Biomedical subjects

J M Jacobs

Publications and source records attributed to J M Jacobs.

At least 37 records · Page 2Linked to original sources

PubMed1996

Regeneration through a long nerve graft used in the correction of facial palsy. A qualitative and quantitative study.

A surgical technique has been developed for the correction of established unilateral palsy in man. A long (20 cm or more) sural nerve graft is anastomosed to a facial nerve branch on the unaffected side and its distal end left lying free in the cheek of the affected side. After regeneration times of 5.5-14.5 months, the distal end of the graft is joined to a free (pectoralis minor) muscle graft. In due course the muscle graft contracts in unison with the unaffected side giving near normal symmetry to facial movements. In 30 cases (ages 6-52 years) qualitative and quantitative examination was made of the distal end of grafts taken at the time of joining the graft to the muscle. Total axon counts, myelinated plus non-myelinated, confirmed abundant regeneration when compared with total axons in the supplying facial nerve; myelinated fibres remained small (mean diameter 2.5 micrometers) over the range of regeneration times. Quantitation included non-myelinated axons because they probably have the potential to become myelinated once the nerve is functional. Numbers of regenerating axons were not correlated with age, nor with regeneration time. Lack of a distal connection did not appear to lead to secondary degeneration of the regenerated myelinated fibres. These were maintained in an 'immature' state for many months. This observation is of practical interest since it has been suggested that delayed connection to the distal target may have a deleterious effect on the outcome of the procedure.

Adolescent↗

PubMed1996

Leprous neuropathies.

Once a terrifying disease, leprosy today has a very hopeful prognosis, provided that it is diagnosed early and treated with modern multidrug chemotherapy, any immunological reactions being recognized quickly and controlled well to prevent (further) peripheral nerve damage after commencing treatment. The diagnosis should be considered in all patients who present with peripheral neuropathy and/or anaesthetic skin lesions who come from or have lived in the tropics and subtropics. Although M. leprae cannot yet be grown in vitro, it is readily grown in experimental animals. A complete gene library has been developed, much of the genome mapped and a number species-specific and common mycobacterial antigens identified. The intricacies of the host-parasite relationship, especially of cell-mediated immunity, and of the important immunological reactions of ENL and reversal reaction have been widely investigated. Modern MDT has caused a dramatic fall in prevalence, although the world annual case detection rate remains at around 600,000 new patients, many being at an early stage of the disease. WHO has launched a campaign to eliminate leprosy as a significant public health risk by the 2000 (with a prevalence of less than 1:10 000 population), which may well be achieved in some endemic countries. Leprosy will, however, remain an important cause of peripheral neuropathy for at least several more decades.

Biopsy↗

PubMed1995

Terminal enzymes of heme biosynthesis in the plant plasma membrane.

Purified plasma membrane fractions from barley leaf exhibited activities of ferrochelatase and iron reductase, two of the terminal enzymes in heme biosynthesis. These activities were also present in purified barley leaf plastid and mitochondrial fractions. The plasma membrane fractions were shown to be free from contamination with plastid and mitochondrial membrane markers. Previous studies had demonstrated that barley plasma membranes exhibited activity for converting protoporphyrinogen to protoporphyrin, another late step in heme synthesis. The presence of the terminal steps of heme synthesis in the plant plasma membrane is compatible with the hypothesis that late heme precursors such as protoporphyrin or protoporphyrinogen synthesized in the chloroplast can be exported and converted to heme within the plasma membrane for subsequent incorporation into plasma membrane hemoproteins.

Cell Membrane↗

PubMed1995

Intractable epistaxis: transantral ligation vs. embolization: efficacy review and cost analysis.

After posterior nasal packing, the two most common therapies for intractable epistaxis are transantral ligation of the internal maxillary artery and percutaneous embolization of the distal internal maxillary artery. However, optimal management of intractable posterior epistaxis remains controversial. We retrospectively reviewed the charts of 21 patients treated for intractable epistaxis and obtained data on presentation, risk factors, treatment, success rates, complications, and cost. Twelve patients received percutaneous embolization, five underwent transantral ligation, and four required both. The success rates for transantral ligation and percutaneous embolization were 89% and 94%, respectively. No mortality or serious morbidity occurred with either technique. A cost comparison revealed that transantral ligation was moderately less expensive than percutaneous embolization ($5941 vs. $6783). Although some authors advocate transantral ligation or percutaneous embolization as the procedure of choice for intractable epistaxis, a direct comparison of efficacy and cost reveals that they are comparable procedures with specific strengths and weaknesses. We present our experience and a review of the literature, highlighting the indications and advantages of each technique. We conclude that the choice of treatment modality should be based on the benefits of each procedure as it pertains to the specific needs of the individual patient.

