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Biomedical subjects

J McDermott

Publications and source records attributed to J McDermott.

At least 55 records · Page 3Linked to original sources

DNA markers linked to Malus floribunda 821 scab resistance.

Breeding resistant apple plants is an alternative way to control fungal pathogens reducing the environmental impact due to the use of pesticides. The breeding of apple cultivars resistant to Venturia inaequalis could be much improved by marker-assisted selection. A molecular marker closely linked to the resistance locus called Vf could replace selection based on infection studies. To find such molecular markers, DNA of progenies from crossings of a resistant and a susceptible apple tree was subject to bulked segregant analysis. Two markers were found with a genetic distance of 10.6% and 19.7% recombination frequency to the Vf locus.

DNA Primers↗

Synthesis of the enantiomers of [N-methyl-11C]PK 11195 and comparison of their behaviours as radioligands for PK binding sites in rats.

The enantiomers of [N-methyl-11C]PK 11195, a radioligand for PET studies of PK (peripheral benzodiazepine) binding sites, have been prepared from the newly synthesized N-desmethyl-enantiomers by 11C-methylation with N.C.A. [11C]iodomethane. The brain uptake and retention of each enantiomer was compared with that of the racemic radioligand after i.v. administration into normal rats and into rats with focal cortical lesions. No significant differences in the uptakes of the enantiomers were observed in regions devoid of PK binding sites. However, the R-enantiomer was retained to a significantly greater extent than the S-enantiomer in olfactory bulbs-tubercles, which contain some PK binding sites, and also in 9-day-old focal cortical lesions, which are greatly enriched in PK binding sites associated with macrophage infiltration. The observed differences are consistent with the approximately 2-fold greater affinity of the R-enantiomer for PK binding sites reported in vitro and imply that the use of this enantiomer would have advantages over the use of the racemate currently used for PET studies.

Animals↗

Outcome of adults with acquired immunodeficiency syndrome in Auckland 1983-9.

AIMS: To assess the survival of Auckland residents diagnosed with AIDS between 1983 and 1989. METHODS: Retrospective case review RESULTS: Sixty nine Auckland residents were diagnosed with AIDS between 1983 and the end of 1989, and were cared for by the infectious disease unit, Auckland Hospital. The overall median survival was 289 days with 48% and 20% surviving at one and two years respectively. Survival was longer among those who were infected through homosexual contact, were younger, and not known to the infectious disease unit prior to the diagnosis of AIDS. Although survival was longer for those diagnosed in 1988 compared to earlier years, it was shorter again for those diagnosed in 1989. Pneumocystis carinii pneumonia, the AIDS defining condition in 63.8% of people, was found less frequently in 1989, and overall was associated with a longer survival than most of the other AIDS-defining diagnoses. A quarter of the people were not known to be infected with HIV prior to the AIDS-defining condition. CONCLUSION: In New Zealand, as in other countries, changes in treatment strategies of people with HIV infection may impinge on the survival of people with AIDS.

Acquired Immunodeficiency Syndrome↗

Hospital associated costs of treating patients with AIDS.

AIM: To determine the hospital associated costs of caring for patients with AIDS. METHOD: We reviewed the notes of all 40 patients with AIDS admitted to the Auckland Hospital infectious disease unit during 1988. We used the resource utilisation system (RUS) to determine costs. RESULTS: Costs were maximal in the month of diagnosis of AIDS (ca $3500/month), falling thereafter to ca $1000/month until they rose again in the last months of life. Total costs were dominated initially by inpatient costs but subsequently by the costs of medicines. CONCLUSION: The hospital costs associated with the care of AIDS patients are not spaced evenly throughout the illness. Extended life will not increase costs proportionately.

Acquired Immunodeficiency Syndrome↗

MEF2C, a MADS/MEF2-family transcription factor expressed in a laminar distribution in cerebral cortex.

