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Biomedical subjects

M Jacobs

Publications and source records attributed to M Jacobs.

At least 145 records · Page 8Linked to original sources
PubMed1993

ICI 169,369, A 5-HT2/5-HT1C antagonist, that can evoke endothelium-dependent relaxation in rabbit aorta.

1. The direct effects of ICI 169,369 on vascular reactivity were investigated in rabbit aortic rings with and without endothelium. 2. ICI 169,369 evoked an endothelium-dependent relaxation in aortic rings precontracted with PGF2 alpha. No direct effects on vascular reactivity were found in endothelial denuded rings. 3. The relaxations induced by ICI 169,369 were inhibited by haemoglobin, an agent known to interfere with the responses to endothelium-derived nitric oxide (EDRF) but not by the cyclo-oxygenase inhibitor, indomethacin. Inhibition of the ICI 169,369-induced relaxation by the L-arginine analogue, NG-monomethyl L-arginine (L-NMMA) confirmed that the relaxations evoked by ICI 169,369 were mediated by the endothelial L-arginine: nitric oxide pathway. 4. Studies with competitive receptor antagonists showed that in the rabbit aorta, ICI 169,369 evoked relaxations which were not elicited by the activation of any known 5-HT1, 5-HT2, 5-HT3, muscarinic, histamine, adenosine receptor or adrenoceptors. 5. The diacylglycerol kinase inhibitor, R 59022 also failed to affect these relaxations. It is concluded that ICI 169,369 has a post-receptor action, possibly by directly affecting intracellular calcium levels in the endothelial cells.

Acetylcholine↗
PubMed1993

Posttraumatic seizures: consensus and controversies.

Seizures after traumatic brain injury may cause acute deterioration in level of consciousness, signal the presence of significant intracranial pathology, herald potentially lethal status epilepticus and carry some risk for the development of a chronic disorder. Specific implications of immediate, early and late seizures are different and vary across age groups. While there is a consensus to manage status epilepticus aggressively, and some agreement to treat a seizure once it has begun, no such unanimity exists about management of patients who have one or more seizures after injury. This article identifies controversies about seizures that occur after traumatic brain injury in paediatric and adult populations. It concludes with a summary of research imperatives for the future.

Brain Injuries↗
PubMed1993

Surveillance for colorectal neoplasia: is patient adherence following treatment a problem?

This study was conducted in order to assess prospective adherence to surveillance colonoscopy and fecal occult blood testing (FOBT) at 1 year following treatment for an index lesion among colorectal cancer and polyp patients. The investigation was carried out in cooperation with two gastroenterology and two surgical practices in Philadelphia and surrounding communities. Subjects in this study were patients who were treated for colorectal cancer (N = 9) or polyps (N = 169) and were recommended to undergo surveillance colonoscopy at 12 months following treatment. Overall, 96 (54%) subjects underwent surveillance colonoscopy. Of the 178 subjects included in the study, 52 (29%) were willing to participate in an assessment of FOBT sensitivity in surveillance. Of the 52 subjects who were mailed an FOBT packet, 24 (46%) actually returned specimen. Of the 24 patients who returned FOBTs, 17 (71%) also underwent colonoscopy, whereas only 10 (36%) of 26 patients who did not do FOBTs underwent colonoscopy. These findings indicate that adherence to surveillance is low, and that adherence to FOBT may be a marker for adherence to colonoscopy.

Adenomatous Polyps↗
PubMed1992

Phase II trial of 5 day continuous intravenous infusion of 6-thioguanine in patients with recurrent and metastatic squamous cell carcinoma of the head and neck.

Fifteen patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck received a 5 day continuous I.V. infusion of 6-thioguanine repeated every five weeks. Dose limiting toxicity was primarily hematological with grade III/IV leucopenia and thrombocytopenia seen in seven patients. Nausea and vomiting was moderate and well controlled with antiemetics. No complete or partial responses were observed, with a median time to progression of 58 days and a median survival of 227+ days for the entire group. Based on these results we do not recommend I.V. 6-thioguanine for the treatment of this disease.

Adult↗
PubMed1992

Role of 5-hydroxytryptamine receptors on luteinizing-hormone-releasing hormone release in the ovariectomized, estradiol-treated rat.