Adult↗

PubMed1994

A morphological study of experimental mononeuropathy in the rat: early ischemic changes.

This paper describes early morphological changes following the placement of four loose ligatures round the rat sciatic nerve, a method used to produce altered pain-related behaviour. The ligatures were tied so as not to constrict the nerve, but there was compression of some epineurial blood vessels. This mild lesion caused behavioural changes and nerve fiber abnormalities within 8.5 h. The distribution of nerve fiber changes was patchy, and initially due to stagnant ischemia, with necrosis of Schwann cells and evidence of axonal stasis. By 48 h, endoneurial oedema increased leading to a compressive lesion and eventually to severe nerve fiber degeneration.

Animals↗

PubMed1994

Mitochondrial DNA mutation underlying Leigh's syndrome: clinical, pathological, biochemical, and genetic studies of a patient presenting with progressive myoclonic epilepsy.

An 18-year-old male patient presented with clinical and radiological evidence of Leigh's syndrome (LS), having developed progressive myoclonic epilepsy and ataxia 11 years previously. Muscle biopsy showed cytochrome oxidase deficiency but no ragged red fibres. Autopsy confirmed the diagnosis of LS; there was additional degenerative change in the cerebellum and dentate and olivary nuclei, and an axonal peripheral neuropathy. Biochemical studies showed reduced activity of complexes I and IV of the respiratory chain in mitochondria from heart, liver and kidney. The mutation of mitochondrial DNA (mtDNA) at position 8344, commonly associated with the syndrome of myoclonic epilepsy and ragged red fibres, was detected in the patient's blood and was present in muscle, brain, liver, heart, and kidney in uniformly high amounts. It is clear that LS is genetically heterogeneous and represents one of the most severe phenotypes of a number of different mtDNA defects.

Adolescent↗

PubMed1994

Multiple alleles for tuber shape in diploid potato detected by qualitative and quantitative genetic analysis using RFLPs.

Tuber shape in potato is commonly regarded as displaying continuous variation, yet at the diploid level phenotypes can be discerned visually, having round or long tubers. Inheritance of qualitative tuber shape can be explained by a single locus Ro, round being dominant to long. With restriction fragment length polymorphisms (RFLPs) the Ro locus was mapped on chromosome 10. Tuber shape was also studied as a quantitative trait, using the length/width ratio as trait value. The estimated broad sense heritability was h2 = 0.80. The morphologically mapped Ro locus explained 75% of the genetic variation, indicating the presence of a major quantitative trait locus (QTL) at the Ro locus and minor genetic factors. RFLP alleles linked with Ro alleles were used to divide the progeny into four genotypic classes: RofemaleRomale:Rofemalero:roRomale:roro = 1:1:1:1. The recessive ro allele is identical by descent in both parents. The significantly different effects (P = 0.0157) of the non-identical alleles Rofemale and Romale provided evidence for multiallelism at the Ro locus. Linkage mapping of the Ro locus was compared with QTL mapping. Only those markers which are polymorphic in both parents allow accurate QTL mapping when genetic factors segregate from both parents. This finding applies to QTL mapping in all outbreeders without homozygous inbred strains.

Alleles↗

PubMed1994

Acute phase vascular endothelial injury: a comparison of temporary arterial occlusion using an endovascular occlusive balloon catheter versus a temporary aneurysm clip in a pig model.

