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Biomedical subjects

J Jacob

Publications and source records attributed to J Jacob.

At least 37 records · Page 2Linked to original sources
PubMed2002

Longitudinal study of a cohort of people with diabetes screened by the Exeter Diabetic Retinopathy Screening Programme.

PURPOSE: To evaluate the long-term outcome of a cohort of people with diabetes screened by the Exeter Diabetic Retinopathy Screening Programme. METHOD: The cohort comprised of diabetic patients from nine market town General Practices around Exeter who first attended the diabetic retinopathy screening programme in 1992. Screening was carried out by a combination of dilated fundoscopy by a screening technician and a single 45 degrees Polaroid photograph of each eye. The prevalence of diabetic retinopathy at the baseline, the incidence of sight threatening diabetic retinopathy (STDR) in the next two rounds of screenings, and the long-term visual outcome are described. RESULTS: The cohort consisted of 775 patients (104 Type I, 517 Type II non-insulin-requiring and 154 Type II insulin-requiring). The mean age was 72.1 years (15-100), with mean disease duration of 13.0 years (1-79). Baseline prevalence was as follows: background retinopathy: 21.4%, proliferative: 2.8%, clinically significant macular oedema: 6.1%. The incidence of proliferative disease was 2.20% and 2.25% respectively in the next two rounds of screening (P > 0.05, chi2 test). The incidence of clinically significant macular oedema was also constant over next two rounds of screening, at 4.79% and 5.18% respectively (P > 0.05, chi2 test). Ninety-five (12.3%) patients were deceased and a further 179 (23%) patients were lost to follow-up by the third round. Only two patients with newly diagnosed STDR suffered deterioration of visual acuity to 6/60 or worse as a result of diabetic retinopathy. CONCLUSION: The incidence of STDR remained constant throughout the period of screening, reflecting the chronic progressive nature of the disease. Significant numbers of patients were lost to follow-up. Screening seemed effective in preserving vision in those patients with newly diagnosed STDR.

Adolescent↗
PubMed2002

Pulmonary volume recruitment manoeuvre restores pulmonary compliance and resistance after apnoea in anaesthetized lambs.

BACKGROUND: We studied the effects of an episode of induced apnoea on the dynamic compliance (Crs) and resistance (Rrs) of the respiratory system in anaesthetized lambs and investigated the mechanisms underlying the effectiveness of a timed reexpansion inspiratory manoeuvre (TRIM). METHODS: Following 2 min of apnoea, three manoeuvres were randomly performed: (i) control: reventilated without TRIM using initial settings and gas composition of 30% oxygen in 70% nitrous oxide; (b) T1: TRIM with 30% oxygen in 70% nitrous oxide, followed by reventilation with the initial settings; and (c) T2: preoxygenate with 100% oxygen, apnoea, then TRIM with 100% oxygen, then reventilation with 100% oxygen at the initial settings. The percentage change in Crs and Rrs was calculated at first breath, second breath, 10, 20, 40, 60, 90, 120 and 180 s postapnoea. RESULTS: Mean control decreased 15% and did not return to baseline during the study period. TRIM increased mean Crs in T1 and T2 by 8% and 9%, respectively, at first breath and returned to baseline and did not deteriorate for the remainder of the study period. Mean Rrs in the control group increased 20% and did not return to baseline during the study period. Mean Rrs in T1 and T2 initially increased 17% and 27%, respectively, at first breath and returned to baseline within 40 s. CONCLUSIONS: These results demonstrate that significant deterioration occurs in Crs and Rrs following 2 min of apnoea in anaesthetized lambs, which is not corrected with normal ventilation but is rapidly and completely reversed with a TRIM. This supports our hypothesis that volume recruitment of alveoli is an effective manoeuvre in restoring lung function. The practice of preoxygenation is also reinforced as the lambs maintained maximal oxygen saturation if they were ventilated with 100% oxygen prior to the 2 min of apnoea.