The present experiments examined the effect of ketanserin [5-hydroxytryptamine-2 (5-HT2) antagonist] and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (5-HT1 agonist) on the in vitro release of luteinizing-hormone-releasing hormone (LHRH) from the medial basal hypothalamus-preoptic area-suprachiasmatic nucleus region (MBH-POA-SCN) of ovariectomized (OVX), estradiol-(E2) treated rats using in vitro superfusion techniques. Regularly cycling female Holtzman rats (250-300 g) were maintained on a photoperiod of 0500-1900 h light at 22 +/- 2 degrees C. Rats were ovariectomized (25-30 days) and received Silastic E2 implants (150 micrograms E2/ml sesame oil) SC 48 h prior to the in vitro superfusion. Following a control period of Krebs-Ringer Phosphate (KRP) superfusion, ketanserin (5-HT2 receptor antagonist, 1 x 10(-6) M) significantly increased LHRH release (p less than 0.05). Subsequent superfusion of 5-HT (1 x 10(-8) M) significantly decreased (p less than 0.05) the effect of ketanserin on LHRH release. The 5-HT2 antagonist Lilly 53857 (1 x 10(-6) M or 1 x 10(-5) M) did not increase LHRH release above control levels. Neither 5-HT nor quipazine had a significant effect on LHRH release at 1 x 10(-6) M. Superfusion of 8-OH-DPAT (5-HT1 receptor agonist 1 x 10(-5) M) significantly (p less than 0.01) increased LHRH release but subsequent superfusion of 8-OH-DPAT + pindolol (mixed 5-HT1a,1b and a beta-adrenergic receptor antagonist, 1 x 10(-6) M) or pindolol alone had no effect on LHRH release. These results suggest that the 5-HT1 receptor plays a role in LHRH release and this effect may be related to the opposing effects of postsynaptic and autoreceptors. However, the failure of Lilly 53857 to reproduce the stimulatory effect of ketanserin on LHRH release suggests that 5-HT2 receptors in the MBH-POA-SCN may not modify LH release during the estrous cycle.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

Ophthalmologic assessment of young patients with Alport syndrome.

BACKGROUND: Alport syndrome is an X-linked disease affecting basement membrane collagen. It is characterized by nephritis associated with high-tone sensorineural hearing impairment and ophthalmic signs. Although ocular changes have been described in adults, few data exist regarding the incidence of abnormal ocular features in adolescence and childhood. METHODS: Fifteen male and five female patients with Alport syndrome underwent ophthalmologic, audiologic, and nephrologic assessments. All patients studied had hematuria and a positive family history of Alport syndrome. Thirteen patients had a renal biopsy that showed characteristic electron microscopic changes of the disease. Eleven patients had high-tone sensorineural impairment. Electrophysiologic investigations performed included electroretinography, visual-evoked potentials, and electro-oculography. RESULTS: Two patients had early signs of anterior lenticonus, three had flecks in the retina, and two patients also had posterior subcapsular cataracts. None of the patients had significant electrophysiologic abnormalities. CONCLUSION: These findings indicate that ocular changes are uncommon and subtle in young patients with Alport syndrome, and suggest that the signs increase in frequency and severity with age.

Adolescent↗
PubMed1992

Management of the subluxed crystalline lens.

There has been a traditional reluctance to remove a subluxed (ectopic) lens because of the high surgical risk. The use of closed intraocular microsurgical techniques, however, now allows greater intraoperative control with few complications. The authors present the results of subluxed lens extraction, by limbal or pars plana lensectomy, in 44 eyes of 24 patients, in which the indication for surgery was lens subluxation causing a reduction in visual acuity or uncorrectable refractive error. Visual acuity was improved in all cases after surgery, with no significant complications. Patients with reduced visual acuity secondary to ectopic lenses have a good visual prognosis after lensectomy using a closed intraocular microsurgical technique.

Adult↗
PubMed1992

Placement of drains in laparoscopic procedures.

The technique of laparoscopic cholecystectomy is, in many areas, replacing the standard open cholecystectomy as the method of choice. Many surgeons are accustomed to the use of peritoneal drainage following cholecystectomy. The authors have developed a simple, effective, and rapid, yet controlled method of placing drains into the abdominal cavity, using laparoscopic techniques.

Cholecystectomy↗
PubMed1992

Analysis of splice sites in the early region of bovine polyomavirus: evidence for a unique pattern of large T mRNA splicing.

The genetic organization of the early region of bovine polyomavirus (BPyV) was studied by analysis of the splice sites used in early mRNA maturation, using reverse transcription-polymerase chain reaction and DNA sequencing techniques. When compared to other polyomaviruses, the BPyV early region appears to have an uncommon organization. In the major early mRNA molecule two small intron sequences of 71 and 77 nucleotides, separated from one another by an 80 nucleotide exon sequence, were identified. Through splicing out both introns, a mRNA molecule is generated that contains an open reading frame with the capacity to encode 619 amino acids. Comparisons with the simian virus 40 large T antigen suggested that this mRNA molecule encodes the BPyV large T antigen. Remarkably, no mRNA product encoding a protein with a size comparable to that of the small t antigens of other polyomaviruses was detected. Another transcript was observed from which only the 77 nucleotide intron sequence had been removed, thereby creating a mRNA molecule with the capacity to encode only 45 amino acids. Whether this mRNA product represents a mature transcript which is translated in BPyV-infected cells or is an intermediate in the formation of the large T mRNA molecule is not known. Analysis of BPyV-specific early mRNA products isolated from BPyV-transformed murine cells revealed only the amplification product representing the putative large T antigen transcript.

