxidation process to the formation of ferryl myoglobin. Metmyoglobin is more readily activated than oxymyoglobin to the ferryl states, which are capable of inducing peroxidative damage to membranes. E.p.r. and optical spectroscopic studies show that the thiol-containing compounds N-(2-mercaptopropionyl) glycine and N-acetylcysteine and the trihydroxamate desferrioxamine attenuate these processes by reducing the ferryl myoglobin species to metmyoglobin, with the formation of thiyl radicals and the desferrioxamine nitroxide radical respectively. Biochemical investigations of the potential for myoglobin in ruptured myocytes to be involved in radical generation, when under oxidative stress, and of the nature of the resulting species, were also undertaken. E.p.r. spectroscopic studies revealed the formation of a radical species which is capable of inducing membrane lipid peroxidation. The interaction of the thiol compounds and desferrioxamine with components of myocardial tissue under these conditions results in the generation of thiol-derived radical species and the desferrioxamine nitroxide radical respectively. These data, along with those obtained using optical spectrocopy, support the assignment of the identity of the radical species generated from the myocytes as the ferryl myoglobin radical.

Acetylcysteine↗

Aggressive papillary middle ear tumour.

A rare middle ear tumour is reported. The clinical presentation was similar to that of a glomus tumour but the pathology that of an aggressive papillary middle ear tumour. This is a recently recognized subgroup of middle ear glandular tumours. Clinical findings, imaging, pathology and treatment are presented.

Adult↗

Definition of two distinct types of AIDS-associated non-Hodgkin lymphoma.

Non-Hodgkin lymphoma (NHL) in a human immunodeficiency virus (HIV)-infected person is an AIDS-defining condition. There is both an increased incidence of NHL and a poorer prognosis for the disease in these HIV-infected persons, compared with patients who spontaneously develop NHL. A series of 41 consecutive patients with HIV-associated NHL treated at St Vincent's Hospital, Sydney, between 1984 and September 1989 was assessed. Of these, 36 had NHL proven on biopsy and NHL was diagnosed clinically in the other five. On histologic examination 11 had high-grade malignant lymphoma, small non-cleaved cell (SNCC) type, similar to Burkitt lymphoma, 18 had high-grade lymphoma large cell immunoblastic (LCI) type, and seven could not be classified due to inadequate material for assessment. The clinical features of these two groups were compared. Those patients with LCI had advanced CD4+ immunodeficiency and poor survival (median = 6 weeks). The other group with SNCC had better preserved immune function, and longer survival (median = 18 weeks). Three patients had survived longer than 3 years all of whom had SNCC lymphoma as their first AIDS-defining illness. The clinical features and prognostic factors demonstrated in this study document heterogeneity of NHL in HIV-infected patients and should be used as a guide to treatment of these patients, by reserving more intensive treatment for those persons with better prognostic features.

Acquired Immunodeficiency Syndrome↗

Effects of a gonadotropin-releasing hormone agonist on sexual behavior in male rhesus monkeys (Macaca mulatta).

Low levels of sexual behavior persist in male rhesus monkeys treated with GnRH-a despite very low levels of T and gonadotropin that occur during such treatment. The behavior of male rhesus monkeys treated with GnRH-a resembles the behavior of surgically castrated male rhesus monkeys more closely than it does the behavior of reproductively quiescent males during the normal nonmating season. The normal, seasonal cessation of sexual behavior in male rhesus monkeys may result from changes in behavioral sensitivity to circulating androgens.

Animals↗

Effects of two different patterns of estradiol replacement on the sexual behavior of rhesus monkeys.

Seven pairs of rhesus monkeys consisting of adult males and adult, ovariectomized females were tested for sexual behavior. Behavioral tests were conducted under two patterns of estradiol treatment of the females. Under the "constant estrogen" condition, females were given SC injections of 10 micrograms estradiol benzoate on 28 consecutive days. Under the "cyclic estrogen" condition, females were given 28 days of estradiol treatment at varying doses based upon the artificial menstrual cycle devised by Michael, Zumpe and Bonsall (6). Rates of male mounting, hip-touch (incomplete mounts), and male threaten-away behavior (redirected aggression) increased during estradiol administration. Mounting peaked at the time of the highest estrogen dosage in the cyclic treatment condition, but was highest during the first portion of the period of constant treatment. Hip-touch and threaten-away behaviors were more frequent in the constant condition than during cyclic treatment. The high levels of these behaviors during the constant treatment suggest a lack of coordination between male and female motivation which is overcome by providing estradiol stimulation in a pattern which mimics the menstrual cycle.