Anesthesia, General↗
PubMed2001

Hydrogen-bond network in cyclodecaamylose hydrate at 20 K; neutron diffraction study of novel structural motifs band-flip and kink in alpha-(1-->4)-D-glucoside oligosaccharides.

A single-crystal neutron diffraction study of cyclodecaamylose (CA10) was carried out at 20 K. CA10 crystallizes with 27.18 water molecules [(C(6)H(10)O(5))(10).27.18H(2)O] in space group C2 with unit-cell constants a = 29.31 (5), b = 9.976 (10), c = 19.34 (2) A, beta = 121.07 (2) degrees. The asymmetric unit contains a half molecule of CA10 and 13.59 water molecules, the other half being related by a crystallographic twofold rotation axis. All H atoms except two water H atoms could be located from difference neutron-density maps; structure refinement converged at R = 0.635. Two of the five CH(2)-O6 groups and one of the 15 O2, O3 hydroxyl groups of CA10 are twofold orientationally disordered. A total of 13.59 water molecules in the asymmetric unit are distributed over 23 positions; 20 of which are in the CA10 cavity, and the other three occupy intermolecular interstices. Of the 123 symmetry-independent hydrogen bonds, 25 (= 20%) are three-centered and 7 (= 6%) are four-centered. Water molecules and O-H groups of CA10 form an extended network with cooperative O-H...O-H...O-H hydrogen bonds. They are arranged in 11 polygons with three, four, five, six and eight O-H bonds and in homodromic, antidromic and heterodromic arrangements. Nine polygons are located within the cavity and the others are outside.

Journal Article↗
PubMed2001

Disulfide-mediated dimerization of L1 Ig domains.

The neural cell adhesion molecule L1 contains immunoglobulin-like (Ig) domains in its extracellular region that mediate homophilic binding, neurite outgrowth and other activities relevant to CNS development. To correlate conformations of these domains to biological function, several L1-Fc fusion proteins whose bioactivities were previously characterized were analyzed by rotary shadowing electron microscopy. We found that bioactive L1-Fcs containing Ig domains 1-4 or 1-6 exhibited extended, branched structures. In contrast, inactive L1-Fcs containing only the first two or three Ig domains assumed compact shapes that suggested interactions between the L1 arms of these proteins. Analysis of an untagged L1 fragment composed of Ig domains 1-3 demonstrated a mixture of monomeric and dimeric forms. Surprisingly, these dimers were stabilized by intermolecular disulfide bonds. Finally, cell surface L1-GFP fusion proteins containing only the first two or three Ig domains in the extracellular region also engaged in disulfide-mediated dimerization. These results suggest a novel mechanism by which mutations in L1 could interfere with its biological functioning.

Binding Sites↗
PubMed2001

Mechanisms and molecules in motor neuron specification and axon pathfinding.

The vertebrate nervous system performs the most complex functions of any organ system. This feat is mediated by dedicated assemblies of neurons that must be precisely connected to one another and to peripheral tissues during embryonic development. Motor neurons, which innervate muscle and regulate autonomic functions, form an integral part of this neural circuitry. The first part of this review describes the remarkable progress in our understanding of motor neuron differentiation, which is arguably the best understood model of neuronal differentiation to date. During development, the coordinate actions of inductive signals from adjacent non-neural tissues initiate the differentiation of distinct motor neuron subclasses, with specific projection patterns, at stereotypical locations within the neural tube. Underlying this specialisation is the expression of specific homeodomain proteins, which act combinatorially to confer motor neurons with both their generic and subtype-specific properties. Ensuring that specific motor neuron subtypes innervate the correct target structure, however, requires precise motor axon guidance mechanisms. The second half of this review focuses on how distinct motor neuron subtypes pursue highly specific projection patterns by responding differentially to spatially discrete attractive and repulsive molecular cues. The tight link between motor neuron specification and axon pathfinding appears to be established by the dominant role of homeodomain proteins in dictating the ways that navigating motor axons interpret the plethora of guidance cues impinging on growth cones.

