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Biomedical subjects

T Allen

Publications and source records attributed to T Allen.

At least 19 recordsLinked to original sources
PubMed2000

Sequence and expression of the kettin gene in Drosophila melanogaster and Caenorhabditis elegans.

Kettin is a large modular protein associated with thin filaments in the Z-disc region of insect muscles. The sequence of a 21.3 kb contig of the Drosophila gene has been determined. The corresponding protein sequence has 35 immunoglobulin-like (Ig) domains which are separated by shorter linker sequences, except near the N and C termini of the molecule where linker sequences are short or missing. This confirms a model in which each Ig domain binds to an actin protomer. The Drosophila kettin gene is at 62C 1-3 on the third chromosome. Two P-element insertions, l(3)j1D7 and l(3)rL182 are in the kettin gene, and complementation tests showed that existing l(3)dre8 mutations are in the same gene. The RNA was detected in wild-type Drosophila embryos at stage 11, first in the gut invagination region of the mesoderm, and by stage 13 in both visceral and somatic mesoderm. Somatic mesoderm expression became segmental at stage 13. RNA expression was greatly reduced in embryos of P-element homozygotes but normal in heterozygotes. The structure of the flight muscle in all the heterozygous mutants was normal, including the myofibril-cuticle connections, and they were able to fly. Kettin sequence homologous to the Drosophila protein, was identified in the Caenorhabditis elegans genome database. The RNA was detected in pharyngeal, body wall and anal depressor muscles of larvae and adult worms, as well as in the male gonad. Antibody to insect kettin labelled the pharyngeal, body wall, anal depressor and proximal gonadal muscles in adult worms. Body wall muscles were labelled in an obliquely striated pattern consistent with the Z-disc localisation in insect muscle. The relationship of kettin to D-titin, which has been assigned to the same chromosomal locus in Drosophila, is discussed.

Amino Acid Sequence↗
PubMed2000

Effects of dietary polyunsaturated fatty acid supplementation in early renal insufficiency in dogs.

Dietary supplementation with polyunsaturated fatty acids (PUFAs) alters the course of experimental kidney disease in dogs. In particular, supplementation with omega-6 PUFAs hastens the decline of kidney function, and omega-3 PUFAs are renoprotective. We investigated the early stages of renal insufficiency to determine whether PUFA supplementation altered the magnitude of hypercholesterolemia or glomerular hemodynamics. Two months after 11/12 nephrectomy, dogs were randomly divided into three groups of 6 animals each. Each group of dogs was then fed a low-fat basal diet supplemented with one of three sources of lipid to achieve a final concentration of 15% added fat. Fat sources were rich in omega-3 PUFAs (menhaden fish oil, group FO), omega-6 PUFAs (safflower oil, group SO), or saturated fatty acids (beef tallow, group C). Early in renal insufficiency, before significant kidney damage, group FO had a lower (P<.05) serum cholesterol concentration and tended to have a lower urinary prostaglandin E2 (PGE2) and thromboxane A2 (TxA2) excretion than group C. In contrast, group SO had a higher mean glomerular capillary pressure (P<.05) and more glomerular enlargement (P<.05) and tended to have higher eicosanoid excretion rates than group C. These differences in lipid metabolism, glomerular hypertension and hypertrophy, and urinary eicosanoid metabolism could explain, in part, the beneficial effects of omega-3 PUFAs and the detrimental effects of omega-6 PUFAs when administered on a long-term basis in this model of renal insufficiency.

Animals↗
PubMed1999

The pro-apoptotic proteins, Bid and Bax, cause a limited permeabilization of the mitochondrial outer membrane that is enhanced by cytosol.

