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Biomedical subjects

M King

Publications and source records attributed to M King.

At least 289 records · Page 16Linked to original sources
PubMed1990

Variation within and between nucleolar organizer regions in Australian hylid frogs (Anura) shown by 18S + 28S in-situ hybridization.

Five distinct classes of secondary constriction are found in the hylid frogs from the genera Litoria and Cyclorana, each of which is defined by its C-banding pattern and morphology (King, 1980, 1987). In-situ hybridization experiments utilizing 18S + 28S copy RNA probes derived from Xenopus and Drosophila rDNA templates, were made on nine species of frogs possessing the major constriction types. Types 1, 2, 4, and 5 are confirmed as being NORs. These results also indicate that type 1 and 2 constriction types are not differentially despiralized as previously suggested, but show absolute differences in the quantity of ribosomal DNA present. This variation took two forms, deletion polymorphism and amplification polymorphism. These differences were observed between homologues within cells and between cells within individuals. Animals possessing these 'despiralized' constrictions are therefore mosaics for both deletion and amplification polymorphisms. Polymorphism frequencies vary greatly between constriction types. Some specimens have a higher level of presence/absence heterozygosity, (L. moorei, type 2, L. nannotis type 5, L. raniformis (animal A, pair 8 type 2), than do others (L. peronii, L. rothii, L. caerulea). The above species also vary markedly in the degree and frequency of amplification of the NORs. The type 4 constrictions analysed (L. coplandi, L. lesueuri and C. novaehollandiae) have a particularly low frequency of presence/absence heterozygosity, and they have fewer size heteromorphisms between homologues. The type 3 ephemeral constrictions did not hybridize to cRNA probes at any stage. In all but one of the species studied, a single pair of chromosomes possessed an NOR. However, in L. raniformis these occurred on two pairs of chromosomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Characterization of the Fc gamma receptor on human platelets.

IgG-containing immune complexes may play a role in the immune destruction of human platelets by interacting with an Fc gamma receptor on the platelet surface. We studied the platelet Fc gamma receptor and characterized its interaction with IgG ligand and anti-Fc gamma receptor monoclonal antibodies. Oligomers of IgG, but not monomeric IgG, bound to platelets and the number of binding sites was significantly increased at low ionic strength. Ligand-binding studies indicated that normal human platelets express a single Fc gamma receptor (Fc gamma RII) with 8559 +/- 852 sites per cell, Kd = 12.5 +/- 1.7 X 10(-8) M using trimeric IgG. Results of studies with bivalent and Fab monoclonal anti-Fc gamma RII were consistent with each Fc gamma receptor expressing two epitopes recognized by the antibody. The number of Fc gamma binding sites and affinity of binding were unchanged by the presence of 2.0 mM Mg2+ or 10 micrograms/ml cytochalasin B. Platelet stimulation with thrombin or ADP in the presence of fibrinogen also did not alter the number of Fc gamma binding sites or the affinity of binding. However, platelets preincubated with 5 microM dexamethasone expressed a decreased number of Fc gamma binding sites as well as decreased IgG-dependent platelet aggregation. Platelets from patients with Glanzmann's thrombasthenia and from patients with the Bernard Soulier syndrome expressed a normal number and affinity of Fc gamma binding sites. The data suggest that platelet Fc gamma RII binding of trimeric IgG occurs independent of actin filament interaction, Mg2+, ADP, or thrombin and does not require GPIIb/IIIa or GPIIb/IIIa-fibrinogen interaction. Furthermore, this receptor appears to be normally expressed on GPIb-deficient platelets and susceptible to modulation by glucocorticoids. Finally, the Fc gamma-binding protein was isolated from whole platelets as a 220-kDa protein which upon reduction dissociates into 50,000 Mr subunits.

Adult↗
PubMed1990

Tumor trapping of 5-fluorouracil: in vivo 19F NMR spectroscopic pharmacokinetics in tumor-bearing humans and rabbits.