Animals↗
PubMed2001

Effects of chronic food restriction and exercise training on the recovery of cardiac function following ischemia.

Clinical and experimental data suggest that exercise training (ET) and food restriction (FR) improve cardiovascular function. However, the effects of long-term FR or FR in combination with ET on the recovery of cardiac function following ischemia have not been determined. Male Wistar rats were assigned to ad libitum-fed, FR, ad libitum-exercise, and FR-exercise groups. Mechanical function of isolated working hearts was assessed in response to increases in afterload resistance and following global no-flow ischemia. At low workload, there was a significant FR effect on aortic flow as well as an interaction between FR and ET on systolic pressure. These effects remained when hearts were subjected to increases in aortic afterload resistance. During reperfusion of ischemic hearts, there was a significant FR effect on aortic flow and systolic pressure and a significant ET effect on diastolic pressure. An interaction between FR and ET on heart rate was also seen during reperfusion. In terms of percent recovery of heart function following ischemia, FR continued to affect aortic flow, and we observed an interaction between FR and ET on aortic flow. Our results clearly indicate that the myocardium from the FR animal or the FR, exercise-trained rat is more resistant to ischemia.

Animals↗
PubMed2001

X-deficient woodchuck hepatitis virus mutants behave like attenuated viruses and induce protective immunity in vivo.

The X protein (HBX) of the hepatitis B virus (HBV) has been shown to be important for the establishment of HBV infection in vivo. Our previous studies suggested that interaction of HBX with the proteasome complex may underlie the pleiotropic functions of HBX. In this study, we generated a series of woodchuck hepatitis virus (WHV) X mutants, including mutants of the domain interacting with the proteasome, and studied their infectivity in woodchucks. Many of the mutants were defective in transactivation but none of them were completely replication defective in vitro. In vivo, all the wild-type and some X mutant-transfected animals demonstrated evidence of infection with anti-WHc and/or anti-WHs seroconversion. Most of the wild-type- and X mutant-transfected animals had transient viremia. Some animals were later challenged with infectious WHV. Animals inoculated with X mutants, including those with no serologic evidence of infection, were protected from the challenge, suggesting previous infection with resulting protective immunity. Our study demonstrates that the previously described functional domains of HBX are biologically important and the X-defective mutants, possibly as attenuated viruses, are not completely replication defective in vivo.

Animals↗
PubMed2001

Lipid and lipoprotein levels in premenopausal systemic lupus erythematosus patients.

The purpose of this study was to assess the prevalence of dyslipoproteinemia and to analyze the clinical variables that are associated with it in a sample of premenopausal systemic lupus erythematosus (SLE) patients. We studied 53 premenopausal (34.5 y) SLE outpatients and 45 controls. Clinical variables studied included patient age, weight, height, body mass index (BMI), age at disease onset, disease duration, clinical activity of SLE, renal involvement and drug therapy. Total cholesterol (TC), high- and low-density lipoprotein cholesterol (HDL-C and LDL-C), and triglycerides were measured using standard enzymatic techniques. Apolipoproteins (apo) A-I and B were determined by radial immunodiffusion. Twenty-nine patients (55%) and 14 controls (30%) had dyslipoproteinemia. An increase in TC, triglycerides, HDL3-C, apo A-I and apo B, and a decrease in HDL2-C and HDL-C/TC index was found in SLE patients in comparison with controls. TC (P = 0.007), apo B (P = 0.02), LDL-C (P = 0.03) and triglycerides (P = 0.0001) were significantly correlated with proteinuria. Patients on prednisone therapy had higher triglycerides levels (P = 0.03) than untreated patients. TC (P = 0.01), LDL-C (P = 0.006) and triglycerides (P = 0.04) were also correlated with the dose of prednisone. Dyslipoproteinemia is a common feature in adult SLE premenopausal patients which is characterized by an increase in TC, triglycerides and apo B, and an abnormal distribution of HDL subclasses. Corticosteroid therapy and proteinuria are the best predictors of dyslipoproteinemia in these patients.

