Biomedical subjects

J Phillips

Publications and source records attributed to J Phillips.

At least 109 records · Page 6Linked to original sources

PubMed1997

Ocular morbidity in very low birth-weight infants with intraventricular hemorrhage.

PURPOSE: To document ocular outcomes and prevalence of ocular disease in very low birth-weight infants with intraventricular hemorrhage. METHODS: We retrospectively reviewed the records of all surviving very low birth-weight infants (1,500 g or less) admitted to the neonatal intensive care unit of our institution during 1992 and 1993. Of 252 survivors, 74 had complete ophthalmologic examinations at a mean adjusted age of 11 months. Of these 74 infants, 38 had intraventricular hemorrhage. Chi-square and multivariate analysis were used for statistical testing, in controlling for race, sex, and birth weight, and for other disease processes associated with prematurity. RESULTS: Of 38 infants with intraventricular hemorrhage, strabismus occurred in 14 (37%), esotropia in 12 (32%), and exotropia in two (5%). Of the 20 infants with grades III and IV intraventricular hemorrhage, 11 (55%) had esotropia; none had exotropia. Infants with grades III and IV intraventricular hemorrhage were at significantly greater risk for the development of esotropia than were infants with less severe or no hemorrhage (odds ratio, 5.0; P = .04). Mean adjusted age at diagnosis of strabismus was 8.5 months. Infants with periventricular leukomalacia (odds ratio, 6.3; P = .036) and neonatal seizures (odds ratio, 7.3; P = .019) were at significantly greater risk of developing optic atrophy. CONCLUSIONS: Very low birth-weight infants with more severe neurologic morbidity are at significant risk for development of esotropia and optic atrophy. Ophthalmologic screening of all very low birth-weight survivors may allow earlier diagnosis and intervention for these at-risk infants.

Cerebral Hemorrhage↗

PubMed1997

Optimization of scFv antibody production in transgenic plants.

BACKGROUND: Plants offer various advantages for the production of pharmaceutical proteins over conventional production systems such as bacterial or mammalian cell culture. In order to explore transgenic plants for large-scale production and storage of recombinant antibodies we tried to optimize the accumulation and stability of functionally active single chain Fv (scFv) antibodies in transgenic tobacco plants. OBJECTIVES: Two different scFv antibodies which were expressed in different plant organs and plant cell compartments have been used for the study. Accumulation levels and antibody properties such as stability and antigen-binding activity were investigated. STUDY DESIGN: For ubiquitous expression in tobacco plants, transcription of the scFv genes was controlled by the strong cauliflower mosaic virus (CaMV) 35S promoter. We used seed specific legumin B4 (LeB4) and the unknown seed protein (USP) promoters from Vicia faba for storage organ specific expression. RESULTS: High accumulation of the two different scFv proteins in transgenic tobacco plants was only achieved by retention of the recombinant antibodies in the lumen of the endoplasmic reticulum (ER). Expression levels of scFv antibodies reached up to 4-6.8% of total soluble proteins (TSP) in leaves and up to 3-4% in ripe tobacco seeds. Transgenic tobacco seeds as well as tobacco leaves facilitated stable storage of ER-accumulated scFvs over an extended (seeds) or a short (leaves) period of time. Functionally active scFv proteins could be extracted after harvesting of the leaf material--drying and storage for 1 week at room temperature. Both the amount and the binding activity of the scFv proteins remained unchanged. CONCLUSION: A plant expression system where the scFv-proteins are targeted in the ER provides not only the highest accumulation level of active single chain Fv antibodies ever reported but also a short- or long-term storage of the foreign protein in the harvested plant material.

Chimera↗

PubMed1997

In utero lysis of amniotic bands.