During apoptosis, an important pathway leading to caspase activation involves the release of cytochrome c from the intermembrane space of mitochondria. Using a cell-free system based on Xenopus egg extracts, we examined changes in the outer mitochondrial membrane accompanying cytochrome c efflux. The pro-apoptotic proteins, Bid and Bax, as well as factors present in Xenopus egg cytosol, each induced cytochrome c release when incubated with isolated mitochondria. These factors caused a permeabilization of the outer membrane that allowed the corelease of multiple intermembrane space proteins: cytochrome c, adenylate kinase and sulfite oxidase. The efflux process is thus nonspecific. None of the cytochrome c-releasing factors caused detectable mitochondrial swelling, arguing that matrix swelling is not required for outer membrane permeability in this system. Bid and Bax caused complete release of cytochrome c but only a limited permeabilization of the outer membrane, as measured by the accessibility of inner membrane-associated respiratory complexes III and IV to exogenously added cytochrome c. However, outer membrane permeability was strikingly increased by a macromolecular cytosolic factor, termed PEF (permeability enhancing factor). We hypothesize that PEF activity could help determine whether cells can recover from mitochondrial cytochrome c release.

Adenylate Kinase↗
PubMed1999

Temporal differences in the appearance of NEP-B78 and an LBR-like protein during Xenopus nuclear envelope reassembly reflect the ordered recruitment of functionally discrete vesicle types.

In this work, we have used novel mAbs against two proteins of the endoplasmic reticulum and outer nuclear membrane, termed NEP-B78 and p65, in addition to a polyclonal antibody against the inner nuclear membrane protein LBR (lamin B receptor), to study the order and dynamics of NE reassembly in the Xenopus cell-free system. Using these reagents, we demonstrate differences in the timing of recruitment of their cognate membrane proteins to the surface of decondensing chromatin in both the cell-free system and XLK-2 cells. We show unequivocally that, in the cell-free system, two functionally and biochemically distinct vesicle types are necessary for NE assembly. We find that the process of distinct vesicle recruitment to chromatin is an ordered one and that NEP-B78 defines a vesicle population involved in the earliest events of reassembly in this system. Finally, we present evidence that NEP-B78 may be required for the targeting of these vesicles to the surface of decondensing chromatin in this system. The results have important implications for the understanding of the mechanisms of nuclear envelope disassembly and reassembly during mitosis and for the development of systems to identify novel molecules that control these processes.

Animals↗
PubMed1999

Phylogenetic analysis of L4-mediated autogenous control of the S10 ribosomal protein operon.

We investigated the regulation of the S10 ribosomal protein (r-protein) operon among members of the gamma subdivision of the proteobacteria, which includes Escherichia coli. In E. coli, this 11-gene operon is autogenously controlled by r-protein L4. This regulation requires specific determinants within the untranslated leader of the mRNA. Secondary structure analysis of the S10 leaders of five enterobacteria (Salmonella typhimurium, Citrobacter freundii, Yersinia enterocolitica, Serratia marcescens, and Morganella morganii) and two nonenteric members of the gamma subdivision (Haemophilus influenzae and Vibrio cholerae) shows that these foreign leaders share significant structural homology with the E. coli leader, particularly in the region which is critical for L4-mediated autogenous control in E. coli. Moreover, these heterologous leaders produce a regulatory response to L4 oversynthesis in E. coli. Our results suggest that an E. coli-like L4-mediated regulatory mechanism may operate in all of these species. However, the mechanism is not universally conserved among the gamma subdivision members, since at least one, Pseudomonas aeruginosa, does not contain the required S10 leader features, and its leader cannot provide the signals for regulation by L4 in E. coli. We speculate that L4-mediated autogenous control developed during the evolution of the gamma branch of proteobacteria.

Base Sequence↗
PubMed1999

The simian immunodeficiency virus envelope glycoprotein contains two epitopes presented by the Mamu-A*01 class I molecule.

Cytotoxic T lymphocyte (CTL) responses against the simian immunodeficiency virus (SIV) envelope and Gag proteins were monitored in a Mamu-A*01-positive rhesus macaque infected with SIVsmE660. Peripheral blood mononuclear cells (PBMC) cultured with synthetic peptides spanning the entire gp160 and Gag coding region recognized a total of three epitopes. One located in Gag was identified as the previously described Mamu-A*01-restricted p11cC-->M epitope (CTPYDINQM). The other two epitopes, designated p15m and p54m, were located in the gp160 envelope protein. Both were nine amino acids in length and were predicted to bind Mamu-A*01 because they contained proline and leucine residues at positions 3 and 9, respectively. Indeed, expression of this class I major histocompatibility complex molecule was required for target cell recognition by envelope-specific CD8(+) T cells directed against both epitopes. These Mamu-A*01-restricted epitopes in the SIV envelope will be useful for monitoring immune responses in vaccinated or infected animals.