The pharmacokinetics of 5-fluorouracil (5FU) were studied in vivo in patients with discrete tumors and in rabbits bearing VX2 tumors by using 19F NMR spectroscopy. The human studies were conducted in a 1.5-T Magnetom magnetic resonance imager (Siemens), and the rabbit studies were conducted in a 4.7-T GE/Nicolet 33-cm bore magnet. Free 5FU was detected in the tumors of four of the six patients and in all VX2 tumors but not in normal rabbit tissues. No other metabolites were seen in these tumors, contrary to the extensive catabolism we had previously documented using 19F NMR spectroscopy in both human and animal livers. The tumor pool of free 5FU in those human tumors that trapped 5FU was determined to have a half-life of 0.4-2.1 hr, much longer than expected and significantly longer than the half-life of 5FU in blood (5-15 min), whereas the half-life of trapped 5FU in the VX2 tumors ranged from 1.05 to 1.22 hr. In this initial experience, patient response to chemotherapy may correlate with extent of trapping free 5FU in the human tumors. These studies document that NMR spectroscopy is clinically feasible in vivo, allows noninvasive pharmacokinetic analyses at a drug-target tissue in real time, and may produce therapeutically important information at the time of drug administration. Demonstration of the trapping of 5FU in tumors provides both a model for studying metabolic modulation in experimental tumors (in animals) and a method for testing modulation strategies clinically (in patients).

Adenocarcinoma↗
PubMed1990

Inhaled particle deposition and body habitus.

As a result of the intrapleural pressure gradient that exists in the human lung, both ventilation and particle deposition increase from apex to base. Since the intrapleural gradient varies with the height of the subject, it was decided to compare regional particle deposition in tall, short, and obese subjects to ascertain whether it was influenced by height and weight. Surprisingly, deposition in the vertical plane was not significantly influenced by the height of the subject when corrected for ventilated lung volume. In addition, it was shown that in obese subjects there was increased deposition in the middle zones relative to the apices and bases. This finding persisted after correction for ventilated lung volume and differential attenuation resulting from non-uniform thickness of the fat layer in the obese subject's chest. In the tall and short groups there was a consistent pattern in the concentric deposition of particles with there being a gradient from the central or hilar region to the periphery of the lungs, with the latter showing the most deposition.

Adipose Tissue↗
PubMed1990

Resorptive clearance and transepithelial potential difference in capsaicin-treated F344 rats.

The long-term effects of substance P (SP) depletion on epithelial integrity were assessed by measurements of airway transepithelial potential difference (PD) and resorptive clearance. Both techniques are highly sensitive to differences in epithelial permeability. PD (mV) was assayed with a KCl-saturated agar bridge technique in the lower trachea of Fischer 344 rats depleted of SP by neonatal capsaicin treatment. Capsaicin treatment is known to ablate a subpopulation of primary afferent fibers containing SP. Resorptive clearance (clearance in 1 h) was measured with 99mTc-labeled diethylenetriaminepentaacetic acid administered as a 100-microliters (100 microCi) bolus. Depletion of SP by neonatal treatment with capsaicin resulted in a highly significant increase in resorptive clearance (P less than 0.001). There was also a significant difference in PD in the lower trachea, the values being less negative for the capsaicin-treated rats (P less than 0.005). The increase in resorptive clearance may reflect the leakiness of the epithelial membrane, as also suggested by the decrease in PD. Aside from its known involvement as a neurotransmitter in neurogenic inflammation, SP may, under normal physiological conditions, have an additional role in the maintenance of epithelial barrier function.

Animals↗
PubMed1990

Mucus-depleted frog palate as a model for the study of mucociliary clearance.

To better understand the frog palate model of mucociliary transport, we measured the transport rate of mucus (MTR) from the leopard frog, Rana pipiens, and from the bullfrog, R. catesbeiana, recorded the stability of the MTR over a period of hours and days and over the course of 1 yr, and measured the viscoelasticity, percent solid composition, and spinnability (filance) of mucus from both species. Bullfrog mucus was less rigid than leopard frog mucus (log G* at 1 rad/s 2.09 vs. 2.61; P less than 0.01) and had a higher viscosity-to-elasticity ratio (tan delta at 1 rad/s 0.36 vs. 0.26; P less than 0.05). It also had a lower solids content (8.71 vs. 13.72%; P = 0.02), and there was a trend to lower spinnability for bullfrog mucus (filance 26.7 vs. 33.5 mm). These data suggest that bullfrog mucus has viscoelastic properties similar to normal mammalian respiratory mucus and leopard frog mucus has viscoelasticity similar to sputum samples. MTR was significantly slower in the winter than in the summer months (17 vs. 30 mm/min; P less than 0.0001). Although the leopard frog palate could be used for at least 7 consecutive days without exhaustion, bullfrog palates could be used for only 5 days. Palates of either species could generally be tested for 6 h/day without a significant decrease in MTR. These data clarify some of the sources of variability in the use of this system and suggest methods of standardization.

Animals↗
PubMed1990

Acute and long-term amiloride inhalation in cystic fibrosis lung disease. A rational approach to cystic fibrosis therapy.