Amniotic band syndrome is a sporadic condition that occurs in approximately 1:1200 to 1:15,000 live births and that may result in amputations, constrictions and other deformities of the fetus. Although some cases present with congenital anomalies that are beyond surgical repair, a selected group of fetuses may show isolated limb constriction. It has been speculated that, without treatment, amputation or severe dysfunction of the limb may occur. Despite these potential complications, surgical treatment for this selected group of fetuses has not been previously performed. We report two cases that were successfully treated using novel minimally invasive surgical techniques. The cases involved fetuses with amniotic band syndrome with associated limb constriction in which the amniotic band was surgically interrupted to avoid spontaneous amputation of the extremity. Adequate blood flow distal to the obstruction was preserved and significant functional improvement of the extremity occurred in both cases, preserving the limbs. These cases represent the first prenatal surgical intervention successfully used to treat constricting amniotic bands in humans. In addition, these cases represent the first time that a non-lethal fetal entity has been surgically treated in utero. The results of this innovative therapy will encourage the efforts to continue developing minimally invasive techniques for the correction of birth defects.

Adult↗

PubMed1997

Detection of infection with human immunodeficiency virus type 1 before seroconversion: correlation with clinical symptoms and outcome.

Early (pre-seroconversion) infection with human immunodeficiency virus type 1 (HIV-1) was identified in 50 of 267 participants in the Multicenter AIDS Cohort Study. These 50 men had a positive EIA result, which detected IgM antibody (n = 35), p24 antigen, or serum HIV RNA (n = 15) at their last "seronegative" visit. At that visit, the mean CD4 lymphocyte number (890/mm3 vs. 1038/mm3) was significantly lower than in men who subsequently seroconverted but had no evidence of early infection. The decline in CD4 cells was slower and the duration of AIDS-free time longer in the 19 men who were symptomatic in comparison to the 31 asymptomatic men with early infection, but differences were not significant.

Acquired Immunodeficiency Syndrome↗

PubMed1997

Lipoprotein (a): a potential biological marker for unruptured intracranial aneurysms.

OBJECTIVE: The diagnosis and treatment of intracranial aneurysms (IAs) prior to rupture reduces the high morbidity and mortality associated with their occurrence. Elevated serum lipoprotein (a) [Lp(a)] level, an independent risk factor for atherogenesis, has been demonstrated in sporadic IA disease (1). The purpose of this study was to assess the degree of correlation between elevated Lp(a) levels and the occurrence of IAs in asymptomatic first degree relatives of index cases from three families exhibiting a familial tendency towards IA development. METHODS: 25 family members and 41 healthy controls were screened by random serum Lp(a) sampling. All family members received 4-vessel cerebral angiography. RESULTS: Eleven family members were found on angiography to harbour asymptomatic aneurysms and all were successfully treated by surgery. Of these 11, ten had significantly raised serum Lp(a) levels (> 30 mg%). Fourteen family members had negative angiograms. Eight of this latter group, mean age 43.6 +/- 3.8 years, had serum Lp(a) levels above the normal range. Mean Lp(a) levels were 53.7 +/- 1.2 mg% in subjects with aneurysms compared with 22.1 +/- 1.45 mg% in subjects without demonstrable aneurysms and 10.5 +/- 0.48 mg% in the control population. CONCLUSION: The prevalence of elevated Lp(a) levels in these families and the high degree of association of raised Lp(a) levels with the presence of IAs in several family members warrants follow up of angiographically negative young subjects. We require a case-control study to establish whether particular polymorphisms at the apoprotein (a) gene level are associated with the occurrence of IAs in these families.

Adult↗

PubMed1997

Initiation rate and duration of breast-feeding in the Melbourne aboriginal community.

