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Biomedical subjects

D J Smith

Publications and source records attributed to D J Smith.

At least 271 records · Page 15Linked to original sources
PubMed1992

Ontogeny of immunity to oral microbiota in humans.

This article reviews the ontogeny of immune systems in the human oral cavity that may influence the colonization, accumulation, or pathogenesis of oral microbiota. The prenatal development of cellular components associated with the secretory immune system reveals that the initial organization of tissue into Peyer's patches can first be detected immunohistologically at 11 weeks gestation. Epithelial cells positive for secretory component and immunocytes positive for IgM can be detected in salivary gland tissue by 19 to 20 weeks and continue to predominate during gestation. After birth, immunocytes containing IgA begin to dominate. Essentially, no IgA can be detected in saliva at birth. However, salivary IgA and IgM often appear soon thereafter, presumably in response to environmental antigenic and mitogenic challenges. Salivary IgA in young infants has molecular characteristics of secretory IgA and becomes the quantitatively predominate Ig in saliva. Both IgA subclasses are present in proportions characteristic of adult pure glandular salivas in many 1- to 2-month-old infants, although the appearance of IgA2 is delayed in some subjects. Many innate, antibody, and cellular immune components are found in maternal colostrum and breast milk. The antibacterial properties of these maternal factors are diverse and can exert multifaceted protective effects on the infant's alimentary tract. The infant apparently can mount mucosal immune responses quite early in life. For example, salivary antibody activity to organisms that originally colonize the gut (e.g., E. coli) or the oral cavity (e.g., S. mitis, S. salivarius) can be detected by 1 to 2 months of age. Most of this antibody activity has characteristics of secretory IgA, although some IgM antibody can also be initially detected. Salivary IgA1 and IgA2 antibody specificities to S. mitis and S. salivarius components increase qualitatively and quantitatively during the first few years of life. Salivary IgA antibody to components of streptococci that require hard surfaces for colonization (e.g., S. sanguis and mutans streptococci) generally appear after tooth eruption. The loss of placentally derived maternal IgG antibody specificities to these microbiota in the circulation is replaced by de novo synthesis, presumably as a result of the teething process. These IgG antibodies can enter the oral cavity in the gingival crevicular fluid and by the process of teething.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacteria↗
PubMed1992

Inhibition of human and rabbit liver steroid and xenobiotic UDP-glucuronosyltransferases by tertiary amine drugs--implications for adverse drug reactions.

1. To investigate the hypothesis that disruption of glucuronidation of endogenous compounds by drugs represents a potential mechanism for pathogenesis of adverse drug reactions, the effects of a range of tertiary amine and amide drugs (many with effects on sex hormone function) on steroid hormone and xenobiotic UDP-glucuronosyltransferase activities in human and rabbit liver microsomes were studied in vitro. 2. Chlorpromazine, amitriptyline, imipramine, promethazine and cyproheptadine were consistently the most potent inhibitors of the glucuronidation of testosterone, androsterone, oestriol and 1-naphthol, the steroid activities being more susceptible to inhibition (up to 90%). 3. Carbamazepine, diphenhydramine, sulphadimethoxine, dimenhydrinate and (+/-)-chlorpheniramine had little effect on the UDPGT activities measured. 4. The structural features within this group of compounds required for inhibitory potency were the presence of a rigid tricyclic ring (e.g. phenothiazine) and either a dimethylaminopropyl or a methylpiperidine side-chain. 5. The implications of these data for involvement of disruption of the normal cellular function of glucuronidation in the pathogenesis of frequently observed adverse side-effects associated with these compounds are discussed.

Amines↗
PubMed1992

Effect of a high concentration perfluorocarbon emulsion on platelet function.

Perfluorocarbon (PFC) and lipid emulsions (eg. Fluosol, Intralipid,) containing phospholipid have been reported to modify platelet function after intravenous infusion. Platelet activation might be responsible for the generation of mediators responsible for PFC-induced side effects. In view of this, we investigated the effect of a highly concentrated perfluorocarbon emulsion containing 90% (w/v) perfluorooctylbromide (perflubron; PFOB), on porcine and human platelet activation and function. We measured both: a) stimulated ex-vivo porcine platelet aggregation pre and post infusion of either perflubron or control (vehicle only) emulsions, and b) stimulated in vitro human platelet calcium flux in the presence of perflubron emulsion or control emulsions. Platelet aggregation stimulated by collagen, ADP or arachidonic acid (AA) was inhibited in ex-vivo porcine platelets following infusion of perflubron emulsion at a dose of 3 ml/kg (0.2 ml/kg/min). Inhibition was dose dependent and was decreased when the dose of perflubron emulsion was reduced to 1.0 or 0.3 ml/kg. Infusion of saline or "vehicle" emulsions had little or no effect on stimulated ex-vivo pig platelet aggregation. Fluosol, infusion was associated with inconsistent inhibition of platelet aggregation. A23187- or AA-stimulated calcium flux of human platelets in vitro was inhibited in the presence of 1% (v/v) perflubron emulsion. Similar effects were seen with Fluosol, or Intralipid. This inhibition was agonist dose-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Pneumothorax as a complication of recompression therapy for cerebral arterial gas embolism.