Amino Acid Sequence↗
PubMed1999

Management of ectopic ureterocele associated with renal duplication: a comparison of partial nephrectomy and endoscopic decompression.

PURPOSE: We compared the efficacy of primary endoscopic decompression versus partial nephrectomy for treating ectopic duplex ureteroceles. MATERIALS AND METHODS: We retrospectively reviewed the records of patients with renal duplication and upper pole ectopic ureterocele. Patients were classified according to the initial radiological evaluation. The operation performed was arbitrarily chosen by the surgeon. RESULTS: A total of 54 patients had unilateral upper or bilateral upper pole ureterocele with no associated vesicoureteral reflux. Partial nephrectomy was performed in 26 patients, of whom 4 (15%) required additional surgery for new onset ipsilateral lower pole reflux. Endoscopic decompression was performed in 28 patients, of whom 18 (64%) required additional treatment due to reflux into the ipsilateral lower pole ureter and ureterocele in 9, reflux into the ureterocele only in 4, ipsilateral lower pole reflux only in 3 and persistent ureterocele obstruction in 2 (p<0.01). An ectopic ureterocele with vesicoureteral reflux into 1 or more moieties was identified in 111 patients, including 56 of 67 (84%) treated with partial nephrectomy and 37 of 44 (84%) treated with endoscopy who have persistent reflux or required further surgery for reflux resolution. CONCLUSIONS: In patients with an ectopic ureterocele and no vesicoureteral reflux partial nephrectomy should be considered the treatment of choice. However, when the initial cystogram reveals vesicoureteral reflux, partial nephrectomy and endoscopic ureterocele decompression have identical definitive cure rates of only 16%. The majority of the latter patients require continued observation and/or additional surgery for managing persistent reflux.

Abnormalities, Multiple↗
PubMed1999

A comparison of Notch, Hes and Grg expression during murine embryonic and post-natal development.

Mammalian Hairy/Enhancer-of-split-like (Hes) proteins interact with transcriptional corepressors encoded by the Groucho-related genes (Grg in mice). We have examined the embryonic and postnatal expression of the Hes1 and Hes3 genes as well as all four murine Grgs in order to determine where spatial and temporal overlaps of Hes and Grg corepressors may occur. Both within and between gene families, expression was found to occur in unique but overlapping patterns during embryonic and postnatal development. Areas where the members of these gene families are coexpressed also overlap with areas where Notch signaling is thought to maintain cells in undifferentiated or "precursor" states. Our data suggest that the coordinated transcriptional control of these genes occurs during development and that precise Hes and Grg pairings may play a role in mediating the morphogenesis of CNS and epithelialized structures.

Animals↗
PubMed1998

Ipsapirone neuroendocrine challenge: relationship to aggression as measured in the human laboratory.

Thirty-one human subjects were administered a neuroendocrine challenge with the 5-HT1a agonist ipsapirone after completing six sessions of a laboratory measure of aggression, the Point Subtraction Aggression Paradigm (PSAP), in order to determine if a laboratory measure of aggression was related to serotonin function. Subjects who showed more aggressive responding on the PSAP (n = 11) had a significantly blunted temperature response to ipsapirone compared to those with less aggressive responding (n = 20). There was no difference between the two groups on the cortisol response to ipsapirone. This study supports a relationship between serotonin function and aggression as measured in the human laboratory, similar to the well-documented association between self-reported aggression and serotonin.

Adult↗
PubMed1998

Study of ionic currents across a model membrane channel using Brownian dynamics.