We have cloned cDNA encoding a human transcription factor that belongs to the MEF2 (myocyte-specific enhancer-binding factor 2) subfamily of the MADS (MCM1-agamous-deficiens-serum response factor) gene family. This factor, which we have named MEF2C, binds specifically to the MEF2 element and activates transcription via this element. Specific isoforms of this factor are found exclusively in brain and are robustly expressed by neurons in cerebral cortex. In situ hybridization indicates that the factor is expressed preferentially in certain neuronal layers of cortex and that expression declines during postnatal development. The unusual pattern of expression in brain suggests that this transcription factor may be important in the development of cortical architecture.

Amino Acid Sequence↗

Dexfenfluramine, fluoxetine, and weight loss among female carbohydrate cravers.

The consumption of excess calories as carbohydrates (CHO)-rich, protein-poor snacks characterizes the overeating of obese CHO cravers, premenstrual women, patients with Seasonal Affective Disorder, and former smokers. This specific appetite for CHOs may involve brain serotonin, as the synthesis and release of this neurotransmitter can increase following consumption of CHO-rich foods. To examine whether weight loss produced by serotoninergic drugs involves a selective reduction in CHO intake, obese females who consumed at least 30% of their daily calories from CHO-rich snacks were treated with dexfenfluramine ([DF] 15 mg b.i.d.); fluoxetine ([FL] 20 mg t.i.d.); or placebo (PL) for 12 weeks. Weekly weight loss for 25 of 29 PL completers was 0.22 kg +/- 0.06 (mean +/- SEM); for 21 of 28 DF completers, 0.56 +/- 0.08 kg; and for 18 of 30 FL completers, 0.58 +/- 0.09 kg (PL < DF = FL; p = .039). Seven FL subjects, 2 PL subjects, and 1 DF subject withdrew from the study due to side effects; other withdrawals were due to intercurrent illness or personal problems. Prior to treatment, subjects consumed over 40% of their daily CHO intake from snacks. Both of the drugs selectively decreased CHO snack intake (p < 0.05); DF, but not FL, also decreased meal CHO intake (p < .025). These results suggest that weight loss following treatment with serotoninergic drugs may relate to a selective decrease in CHO appetite.

Adult↗

Conditional infectivity of a human immunodeficiency virus matrix domain deletion mutant.

We constructed a human immunodeficiency virus (HIV) matrix (MA) deletion mutant by deletion of about 80% of the HIV type 1 Gag MA domain but retaining myristylation and proteolytic processing signals. The effects of this deletion matrix (dl.MA) mutant on HIV particle assembly, processing, and infectivity were analyzed. Surprisingly, the dl.MA mutant still could assemble and process virus particles, had a wild-type (wt) retrovirus particle density, and possessed wt reverse transcriptase activity. RNase protection experiments showed that dl.MA mutant particles preferentially packaged viral genomic RNA. When both mutant and wt particles were pseudotyped with an amphotropic murine leukemia virus envelope protein, mutant infectivity was about 10% of wt level. In contrast, infectivity of the dl.MA mutant was 1,000-fold less than that of wild-type when mutant and wt particles were pseudotyped with the HIV envelope protein. Protein analyses of pseudotyped virions indicated that there were no major differences between mutant and wt viruses in the efficiency of amphotropic murine leukemia virus envelope protein incorporation. In contrast, there was a reduction in the amount of mutant particle-associated HIV envelope protein gp120. Our results suggest that an intact HIV matrix domain is not absolutely required for reverse transcription, nuclear localization, or integration but is necessary for appropriate HIV envelope protein function.

Amino Acid Sequence↗

Syphilis-associated perinatal and infant mortality in rural Malawi.

In Mangochi District, a rural area of Malawi, the prevalence of active syphilis was 3.6% among 3591 women who had singleton births and who were negative for human immunodeficiency virus (HIV). Compared with non-syphilitic women, those with active syphilis (positive Venereal Disease Research Laboratory/rapid plasmin reagin tests (titre > or = 1:8) and a reactive microhaemagglutination assay) were more likely to experience stillbirths as well as the early and late neonatal deaths and even postneonatal deaths of their children. Characteristics associated with active syphilis were not very useful in targeting women at high risk of having the condition, which makes universal screening in antenatal programmes the most efficacious way to prevent syphilis-associated morbidity and mortality. The potential for a programme to prevent congenital syphilis in the perinatal, neonatal, and post-neonatal periods is evident. In considering resource allocation to child survival programmes in areas where the prevalence of syphilis is high, officials need to include antenatal syphilis screening, using rapid tests and treatment at the first contact of the mother with the health care system.