Breast-feeding is important for child health and helps to protect the child against infections. The objective of this study was to determine baseline breast-feeding rates in the Melbourne Aboriginal community prior to a breast-feeding promotion project. A brief questionnaire was administered to 116 mothers of infants up to two years of age with a Melbourne metropolitan address. During their pregnancies, 99 (85.3 per cent) of the women had planned to breast-feed, and 98 (84.5 per cent, 95 per cent confidence interval (CI) 77.9 to 91.1 per cent) initiated breast-feeding. However, 10 (8.6 per cent) stopped within the first week, and seven (6 per cent) more stopped within the first four weeks. Only 50 per cent of the babies (CI 40.9 to 59.1 per cent) were still being breast-fed at three months of age and 32 per cent were still being breast-fed at six months of age (CI 23.5 to 40.5 per cent). Younger mothers were less likely to choose to breast-feed (73 per cent) than women 20 years and over (87 per cent) and were also more likely to stop breast-feeding within three months. A total of 45 (51.1 per cent) of the babies received food other than breast milk or formula earlier than the recommended minimum age of four months. These results are similar to those for the general Victorian population. They show that while most Aboriginal women choose to breast-feed, many cease breast-feeding before they had intended.

Adult↗

PubMed1997

Influences on infant-feeding beliefs and practices in an urban aboriginal community.

The Victorian Aboriginal Health Service initiated a project to increase breast-feeding rates in the Melbourne Aboriginal community. The results of focus-group discussions on infant-feeding experiences and beliefs provided a wealth of information for the design of appropriate interventions. Most women wanted and expected to breast-feed. Some chose artificial feeding because of embarrassment, a belief that it is as good as breast-feeding, or perceptions that breast-feeding is painful and inconvenient. The most common reasons that women stopped breast-feeding were sore nipples, worries about their supply of milk and tiredness. Lack of knowledge, hospital practices, lack of support and appropriate advice, and lack of confidence and self-esteem contributed to these problems. Disruption of the passing on of knowledge of healthy infant-feeding practices between generations is another cultural loss suffered by Aboriginal communities. Efforts to restore traditional rates of breast-feeding need to be under Aboriginal control and to take account of these influences.

Adolescent↗

PubMed1997

Testosterone replacement increases fat-free mass and muscle size in hypogonadal men.

Testosterone-induced nitrogen retention in castrated male animals and sex-related differences in the size of the muscles in male and female animals have been cited as evidence that testosterone has anabolic effects. However, the effects of testosterone on body composition and muscle size have not been rigorously studied. The objective of this study was to determine the effects of replacement doses of testosterone on fat-free mass and muscle size in healthy hypogonadal men in the setting of controlled nutritional intake and exercise level. Seven hypogonadal men, 19-47 yr of age, after at least a 12-week washout from previous androgen therapy, were treated for 10 weeks with testosterone enanthate (100 mg/week) by im injections. Body weight, fat-free mass measured by underwater weighing and deuterated water dilution, and muscle size measured by magnetic resonance imaging were assessed before and after treatment. Energy and protein intake were standardized at 35 Cal/kg.day and 1.5 g/kg.day, respectively. Body weight increased significantly from 79.2 +/- 5.6 to 83.7 +/- 5.7 kg after 10 weeks of testosterone replacement therapy (weight gain, 4.5 +/- 0.6 kg; P = 0.0064). Fat-free mass, measured by underwater weighing, increased from 56.0 +/- 2.5 to 60.9 +/- 2.2 kg (change, +5.0 +/- 0.7 kg; P = 0.0004), but percent fat did not significantly change. Similar increases in fat-free mass were observed with the deuterated water method. The cross-sectional area of the triceps arm muscle increased from 2421 +/- 317 to 2721 +/- 239 mm2 (P = 0.045), and that of the quadriceps leg muscle increased from 7173 +/- 464 to 7720 +/- 454 mm2 (P = 0.0427), measured by magnetic resonance imaging. Muscle strength, assessed by one repetition maximum of weight-lifting exercises increased significantly after testosterone treatment. L-[1-13C]Leucine turnover, leucine oxidation, and nonoxidative disappearance of leucine did not significantly change after 10 weeks of treatment. There was no significant change in hemoglobin, hematocrit, creatinine, and transaminase levels. Replacement doses of testosterone increase fat-free mass and muscle size and strength in hypogonadal men. Whether androgen replacement in wasting states characterized by low testosterone levels will have similar anabolic effects remains to be studied.

Adult↗

PubMed1997

Lothian inter-agency child protection guidelines: impact on a children's NHS trust.