Amino Acid Sequence↗
PubMed1992

Two Feedback-Insensitive Enzymes of the Aspartate Pathway in Nicotiana sylvestris.

Lysine and threonine overproducer mutants in Nicotiana sylvestris, characterized by an altered regulation of, respectively, dihydrodipicolinate synthase and aspartate kinase activities, were crossed to assess the effects of the simultaneous presence of these genes on the biosynthesis of aspartate-derived amino acids. The monogenic dominant behavior of both resistance traits was confirmed, and their loci were found to be unlinked. Study of the inhibition properties of dihydrodipicolinate synthase and aspartate kinase activities in RAEC-1 x RLT 70 confirmed the heterozygote state of both mutations, because only half of their lysine-sensitive activity could still be inhibited by this negative effector. Analysis of the free amino acid pool during the growth of the double mutant revealed a major free lysine overproduction reaching up to 50% of the total pool, whereas the other aspartate-derived amino acids remained equally or even less abundant than in the wild type. An abnormal phenotype was clearly associated with such high levels of lysine accumulation, which points out the possible role of this amino acid in the developmental features of the plant. Comparison of the amino acid content, free and total (free + protein-bound), between the wild type, the two mutants, and the double mutant obtained by crossing them brings new insights on the regulation of the aspartate pathway, and on its implications in relationship to plant nutritional value improvement.

Journal Article↗
PubMed1992

The objective assessment of abnormal eye movements in infants and young children.

Recordings of eye movements from infants and young children can be of clinical value in patients with certain neuro-ophthalmological problems. This requires that the characteristics of normal eye movements in this same age-group are known. Using an electro-oculographic technique in a specially developed laboratory we have been able to assess the saccades, binocular and monocular smooth pursuit, binocular and monocular optokinetic nystagmus (OKN), and sustained vestibular rotation in infants and young children; these recordings were performed in one session lasting approximately 35 minutes. The recordings from four children with abnormal eye movements (delayed visual maturation, hemicerebral cyst, congenital ocular motor apraxia, and gaze-paretic nystagmus) are briefly reported and compared to normal eye movements of age-related children. The limitations of this procedure are discussed.

Adolescent↗
PubMed1992

Oxidative modification of low-density lipoproteins and the inhibition of relaxations mediated by endothelium-derived nitric oxide in rabbit aorta.

1. The mechanism by which Cu(2+)-oxidized low-density lipoproteins (oxLDL) inhibit acetylcholine (ACh)-evoked relaxations mediated by endothelium-derived nitric oxide (EDRF) in rabbit aortic rings was investigated. The proposed role of lysophosphatidylcholine (LPC) in the inhibition was also studied. 2. The kinetics of lipid peroxidation of native low-density lipoproteins (LDL) from individual donors, as measured by changes in conjugated diene concentration, were related to the inhibitory effects of the resultant oxLDL. It was found that the more susceptible LDL was to oxidation, the greater the inhibition. 3. No correlation was found between the inhibitory effects of oxLDL and LPC content. 4. Synthetic 1-palmitoyl LPC produced an inhibition of ACh-induced relaxations and when added to precontracted rings evoked nitric oxide-mediated endothelium-dependent relaxation. This latter effect was not elicited by oxLDL. 5. Synthetic 1-palmitoyl (10 microM) had no effect on relaxations evoked by glyceryl trinitrate in endothelium-denuded aortic rings in contrast to the inhibition found previously for oxLDL. 6. Concentrations of oxLDL and phospholipase A2-treated LDL which inhibited relaxation contained very different LPC concentrations. Unlike oxLDL, the inhibitory effects of phospholipase A2-treated LDL preparations were independent of the donors and showed no lag period. 7. We suggest that there are differences in the mechanisms by which oxLDL and 1-palmitoyl LPC exert their inhibitory effects on relaxation. 8. The inhibition of relaxation by oxLDL (1-2 mg protein ml-1) was prevented by the presence of high-density lipoproteins (HDL; 1-2 mg protein ml-1).9. It is proposed that prevention of the inhibition of relaxation by HDL is consistent with the inhibitory factor(s) being lipophilic constituents of oxLDL. However, variations in the inhibitory effects of oxLDL preparations are not due to differences in their LPC content and factors other than LPC must contribute to the inhibition.

Animals↗
PubMed1992

Eye movement tics.

An 8-year-old girl presented with opsoclonus-like eye movement and an 18 month history of intermittent facial tics. Investigations were all normal. Electro-oculography showed the eye movements to be of variable amplitude (10-40 degrees), with no intersaccadic interval, and with a frequency of 3-4 Hz. Saccades, smooth pursuit, optokinetic, and vestibular reflexes were all normal. These abnormal eye movements eventually disappeared. It is thought that they were a form of ocular tics.

Child↗