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Biomedical subjects

L Martin

Publications and source records attributed to L Martin.

At least 19 recordsLinked to original sources

Polyphosphoinositide hydrolysis and protein kinase C activation in guinea pig tracheal smooth muscle cells in culture by leukotriene D4 involve a pertussis toxin sensitive G-protein.

Leukotriene D4 (LTD4) at concentrations greater than 1 nM induced phosphatidylinositol bisphosphate (PIP2) hydrolysis and protein kinase C (PKC) activation in primary culture of airway smooth muscle cells. Within seconds of activation, an increase in inositol 1,4,5-trisphosphate (IP3) was observed reaching a maximum at 5 min. The level of IP3 decreased after 5 min and was followed by an increase in inositol 1,4-bisphosphate (IP2) and inositol 1-monophosphate (IP1). LTD4-induced PIP2 hydrolysis was inhibited by 1 h pretreatment of cells with 10 micrograms/ml of pertussis toxin (PTX). LTD4 activated both soluble and particulate forms of PKC by 2-3-fold. The LTD4-induced PKC activation was blocked by treatment of cells with PTX, suggesting the involvement of a PTX-sensitive G-protein. To assess the involvement of G(i) in smooth muscle cell receptor activation, the modulation of adenylyl cyclase activity was investigated. LTD4 did not stimulate cAMP formation in smooth muscle cells, and did not inhibit forskolin-induced cAMP formation. These data suggest that the LTD4 receptor in airway smooth muscle cells is coupled to a PTX-sensitive G-protein, possibly G(o).

Adenylate Cyclase Toxin

Involvement of hypothalamic noradrenergic systems in the modulation of intestinal motility in rats.

Selective lesions of the noradrenergic systems of the paraventricular nucleus (PVN) of the hypothalamus with 6-hydroxydopamine (6-OHDA) lengthen the periodicity of the migrating myoelectric complex (MMC), an index of intestinal motility, in rats. These lengthening effects resemble those obtained after lesions of the locus coeruleus (LC), thus suggesting that noradrenergic terminals from LC to the PVN are involved in this modulation.

Analysis of Variance

Laparoscopic evaluation of tangential abdominal gunshot wounds.

The use of laparoscopy in abdominal trauma has been proposed for several decades; however, it has not been widely used. With the advent of laparoscopic cholecystectomy, general surgeons are realizing the potential of this technique. This should result in an expanded role for laparoscopy, including the evaluation of abdominal trauma. We present a series in which laparoscopy was used in the evaluation of tangential gunshot wounds to the abdomen. Laparoscopy enabled us to demonstrate whether the missile had violated the peritoneal cavity and to avoid laparotomy in cases without peritoneal penetration.

Abdominal Injuries

MSA-36: a chromosomal and mitotic spindle-associated protein.

We have identified a novel M(r) 36,000 protein (MSA-36) that has a complex cell cycle dependent distribution. This protein is first detected in interphase nuclei just prior to the onset of chromosome condensation. MSA-36 is found along condensing chromosomes and is a component of the centromere through metaphase. At anaphase, this protein is no longer detected in association with the chromosomes but appears at the forming stembodies and subsequently within the intercellular bridge at either side of the midbody. At the completion of cell division, the amount of MSA-36 in the bridge appears to decline concurrent with the appearance of this protein briefly within the reforming nucleus. To investigate whether MSA-36 is an active component of the chromosome or a passive passenger protein, we studied the behaviour of this protein in cells exhibiting premature chromosome condensation and in cells during and following recovery from mitotic arrest. These studies suggest that MSA-36 is not essential for a variety of major chromosome-associated events.

Autoantigens

Influence of Corynebacterium parvum-PER on disease progression in the NZB/W model of systemic lupus erythematosus.

Murine models of systemic lupus erythematosus (SLE) exhibit some, but not all, of the characteristics of human disease. Disease progression in the animal models is regulated by autoantibodies, genetics and inflammatory processes. In the present study, the influence of the pyridine extract residue of Corynebacterium parvum Type I (CP-PER) on disease progression in the NZB/W model of SLE was investigated. CP-PER is known to activate the reticuloendothelial (RE) system of mice and can alter a number of host responses. Injection of NZB/W females with CP-PER at 10 weeks of age, prior to the onset of overt disease, led to a transient activation of the RE system which then appeared to return to levels observed in untreated animals. Sera from treated and untreated animals were analyzed for anti-nuclear antibodies, and anti-ssDNA antibodies. The most prominant change in the treated animals was an increase in the titer of anti-ssDNA. On average, animals in the early treatment group also lived somewhat longer than those in the untreated control group. Treatment of animals with CP-PER at 6 months of age, when the disease was evident, again led to transient RES activation and an altered autoantibody profile. Animals treated with CP-PER at 6 months of age exhibited a slightly accelerated death rate when compared with the untreated controls. These results indicate that bacterial response modifiers such as C. parvum-PER, which contains primarily the RES activating activity of C. parvum, can alter disease progression in the NZB/W model.

Animals

[Postoperative re-expansion causing unilateral pulmonary edema].