Child Welfare↗

Setting up a no smoking support group.

Smoking is the single greatest cause of ill-health and disability in the UK; some one million people die from smoking relating disease each year. It is a clear target for the health visitor's health promoting activities, argues Jayne McDermott. Here she describes setting up a successful 'No smoking' support group.

Community Health Nursing↗

The aromatic amino acid decarboxylase inhibitor, NSD-1015, increases release of dopamine: response characteristics.

Addition of the aromatic amino acid decarboxylase inhibitor, NSD-1015 (10 microM), to Krebs'-Ringer phosphate (KRP) superfusion medium, significantly increased the release of dopamine in vitro from superfused corpus striatum tissue fragments of male rats. A dose-dependent increase in release of dopamine was obtained in response to increasing concentrations of NSD-1015, with 1.0 microM being the minimally effective dose. In addition to the striatum, NSD-1015 also increased the release of dopamine from superfused hypothalamic tissue fragments. This capacity of NSD-1015 to increase release of dopamine was calcium-independent, appeared to be somewhat specific and could apparently increase the release of dopamine in vivo, as indicated by increases in the release of the metabolite of dopamine, DOPAC, under conditions of push-pull perfusion. Although the putative role of NSD-1015 is as an aromatic amino acid decarboxylase inhibitor, the present results demonstrate that, either as a result of this function and/or in addition to this role, NSD-1015 is a potent activator of the release of dopamine.

3,4-Dihydroxyphenylacetic Acid↗

Effect of lidocaine on somatosensory evoked response and cerebral blood flow after canine cerebral air embolism.

BACKGROUND AND PURPOSE: Victims of air embolism often recover rapidly on hyperbaric treatment then deteriorate again, even if hyperbaric treatment is continued. In previous animal experiments, lidocaine has been shown to improve recovery of somatosensory evoked response amplitude after air embolism. However, animals in these experiments rarely deteriorated. We have shown that the induction of air embolism and transient hypertension in canines produces deterioration despite hyperbaric treatment, and we decided to test the effect of lidocaine on somatosensory evoked potential recovery and cerebral blood flow in this model. METHODS: Dogs were treated with repeated doses of lidocaine or equivalent volumes of saline during hyperbaric therapy after internal carotid air embolism and transient hypertension. The investigators were unaware of treatment group assignment during the experiments. The amplitude of the median nerve somatosensory evoked potential and cerebral blood flow measured with carbon-14-labeled iodoantipyrine autoradiography were used to assess effect of therapy. RESULTS: Lidocaine-treated dogs recovered 60 +/- 10% (mean +/- 95% confidence limits) of the baseline somatosensory evoked potential amplitude 220 minutes after air embolism; saline-treated dogs recovered 32 +/- 10% (a significant difference at p less than 0.01). Lidocaine-treated dogs also had higher cerebral blood flow values than saline-treated dogs 220 minutes after air embolism. CONCLUSIONS: Lidocaine ameliorated the delayed deterioration of evoked potential associated with air embolism and hypertension in this canine model. The improved cerebral blood flow may be a mechanism of action of lidocaine or an associated effect of improved neuronal survival.

Animals↗

Striatal dopamine release in vitro from immature male rats shows enhanced responsiveness to pulsatile, but not continuous, infusions of L-dopa.

