Biomedical subjects

D Jones

Publications and source records attributed to D Jones.

At least 415 records · Page 23Linked to original sources

PubMed1994

Isomeric and quaternary properties of homogenous 33 kDa protein from the venom of Chelonus near curvimaculatus.

The 33,000 Dalton venom protein of Chelonus near curvimaculatus was characterized for structural properties of charge, quaternary associations, and relationship to polydnavirus encoded proteins. Homogenous isoforms of the protein were isolated from the venom by sequential steps of 1) microdissection, 2) separation based on charge (Mono-Q column HPLC or narrow-range electrofocusing), and 3) centrifugal filtration based on molecular weight using Centricon microconcentrators. The purified protein dimerized under native conditions, and this quaternary association became denaturation resistant under certain conditions. Chemical modification of lysine epsilon amino groups did not disrupt such dimerization. The cDNA for the protein did not possess high similarity to any sequence encoded in the polydnavirus, as indicated by results of Southern blotting, but does possess similarity in its repeats to the repeats of the immunologically protective surface glycoprotein of Leishmania amazonensis.

Amino Acid Sequence↗

PubMed1994

A transcribed polymorphism and sub-localisation of MDM2.

An NlaIV polymorphism in the 5' untranslated region of the MDM2 gene is described. MDM2 was sublocalised by fluorescence in situ hybridisation with a yeast artificial chromosome probe to 12q14.3-12q15. We demonstrate the use of the polymorphism to assess allelic imbalance in breast tumours.

Alleles↗

PubMed1994

Urinary N-acetyl-beta-glucosaminidase as a screening technique for vesicoureteral reflux.

OBJECTIVE: To determine if urinary N-acetyl-beta-glucosaminidase (NAG) assays could be applied as a screening test for early detection of vesicoureteral reflux. METHODS: Two hundred eighty-eight urine samples from children undergoing voiding cystourethrography (VCU) for a variety of urologic problems were assayed for N-acetyl-beta-glucosaminidase using spectrophotofluorimeter techniques. Sample creatinine levels were also determined using an auto analyzer. The urinary NAG to creatinine ratio for each patient was then compared to their VCU results, which were interpreted independently of the assay values and graded according to the International Reflux Classification system. The NAG to creatinine ratios were then classified according to their grade of reflux, and the mean NAG levels, plus one standard deviation, were calculated for each as well as for the nonrefluxing controls. Statistical analysis was done with P values obtained by Student's t-test. RESULTS: A total of two hundred thirty-two specimens were evaluable with ninety (38.8%) samples collected from refluxing patients and one hundred forty-two (61.2%) samples from nonrefluxers. The NAG levels standardized to urine creatinine revealed a mean value among refluxers of 15.514 mumol/g creatinine. This compared with a mean value of 14.611 mumol/g creatinine in the nonrefluxing group, with the difference being insignificant. When the mean NAG levels were compared for each grade of reflux to the nonrefluxing controls, only grade V had a significant elevation (44.561 mumol/g creatinine) above the nonrefluxers (P = 0.0001). CONCLUSIONS: With the exception of grade V vesicoureteral reflux, urinary NAG levels do not reliably detect the presence of reflux and therefore cannot be accurately applied as a screening test for detection of this common urologic problem.

Acetylglucosaminidase↗

PubMed1994

Characterization of a novel protein associated with the parasitization of lepidopteran hosts by an endoparasitic wasp.

We report basic biochemical characteristics of a parasitism-specific protein (PSP) expressed in hosts (Trichopluisa ni) of a parasitic wasp (Chelonus near curvimaculatus). Size exclusion HPLC and SDS-PAGE analysis of cross-linked products indicated the native conformation of the protein is as a monomeric polypeptide with an estimated M(r) of 185,000. Resolution by non-denaturing PAGE revealed two major PSP bands with different charges, PSP-1 and PSP-2, each of which corresponded to several isoforms on native IEF with a pl range of 4.57-5.45. Sequences for the N-terminus region and internal peptides after fragmentation of purified preparations of PSP-1 and PSP-2 did not resemble the sequence of any reported protein. Immunological characterization of PSP using antibodies generated against virus proteins from C. near curvimaculatus female wasps revealed that PSP shares a common epitope(s) with some structural components of the wasp polydnavirus.