A case of re-expansion pulmonary oedema is reported. A 7-year-old girl, after having been operated on for a lung tumour, had a postoperative haemothorax combined with atelectasis of the left upper lobe. After she had recovered from the first dose of chemotherapy, the thoracotomy wound was reopened to remove the partially organised and lysed haemothorax, as well as the very thickened pleura. The patient developed clinical signs of pulmonary oedema very shortly after the end of the anaesthetic (tachypnoea, cyanosis, a decrease in oxygen saturation when FIO2 < 1, pink frothy secretions in the endotracheal tube). End-inspiratory crepitations became audible in the left lung field only. The chest film showed left-sided diffuse nodular alveolar opacities. The girl was again ventilated, with + 5 cmH2O positive end-expiratory pressure. She was extubated 36 h later, and discharged a few days later without any sequela. This case was the first to be described in a child after pleural surgery. The death rate, estimated from a literature survey, is about 20%.

Child

Lipid peroxidation in stored red cells.

Lipid peroxidation is initiated by the production of oxygen-free radicals; it is increased in a wide variety of diseases, including various hemolytic anemias, and in hemoglobin disorders. Increased lipid peroxidation occurs in red cells in the presence of reactive iron species and some heme moieties. In this study, greatly reduced concentrations of malondialdehyde, an indicator of lipid peroxidation, were observed in stored blood upon the addition of both deferoxamine mesylate and diethylenetriaminepentaacetic acid (p less than 0.001). The antioxidant glutathione was much less effective (p less than 0.01 or less than 0.05, depending on incubation time). On the other hand, the addition of dimercaptosuccinic acid and ascorbic acid both significantly increased malondialdehyde production over controls (p less than 0.001 and p less than 0.05, respectively). Ascorbic acid, in the presence of deferoxamine mesylate, added no red cell protection over that of deferoxamine mesylate alone. The addition of metal chelators and, possibly, certain antioxidants to stored blood may be effective in increasing the viability and longevity of transfused red cells.

Blood Component Transfusion

Effects of the progesterone antagonist RU486 on myometrial activity in vivo in early pregnant and pseudopregnant rats.

Myometrial activity in vivo was quantified by video-laparoscopy in early pregnant rats given doses of RU486 which caused embryo abortion and blocked the action of progesterone on the vagina. All treatments diminished the frequency of circular contractions and abolished the curling movements of the uterus which are characteristic of pregnant, pseudopregnant and progestin-treated rats. The effects of RU486 on circular contractions were similar in pseudopregnant rats, i.e. they were not a consequence of embryo abortion. These results support the thesis that increased myometrial circular contractions in early pregnancy and pseudopregnancy are induced by increasing levels of progesterone. Effects of RU486 on longitudinal contractions were more complex: the highest dose inhibited longitudinal contractions on Day 5 of pregnancy and pseudopregnancy, but increased their frequency on Day 6. The acute inhibition of longitudinal contractions by RU486 was unexpected and the mechanism remains to be elucidated. The later increase in the frequency of longitudinal contractions appears to be due to antagonism of progesterone by RU486. The frequency of caudal longitudinal contractions on Day 6 in mated rats given RU486 was similar to that in unmated oestrous rats, but the frequency of cranial longitudinal contractions was significantly higher. These results support the hypothesis that stimuli received during copulation may have long-term effects on myometrial activity, by increasing pacemaker activity at the cervix.

Animals

Inhibition of human neutrophil responses by alpha-cyano-3,4-dihydroxythiocinnamamide; a protein-tyrosine kinase inhibitor.

1. Activation of neutrophils results in increased tyrosine phosphorylation of several proteins that may have important roles in receptor/effector coupling. In this study, the effect of a protein tyrosine kinase inhibitor on receptor-mediated neutrophil activation by platelet-activating factor (PAF), leukotriene, B4 (LTB4) and N-formylmethionylleucylphenylalanine (FMLP) is investigated. 2. alpha-Cyano-3,4-dihydroxythiocinnamamide dose-dependently inhibited intracellular calcium release and superoxide generation from human neutrophils activated by 1 microM LTB4, PAF, and FMLP. 3. In the presence of cytochalasin B, FMLP stimulated elastase release from neutrophils was also inhibited to unstimulated levels by 5 min pretreatment with alpha-cyano-3,4-dihydroxythiocinnamamide. 4. The inhibitory action of alpha-cyano-3,4-dihydroxythiocinnamamide was found to be at or upstream of phospholipase C activation, blocking both phosphatidylinositol hydrolysis and protein kinase C activation. alpha-Cyano-3,4-dihydroxythiocinnamamide did not affect agonist receptor binding sites or receptor affinity in neutrophils. 5. Immunoblot analysis demonstrated the tyrosine phosphorylation of proteins of 41, 56, 66, and 104 kDa in neutrophils treated with agonists. Treatment of neutrophils with alpha-cyano-3,4-dihydroxythiocinnamamide prior to stimulation with chemoattractants reduced tyrosine phosphorylation of the above phosphoproteins. 6. These results indicate that alpha-cyano-3,4-dihydroxythiocinnamamide might be a useful agent in characterizing the essential proteins and biochemical pathways that regulate neutrophil activation.