In the present experiment we compared the effects of continuous versus pulsed infusions of L-beta-3,4,dihydroxyphenylalanine (L-DOPA) upon dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) release in vitro from superfused corpus striatal tissue fragments of immature (25-32 day) and adult (90-120 day) male rats. In response to two pulse infusions of L-DOPA (5 microM) a significantly greater amount of dopamine and DOPAC was released from the striatal fragments of immature vs adult males. In contrast, when L-DOPA was infused continuously throughout the superfusion virtually identical amounts of dopamine and DOPAC were obtained for immature and adult male rats. No differences in postsuperfusion dopamine tissue content were obtained between adult and immature rats following the two pulses or continuous infusion of L-DOPA. These results suggest that the corpus striatum of the immature rat has an enhanced capacity to convert and release dopamine in response to a submaximal pulsatile infusion of L-DOPA.

3,4-Dihydroxyphenylacetic Acid↗

Characterization of aminopeptidases in human kidney soluble fraction.

Fractionation of human kidney soluble extract (with which the majority of cellular aminopeptidase activity is associated) via anion exchange chromatography resolved four types of separable aminopeptidase (relative activity in parenthesis): alanyl aminopeptidase (EC 3.4.11.14; 50%); arginyl aminopeptidase (EC 3.4.11.6; 30%); leucyl aminopeptidase (EC 3.4.11.1; 18%) and pyroglutamyl aminopeptidase (EC 3.4.19.3; 2%). The further purification (via gel filtration chromatography and preparative electrophoresis) and characterization of each aminopeptidase has been described; the aminopeptidase tissue profile for human kidney was found to be similar to that previously obtained for human skeletal muscle and brain tissue using a similar experimental approach, i.e. the same enzymes, with corresponding similar characteristics, are present in each tissue. These results suggest that soluble aminopeptidases may be of fundamental importance in general cell protein catabolism. Degradation of the following aminoacyl-AMC derivatives via kidney soluble extract has been shown to be due principally to hydrolysis by alanyl aminopeptidase: glutamyl, glycyl, isoleucyl, methionyl, ornithyl, phenylalanyl, prolyl, seryl, tyrosyl and valyl. We would suggest that measurement of the soluble extract-derived aminopeptidases described in this paper in urine may lead to an improvement upon existing assay procedures for early detection of kidney damage.

Aminopeptidases↗

Lower extremity percutaneous transluminal angioplasty: multifactorial analysis of morbidity and mortality.

We analyzed the outcome of 202 percutaneous transluminal angioplasty (PTA) procedures performed between 1983 and 1989 to quantitate procedural risks and define factors associated with suboptimal results or immediate clinical failure. Premorbid factors studied included age, sex, treatment of single versus multiple lesions, stenoses versus occlusions, premorbid status of the limb (claudication vs limb threat), and most distal level of PTA. Adverse outcomes included complications (hematoma, acute occlusion, or thrombosis of PTA site, distal embolization, failure to dilate or cross, arterial dissection, rupture, and significant systemic derangement), major amputations (below knee and above knee), and deaths. There were 66 complications (32.7%), 22 amputations (10.9%), and 12 deaths (5.9%) in our series. Logistic regression analysis revealed that the major predictive variable for the occurrence of a complication (p = 0.002), and the only predictive variable for the outcomes of amputation and death (p = 0.0001 and p = 0.0139, respectively), was the premorbid clinical status of the limb. Lower extremity PTA is not an intrinsically benign procedure and is associated with a significant risk of complication, amputation, and procedure-associated death. These adverse outcomes cluster in patients with limb threat. Therefore it may be reasonable to restrict the use of PTA to patients with claudication and strictly selected cases of limb threat.

Adult↗

Fibrous disease of the breast in juvenile diabetes.

The association between Type I diabetes mellitus and breast masses whose extreme hardness suggests cancer has only recently been recognized. The present report consists of 11 cases of patients with juvenile diabetes who were identified by a retrospective review of 3,219 patients seen in our breast clinic over an eight-year period. All 11 patients were referred for possible biopsy and this was carried out routinely before the condition was recognized. The patients with diabetes were carefully reviewed in order to identify specific features of the breast lesions and a management plan was devised that should reduce the need for biopsy in these patients in the future.

Adult↗