Animals↗

Fatty acid synthetase in control, starved and refed Richardson's ground squirrels.

1. Starvation for 6 days reduced whole body mass and total body lipids to 76 and 71%, respectively, of pre-starvation levels in weight-gain phase ground squirrels. After 4 days of refeeding, body mass increased to 86% of pre-starvation level but total body lipids had not changed from starvation levels. 2. Compared to the fed state, fatty acid synthetase (FAS) activity in white adipose tissue (WAT) was 15 and 31% in starved and refed 4-day animals, respectively, and in liver was 26 and 21% in starved and refed 4-day animals, respectively. Lipids depleted by starvation during prehibernatory fattening were not rapidly restored in Richardson's ground squirrels. 3. Changes in these parameters with starvation and refeeding were similar in weight-loss phase animals. 4. In control animals of both phases, WAT accounted for at least 90% of total FAS activity and liver nearly all of the remainder.

Adipose Tissue↗

Planned short-stay admission to a geriatric unit: one aspect of respite care.

Our unit aims to provide planned short-term in-patient care for any disabled elderly person who requests it. The patients using the service over a 12-month period are described. Most were heavily disabled and it seems unlikely that their carers could cope at home without the opportunity of a break from time to time. The service is cheap, as relatively few beds are needed and those mostly in the summer. Morbidity amongst patients (and their carers) was high but we could find no evidence to support recent suggestions that admitting such patients was harmful.

Aged↗

Silent ovulation in rhesus monkeys (M. mulatta): dissociation of hormonal and behavioral states.

Ovarian hormone levels were monitored in rhesus monkeys during the breeding and non-breeding seasons. Ovulation (as inferred from progesterone levels in blood serum in excess of 1.5 ng/ml) was most frequent in the breeding season but was absent only during the month of August. Summer (non-breeding season) ovulations were more frequently "silent," or without heterosexual behavior, than were winter ovulations. This finding suggested that estradiol stimulation may cause different behavioral responses at different times of the year. To test this hypothesis, ovariectomized females were treated with subcutaneously implanted estradiol capsules at different times within and outside the normal breeding season. In either season, treatment with estradiol resulted in increased female-to-female sexual behavior. Only during the breeding season, however, did the estradiol-treated ovariectomized females interact sexually with males. Although males copulated with both estradiol-treated and gonadally intact, untreated females during the breeding season, their rate of copulation with the intact females was higher. The results suggest that: (1) Some female rhesus monkeys displaying strictly seasonal breeding behavior continue to have luteal activity indicative of ovulation in May, June and July, (2) Summer ovulatory cycles are rarely accompanied by sexual behavior, (3) Estradiol treatment of ovariectomized females induces female-to-female sexual behavior both in the breeding and non-breeding seasons, and (4) Males are less responsive to the presence of estrogen-stimulated females in the non-breeding season than in the breeding season.

Animals↗

Resumption of seasonal breeding patterns in male and female rhesus monkeys transferred from an indoor to an outdoor environment.

Seasonal aspects of social behavior and sex steroid levels were observed in two groups of rhesus monkeys from March through December. One group (3 males, 7 females) had lived outdoors for several years. The other group (6 males, 5 females), transferred outdoors in late February, had lived indoors for several years. In March-April, the long-term outdoor residents displayed the expected seasonal pattern of sexual behavior, characterized by absence of complete sequences of copulatory behavior. At this time the indoor-adapted group displayed high levels of copulatory behavior. Thereafter, frequencies of sexual behavior of the two groups were similar. Testosterone in the males was positively correlated with frequency of sexual behavior in each group. Females in the indoor-adapted group displaced menstrual cycles in March and April and 3 of 5 became pregnant at this time. The two remaining indoor-adapted females continued to display ovulatory cycles, but little sexual behavior, throughout the summer. Interestingly, two females in the outdoor-adapted group also displayed summer ovulatory cycles; without concomitant sexual activity. These data show that the disruption of seasonal breeding patterns produced by lengthy indoor housing remains briefly apparent following transfer outdoors, but is substantially overcome within a few months.