Cystic fibrosis (CF) is the most common inherited fatal disorder among Caucasians. Bronchial mucus in CF contains more potassium and less sodium, which may be due to increased sodium absorption, resulting in a reduced airway water content. We studied 23 patients with CF after inhalation of normal saline or amiloride (10(-3) M), a sodium transport blocker. Mucociliary clearance (MC) and cough clearance (CC) were determined with a gamma camera that traced the movement of 99mTc-labeled, hardened erythrocytes over a 1-h period after the patients inhaled these particles as an aerosol. Before and after each investigation pulmonary function tests (PFT) and blood pressure (BP) were measured. Sputum thread formation was measured by means of a filancemeter. Six of the patients also completed a 3-wk trial of amiloride inhalation therapy. MC increased significantly (p less than 0.001) after acute amiloride inhalation (bronchial deposition, 0.07 mg amiloride) compared with that in the saline control. CC also increased, but not as much as MC. After 3 wk of amiloride inhalation (2 times a day) clearance values (both MC and CC) were markedly enhanced (p less than 0.01); after a similar period of saline inhalation, clearance values were not different from baseline. Sputum filance values also decreased significantly after amiloride inhalation. There were no adverse effects of the amiloride inhalation compared with saline. We conclude that amiloride inhalation administered as a single dose or as long-term therapy is able to increase MC and CC in CF airways and that the effect of 10(-3) M amiloride inhalation on MC lasts at least 40 min. (ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1990

Collection and analysis of respiratory mucus from subjects without lung disease.

We collected the respiratory mucus coating the endotracheal tubes used during short surgical procedures in 27 patients with no clinical evidence of respiratory disease. Twelve were male and 15 were female, and they ranged from 1 to 64 yr of age (mean, 28.7 yr). The viscoelastic properties, frog palate transport rate, and percent solid composition were in the normal range reported for both canine and human mucus collected using the bronchoscopy brush technique. There were no significant differences noted between male and female patients, and there were no changes in mucus or transport properties seen with aging. Mucus was also collected separately from the inside of the tube exposed to constant gas flow (13 patients), and from the outside of the endotracheal tubes in 25 patients. Although there were no significant differences in viscoelastic properties between inside and outside mucus, there was a greater thread formation (filance, 45 versus 26 mm; p less than 0.005) and a higher percentage of solids in mucus from the inside of the endotracheal tube (15.9 versus 11.4%; p less than 0.05), which is compatible with reduced hydration. The duration of anesthesia ranged from 25 to 195 min (mean, 85 min). There was no effect of duration of anesthesia on any of the measured mucus properties. This technique for mucus collection allows us to study alterations in mucus properties in patients with and without pulmonary disease at the time of incidental surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Tracheal mucus rheology in patients undergoing diagnostic bronchoscopy. Interrelations with smoking and cancer.

We examined the differences in tracheal mucus rheology between nonsmokers and smokers, and between smokers with and without lung cancer. Mucus was collected from patients undergoing diagnostic bronchoscopy without atropine by holding a cytology brush in contact with the tracheal mucosa for 10 to 15 s. Samples were obtained from 43 patients 24 to 79 yr of age: nine nonsmokers, 18 current smokers, and 16 exsmokers (greater than 6 months); 12 patients (nine smokers, three exsmokers) had lung cancer. Pulmonary function testing showed that the nonsmoker patients had significant restrictive lung disease, and the patients with cancer had significant irreversible airway obstruction. The viscoelastic properties of the mucus samples were determined by magnetic microrheometry. Two parameters are reported: G* (modulus of rigidity) and tan delta (loss tangent), each measured at 1 and 100 rad/s. G* is an index of overall deformability (elastic and viscous), and tan delta is the ratio of viscous to elastic deformability. For nonsmoker patients, the viscoelastic parameters were virtually identical to those found previously for normal volunteers. For smokers without cancer, the mucus had a lower value of tan delta 1 rad/s and therefore was predicted to be more easily transportable by ciliary action; for exsmokers without cancer, ciliary transportability as calculated from viscoelasticity was even higher because of both low tan delta and low G*. Mucus from patients with cancer was not significantly different from that of nonsmokers; however, the mucus was predicted to be less easily clearable by ciliary action than was that from smokers and exsmokers without cancer, mainly because of a higher tan delta at 1 rad/s.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Cellularity of the alveolar walls in smokers and its relation to alveolar destruction. Functional implications.