Amino Acid Sequence↗

PubMed1994

Cholecystectomy for cholecystitis in patients with acquired immune deficiency syndrome.

Acalculous cholecystitis, a recognized manifestation of acquired immune deficiency syndrome (AIDS), causes abdominal pain which can be relieved by cholecystectomy. The indications for cholecystectomy have remained undefined, however, because the cholecystitis is usually accompanied by generalized cholangitis and it is difficult to distinguish the relative clinical importance of the two problems. Since 1985, we have performed cholecystectomy on 8 patients with AIDS who had clinical manifestations of acute cholecystitis associated with a thickening of the gallbladder wall by 5 mm to 12 mm. Two of the 8 had gallstones and 4 had associated cholangitis. All had been treated with antibiotics for 20 to 180 days before surgery, but physical deterioration had progressed in every case. At the moment of surgical intervention, 4 patients had multiple organ failure. One patient died 3 days postoperatively, but the rest recovered rapidly with resolution of the abdominal pain and sepsis. Two patients died 20 days after surgery due to complications of AIDS. The remaining 5 died due to AIDS at 6, 9, 10, 12, and 14 months after surgery. Two of this group developed progressive cholangitis with raised serum alkaline phosphatase. Our experience indicates that cholecystectomy should be considered for the treatment of severe and persistent symptoms of hepatobiliary manifestations of AIDS notwithstanding the presence of cholangitis.

AIDS-Related Opportunistic Infections↗

PubMed1994

The amino-terminal region of the retinoblastoma gene product binds a novel nuclear matrix protein that co-localizes to centers for RNA processing.

The tumor suppressing capacity of the retinoblastoma protein (p110RB) is dependent on interactions made with cellular proteins through its carboxy-terminal domains. How the p110RB amino-terminal region contributes to this activity is unclear, though evidence now indicates it is important for both growth suppression and regulation of the full-length protein. We have used the yeast two-hybrid system to screen for cellular proteins which bind to the first 300 amino acids of p110RB. The only gene isolated from this screen encodes a novel 84-kD nuclear matrix protein that localizes to subnuclear regions associated with RNA processing. This protein, p84, requires a structurally defined domain in the amino terminus of p110RB for binding. Furthermore, both in vivo and in vitro experiments demonstrate that p84 binds preferentially to the functionally active, hypophosphorylated form of p110RB. Thus, the amino terminus of p110RB may function in part to facilitate the binding of growth promoting factors at subnuclear regions actively involved in RNA metabolism.

Amino Acid Sequence↗

PubMed1994

Hospital care and discharge: patients' and carers' opinions.

Recent policy has emphasized the importance of patients as health service consumers and of care in the community. This paper describes a postal study which investigated patients' and carers' opinions of hospital care and discharge in three district health authorities. Overall, comments were positive about nursing care but more critical of environmental issues. More carers than patients made positive comments and more patients than carers made negative comments about the time spent in hospital. Carers were more likely to comment on medical aspects whereas patients seemed more concerned with social and environmental issues. Carers were more likely than patients to be dissatisfied with discharge arrangements, including length of notice, and more likely to think that discharge had been premature. These differences indicate the value of collecting both patients' and carers' opinions.

Aged↗

PubMed1994

The G-C specific DNA binding drug, mithramycin, selectively inhibits transcription of the C-MYC and C-HA-RAS genes in regenerating liver.

Expression of the c-myc and c-Ha-ras protooncogenes is dramatically increased in regenerating rat liver as an early response to partial hepatectomy. Nuclear runon transcription studies confirm that the increased c-myc and c-Ha-ras mRNA levels in regenerating livers reflect transcriptional activation of these genes. Mithramycin, a G-C specific DNA binding drug, prevents the increased transcriptional activity of c-myc and c-Ha-ras genes after hepatectomy but does not alter the transcriptional activity of the beta-actin gene. Continuous exposure of rats to mithramycin after hepatectomy prevents the increase in both c-myc and c-Ha-ras expression and blocks the increased cellular proliferation characteristic of regeneration. The delayed increase in c-myc and c-Ha-ras gene expression is associated with a delay in cellular proliferation. The inhibition of c-myc and c-Ha-ras transcription by mithramycin, the delay in cellular proliferation, and the ability of mithramycin to prevent protein binding to the c-myc promoter, suggest that the increased expression of these genes is a necessary component of liver regeneration.