Agonistic Behavior↗

Negative feedback effects of oestradiol-17 beta on luteinizing hormone in female rhesus monkeys under different seasonal conditions.

Suppression of luteinizing hormone (LH) by sc implanted oestradiol-17 beta (E2) pellets was examined in 4 ovariectomized female rhesus monkeys during the breeding season, the non-breeding season and during the transition between the breeding and non-breeding season. Immunoreactive LH was suppressed to 58, 78 and 75% of untreated levels for the respective seasonal conditions. Bioactive LH was suppressed to 29, 49 and 33% of baseline. Bioactive LH (determined by testosterone release from rat interstitial cells) was significantly correlated (r = 0.84) with immunoactive LH from the same samples. It is concluded that E2 treatment of ovariectomized female rhesus monkeys results in suppressed levels of LH, regardless of the time of year.

Animals↗

The development of a microassay for human committed progenitor cells.

A microassay for human committed progenitor cells (CFU-c) has been developed using 24-well, 16 mm diameter culture dishes. Comparisons were made of simultaneous cultures of 21 samples in both 35 mm and 16 mm culture dishes employing two sources of colony-stimulating factor (CSF). The microassay does not differ significantly from the standard 1 ml 35 mm assay, apart from some enhancement of colony numbers in the 16 mm dish. Other advantages of the microassay are that it is economical with respect to cells, media, and space; and it is possible to increase the number of experiments fivefold which can be performed with the same number of cells.

Adolescent↗

Endocrine changes induced by venipuncture in rhesus monkeys.

An animal-worn, remotely activated blood collection device was used to obtain estimates of baseline levels of testosterone (T), growth hormone (GH) and prolactin (PRL) from unrestrained and active male rhesus monkeys. As soon as possible after this baseline period, the males were captured and a final venipuncture sample was obtained. Venipuncture produced elevated GH levels compared to values obtained using the blood collection device, but was without detectable effect upon levels of T and PRL. Cortisol values, available only from a single animal, displayed an increase in response to venipuncture, much like that seen for GH.

Animals↗

The vascular lesions associated with skin necrosis in renal disease.

Three renal allograft recipients and one uraemic patient presented with skin necrosis. In all cases, the subcutaneous arteries and arterioles were narrowed or occluded by mural calcification with or without intimal fibrosis. A review of the literature shows that uraemic patients or allograft recipients with skin necrosis involving the trunk or thighs have a poor prognosis while recovery is common in patients with more peripheral lesions. The aetiology of the arterial lesions is unknown. Their relationship to renal disorders and/or hyperparathyroidism is uncertain and therapy remains unsatisfactory.

Adult↗

Autopsy findings in bone marrow transplantation.

Autopsies were performed on 2 patients with aplastic anaemia and 7 with acute leukaemia dying after bone marrow transplantation. Neutropenic enterocolitis was found in 2 of the 3 early deaths occurring before marrow engraftment and was related to radiation or cytotoxic drug damage to the bowel mucosa in the presence of profound neutropenia, allowing infection by bowel organisms. Cytomegaloviral infection was universal in engrafted patients. One had cytomegaloviral (CMV) pneumonia, one CMV hepatitis and enteritis and one CMV enteritis. Three patients had occasional CMV inclusions in various organs without obvious harmful effects. One nonengrafted patient also had CMV pneumonia. Graft versus host disease (GVHD) was a significant finding in 4 engrafted patients. This was difficult to separate histologically from the effects of CMV in the bowel, but easier in liver and skin. The skin changes of GVHD were the most easily interpretable. Interstitial pneumonia was due to CMV in one nonengrafted and one engrafted patients and had no obvious infective cause in 2 engrafted patients. The presence of bizarre epithelial cells in the lungs of these patients suggested an aetiological role for radiation or cytotoxic drugs. Modification of the conditioning regimen may reduce tissue damage and lessen many of these side-effects.

Adult↗