Calcium

Locus ceruleus modulates migrating myoelectric complex in rats.

The role of the locus ceruleus (LC) in the control of migrating myoelectric complex (MMC) was investigated in rats with lesions induced by injections of 6-hydroxydopamine (6-OHDA). Control animals received the vehicle alone. MMC was recorded in conscious rats chronically fitted with electrodes. After 6-OHDA was injected into the LC, lesions of the LC were total, partial (mostly rostral), or ineffective. The MMC period was significantly longer in animals with a total or partial lesion but was unchanged in animals with an ineffective lesion. No lesion of other brain noradrenergic nuclei was observed. The longer MMC period is comparable to that obtained after intracerebroventricular injection of 6-OHDA, which is responsible for a more diffuse destruction of brain noradrenergic systems, including LC itself. Bilateral lesions of the central tegmental tract, which carries ascending noradrenergic axons from the medullary and pontine cell groups outside the LC, do not alter the MMC cycle. Consequently, the LC is most likely the major brain noradrenergic candidate for modulating the MMC pattern in rats.

Animals

An evaluation of the functions of the 22-kilodalton (kDa), the 20-kDa, and the N-terminal polypeptide forms of human growth hormone using transgenic mice.

Multiple peptide hormones can be derived from the single human GH gene. In addition to the full-length 191-amino acid 22-kilodalton (kDa) form, a 20-kDa variant can be produced by alternative splicing, and a 5-kDa variant can be produced by posttranslational cleavage. To more fully appreciate the physiological roles of these proteins, we have made a comparison of transgenic mice that constitutively overexpress one or another of these variants. We have found that both the 22-kDa and the 20-kDa forms of human GH stimulate linear growth and liver hypertrophy. The increase in linear growth in 22-kDa transgenic mice does not, however, correlate with an increase in circulating IGF-I; rather, the increase in IGF-I that does finally occur correlates with marked liver pathology. Both groups of mice also develop glomerulosclerosis and suffer from hyperinsulinemia. Although there are histologically obvious lesions in the livers of both the 22-kDa and the 20-kDa transgenic mice, only the former exhibit hyperalbuminemia and hypercholesterolemia. Both forms of GH lead to anemia, which is normocytic in the 20-kDa transgenic mice and macrocytic in the 22-kDa transgenic mice. Despite the presence of high levels of the 5-kDa N-terminal form of human GH, the transgenic mice that express this protein are indistinguishable from their nontransgenic littermates.

Animals

Upper airway disease in systemic lupus erythematosus: a report of 4 cases and a review of the literature.

We report the occurrence of life threatening upper airway complications in 4 of 158 patients with systemic lupus erythematosus (SLE) admitted to our hospital over a 6-year period and review published reports on this complication. The patients included in our study were identified through a computer search of our hospital medical records. Patients' charts were reviewed and the diagnosis confirmed by currently accepted criteria. The clinical features of SLE in all the published cases were assessed and compared to those found in our patients. We found that although upper airway involvement is uncommon in SLE, occurring with a relative frequency of 4/158 patient admissions, endotracheal intubation in patients with active SLE may result in the development of life threatening upper airway complications. We suggest that patients with active SLE who require intubation should be observed for the development of upper airway symptoms.

Adult

Illness intrusiveness in rheumatoid arthritis: differential impact on depressive symptoms over the adult lifespan.

Depressive symptoms in rheumatoid arthritis (RA) were hypothesized to derive from illness intrusiveness--illness-induced lifestyle disruptions. Differences over the adult lifespan were also investigated in 110 outpatients with RA, aged 24-78 years who completed standardized psychological tests. A significant Age x Illness Intrusiveness interaction indicated that depressive symptoms intensified more sharply among comparatively younger vs older individuals as the intrusiveness of RA increased. We conclude illness intrusiveness is an important determinant of depressive symptoms in RA. However, its impact may vary over the course of adult psychological development.

Adult

Hominoid dietary evolution.

During the later Palaeocene and early Miocene, catarrhine primates and the evolving hominoids had adaptations for frugivorous diets, with the emphasis on soft foods. Early in the middle Miocene the hominoids underwent a major shift, both in morphology and in habitat, with the morphology characterized by thickened enamel on the molars, enlarged incisors and massive jaws. The diet indicated by this morphology is interpreted as still mainly frugivorous but with changed emphasis, possibly towards harder objects. The thick-enamelled hominoids are found associated with more open forest habitats, and the distribution of food resources in equivalent habitats today is discontinuous both in time and in space, leading to evolutionary pressures particularly affecting locomotion, brain size and social behaviour. The earliest known hominid fossils differed little in dental and mandibular morphology from the middle Miocene apes, and the implied dietary similarity, together with ape-like patterns of dental development and retained arboreal adaptations of the postcrania, suggests little change in the foraging strategies of the earliest hominids compared with their ape ancestors and further suggests similarity in evolutionary grade. This similarity may have extended to other aspects of behaviour, for example to patterns of tool making and use, which may have been similar in the common ancestor of apes and humans to the pattern shared by the earliest australopithecines and chimpanzees.

Animals