Animals↗

PubMed1994

A prospective population-based study of HIV perinatal transmission.

OBJECTIVE: To estimate the perinatal HIV transmission rate and describe the natural history of infant HIV infection in a situation in which HIV status is known in more than 95% of delivering women. DESIGN: A cohort of HIV-exposed infants born between 7 July 1987 and 30 June 1990, whose mothers were identified by routine voluntary universal HIV testing, were followed using clinical and laboratory measures. SETTING: Grady Memorial Hospital, a major health-care site for individuals of lower socioeconomic status in Atlanta, Georgia, USA, with approximately 7000 deliveries per year. PATIENTS: HIV-exposed infants (n = 165), 98% of whom were African American. RESULTS: Annual maternal HIV seroprevalence increased from 0.58 to 0.86%. The annual proportion of HIV-positive women having a second delivery increased from 4.3 to 25%. Clinical outcome was known for 132 out of 165 infants (22 infected and 110 uninfected), the transmission rate was 17% (confidence interval, 11-24%). The rate declined to 11% by the third year of the study. Gestational growth, prematurity and mode of delivery were unrelated to infant outcome. There was a trend for intravenous drug use to be more common in mothers of infected infants (P = 0.08). After 35 months median follow-up of infected infants, eight out of 22 (36%) had an opportunistic infection (seven Pneumocystis carinii pneumonia); three out of 22 (14%) had lymphocytic interstitial pneumonia, and 10 out of 22 (45%) were asymptomatic or had only nonspecific symptoms. Cumulative mortality in infected infants was 9, 32 and 32% by 1, 2 and 3 years of age, respectively. CONCLUSION: In this cohort of HIV-exposed infants, perinatal HIV transmission was 17% overall. Factors affecting the transmission rate and possible future changes in the rate require further study.

AIDS-Related Opportunistic Infections↗

PubMed1994

The transcription factor E2F-1 mediates the autoregulation of RB gene expression.

The retinoblastoma (RB) gene is the prototype tumor suppressor gene. Mutations in this gene are often associated with the occurrence of various tumors. Several mutations have been found in the promoter region of the gene, suggesting that inappropriate transcriptional regulation of the RB gene contributes to tumorigenesis. Sequence analysis of the RB promoter has revealed a potential E2F recognition site within a region critical for RB gene transcription. By using the cloned E2F-1 gene, here we report that (i) RB expression is negatively regulated by its own gene product, (ii) E2F-1 binds specifically to an E2F recognition sequence in the RB promoter and transactivates the RB promoter, (iii) overexpression of RB suppresses E2F-1-mediated stimulation of RB promoter activity, and (iv) the expression of the RB gene is paralleled by the expression of the E2F-1 gene during cell cycle progression. These results demonstrate that expression of RB is negatively autoregulated through E2F-1.

Animals↗

PubMed1994

Detection of tumour necrosis factor alpha in sarcoidosis and tuberculosis granulomas using in situ hybridisation.

AIMS: To determine the site of tumour necrosis factor alpha (TNF alpha) product and mRNA in granulomas. METHOD: In situ hybridisation with digoxigenin labelled or biotinylated oligonucleotide probes was used to demonstrate the presence of total mRNA, and then the presence of TNF alpha mRNA in the biopsy specimens of 37 granulomas (31 sarcoidosis, six tuberculosis). RESULTS: TNF alpha mRNA was detected in epithelioid cells, giant cells, and lymphocytes in the granulomas. Some sarcoidosis specimens did not contain detectable mRNA for TNF, but did contain TNF peptide in the epithelioid or giant cells on immunostaining. This may have been due to stored TNF present in cells in which mRNA for TNF is no longer being produced. CONCLUSION: The results suggest that giant cells should not be regarded as effete cells, as they contain large amounts of mRNA and seem to be actively producing TNF alpha.