We compared the degree of acute endothelial injury after temporary vessel occlusion using two different occlusion modalities--external clipping and endovascular balloon occlusion. The common carotid and subclavian arteries in eight weanling pigs were temporarily occluded with either a 5 Fr occlusion balloon catheter or a temporary microvascular clip for 0 (control), 5, 10, and 30 minutes. Two animals (eight vessels; four clip and four balloon occluded) were used at each time interval. Segments of each experimental vessel were harvested and analyzed by scanning electron microscopy. Each vessel specimen was graded on the following scale: Grade 1 showed no evidence of injury; Grade 2 showed minimal evidence of endothelial cell injury; Grade 3 showed moderate evidence of endothelial cell injury; Grade 4 showed marked evidence of endothelial cell injury; Grade 5 showed severe endothelial and subendothelial injury. Control vessels showed no evidence of injury. Grade 2 injuries were seen in both clip- and balloon-occluded vessels at 5 minutes. At 10 minutes, focal Grade 2 and 3 injuries were appreciated in the clip group, with diffuse Grade 2 and 3 injuries in the balloon group. After the 30-minute occlusion, the balloon group showed Grade 2, 3, and 4 injuries, whereas the clip group showed entirely Grade 2 injuries. The degree of injury with either occlusion modality was equivalent and worsened with time. However, clip-occluded vessels displayed injury that was confined to an area closely adjacent to the clip site, whereas balloon-occluded vessels demonstrated a more widespread injury centered around the balloon site.

Animals↗

PubMed1994

Medical-surgical nurses' utilization of research methods and products.

The purpose of this study was: (a) to describe the self-reported use of the methods and products of research by medical-surgical nurses, and (b) to identify attitudes toward the use of research-based knowledge in clinical nursing practice. Two hundred and twelve registered nurses completed the Research Utilization Questionnaire. Survey results indicated that it was difficult for respondents to change practice based on research. Nurses were willing to participate in research if investigations were relevant to practice. Articles from nursing research journals were ranked low by the respondents as sources of knowledge, while information gained from individual patients was ranked high.

Attitude of Health Personnel↗

PubMed1994

Protoporphyrinogen accumulation in cultured hepatocytes treated with the diphenyl ether herbicide, acifluorfen.

Diphenyl ether (DPE) herbicides such as acifluorfen inhibit both the plant and mammalian forms of protoporphyrinogen oxidase, a heme biosynthetic enzyme. Only small amounts of protoporphyrin accumulated in primary cultures of chick embryo and rat hepatocytes treated with acifluorfen and the porphyrin precursor, 5-aminolevulinic acid. However, there was a large accumulation of the porphyrin precursor, protoporphyrinogen, which was detected after oxidation to protoporphyrin by an E. coli membrane enzyme. In contrast, conventional methods of porphyrin analysis which depend on quantitative autoxidation of protoporphyrinogen failed to detect this accumulation of protoporphyrinogen. This is the first demonstration that protoporphyrinogen can accumulate to high levels and remain stable in liver cells. In addition, we found that the effect of a protoporphyrinogen oxidase inhibitor such as acifluorfen on the regulation of heme synthesis in hepatocyte cultures differed from that of an iron chelator.

Aminolevulinic Acid↗

PubMed1994

MR imaging and MR angiography in the evaluation of pulsatile tinnitus.

PURPOSE: 1) To evaluate the scope of imaging findings seen with spin-echo MR and MR angiography (MRA) in patients with pulsatile tinnitus; 2) to determine whether MRA adds additional imaging information (to that provided by spin-echo MR) necessary for determining the cause of pulsatile tinnitus; and 3) to suggest MR and MRA imaging techniques for evaluation of patients with pulsatile tinnitus. METHODS: Forty-nine patients with pulsatile tinnitus were evaluated with MR and MRA. Seventeen of these patients had conventional angiography. RESULTS: Vascular lesions or paraganglioma were demonstrated in 28 patients. Of these 28 lesions, the majority were seen best (46%) or only (36%) on MRA. The spectrum of lesions detected included dural arteriovenous fistula (nine), extracranial arteriovenous fistula (three), paraganglioma (five), jugular bulb variants (three), aberrant internal carotid artery (one), internal carotid artery stenosis (one), tortuous internal carotid artery (one), carotid dissection with pseudoaneurysm (one), stenosis of the transverse sinus (two), and arteriovenous malformation (two). CONCLUSIONS: MRA, in conjunction with spin-echo imaging, markedly enhances the ability of MR to diagnose the lesions responsible for pulsatile tinnitus.

Adolescent↗

PubMed1994

Comparison of a three-component acellular pertussis vaccine with a whole-cell pertussis vaccine in 15- through 20-month-old infants.

