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Biomedical subjects

J Martin

Publications and source records attributed to J Martin.

At least 361 records · Page 20Linked to original sources
PubMed1997

MEDOS HIA-VAD biventricular assist device for bridge to recovery in fulminant myocarditis.

Successful weaning from biventricular mechanical support with full recovery of the myocardial function is extremely rare in fulminant myocarditis. We report on our experience with the MEDOS HIA-VAD ventricular assist device. The device worked for 17 days and provided adequate hemodynamics. Despite anticoagulation therapy, we had to change both ventricles because of clot formation on the surface of the outflow tract. After 17 days the myocardial function had recovered and we could remove the assist system.

Acute Disease↗
PubMed1997

Chaperone-assisted protein folding.

Molecular chaperones of the Hsp70 and chaperonin families are basic constituents of the cellular machinery that mediates protein folding. Recent functional and structural studies corroborate existing models for the mechanism of these components. Highlights of the past year include the X-ray crystallographic analysis of the peptide-binding domain of the Escherichia coli Hsp70 homolog, DnaK, the direct demonstration of protein folding in the central cavity of the chaperonin GroEL, and the visualization of conformational changes in GroEL during the chaperonin folding cycle.

Chaperonins↗
PubMed1997

Identification and treatment of sleep problems in the elderly.

For many adults, changes in sleep occur with aging. An estimated 15 million elderly, or 50% of older Americans, experience some sleep problem. The elderly complain that their sleep is more fragmented and that as they have gotten older, they experience more daytime sleepiness. Laboratory studies have confirmed these complaints. Research has shown that it is not the need for sleep that decreases with age, but rather the ability to sleep. Circadian rhythm disturbances, sleep disorders such as sleep disordered breathing and periodic movements in sleep, medical illness, medication use, and impaired cognitive functioning all contribute to poor sleep and decreased daytime alertness. In institutionalized elderly, sleep is even more disturbed and disrupted. With careful assessment, many of these problems can be addressed and treated, and sometimes cured.

Journal Article↗
PubMed1997

The T bag.

Explore the source record for details and available documents.

Equipment Design↗
PubMed1997

Molecular chaperones and mitochondrial protein folding.

Precursor proteins destined for the mitochondrial matrix traverse inner and outer organelle membranes in an extended conformation. Translocation events are therefore integrally coupled to the processes of protein unfolding in the cytosol and protein refolding in the matrix. To successfully import proteins from the cytoplasm into mitochondria, cells have recruited a variety of molecular chaperone systems and folding catalysts. Within the organelles, mitochondrial Hsp70 (mt-Hsp70) is a major player in this process and exerts multiple functions. First, mt-Hsp70 binds together with cohort proteins to incoming polypeptide chains, thus conferring unidirectionality on the translocation process, and then assists in their refolding. A subset of imported proteins requires additional assistance by chaperonins of the Hsp60/Hsp10 family. Protein folding occurs within the cavity of these cylindrical complexes. A productive interaction of precursor proteins with molecular chaperones in the matrix is not only crucial for correct refolding and assembly, but also for processing of presequences, intramitochondrial sorting, and degradation of proteins. This review focuses on the role of mt-Hsp70 and Hsp60/Hsp10 in protein folding in the mitochondrial matrix and discusses recent findings on their molecular mechanism of action.

Chaperonin 10↗
PubMed1997

Exposure of human renal proximal tubular cells to glucose leads to accumulation of type IV collagen and fibronectin by decreased degradation.