Antisense Elements (Genetics)↗

PubMed1994

The favoured child?

This case conference concerns a child who has been in care following a diagnosis of emotional abuse and a serious incident of physical abuse. She wants to return home again, and her parents, who had previously scapegoated her, now blame the family's previous ills on her sister instead. The Children Act 1989 gives considerable weight to the child's wishes, but what if the child returns home and is re-abused? In this case conference a child psychiatrist, a philosopher and a lawyer discuss the issues of clinicians' responsibilities, moral luck, and child care law.

Australia↗

PubMed1994

Clinical pharmacodynamics of continuous infusion topotecan in children: systemic exposure predicts hematologic toxicity.

PURPOSE: Topotecan pharmacokinetics and pharmacodynamics were studied following a 72-hour continuous infusion in 20 children with cancer (median age, 8 years; range, 3.5 to 18). METHODS: Serial plasma and urine samples were collected during the infusion and for up to 6 hours following the end of infusion. Topotecan (lactone) and total (lactone plus hydroxy acid) concentrations were determined by a sensitive and specific high-performance liquid chromatography (HPLC) assay with fluorescence detection. Using maximum a posteriori-Bayesian modeling, lactone and total plasma concentrations were described separately by a two-compartment model. Hematologic toxicity was expressed as the percent decrease in absolute neutrophil count (ANC) and platelet count. The relation between systemic exposure (SE) and hematologic toxicity was modeled using a sigmoid maximum-effect model. RESULTS: Systemic clearance rates for lactone and total topotecan were (mean +/- SD) 18.5 +/- 7.0 and 6.5 +/- 2.4 L/h/m2, respectively. Urinary recovery of total topotecan was (mean +/- SD) 67.5% +/- 25.2% (n = 12 patients). SE (area under the concentration-time curve from zero to infinity [AUC] or steady-state plasma concentration [Cpss]) to either topotecan lactone or total topotecan was significantly correlated to hematologic toxicity (P < .05). Overall, patients with a higher SE to topotecan experienced greater hematologic toxicity. CONCLUSION: These data demonstrate a relation between systemic exposure to topotecan and clinical effect (myelosuppression). Moreover, these data provide the basis for development of individualized topotecan administration schedules.

Adolescent↗

PubMed1994

THE INFLUENCE OF HEMATOCRIT, TEMPERATURE AND SHEAR RATE ON THE VISCOSITY OF BLOOD FROM A HIGH-ENERGY-DEMAND TELEOST, THE YELLOWFIN TUNA THUNNUS ALBACARES

The high cardiac output, arterial blood pressure and cardiac energy demand of tuna make it likely that blood viscosity has an important influence on cardiovascular function. Furthermore, tuna regularly subject themselves to ambient temperature changes of 10°C or more during their daily vertical migrations. They can also maintain muscle temperatures several degrees Celsius above ambient and reach maximum muscle temperatures of approximately 15°C above ambient. The blood of tuna is, therefore, subjected to more frequent and rapid temperature changes than those that occur in other teleosts. Nothing is known, however, about the effects of temperature, shear rate or hematocrit on the viscosity of tuna blood. Viscosity of yellowfin tuna blood (hematocrits of 055 %) was measured at 15, 25 and 35°C and at shear rates of 45, 90, 225 and 450 s-1 using a cone-plate viscometer. As found for the blood of other vertebrates, viscosity increased with increasing hematocrit. Viscosity also increased nonlinearly with decreasing shear rate, until a shear rate of 90 s-1 was reached. There was no significant increase in viscosity when shear rate was decreased further, to 45 s-1. Because of the relatively flat hematocritviscosity curves, predicted optimal hematocrit curves were nearly flat above a hematocrit of approximately 30 %.