Adult↗
PubMed2001

System for cleavable Fc fusion proteins using tobacco etch virus (TEV) protease.

We describe a novel Fc fusion protein system that can be cleaved by tobacco etch virus (TEV) protease. This system is desirable because it takes advantage of the high specificity of TEV protease and its activity at 4 degrees C. We produced two TEV-Fc fusion proteins that contain the first three Ig domains and all six Ig domains of the cell adhesion molecule L1. Both proteins were efficiently cleaved by TEV protease at 4 degrees C. Functional analysis of the cleavage products in neurite outgrowth assays showed they had similar activities to their parental Fc fusion proteins. Therefore, TEV-Fc fusion proteins may increase the utility and flexibility of the Fc fusion protein system.

Animals↗
PubMed2000

Prenatal diagnosis of trisomy 4 mosaicism.

Trisomy 4 mosaicism is rare. To our knowledge only two cases of prenatally diagnosed trisomy 4 mosaicism have been reported. One case resulted in a normal liveborn male, the other resulted in an abnormal liveborn female. The karyotype of our case at the time of amniocentesis was 47,XY,+4[3]/ 46,XY[33] and resulted in a normal liveborn male. FISH analysis using an alpha satellite chromosome 4 probe was performed to confirm the cytogenetic findings. Follow-up chromosome analysis of cord blood, peripheral blood, foreskin, and umbilical cord fibroblasts showed a normal 46,XY male karyotype in all cells. FISH analysis of cord blood, umbilical cord fibroblasts, and amniotic fluid cells demonstrated two signals in 246 nuclei (i.e., 46,XY) and three signals in six nuclei (i.e., 47,XY,+4). Here we describe the present case of trisomy 4 mosaicism, the literature is reviewed, and the significance of this finding is discussed.

Adult↗
PubMed2000

Facial visceral motor neurons display specific rhombomere origin and axon pathfinding behavior in the chick.

In the chick embryo, facial motor neurons comprise branchiomotor and visceral motor subpopulations, which innervate branchial muscles and parasympathetic ganglia, respectively. Although facial motor neurons are known to develop within hindbrain rhombomere 4 (r4) and r5, the precise origins of branchiomotor and visceral motor neuron subpopulations are unclear. We investigated the organization and axon pathfinding of these motor neurons using axonal tracing and rhombomere transplantation in quail-chick chimeras. Our results show that a large majority of branchiomotor neurons originate in r4 but that a cohort of these neurons undergoes a caudal migration from r4 into r5. By contrast, visceral motor neurons develop exclusively in r5. We found that a striking property of facial visceral motor neurons is the ability of their axons to navigate back to appropriate ganglionic targets in the periphery after heterotopic transplantation. These results complement previous studies in which heterotopic facial branchiomotor neurons sent axons to their correct, branchial arch, target. By contrast, when trigeminal branchiomotor neurons were transplanted heterotopically, we found that they were unable to pathfind correctly, and instead projected to an inappropriate target region. Thus, facial and trigeminal motor neuron populations have different axon pathfinding characteristics.

Animals↗
PubMed2000

Experimental evidence for crossover to mean-field tricritical behavior in a concentrated salt solution

We have discovered a mean-field multicritical point on the critical locus in an aqueous solution of 3-methylpyridine and sodium bromide. Light-scattering measurements indicate Ising-like asymptotic critical behavior at the lower salt concentrations. However, the temperature range of Ising critical behavior shrinks with increasing salt concentration and the critical behavior becomes mean-field-like at a concentration of about 17% mass fraction of NaBr. Emergence of a new characteristic length scale diverging at this point and a simultaneous pronounced increase in the background scattering suggests mean-field tricritical behavior associated with the formation of a microheterogeneous phase due to clustering of ions and molecules.