The danger from pneumothorax in patients who undergo compression chamber treatment for cerebral arterial gas embolism (CAGE) following pulmonary barotrauma is frequently emphasized. Two cases of CAGE treated by recompression after submarine escape tank training (SETT) accidents are described. Both were complicated by bilateral pneumothoraces but the first case, treated on an air table, required thoracentesis in the chamber, whereas the second case, treated on an oxygen table, escaped the need for in-chamber thoracentesis despite large pneumothoraces. Review of similar Royal Navy and United States Navy SETT accidents suggests that the danger from pneumothorax during recompression treatment of CAGE victims may be overstated. Modern management on oxygen-based therapeutic recompression tables may significantly reduce the risk. Thoracentesis while under pressure should be reserved for cases developing symptoms or signs of tension pneumothorax. Treatment options for these cases are discussed and a decision algorithm is proposed.

Atmosphere Exposure Chambers↗
PubMed1992

Training at moderate altitude: iron status of elite male swimmers.

Laboratory evidence of suboptimal iron status is endemic in chronically training athletes, yet the importance of low serum ferritin values to athletic performance is unclear. The purpose of this study was to monitor iron status in nine male elite swimmers during and after a 3-week training camp at 2225 m altitude. Values for hemoglobin, hematocrit, serum iron, serum transferrin, and transferrin saturation were within the normal range and remained unchanged over the 54-day monitoring period. Serum ferritin level was significantly decreased by day 13 and continued to decline over the period at altitude. Significant recovery was observed by day 35, by which the workload and altitude were reduced. Reticulocyte counts were raised above normal values by the fifth day at altitude and remained elevated for the duration of the study, indicating increased erythropoiesis. In contrast, neither ferritin levels nor reticulocyte counts were changed in six of the nine subjects after 1 month's training at 1000 m. Food histories revealed dietary iron intakes two to three times as great as the recommended dietary allowance for iron. The draw on body iron reserves observed in this study over the heavy training period at moderate altitude indicates that adequate iron stores are necessary to provide a reservoir of iron during periods of increased iron utilization or loss. Further work is required to elucidate the sources and endpoints of the observed iron flux.

Adult↗
PubMed1992

Making the burned hand functional.

The goal of treatment of the burned hand is to make the hand functional at the conclusion of treatment. Function should ideally include both fine pinch and power grip but will ultimately be determined by the individual patient's needs. At no time, however, can the care of the burned hand be performed in a vacuum, losing sight of the patient as a whole. It must also be remembered that the hand functions as part of the upper extremity. Full hand motion is useless if significant contractures of the elbow or axilla prevent the patient from positioning the hand so that this motion can be utilized. Rehabilitation must render the entire extremity functional. Thus, it becomes obvious that a team effort is mandatory. This usually will include the following individuals: physician, nurse, occupational therapist, physical therapist, vocational rehabilitation counselor, and social worker. A functional upper extremity means that the goal must be to return patients to their preburn vocations and avocations. A clear understanding of job requirements and work habits will allow realistic goals to be established. However, when the goal of optimal function cannot be reached, early retraining will help to obtain optimal rehabilitation.

Acute Disease↗
PubMed1992

Reconstruction of burns of the trunk and breast.

This article discusses the pathogenesis and reconstruction of hypertrophic scarring of the burned trunk. General reconstruction schemata are provided. Reconstruction of specific problems of the chest, abdominal wall, breasts, and perineum are also discussed.

Adult↗
PubMed1992

Xanthine oxidase: its role in the no-reflow phenomenon.