Thickening and reduplication of the tubular basement membrane has been reported as an early event in diabetic nephropathy. In the current study we examined the effects of elevated D-glucose concentrations on human proximal tubular (HPTC) type IV collagen and fibronectin turnover. Incubation of confluent growth arrested HPTC with 25 mM D-glucose led to accumulation of both type IV collagen and fibronectin. This effect was maximal at 48 hours and represented a sevenfold increase for fibronectin (N = 4, P = 0.04), and a threefold increase for type IV collagen (N = 3, P = 0.03) over cells exposed to 5 mM D-glucose controls. This increase was not dependent on new gene transcription for either protein. Tissue inhibitor of metalloproteinases (TIMP 1 + TIMP 2) were induced following addition of 25 mM D-glucose, but not when cells were exposed to 5 mM D-glucose. Twenty-four hours after the addition of 25 mM D-glucose there was an eightfold increase in TIMP 1 (P = 0.009, N = 4), and a tenfold increase in TIMP 2 levels (P = 0.003, N = 4), over the control values for both inhibitors. The increase in both TIMP 1 and TIMP 2 in response to 25 mM D-glucose was abrogated in a dose dependent manner by the aldose reductase inhibitor sorbinil. Gelatin-substrate gel zymography showed increased activity of gelatinase A, but not of gelatinase B in response to the addition of 25 mM D-glucose to HPTC. The induction of gelatinase A was accompanied by increased gelatinase A mRNA expression, which was inhibited both by protein kinase C (PKC) depletion using PMA pre-treatment, and by the addition of a PKC inhibitor. These data demonstrate that the glucose-induced accumulation of type IV collagen and fibronectin is unrelated to increased gene transcription, but may involve alterations in the degradative pathway of these basement membrane constituents. Furthermore, the data demonstrate that glucose may simultaneously activate two intracellular pathways (the polyol pathway and a PKC dependent activation pathway), which are involved in mediating separate, complementary effects on cell function.

Cells, Cultured↗
PubMed1997

A cell surface tethered enzyme improves efficiency in gene-directed enzyme prodrug therapy.

The potential for expressing the bacterial enzyme carboxypeptidase G2 (CPG2) tethered to the outer surface of mammalian cells was examined for use in gene-directed enzyme prodrug therapy. The affinity of CPG2 for the substrate methotrexate was unaffected by three mutations required to prevent N-linked glycosylation. Breast carcinoma MDA MB 361 cells expressing CPG2 internally showed only a very modest increase in sensitivity to the prodrug CMDA because the prodrug did not enter the cells. Cells expressing surface-tethered CPG2, however, became 16-24-fold more sensitive to CMDA and could mount a good bystander effect. Systemic administration of CMDA to mice bearing established xenografts of the transfected cells led to sustained tumor regressions or cures.

3T3 Cells↗
PubMed1997

Selective inhibition and induction of CYP activity discriminates between the isoforms responsible for the activation of butylated hydroxytoluene and naphthalene in mouse lung.

1. Selective induction and inhibition experiments have been used to identify the cytochrome P450 (CYP) isoforms responsible for butylated hydroxytoluene (BHT) bioactivation in mouse lung. 2. Pre-treatment of BALB/c mice with O,O,O-trimethylphosphorothioate (OOOMeP(S)), which prevented all the signs of toxicity observed following BHT treatment, inhibited the pulmonary activity of pentoxyresorufin O-dealkylase (PROD) and coumarin hydroxylase but not 4-nitrophenol hydroxylase. 3. Pulmonary coumarin hydroxylase activity was greater in DBA than in BALB/c mice but the severity of BHT-induced lung injury was similar. 4. Pre-treatment with pyrazole, which exacerbated BHT-induced lung injury, did not affect pulmonary coumarin hydroxylase or 4-nitrophenol hydroxylase activity but increased that of PROD. 5. Pre-treatment with OOOMeP(S) prevented the lethargy and weight-loss associated with naphthalene poisoning but not the pulmonary injury. Pre-treatment with pyrazole did not exacerbate naphthalene-induced injury. 6. Members of both CYP2F and 2B sub-families have been shown to exhibit PROD activity and 2F2 activates naphthalene in mouse lung. The current studies, however, indicate that 2F2 is unlikely to be a significant component of PROD activity in mouse lung. 2F2, like coumarin hydroxylase (2A5) and 4-nitrophenol hydroxylase (2E1), is not responsible for the pulmonary activation of BHT, which is largely attributable to an isoform of 2B, probably 2B10.

Animals↗
PubMed1997

Open fluoxetine treatment of mixed anxiety disorders in children and adolescents.