Journal Article↗

PubMed1994

PERIODIC AIR-BREATHING BEHAVIOUR IN A PRIMITIVE FISH REVEALED BY SPECTRAL ANALYSIS

The ventilatory patterns of air-breathing fish are commonly described as 'arrhythmic' or 'irregular' because the variable periods of breath-holding are punctuated by seemingly unpredictable air-breathing events (see Shelton et al. 1986). This apparent arrhythmicity contrasts with the perceived periodism or regularity in the gill ventilation patterns of some fish and with lung ventilation in birds and mammals. In this sense, periodism refers to behaviour that occurs with a definite, recurring interval (Bendat and Piersol, 1986). The characterisation of aerial ventilation patterns in fish as 'aperiodic' has been generally accepted on the basis of qualitative examination and it remains to be validated with rigorous testing. The bowfin, Amia calva (L.), is a primitive air-breathing fish that makes intermittent excursions to the airwater interface to gulp air, which is transferred to its well-vascularized gas bladder. Its phylogenetic position as the only extant member of the sister lineage of modern teleosts affords a unique opportunity to examine the evolution of aerial ventilation and provides a model for the examination of ventilatory patterns in primitive fishes. To establish whether Amia calva exhibit a particular pattern of air-breathing, we examined time series records of aerial ventilations from undisturbed fish over long periods (8 h). These records were the same as those used to calculate average ventilation intervals under a variety of experimental conditions (Hedrick and Jones, 1993). Their study also reported the occurrence of two distinct breath types. Type I breaths were characterised by an exhalation followed by an inhalation, whereas type II breaths were characterised by inhalation only. It was also hypothesized that the type I breaths were employed to meet oxygen demands, whereas the type II breaths were used to regulate gas bladder volume. However, they did not investigate the potential presence of a periodic ventilatory pattern. We now report the results of just such an analysis of ventilatory pattern that demonstrates a clear periodism to air-breathing in a primitive fish.

Journal Article↗

PubMed1994

Economic outcomes of colfosceril palmitate rescue therapy in infants weighing 1250g or more with respiratory distress syndrome: results from a randomised trial.

An analysis of the economic data from a multicentre, randomised, placebo-controlled clinical trial of colfosceril palmitate in infants with neonatal respiratory distress syndrome (NRDS) and birthweights of 1250g or more is presented. Two 5 ml/kg (67.5 mg/kg) doses of a synthetic surfactant (colfosceril palmitate) or air placebo were administered to 1237 infants who were receiving mechanical ventilation and had an arterial/alveolar oxygen tension ratio of less than 0.22. In addition to the clinical end-points for safety and efficacy, data were collected on length of hospital stay, days in the neonatal intensive care unit, days on mechanical ventilation, days on oxygen, and hospital charges until the child reached 1-year adjusted age. One-year adjusted age is attained when the time elapsed since birth is equal to 365 days plus the number of days of prematurity. Rescue treatment with synthetic surfactant therapy has been shown to reduce the incidence of complications of NRDS. Growth and development of infants who received colfosceril palmitate therapy in the study and survived to 1-year adjusted age were equivalent to those of the survivors in the air placebo group. For the cohort of treated infants, colfosceril palmitate reduced the average length of stay at 2 levels of care needed during both the initial hospitalisation (a reduction of 8 days overall and 5 days in intensive care) and all first year hospitalisations (a reduction of 9 days overall and 5 days in intensive care). Total hospital charges for the initial hospitalisation and through 1-year adjusted age for a hypothetical cohort of 100 infants treated with colfosceril palmitate were less than those for a comparable cohort in the air placebo group. The results would, therefore, suggest that rescue therapy with colfosceril palmitate in infants with NRDS and birthweights over 1250g can result in substantial reductions in hospital resource utilisation and charges in addition to the clinical benefits associated with its use.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1994

A review of analgesia for knee surgery.

This review demonstrates that there are inadequate data to draft a protocol in pain management after knee surgery. The review is intended to provide a stimulus for those who manage their orthopedic patients in a particular manner to test their pain management strategy in a random, prospective, controlled manner. They should aim to provide a data base that will assist in solving the knee surgery conundrums which inhibit identification of the most efficacious delivery of analgesia.

Analgesia↗

PubMed1994

Ocular complications related to breast cancer.

One in 10 women will be affected by breast cancer in their lifetime. The potential for loss of vision from breast cancer metastases to the eye will affect a small proportion of these women. Ocular complications related to these metastases and cancer treatments (drugs, irradiation) and the psychosocial support for the patient and family make the role of the ophthalmic nurse an extremely important one. This article will review these issues.

Antineoplastic Agents↗