OBJECTIVE: To compare the immunogenicity and reactogenicity of a diphtheria and tetanus toxoids and three-component acellular pertussis vaccine (DTaP) with a diphtheria and tetanus toxoids and whole-cell pertussis vaccine (DTwP) when administered as a booster dose to infants 15 through 20 months of age. DESIGN: Randomized, double-blind, comparative study. SETTING: Three pediatric practices (two private; one hospital-based). PARTICIPANTS: One hundred and sixty-five healthy 15- through 20-month old infants. SELECTION PROCEDURES AND INTERVENTIONS: Infants were randomly assigned in a 2:1 ratio to receive vaccine from a single lot of DTaP or from commercially available DTwP. DTaP contained 25 micrograms of pertussis toxoid, 25 micrograms of filamentous hemagglutinin, 8 micrograms of pertactin (69-kilodalton outer membrane protein), 25 flocculating units of diphtheria toxoid, and 10 flocculating units of tetanus toxoid per 0.5-mL dose. DTwP contained one half the concentrations of diphtheria and tetanus toxoids compared with DTaP and a pertussis component with a potency of 4 U/0.5-mL dose. Serum samples were obtained on the day of immunization and 4 weeks later. Adverse reactions were recorded by parents for 7 days after immunization. An interval history was obtained 4 weeks after immunization. MEASUREMENTS AND RESULTS: IgG antibody to pertussis toxoid, filamentous hemagglutinin, pertactin, diphtheria toxoid, and tetanus toxoid was measured by an indirect enzyme-linked immunosorbent assay (ELISA) method. One month after immunization, the geometric mean antibody levels after DTaP compared with DTwP were: pertussis toxoid, 70.6 vs 28 ELISA U/mL (P = .003); filamentous hemagglutinin, 183.4 vs 43 ELISA U/mL (P < .001); pertactin, 216 vs 49.9 ELISA U/mL (P < .001); diphtheria, 14.1 vs 14.9 IU/mL (P = .74); and tetanus, 11.9 vs 14.8 IU/mL (P = .089). After immunization with DTaP, most local and systemic adverse experiences were significantly fewer compared with DTwP (P < .05). CONCLUSIONS: This three-component DTaP vaccine demonstrates significantly greater immune responses to pertussis toxoid, filamentous hemagglutinin, and pertactin, equivalent immune responses to diphtheria and tetanus toxoids, and significantly less reactogenicity compared with a licensed DTwP.

Antibodies, Bacterial↗

PubMed1993

Ascorbic acid inhibition of cytochrome P450-catalyzed uroporphyrin accumulation.

Previous studies on the mechanism of the uroporphyria caused by polyhalogenated aromatic hydrocarbons have indicated a key role of cytochrome P450 of the 1A subfamily in catalyzing uroporphyrinogen (UROgen) oxidation. Here we report that ascorbic acid (ASC) inhibits UROgen oxidation in primary cultures of chick embryo hepatocytes and hepatic microsomes from chickens and mice. In hepatocyte cultures, 0.15 mM ASC totally prevented the accumulation of uroporphyrin (URO) induced by treatment of cells with the combination of 3,4,3',4'-tetrachlorobiphenyl (TCB) and 2-propyl-2-isopropylacetamide (PIA), but had no effect on the induction of protoporphyrin accumulation by PIA and desferrioxamine. However, addition of 5-aminolevulinic acid (ALA) to cultures treated with PIA plus TCB decreased the ability of ASC to prevent URO accumulation, suggesting that the effectiveness of ASC was dependent on the intracellular concentration of ALA or its metabolites. Similarly, when chick hepatocyte cultures were treated with TCB plus exogenous ALA to produce URO accumulation, the effectiveness of ASC was also less than when ALA was produced endogenously. Under this condition, addition of piperonyl butoxide, a P450 inhibitor, increased ASC inhibition of URO accumulation. ASC competitively inhibited the oxidation of UROgen by hepatic microsomes from chicks or mice treated with 3-methylcholanthrene (MC) with Ki for ASC being about 0.1 mM. ASC prevented formation of a 500-nm absorbing compound, probably tetrahydrouroporphyrin, the first intermediate in UROgen oxidation. These results are consistent with ASC preventing URO accumulation in hepatocytes by competitive inhibition of the first step of UROgen oxidation and suggest a new physiological role of ASC, that of maintaining UROgen in the reduced state.

Animals↗

PubMed1993

A morphological study of nerve biopsies from cases of multibacillary leprosy given multidrug therapy.