Inflammatory cells are believed to play an important role in the pathogenesis of emphysema; however, a relationship between presence of cells in the lung parenchyma and its destruction has never been shown. The aim of this study was to quantitate alveolar septal cellularity in smokers' lungs and to investigate its relationship with parenchymal destruction and lung function. The lungs of 23 smokers (SS) undergoing thoracotomy for localized pulmonary lesions were compared with those of eight nonsmokers (NS) and five smokers (AS) who died suddenly of nonrespiratory causes. Pulmonary function tests were performed within 1 wk of surgery in SS. For each subject, we quantitated alveolar wall cells (CELLS), an index of alveolar wall destruction (DI), and the mean linear intercept (Lm). As no significant differences were found between S and AS with regard to these indices, we combined them (Group S) for comparison with NS. Although Lm was not significantly different between S and NS, (0.331 +/- 0.072 versus 0.288 +/- 0.038), CELLS and DI were higher in S than in NS (48 +/- 8 versus 25 +/- 2 cells/mm, p less than 0.001; 47 +/- 20 versus 17 +/- 5, p less than 0.001, respectively). Further, CELLS and DI were significantly correlated (r = 0.799, p less than 0.001). The number of polymorphonuclear cells (PMN) in S can exceed that in NS by as much as 5-fold; however, PMN were inversely correlated with parenchymal destruction (DI) (r = 0.598, p less than 0.01). Thus, smokers' lungs have alveolar septal hypercellularity, possibly inflammatory, and closely related to destruction involving cells other than the PMN.

Aged↗
PubMed1990

Human tumor fluorouracil trapping: clinical correlations of in vivo 19F nuclear magnetic resonance spectroscopy pharmacokinetics.

We previously reported that fluorouracil (5FU) accumulation and metabolism in human livers and tumors can be studied by in vivo nuclear magnetic resonance spectroscopy (NMRS). We have extended these observations by evaluating the pharmacokinetics of 5FU in the tumors of 11 patients with carcinoma of the breast, colon, endometrium, cervix, and kidney, using 19F-NMRS in a 1.5 Magnetom (Siemens Medical Systems, Cerrito, CA) magnetic resonance imaging unit (MRI). These NMRS measurements detected a long-lived tumor pool of 5FU in six of 11 tumors in our patients including carcinomas in the pelvis, breast, lung, and liver. The half-life (T1/2) of this tumor pool of "trapped" 5FU was 0.33 to 1.3 hours (20 to 78 minutes), much longer than the T1/2 of 5FU in blood (5 to 15 minutes). Neither the anabolites of 5FU (fluorinated nucleosides, nucleotides, 5FU-RNA, or 5FU-thymidylate synthase) nor the catabolites (eg, fluorobetaalanine [FBAL]) were detectable by 19F NMRS. Patient response to chemotherapy appeared to correlate with the extent of trapping of free 5FU in the human tumors: in the seven patients receiving 5FU, or 5FU or FUdR plus leucovorin, four of four patients whose tumors trapped 5FU responded to fluorinated pyrimidine chemotherapy, whereas three patients in whom there was a failure to detect tumor trapping were resistant to 5FU. We conclude that NMRS is clinically feasible, and enables investigators to study 5FU pharmacokinetics and metabolism in tumors in vivo. 19F-NMRS of 5FU allows for in vivo evaluation of 5FU metabolic modulation and might be able to guide therapeutic decisions.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

General anesthesia does not alter the viscoelastic or transport properties of human respiratory mucus.

Observations that mucus transport rates (MTR) are depressed in anesthetized animals and humans have led to speculation that general anesthesia depresses ciliary activity or adversely alters the physical properties of the respiratory mucus (RM). We investigated the possibility that anesthesia changes the physical properties of RM in such a way as to depress ciliary transport. We collected 33 samples of RM from the endotracheal tubes (ETTs) of 25 people aged 1 to 79 years undergoing elective surgery who had no clinical evidence of lung disease. We measured the rigidity, viscoelasticity, spinnability, and the percentage of solid composition of these specimens as well as the transport of the collected RM across the mucus-depleted frog palate. These physical properties were not significantly different from RM collected from awake volunteers using the bronchoscopy brush collection technique. Differences in spinnability, transportability, and solid content of paired mucus samples from the inside and outside of the ETTs are suggestive of altered RM hydration, but this requires further study. The decrease in MTR during general anesthesia is probably due to mechanisms other than alterations in the physical properties of mucus.

Adolescent↗
PubMed1990

Tracheal mucus rheology and epithelial potential difference in two day old puppies.