Journal Article↗
PubMed2000

The transfer of harm-reduction strategies into prisons: needle exchange programmes in two German prisons.

In Autumn 1995, the Minister of Justice of Lower Saxony (a northern state of Germany) gave the green light for the implementation of a 2-year pilot project. This project provided for the distribution of sterile injection equipment and provision of communicative methods of prevention to drug addicted inmates in a women's prison with 170 inmates (Vechta) and a men's prison with 230 inmates (Lingen). The decision to go ahead with the project was based on positive experiences in Swiss prisons and the supporting recommendations of a panel of experts. The pilot project in Vechta started on 15 April 1996, using five dispensing machines which allow a needle exchange to guarantee an anonymous access. The project in the men's prison started on 15 July 1996. Here the staff of the drug counselling service and of the health care unit hand out sterile syringes to inmates. The social scientific evaluation was carried out by the Carl von Ossietzky University in Oldenburg. The study focused on the aim of the project which is to assess the feasibility, usefulness and efficacy of the measures undertaken. Of special interest was whether and how changes occured in the prison system itself (i.e. acceptance of the measures by staff, medical service and management), and in the drug user's behaviour and knowledge (i.e. development of needle sharing, change in drug use patterns). The study used a multi-methodological approach: documentation of the project practice, half standardized, longitudinal examination of inmates (n=224) and staff (n=153), qualitative examination of management, selected groups of prisoners, staff and external organisations (AIDS-Help-Groups; n=75) for at least two times. The evaluation intended to be dynamic, process accompanying, in order to communicate the empirical data and developments with the practice already during the pilot phase. Results of the final report of the study are presented here. Finally this paper discusses shortly what is known so far about the impact of needle exchange programmes in prisons in Germany and Switzerland.

Journal Article↗
PubMed2000

Detection of carcinogenic aromatic amines in the urine of non-smokers.

Smoking is thought to be one of the most important anthropogenic risk factors involved in the development of urinary bladder cancer in humans. Tobacco smoke contains a complex mixture of chemicals including potent carcinogens such as aromatic amines. In the present study the amounts of several freebase aromatic amines including the potent carcinogens 2-aminonaphthalene and 4-aminobiphenyl have been analyzed in the urine of 48 German urban living smokers and non-smokers. The results indicate that (i) both groups excrete the identical set of four aromatic amines; (ii) smokers excrete approximately twice the total amount of these amines, but similar amounts of 2-aminonaphthalene and 4-aminobiphenyl are found in non-smokers; and (iii) the excreted aromatic amines are decomposed in the urine within a few hours thus, explaining why aromatic amines are difficult to detect in this matrix. Their decomposition could be prevented by adding small amounts of p-toluidine to the freshly collected urine. Unlike smokers the origin of aromatic amines detected in the urine of non-smokers is at present unknown. Based on the cotinine levels found in the urine of non-smokers environmental tobacco smoke can be excluded as a major source of aromatic amines. In addition, neither diesel exhaust-related nitroarenes nor the corresponding amino-derivatives, to which they may be metabolically converted, were found. The detected urinary levels of aromatic amines arising from sources other than tobacco smoke or diesel exhaust may play a role in the bladder cancer etiology of non-smokers.

2-Naphthylamine↗
PubMed2000

Role of the target in the pathfinding of facial visceral motor axons.

Axon navigation depends, in part, on guidance cues emanating from the target. We have investigated the possible role of the target in the pathfinding of visceral motor axons to cranial parasympathetic ganglia. Mice homozygous for a tau-LacZ transgene targeted in the Phox2a locus lack the sphenopalatine ganglion, which is the normal target of visceral motor axons of the facial nerve. We found that in these mutants, facial visceral motor axon pathfinding was disrupted, and some axons were misrouted to an alternative parasympathetic ganglion. Moreover, the absence of correct facial visceral motor pathways was concomitant with defects in the pathfinding of rostrally-projecting sympathetic axons.

Animals↗