An open-label pilot study examined fluoxetine treatment in 16 outpatients (9-18 years old) with mixed anxiety disorders. Following nonresponse to psychotherapy, fluoxetine monotherapy was started at 5 mg daily and was increased weekly by 5 or 10 mg daily for 6-9 weeks until improvement occurred or to a maximum of 40 mg (children under 12) or 80 mg (adolescents). Among patients on fluoxetine, severity of illness ratings were "much improved" (mean final Clinical Global Impression scale score 2.8 +/- 0.7). Clinical improvement occurred in 10 of 10 patients with current separation anxiety disorder, 8 of 10 with social phobia, 4 of 6 with specific phobia, 3 of 5 with panic disorder, and 1 of 7 with generalized anxiety disorder. Mean time to improvement was 5 weeks. Mean doses were 24 mg (0.7 mg/kg) for children and 40 mg (0.71 mg/kg) for adolescents. Side effects were transient and included drowsiness (31% of patients), sleep problems (19%), decreased appetite (13%), nausea (13%), abdominal pain (13%), and excitement (13%). No patient developed disinhibition, akathisia, or suicidality. These preliminary findings suggest fluoxetine effectiveness in separation anxiety disorder and social phobia. Youths with only one anxiety disorder appeared to respond to lower doses of fluoxetine than patients with multiple anxiety disorders (0.49 +/- 0.14 versus 0.80 +/- 0.28 mg/kg, p < 0.05).

Adolescent↗
PubMed1997

Systematic assessment of 50 children with selective mutism.

OBJECTIVE: To clarify the diagnostic significance of selective mutism (elective mutism in DSM-III-R). METHOD: Fifty children with selective mutism were evaluated systematically by means of semistructured clinical interviews and rating scales to obtain detailed diagnostic information. RESULTS: All 50 children met DSM-III-R criteria for social phobia or avoidant disorder and 24 (48%) had additional anxiety disorders. Clinical measures of anxiety and behavioral symptoms supported the presence of anxiety disorders as a characteristic of selectivity mute children. Only one case each of oppositional defiant disorder and attention-deficit hyperactivity disorder was found. CONCLUSIONS: Persistent selective mutism typically presents in the context of anxiety disorders.

Adolescent↗
PubMed1997

Oxygen enrichment during emergence with the laryngeal mask--the 'T-bag' versus the T-piece.

We have compared the performance of a new oxygen enrichment device, the 'T-bag', with a T-piece during emergence from spontaneous breathing anaesthesia with the laryngeal mask airway. Thirty patients were randomly allocated to each group. Inspired and end-tidal gases were sampled from the proximal end of the laryngeal mask airway. Cardiorespiratory variables were recorded immediately prior to discontinuation of anaesthesia, 2 min later and then at 5-min intervals until removal of the laryngeal mask airway. The mean inspired oxygen concentration was greater than 70% and the inspired carbon dioxide was less than 2 mmHg in both groups throughout emergence. There were no episodes of hypoxia (oxygen saturation < 92%). Both devices performed well, but the 'T-bag' offered advantages in terms of respiratory monitoring and ventilatory capability.

Adult↗
PubMed1997

Human endogenous retrovirus type I-related viruses have an apparently widespread distribution within vertebrates.

Retroviruses from lower vertebrate hosts have been poorly characterized to date. Few sequences have been isolated, and those which have been reported are all highly divergent when compared to the retroviruses known to be harbored by mammals and birds. Here we show that retroviruses with significant homology to the human endogenous retrovirus type I (HERV-I) are present within the genomes of fish, reptiles, birds, and mammals and that they may well be widespread within many vertebrates. Phylogenetic analysis of nucleotide sequences strongly supported the inclusion of viruses from each of these vertebrate classes into one monophyletic group. This analysis also demonstrated that the HERV-I-related viruses are more closely related to retroviruses belonging to the murine leukemia virus genus than to members of the other retroviral genera. The presence of HERV-I-related retroviruses in so many disparate vertebrate hosts suggests that other endogenous human retroviruses may also have a much wider distribution than is currently appreciated.

Amino Acid Sequence↗