This study was designed to probe the hypothesis that oxygen-derived free radicals are involved in initiation of the no-reflow phenomenon. We developed a reproducible model of no reflow in the rat hind limb. Laser Doppler studies confirmed that the hind limbs perfused well after 2 or 4 hours of ischemia, but perfusion ceased in the first 10 minutes after 6 hours of ischemia. Venous blood samples and biopsy specimens of skin and muscle were taken after 2 and 4 hours of ischemia to study tissue injury. Blood samples were evaluated for xanthine oxidase (XO), xanthine dehydrogenase, and creatine phosphokinase (CPK) activities. Conjugated dienes and iodine 125-labeled albumin extravasation were quantified in tissue samples. Groups of animals were treated with inhibitors of XO (allopurinol), antioxidant enzymes (superoxide dismutase plus catalase), and free radical scavengers (dimethyl sulfoxide and dimethyl thiourea) to assess the roles of free radicals in ischemia-reperfusion injury in the hind limbs. After 4 hours of ischemia followed by reperfusion, plasma XO activity rose threefold over preischemia levels (p less than 0.05). Xanthine dehydrogenase activity did not change; conjugated diene levels in muscle rose twofold; CPK levels rose sixfold, and 125I albumin extravasation rose twofold (p less than 0.05). Pretreatment with the XO inhibitor allopurinol reduced XO activity to negligible levels and significantly attenuated conjugated diene levels, CPK levels, and albumin extravasation. Albumin extravasation was also significantly attenuated by pretreating animals with superoxide dismutase together with catalase, dimethyl thiourea, and dimethyl sulfoxide. In all animals pretreated with allopurinol or superoxide dismutase and catalase, reperfusion persisted after 6 hours of ischemia. These data suggest that, in ischemia followed by reperfusion, tissue injury is related to oxygen products derived from XO activity.

Allopurinol↗
PubMed1992

Effects of extraerythrocytic hemoglobin and its components on mononuclear cell procoagulant activity.

Earlier studies performed in rabbits in this laboratory showed that human hemoglobin causes leukocyte infiltration into heart and lung tissues and coagulation abnormalities including thrombosis. Since stimulation of peripheral blood mononuclear cells induces procoagulant activity, we investigated the possibility that isolated peripheral blood mononuclear cells from humans and rabbits were stimulated by hemoglobin to produce a procoagulant activity response. Stroma-free hemoglobin and its purified components were assayed for their stimulatory effect on peripheral blood mononuclear cells. The added effect of endotoxin contamination was also explored. A significant dose-dependent effect of stroma-free hemoglobin on procoagulant activity was found with both human and rabbit peripheral blood mononuclear cells, but rabbit cells were found to be 50-fold more sensitive than human cells. Hematin, methemoglobin, and purified hemoglobin Ao elicited procoagulant activity effects with human peripheral blood mononuclear cells, but isolated globin did not. We also studied the effects of these compounds on activation of complement, a known mediator of the procoagulant activity response. Stroma-free hemoglobin, hematin, purified hemoglobin Ao, and methemoglobin were all found to cleave complement fraction C3 to C3a but at concentrations much higher than those required for procoagulant activity. The data suggest that heme itself may be responsible for the procoagulant effect of stroma-free hemoglobin solutions.

Animals↗
PubMed1991

Evaluation of the interactions of serotonergic and adrenergic drugs with mu, delta, and kappa opioid binding sites.

Several serotonergic and adrenergic agents were tested for an ability to interact with mu, delta, and kappa opioid binding sites. Spiroxatrine interacted nearly equipotently with all three opioid subtypes, yielding Ki values near 110 nM. A number of other serotonergic and adrenergic agents interacted with affinities in the 1-50 microM range. Most of the other compounds tested in this study were found to compete for opioid binding to some degree, though not achieving a 50% inhibition of binding at concentrations up to 100 microM. If this interaction between monoaminergic agents and opioid receptors is found to have functional significance, it must be considered in the interpretation of results from studies using these agents to evaluate the contribution of monoaminergic systems to opioid-mediated events.

Animals↗
PubMed1991

Expression and characterization of recombinant human ciliary neurotrophic factor from Escherichia coli.

The gene for ciliary neurotrophic factor (CNTF) was cloned from a human genomic DNA library by screening with a DNA fragment amplified from human genomic DNA using the polymerase chain reaction. A DNA sequence coding for human CNTF was placed under control of an regulatable promoter in the expression vector pJU1003 and transformed into Escherichia coli strain BL21(DE3). Induction of expression in cultures of this transformant led to the accumulation of approx. 25 mg/l per A600 unit of human CNTF. CNTF was purified to homogeneity from cell lysates via anion-exchange, cation-exchange and Zn(2+)-affinity chromatography. Purified CNTF contained less than 0.1% contaminating E. coli proteins, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), Western blot analysis and reversed-phase high-pressure liquid chromatography (HPLC). The protein exhibited an ultraviolet absorption maximum at 279 nm with a calculated extinction coefficient of A1%(279) = 9.0. Peptide map and amino acid sequence analyses confirmed that the expressed protein has the amino acid sequence expected for human CNTF, except for the absence of the amino-terminal methionine. High-purified recombinant human CNTF supported the survival of chick embryo parasympathetic, sympathetic and sensory neurons in culture at low picomolar concentrations. These results indicate that the biological activities previously ascribed to impure CNTF preparations indeed reside in one molecule.

Amino Acid Sequence↗
PubMed1991

The local monoaminergic dependency of spinal ketamine.