Brownian dynamics simulations have been carried out to study ionic currents flowing across a model membrane channel under various conditions. The model channel we use has a cylindrical transmembrane segment that is joined to a catenary vestibule at each side. Two cylindrical reservoirs connected to the channel contain a fixed number of sodium and chloride ions. Under a driving force of 100 mV, the channel is virtually impermeable to sodium ions, owing to the repulsive dielectric force presented to ions by the vestibular wall. When two rings of dipoles, with their negative poles facing the pore lumen, are placed just above and below the constricted channel segment, sodium ions cross the channel. The conductance increases with increasing dipole strength and reaches its maximum rapidly; a further increase in dipole strength does not increase the channel conductance further. When only those ions that acquire a kinetic energy large enough to surmount a barrier are allowed to enter the narrow transmembrane segment, the channel conductance decreases monotonically with the barrier height. This barrier represents those interactions between an ion, water molecules, and the protein wall in the transmembrane segment that are not treated explicitly in the simulation. The conductance obtained from simulations closely matches that obtained from ACh channels when a step potential barrier of 2-3 kTr is placed at the channel neck. The current-voltage relationship obtained with symmetrical solutions is ohmic in the absence of a barrier. The current-voltage curve becomes nonlinear when the 3 kTr barrier is in place. With asymmetrical solutions, the relationship approximates the Goldman equation, with the reversal potential close to that predicted by the Nernst equation. The conductance first increases linearly with concentration and then begins to rise at a slower rate with higher ionic concentration. We discuss the implications of these findings for the transport of ions across the membrane and the structure of ion channels.

Algorithms↗
PubMed1998

Beneficial effects of chronic administration of dietary omega-3 polyunsaturated fatty acids in dogs with renal insufficiency.

Dietary supplementation with polyunsaturated fatty acids (PUFA) alters the course of experimental renal disease in rats. However, chronic renal disease in other laboratory animals and in human beings frequently responds differently to experimental manipulations. We investigated the effects of variations in dietary PUFA composition on the chronic course of induced renal disease in dogs. Two months after 15/16 nephrectomy, dogs were randomly divided into three groups of seven animals each. For the next 20 months, each group of dogs was fed a low-fat basal diet supplemented with one of three sources of lipid to achieve a final concentration of 15% added fat. Fat sources provided omega-3 PUFA (menhaden fish oil, group FO), omega-6 PUFA (safflower oil, group SO), or saturated fatty acids (beef tallow, group BT). Throughout the dietary trial, the magnitude of proteinuria and the plasma concentrations of creatinine, cholesterol, and triglyceride were lower in group FO. The mean overall glomerular filtration rate was 0.89+/-0.18 ml/min per kilogram of body weight in group SO, a value that was significantly less (p < 0.05) than the corresponding values for groups BT and FO (1.21+/-0.18 and 1.43+/-0.20 ml/min/kg, respectively). Renal interstitial fibrosis also was significantly elevated in group SO. The extents of mesangial matrix expansion, glomerulosclerosis, and renal interstitial cellular infiltrate were similar in groups BT and SO, but lower (p < 0.05) in group FO. We conclude that supplementation with omega-6 PUFA enhanced renal injury; supplementation with omega-3 PUFA was renoprotective.

Animals↗
PubMed1998

Perceived efficacy of pain clinics in the rehabilitation of injured workers.

OBJECTIVE: To assess the perceived efficacy of pain clinics in the rehabilitation of injured workers among four groups of professionals. DESIGN: A questionnaire was given to 351 subjects representing four professional groups: physicians, vocational rehabilitation counselors, staff at pain clinics, and employees of a workers compensation program. Subjects rated the effectiveness of pain clinics in eight specific functions, estimated the percentage of workers who return to work after pain clinic treatment, and indicated how soon after injury a worker should be referred to a pain clinic. RESULTS: Pain clinic staff consistently gave the most favorable ratings and workers compensation employees the least favorable ones. There was good agreement across professional groups regarding the need for early referral of injured workers to pain clinics and the specific functions that pain clinics carry out relatively well. Clinics were ranked as most effective in reducing workers' use of opiates, and as least effective in reducing workers' pain. Return-to-work estimates varied significantly across professional groups. Within professional groups, subjects with high estimates gave more favorable overall ratings to pain clinics. CONCLUSIONS: The results provide a profile of the perceived effectiveness of pain clinics in various functions and highlight the importance of getting accurate information about return to work rates following pain clinic treatment. They suggest that workers are not referred to pain clinics early enough.

Accidents, Occupational↗
PubMed1998

I-131 uptake in the breast for thyroid cancer surveillance with biopsy-proven benign tissue.