The transepithelial potential difference (PD) value represents an integral of ion fluxes across the epithelium, and relates to the regulation of airway fluid. We studied six healthy two day old husky puppies for their tracheal mucus rheology and bioelectric properties, since this data in newborns are still unknown. PD (-mV, epithelium vs. subcutaneous space) was measured using the agar bridge technique in two locations - lower trachea and subglottic region. For the rheological analysis, the magnetic microrheometer was employed; data are presented as mechanical impedance log G* and loss tangent tan delta (1 rad/s). The mucus collection rate (mg/min) and the solid content (%) were determined by gravimetry. Mucociliary clearability, normalized to frog mucus, (MCFP) was determined directly by the frog palate method; a cough clearability index (CCI) was computed from simulated cough machine data obtained with mucus-like gels. The mucus collection rates and PD values were considerably lower than those observed in adult dogs; the mechanical impedance values were also reduced in comparison with adult data. The PD profile within the trachea (-13.9 +/- 1.2 mV lower trachea vs. -18.4 +/- 1.4 mV subglottical, i.e. more negative subglottically), however, is similar to that observed in adult dogs. Intratracheal profiles in mucus collection rate and mucus rheology were also comparable between puppies and adult dogs. The low collection rates in puppies, particularly in lower trachea, could indicate either reduced mucus volume or slower clearance. PD and collection rate correlated very strongly (r = 0.82, p = 0.0003). PD also correlated negatively with log G* (r = 0.73, p = 0.003) and positively with tan delta (r = 0.58, p = 0.03). MCFP and % solids correlated positively (r = 0.84, p = 0.0012), in contradistinction to the usual relationship, perhaps due to the presence of non-glycoprotein components that do not contribute to crosslink formation. The apparent maturation of airway bioelectric properties, mucus collection rate and mucus viscoelasticity are all consistent with the maturation of mucociliary clearance, which has previously been reported.

Animals↗
PubMed1990

Diagnosis of vasa previa with transvaginal and color flow Doppler ultrasound.

Vasa previa, which is associated with high fetal mortality, is present when fetal vessels cross the internal cervical os as a velamentous insertion of the umbilical cord with or without a succenturiate lobe or bilobate placenta. This is the first case report of vasa previa not associated with a succenturiate lobe or bilobate placenta and in which the diagnosis was made using a combination of transvaginal ultrasonography and color flow Doppler ultrasound. The infant was delivered by elective cesarean, and the ultrasound findings were confirmed. Color flow Doppler and transvaginal ultrasound facilitate this diagnosis because the internal os and surrounding structures are easier to visualize; in addition, vascular flow and Doppler patterns characteristic of the umbilical cord can be demonstrated in structures suspected to be vessels.

Adult↗
PubMed1990

Swellengrebel lecture. Public health and the ethics of sustainability.

Hitherto, the danger of population increase has never been a constraint on public health programmes. Do we need to rethink this, now that population increase is causing communities to destroy their local ecosystems? 'Sustainability' is now the critical goal. The influence of falling child mortality in reducing fertility, which has been much promoted by UNICEF, is disputed. Our ethical premisses, particularly the absolute value of each human being, and the integrity of the ecosystem, conflict. If public health programmes are desustaining, they need to be balanced by complementary sustaining ones. Desustaining public health programmes should not be introduced just because they are possible. WHO's definition of health should be amended so that "Health is a sustainable state of ...". If this were to happen, a healthy lifestyle would have also to be a sustainable one.

Conservation of Natural Resources↗
PubMed1990

Tracheal mucus clearance in high-frequency oscillation: effect of peak flow rate bias.

We have reported previously that high-frequency oscillation of the chest wall (HFO/CW) enhances the tracheal mucus clearance rate (TMCR) in dogs. This enhancement of TMCR may be due in part to the expiratory bias in peak flow rate (VE/VI greater than 1) that occurs during HFO/CW. We examined this factor in 8 anaesthetized, spontaneously breathing dogs by comparing TMCR during the following manoeuvers: 1) HFO/CW, applied by means of a thoracic cuff; 2) symmetric high-frequency oscillation via the airway opening (HFO/AO), applied by means of a piston pump driven by sinusoidal signal; 3) HFO/AO with an expiratory bias in peak flow, and 4) HFO/AO with an inspiratory bias in peak flow. All manoeuvers were of 5 min duration and were performed at 13 Hz and an oscillatory tidal volume of 1.5 ml.kg-1. In the latter two manoeuvers, the piston pump was driven by a nonsinusoidal signal such that peak VE/VI was greater than and less than unity, respectively. A high-impedance, cross-current flow of warmed, humidified air was provided at the tracheal tube. The order of manoeuvers 2, 3 and 4 was randomized, while manoeuver 1 was repeated at the end. TMCR was determined by direct bronchoscopic visualization of charcoal particle transport. Each HFO manoeuver was bracketed by a control period of spontaneous breathing. We found that TMCR during HFO/CW was 2.4 x control (p less than 0.001), in line with previous results.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