OBJECTIVE: To evaluate the process involved in cases of suspected child abuse within a children's NHS Trust, 6 months after implementation of new inter-agency Child Protection guidelines. DESIGN: Prospective evaluation of case records. SETTING: Four departments within a combined child health trust in Edinburgh. MAIN MEASURES: Review of practice within each department, according to the Inter-Agency guidelines. RESULTS: No standard procedure existed for the child protection process prior to the guidelines. In the first 6 months following implementation of the guidelines, a substantial increase in workload was experienced by community paediatricians. Medical examinations were better co-ordinated, with fewer children receiving repeated, intrusive examinations. However, note keeping was deficient, as 3% of referrals did not appear to be recorded in the case notes. Cross-referencing between departments was variable, with 81% of cases referred to Community Child Health not recorded in hospital case notes. CONCLUSIONS: The Inter-Agency guidelines have resulted in better coordination of the early referral stages. Deficiencies highlighted in this audit are due to record keeping and lack of liaison between departments within a combined children's trust.

Child Abuse↗

PubMed1997

Effective use of ribonucleotide reductase inhibitors (Didox and Trimidox) alone or in combination with didanosine (ddI) to suppress disease progression and increase survival in murine acquired immunodeficiency syndrome (MAIDS).

Ribonucleotide reductase inhibitors (RRIs) have been recently shown to inhibit retroviral replication. We examined a new series of RRIs, 3,4-dihydroxybenzohydroxamic acid (Didox) and 3,4,5-trihydroxybenzohydroxamidoxime (Trimidox) for their ability to alter disease progression in murine acquired immunodeficiency syndrome (MAIDS), both alone and in combination with 2',3'-dideoxyinosine (ddI). MAIDS disease was induced by inoculation of female C57BL/6 mice with the LP-BM5 murine leukemia virus (MuLV) and disease progression characterized by extensive peripheral lymphadenopathy and splenomegaly. Efficacy of treatment with these drugs was based upon their ability to influence survival and disease pathophysiology by monitoring the development of splenomegaly. Toxicity was determined by changes in body weight, total peripheral white blood cell count and hematocrit. Didox or trimidox monotherapy was associated with increased survival and decreased disease pathophysiology, with no apparent toxicity. Combined with ddI, their ability to reduce development of viral induced splenomegaly was enhanced compared to trimidox, didox or ddI alone. These results demonstrate RRIs have potent activity in reversing the disease manifestations characteristic of MAIDS. Further studies are warranted to determine human clinical efficacy.

Animals↗

PubMed1997

Snow mountain-like virus identified in young children with winter vomiting disease in South Africa.

Human caliciviruses have been reported to be associated with both epidemics of acute diarrhoeal illness and with sporadic cases of gastroenteritis in children. In this study, we report the identification of genogroup II small round-structured viruses or human caliciviruses associated with an outbreak of winter vomiting disease in South Africa. The virus was initially identified by electron microscopic examination of the stools and then further characterised by recombinant immunoassay with expressed capsid proteins to human caliciviruses from genogroups I and II. Both antigenically by the EIA and by sequence analysis of a region of the RNA-dependent RNA polymerase gene, the virus was shown to belong to genogroup II of the human Caliciviridae.

Amino Acid Sequence↗

PubMed1996

A discontinuous eight-amino acid epitope in human interleukin-3 binds the alpha-chain of its receptor.