Nerve biopsies were examined from 17 cases of lepromatous leprosy given WHO-recommended multidrug therapy (MDT) for 2 years. The pathological changes were assessed qualitatively and quantitatively to judge the effectiveness of MTD. The nerves varied very considerably in the severity of their lesions. Some regenerating fibres were seen in most of the nerves. In a few cases, the nerves were almost entirely populated by regenerated fibres, confirming that MTD was effective in halting the disease process within the nerve. Mycobacterium leprae showed morphological features of degenerate bacilli. Some pathological features of the lepromatous lesion are described.

Adult↗

PubMed1993

Adaptation of tibial nerve myelinated fibre parameters to reduced limb length caused by irradiation.

Irradiation of a rat hind limb at 15 days of age caused marked shortening of the limb, with a consequent reduction in nerve length. The tibial nerves of the irradiated limbs were examined qualitatively and quantitatively, and compared with the unirradiated nerve. There was no evidence of fibre degeneration and only very occasional myelin abnormalities. Myelinated fibre numbers were very slightly reduced, possibly due to irradiation effects on small myelinated fibres. Internodal lengths were reduced in proportion to limb length. Mean axon diameters were slightly increased, and myelin sheath thickness reduced. This experimental model provides a new method of altering nerve fibre parameters without surgical intervention.

Adaptation, Physiological↗

PubMed1993

Axonal neurofilamentous accumulations: a comparison between human and canine giant axonal neuropathy and 2,5-HD neuropathy.

The neuropathy produced by the hexacarbon 2,5-hexanedione (2,5-HD) resembles human and canine inherited giant axonal neuropathy (GAN) in the presence of giant axonal swellings that contain accumulations of neurofilaments. The accumulations are both paranodal and internodal in GAN and 2,5-HD induced neuropathy. Detailed morphometry on the neurofilaments reveals that the changes in human and canine GAN are closely similar and differ from those of 2,5-HD neuropathy, suggesting that the mechanisms underlying the formation of the axonal neurofilamentous accumulations differ between the two conditions. In both human and canine GAN, the neurofilaments are more closely spaced and are of greater diameter than in 2,5-HD neuropathy. The changes in the NF in GAN may be the consequence of flattening of the side-arms of the neurofilaments against the axis of the filaments.

Animals↗

PubMed1993

Nature and incidence of peripheral nerve syndromes in HIV infection.

Fifty four patients with peripheral nerve syndromes were seen during a 15 month period in a population of about 1500 HIV infected patients at all stages of the disease. Distal symmetrical peripheral neuropathies were seen in 38 of the 54 patients, (11.5% of AIDS patients) and could be distinguished into two forms. The most common (n = 25) was a painful peripheral neuropathy during AIDS, which is distinct clinically and pathologically, having axonal atrophy, and is associated with cytomegalovirus infection at other sites. The 13 non-painful neuropathies seen were more heterogeneous. Lumbosacral polyradiculopathy associated with cytomegalovirus and lymphomatous mononeuritis multiplex occurred in fewer than 1% of AIDS patients. Mononeuropathies were seen in 3% of AIDS patients. No patients with acute or chronic inflammatory demyelinating polyradiculoneuropathies were seen. The annual incidence of neuropathies during the AIDS related complex stage was less than 1%; none were seen in asymptomatic HIV seropositive patients.

AIDS-Related Complex↗

PubMed1993

Nucleotide sequence of the hemG gene involved in the protoporphyrinogen oxidase activity of Escherichia coli K12.

The hemG gene of Escherichia coli K12 is involved in the activity of protoporphyrinogen oxidase, the enzyme responsible for the conversion of protoporphyrinogen IX into protoporphyrin IX during heme and chlorophyll biosynthesis. The gene is located at min 87 on the genetic map of E. coli K12. The hemG gene was isolated by a mini-Mu in vivo cloning procedure. As expected, the hemG gene is able to restore normal growth to the hemG mutant, and the transformed cells display strong protoporphyrinogen oxidase activity. Sequencing of the hemG gene allowed us to identify an open reading frame of 546 nucleotides (181 amino acids), within the minimal fragment able to complement the mutant. The presumed molecular mass of the HemG protein is 21,202 Da, in agreement with values found by SDS-PAGE, in a DNA-directed coupled transcription-translation system. The identity of the first 18 amino acids at the amino-terminal end of the protein was confirmed by microsequencing. To our knowledge, this is the first cloning of a gene involved in the protoporphyrinogen oxidase activity of E. coli.

Amino Acid Sequence↗