The effects of s.c. doses of naloxone, methysergide and phentolamine on ketamine-induced spinal analgesia were assessed to determine the involvement of opiate, serotonergic and noradrenergic components mediating ketamine's antinociceptive action. Ketamine administered intrathecally (i.t.) produced a significant elevation in tail-flick latency in rats. The spinal antinociceptive effects of ketamine were dose dependently reversed by methysergide (ID50 = 0.008 mg/kg s.c.), phentolamine (ID50 = 0.88 mg/kg s.c.) and naloxone (ID50 = 3.0 mg/kg s.c.). Unlike morphine, which remains analgesic and dependent on opiate interactions following bilateral lesions of the dorsolateral funiculus (DLF), ketamine analgesia was absent following DLF lesions. Thus, ketamine appears to produce an antinociceptive response which is dependent upon the neuronal activity of the descending pain-inhibitory pathways. The monoaminergic components comprising the descending pathways appear to be more prominent in the action of ketamine than they are in the spinal action of morphine. Furthermore, the spinal opioid receptors involved in ketamine's effect may be different from the mu subtype preferred by morphine.

Analgesia↗
PubMed1991

Modulation of IgM antibody formation by lipid peroxidation products from burn plasma.

Lipid peroxides (conjugated dienes) have been shown to increase in the plasma of thermally injured animals and in humans. The purpose of this study was to determine if conjugated diene-rich fractions extracted from the plasma of burned rats 3 hours after injury would alter humoral immune function in unburned animals. Plasma diene extracts from burned or normal rats were dissolved in ethanol and given intraperitoneally to Long-Evans rats. Fifteen minutes after diene injection, the rats were immunized with sheep erythrocytes. Five days later, serum and spleen cells obtained from these immunized rats were tested for IgM immunity against sheep erythrocytes. Both plaque-forming cells from spleen and hemagglutination titers in serum were significantly enhanced in the group treated with dienes obtained from the thermally injured rats. These data suggest that conjugated diene-bearing lipid fractions from burn plasma may modulate immune function and support the concept that humoral immunity is enhanced after thermal injury.

Animals↗
PubMed1991

Isolation of Raja erinacea basolateral liver plasma membranes: characterization of lipid composition and fluidity.

Developing a method for isolating skate (Raja erinacea) basolateral liver plasma membranes, as well as characterizing the lipid composition and fluidity of these membranes, was the primary purpose of this study. Membranes were isolated using self-generating Percoll gradients. Marker enzyme studies indicate that this preparation is highly enriched in the basolateral domain of the liver plasma membrane and largely free of contamination by intracellular organelles or canalicular membranes. Further, these membranes contain the agency responsible for Na(+)-dependent alanine transport. This finding indicates that this membrane preparation will be useful for the study of skate liver plasma membrane transport processes. The lipid composition and fluidity (as assessed by the fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene) of the skate basolateral liver plasma membrane shows little variation among preparations. Further, DPH anisotropy plotted as a function of temperature yields a straight line (r = 0.99) which indicates that there is no lipid phase change in these membranes from 4 degrees to 37 degrees C. The membrane preparation does contain substantial phospholipase A2 activity. The function of this enzyme is, in part, to modify membrane lipid composition and fluidity in response to temperature variations; therefore, this finding suggests that in situ lipid metabolizing enzymes may play a central role in the adaptation of skate basolateral liver plasma membranes to changes in the ambient temperature.

Alanine↗
PubMed1991

Isolation of a mercapturate adduct produced subsequent to glutathione conjugation of bioactivated 3-methylindole.

Bioactivation of the pneumotoxin 3-methylindole (3MI) to a methylene imine intermediate has been demonstrated previously by trapping the electrophile with glutathione in goat lung microsomal incubations. To determine whether the same bioactivation process occurs in whole animals, 3MI was administered to goats, mice, and rats, and the urinary metabolites from these three species were analyzed by HPLC for the presence of the mercapturate that would be expected as the processed and excreted form of the 3MI-glutathione adduct. The mercapturate, 3-[(N-acetylcysteine-S-yl)-methyl]indole (3MI-NAC), was identified in the urine from all three species and was isolated from rat urine for structural identification by uv, NMR, and mass spectrometry. Synthetic 3MI-NAC had uv, NMR, and chromatographic characteristics identical to the isolated metabolite. The presence of this mercapturate in the urine of treated animals unequivocally demonstrates that 3MI is bioactivated to the methylene imine in vivo and that the glutathione adduct is also formed, presumably to detoxify the methylene imine.

Acetylcysteine↗
PubMed1991

Maxillary sinus barotrauma with fifth cranial nerve involvement.

A case of neurapraxia of the infraorbital nerve occurring as a result of maxillary sinus barotrauma in a diver is presented. Existing reports of a similar nature are reviewed and the pathogenesis of cranial nerve involvement in barotrauma is discussed. Guidelines for treatment are suggested.

Adult↗