A 37-year-old woman was seen for recurrent papillary carcinoma of the thyroid after thyroidectomy. After repeated surgery and I-131 therapy, follow-up I-131 scanning and thyroglobulin levels were negative. Subsequent I-131 surveillance, however, demonstrated bilateral breast uptake. A biopsy taken of this area in the right breast proved that the increased uptake was secondary to benign disease.

Adult↗
PubMed1997

Changes in the mechanical properties of human and amphibian muscle after eccentric exercise.

Following a series of eccentric contractions, that is stretching of the muscle while generating active tension, the length-tension relationship of isolated amphibian muscle has been shown to shift towards longer muscle length (Katz 1939; Wood et al. 1993). Here we report observations of electrically stimulated ankle extensor muscles of nine human subjects, demonstrating a similar shift in optimum angle for torque generation [3.9 (1.5) degrees] following exercise on an inclined treadmill that involved eccentric contractions in one leg. (All values are means with the SEMs in parentheses). The shift in the unexercised, control leg was significantly less [mean 0.4 (0.7) degree P < 0.05]. Correlated with this shift was a drop in torque [25.1 (5.6)% for the experimental leg; 1.6 (0.7)% for the control leg, P < 0.002]. Optimum angles returned to pre-exercise values by 2 days post-exercise, while torque took a week to recover. A similar shift in optimum length [12 (1.3)% of rest length] was obtained for five toad (Bufo marinus) sartorius muscles subjected to 25 eccentric contractions. Isometrically contracted control muscles showed a smaller shift [3.5 (1.6)%, n = 5]. Accompanying the shift was a drop in tension of 46 (3)% after the eccentric contractions [control isometric, 23 (6)%, P < 0.0001]. By 5 h after the eccentric contractions the shift had returned to control values, while tension had not recovered. When viewed with an electron microscope, sartorius muscles fixed immediately after the eccentric contractions exhibited many small, and a few larger, regions of myofilament disruption. In muscles fixed 5 h after the contractions, no small regions of disruption were visible, and the number of large regions was no greater than in those muscles fixed immediately after the eccentric contractions. These disruptions are interpreted as the cause of the shift in length-tension relationship.

Adult↗
PubMed1997

Cutaneously applied acyclovir acts systemically in the treatment of herpetic infection in the hairless mouse.

Using the SKH-1 hairless mouse (HM) we have addressed the issue as to whether topically applied acyclovir (ACV) may mediate some of its antiviral actions by a systemic effect. When topically applied in a formulation consisting of polyvinyl alcohol (25% w/v):DMSO:cremophor EL:linoleic acid (63:16:16:5, v/v/v/v), ACV penetrated hairless mouse skin in a concentration-dependent manner and dose-dependently reduced cutaneous herpes simplex virus 1 (HSV-1) KOS infection. Topically applied ACV also effectively reduced the mortality associated with disseminated HSV-2 HG-52 infection. At 1 h following topical application of 1.7% w/v ACV the plasma and skin concentrations of ACV were 5.5 nmoles/ml and 120 nmoles/g. At 1 h following an oral dose of ACV with antiviral efficacy comparable to topically applied ACV (1.7% w/v) the plasma and skin concentrations of ACV were 21.3 nmoles/ml and 51 nmoles/g. These findings imply that when applied topically to the HM, ACV can mediate a portion of its antiviral activity through a systemic mode of action.

Acyclovir↗
PubMed1996

Initiating thrombolytic therapy for acute myocardial infarction: whose job is it anyway?

Although thrombolytic therapy has clearly become the standard of care for acute myocardial infarction (AMI), its delivery in Canada continues to be extremely variable. Significant unnecessary delays in the initiation of this treatment still occur in many hospitals and constitute the most common avoidable cause of death in patients with AMI. The authors agree with the statement by representatives of the member organizations of the Emergency Cardiac Care Coalition (see pages 483 to 487 of this issue) that emergency service providers must get patients to hospital sooner and that all eligible patients should receive thrombolytic therapy within 30 minutes of their arrival at hospital. This objective requires that thrombolytic therapy be initiated by emergency physicians and be supported by well-established guidelines for its use.

Emergency Service, Hospital↗