We have previously reported that, within the first helix of human interleukin (IL)-3, residues Asp21 and Glu22 are important for interaction with the alpha- and beta-chains of the IL-3 receptor, respectively. In order to define more precisely the sites of interaction with the receptor, we have performed molecular modeling of the helical core of IL-3 and single amino acid substitution mutagenesis of residues predicted to lie on the surfaces of the A, C, and D helices. The resulting analogues were characterized for their abilities to stimulate proliferation of TF-l cells and for binding to the high affinity (alpha- and beta-chain; IL-3Ralpha/Rbeta) or low affinity (alpha-chain alone; IL-3Ralpha) IL-3 receptor. We found that in addition to Asp21, residues Ser17, Asn18, and Thr25 within the A helix and Arg108, Phe113, Lys116, and Glu119 within the D helix of IL-3 were important for biological activity. Analysis of their binding characteristics revealed that these analogues were deficient in binding to both the IL-3Ralpha/Rbeta and the IL-3Ralpha forms of the receptor, consistent with a selective impairment of interaction with IL-3Ralpha. Molecular modeling suggests that these eight amino acid residues are adjacent in the tertiary structure, consistent with a discontinuous epitope interacting selectively with IL-3Ralpha. On the other hand, Glu22 of IL-3 was found to interact preferentially with the beta-chain with bulky and positively charged substitutions causing greater than 10,000-fold reduction in biological activity. These results show fundamental differences between IL-3 and granulocyte-macrophage colony-stimulating factor in the structural basis for recognition of their receptors that has implications for the construction of novel analogues and our understanding of receptor activation.

Amino Acid Sequence↗

PubMed1996

Cysteine protease inhibitors block schistosome hemoglobin degradation in vitro and decrease worm burden and egg production in vivo.

Schistosome parasites utilize hemoglobin as a major protein source for their metabolism. Degradation of hemoglobin has been hypothesized to be mediated by both cysteine and aspartyl proteases secreted into the lumen of the parasite intestine. We now show that two distinct types of irreversible cysteine protease-specific inhibitors both arrest schistosome hemoglobin degradation in vitro. Arrest of hemoglobin degradation is followed by death of developing schistosomula 1 week later. Schistosome infected mice treated by a dose of 2 mg inhibitor per day for 1 week early in infection, and 2 weeks at the time of egg production, showed a significant reduction in worm burden, hepatomegaly, and the number of eggs produced per female worm. Histopathology showed a minimal immune response to those eggs which were produced, consistent with a delay in egg production relative to untreated infections. By tagging the inhibitor with biotin, specific cysteine protease targets were identified in extracts of schistosome worms.

Animals↗

PubMed1996

T cell regulation in adult transplantation tolerance.

An encounter of the mature immune system with Ag usually leads to an immune response. If Ag is administered with CD4- and CD8-specific mAbs, the outcome of the response can be tolerance. This form of tolerance is peripheral, Ag specific, and maintained lifelong, and is associated with the suppression of nontolerant cells by CD4 cells of the tolerant host. Here we demonstrate that the degree of suppression is dependent on the number of suppressor cells. A neutralizing anti-IL-4 Ab was partially able to inhibit suppression, indicating a role for IL-4 in the regulation of Th1 rejection responses.

Adoptive Transfer↗

PubMed1996

The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men.

BACKGROUND: Athletes often take androgenic steroids in an attempt to increase their strength. The efficacy of these substances for this purpose is unsubstantiated, however. METHODS: We randomly assigned 43 normal men to one of four groups: placebo with no exercise; testosterone with no exercise; placebo plus exercise; and testosterone plus exercise. The men received injections of 600 mg of testosterone enanthate or placebo weekly for 10 weeks. The men in the exercise groups performed standardized weight-lifting exercises three times weekly. Before and after the treatment period, fat-free mass was determined by underwater weighing, muscle size was measured by magnetic resonance imaging, and the strength of the arms and legs was assessed by bench-press and squatting exercises, respectively. RESULTS: Among the men in the no-exercise groups, those given testosterone had greater increases than those given placebo in muscle size in their arms (mean [+/-SE] change in triceps area, 424 +/- 104 vs. -81 +/- 109 square millimeters; P < 0.05) and legs (change in quadriceps area, 607 +/- 123 vs. -131 +/- 111 square millimeters; P < 0.05) and greater increases in strength in the bench-press (9 +/- 4 vs. -1 +/- 1 kg, P < 0.05) and squatting exercises (16 +/- 4 vs. 3 +/- 1 kg, P < 0.05). The men assigned to testosterone and exercise had greater increases in fat-free mass (6.1 +/- 0.6 kg) and muscle size (triceps area, 501 +/- 104 square millimeters; quadriceps area, 1174 +/- 91 square millimeters) than those assigned to either no-exercise group, and greater increases in muscle strength (bench-press strength, 22 +/- 2 kg; squatting-exercise capacity, 38 +/- 4 kg) than either no-exercise group. Neither mood nor behavior was altered in any group. CONCLUSIONS: Supraphysiologic doses of testosterone, especially when combined with strength training, increase fat-free mass and muscle size and strength in normal men.

Adult↗

PubMed1996

Antisense RNA Amplification: A Linear Amplification Method for Analyzing the mRNA Population from Single Living Cells

Cell-specific gene expression is a fundamental area of investigation of various disciplines, but is often complicated by cell heterogeneity, paucity of material, or limits of detection for low-abundance mRNAs. Antisense RNA (aRNA) amplification presents a linear amplification method for analyzing the mRNA population from single living cells. Patch clamp electrodes containing reverse transcriptase, dNTPS, and a poly(T) primer modified 5' with a T7 RNA polymerase promoter sequence are used to isolate the cytoplasmic contents of individual living cells. The cDNAs transcribed therefore contain the T7 promoter sequence. Following subsequent processing for second-strand cDNA synthesis, T7 polymerase is used for amplification, which results in a 2000-fold amplification of antisense RNA. A second round of amplification results in a 10(6)-fold amplification of the initial material. The aRNA amplification method may be used in conjunction with other techniques. Electrophysiology may be conducted first to examine functional properties. Reverse Northerns may be performed, using the aRNA as a probe to identify specific cDNAs loaded onto a slot blot. PCR may be conducted to determine splice variants. Differential display and library construction may be employed to identify unknown or novel genes. Thus, the aRNA amplification may prove a valuable method for providing information on cell-specific gene expression in a variety of studies.

Journal Article↗

PubMed1996

Anterior callosotomy in the management of intractable epileptic seizures: significance of the extent of resection.

We report our series of twenty consecutive patients who underwent corpus callosotomy for medically intractable epilepsy. The follow-up is 6.7 +/- 0.5 years. Sixteen of 20 patients (80%) had a favourable outcome. Six patients have remained free of major generalized motor seizures, and ten further patients experienced significant sustained reduction in the severity and frequency of the seizures. The type of seizures associated with improved outcome were drop attacks, and generalized tonic-clonic seizures, in 11 of 13 (85%) and 14 of 18 (78%) of the patients, respectively. In order to establish the extent of necessary callosal resection to achieve seizure control, the outcome of patients was correlated with the extent of callosal sectioning on postoperative magnetic resonance imaging. This study confirms that an anterior callosal resection of two-thirds (or 65%) is sufficient to achieve significant improvement in seizure control with an acceptable morbidity in judiciously selected patients with medically intractable epilepsy. Results also suggest that the patient's history and clinical classification of the seizures have prognostic value as selection criteria for patients referred for this operation. In this series, no prognostic value was established for pre-operative electroencephalographic patterns, or neuroimaging findings.

Adolescent↗

PubMed1996

Topographical disorientation following unilateral temporal lobe lesions in humans.

Studies of the non-human temporal lobe, particularly the hippocampus, confirm its significant role in learning and memory, particularly allocentric spatial mapping of the environment. The role of the human temporal lobes in topographical orientation was investigated by examining the formation of representations of a large-scale real-world environment after unilateral left and right temporal lobe surgery. Patients and normal control subjects viewed videotape presentations of overlapping routes through a novel urban area. Topographical orientation was then assessed across a range of parameters. Right temporal lobe lesions alone gave rise to deficits in making proximity judgements. However, on all other topographical orientation tasks both right and left temporal lobe lesion groups were impaired relative to the normal control group, but the two patient groups did not differ significantly from each other. These findings suggest that such is the nature of remembering and way-finding in the environment that the integrity of both human temporal lobes is required.

Adult↗