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Biomedical subjects

R J King

Publications and source records attributed to R J King.

At least 19 recordsLinked to original sources
PubMed1992

Rescue ventilation with high frequency oscillation in premature baboons with hyaline membrane disease.

We tested the hypothesis that high-frequency oscillatory ventilation can be efficacious in hyaline membrane disease (HMD) even after lung injury is established. We compared high frequency oscillatory ventilation (HFOV) rescue (n = 8; 15 Hz; I:E = 1:2) after 8 hours of positive pressure ventilation (PPV) with positive end-expiratory pressure, to continued PPV (control, n = 7) in premature baboons with HMD over a 24 hour period. Ventilator settings and physiologic parameters were recorded hourly. At necropsy (24 hours), lung status pressure-volume curves, alveolar phospholipids (PL), platelet activating factor-like activity (PAF), and lung water were determined. Roentgenographic and morphologic differences in lung inflation were quantified by standard techniques. No intergroup differences were found in heart rate, blood pressures, ventilator settings, FiO2, blood gases, or chest radiographs during the first 8 hours. Both groups had progressive physiologic disease. At 8 hours, HFOV-rescue animals, in contrast to controls, had immediate significant time-related improvements in Pa/AO2 (at the same Paw) and in oxygenation index (Pa/AO2/Paw) lasting for 16 hours. No significant intergroup differences in lung/body weight, lung water, lung mechanics, PL, PAF, or frequency of moderate to severe roentgenographic changes existed at 24 hours. Although all animals had morphologic evidence of HMD, saccular aeration was more uniform and airway dilatation less evident in HFOV rescue (P less than 0.0001). Based on the improved gas exchange, we conclude that HFOV rescue was efficacious in the "late' treatment of HMD, presumably because of the more uniform saccular aeration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Oestrogen receptor gene structure and function in breast cancer.

The mechanisms underlying loss of oestrogen responsiveness in breast cancer are not well-defined. Potential mechanisms include loss of receptor expression, alterations in the oestrogen receptor (ER) gene producing proteins with abnormal function, or changes to receptor-dependent or -independent pathways controlling cell proliferation. Examination by Southern analysis of the ER gene in a series of ER-negative and -positive breast tumour biopsies failed to provide evidence of gross rearrangements and in only one of thirty seven tumour DNA samples was significant gene amplification observed. No restriction fragment length polymorphisms were detected for the restriction enzymes EcoR I, Pst I or Hind III. Methylation of the ER gene as assessed by Hpa II and Msp I restriction enzyme digests varied between tumours but the degree of methylation was not correlated with levels of expression of the receptor protein. Similar findings applied in a series of ER-negative and -positive breast cancer cell lines and clonal lines of MCF-7 cells, which were developed as an in vitro model for the acquisition of oestrogen and antioestrogen resistance. In this model there was no evidence that changes to ER receptor function and/or structure at the level of the ER gene, mRNA, ligand binding, and ability to induce progesterone receptor might account for the development of hormone resistance. However, the ability of ER to interact with a DNA sequence containing the vitellogenin promoter oestrogen response element, as assessed by gel retardation assay, was impaired in the clone showing the greatest degree of oestrogen and antioestrogen resistance.

Base Sequence↗
PubMed1992

Influence of menstrual cycle, parity and oral contraceptive use on steroid hormone receptors in normal breast.

Steroid receptor was assessed immunohistochemically in 158 samples of normal breast for variation through the menstrual cycle. Patterns and intensity of reaction were used in a semi-quantitative scoring system to examine the influence of cycle phase, cycle type, parity and age. The changes in oestrogen receptor for natural cycle and oral contraceptive (OC) cycles indicated down-regulation by progestins. Progesterone receptor did not vary significantly in natural cycles, but increased steadily through OC cycles. This study provides strong evidence that both oestrogen and progesterone influence breast epithelium, but dissimilarities from the endometrium are apparent. The interval since pregnancy had a significant negative effect on frequency and score of oestrogen receptor and score of progesterone receptor. Multivariate analysis established the phase of cycle and OC use as independent significant influences on oestrogen receptor. The interval since pregnancy was an independent significant factor for both oestrogen and progesterone receptor presence.

Age Factors↗
PubMed1992

An associationist model of the paranoid process: application of phase transitions in spreading activation networks.

We propose an associationist model of the paranoid process in which the initial paranoid state is characterized by the formation of cognitive associations among temporally contiguous perceptions, an internally generated explanatory schema is produced to give meaning to the associations, and the schema then becomes learned and perpetuated as a crystallized delusion. We suggest that the genesis of the initial paranoid state can be modeled by a spreading activation network of learning and memory whose parameters of activation spread, including connectivity and relaxation rate, are varying over time. Moreover, recently demonstrated abrupt phase transitions that occur in such networks as a function of connectivity provide a particularly useful means for understanding the process by which an initial paranoid state becomes crystallized into a fixed delusion.

Association Learning↗
PubMed1992

Biodegradation of phenoxyacetic acid in soil by Pseudomonas putida PP0301(pR0103), a constitutive degrader of 2,4-dichlorophenoxyacetate.

The efficacy of using genetically engineered microbes (GEMs) to degrade recalcitrant environmental toxicants was demonstrated by the application of Pseudomonas putida PP0301(pR0103) to an Oregon agricultural soil amended with 500 micrograms/g of a model xenobiotic, phenoxyacetic acid (PAA). P. putida PP0301(pR0103) is a constitutive degrader of 2,4-dichlorophenoxyacetate (2,4-D) and is also active on the non-inducing substrate, PAA. PAA is the parental compound of 2,4-dichlorophenoxyacetic acid (2,4-D) and whilst the indigenous soil microbiota degraded 500 micrograms/g 2,4-D to less than 10 micrograms/g, PAA degradation was insignificant during a 40-day period. No significant degradation of PAA occurred in soil inoculated with the parental strain P. putida PP0301 or the inducible 2,4-D degrader P. putida PP0301(pR0101). Moreover, co-amendment of soil with 2,4-D and PAA induced the microbiota to degrade 2,4-D; PAA was not degraded. P. putida PP0301-(pR0103) mineralized 500-micrograms/g PAA to trace levels within 13 days and relieved phytotoxicity of PAA to Raphanus sativus (radish) seeds with 100% germination in the presence of the GEM and 7% germination in its absence. In unamended soil, survival of the plasmid-free parental strain P. putida PP0301 was similar to the survival of the GEM strain P. putida PP0301(pR0103). However, in PAA amended soil, survival of the parent strain was over 10,000-fold lower (< 3 colony forming units per gram of soil) than survival of the GEM strain after 39 days.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1992

Surfactant proteins and lipids are regulated independently during hyperoxia.

Adult hamsters were exposed to 100% oxygen for up to 8 days. At time of death lung tissue was analyzed for the expression of surfactant protein (SP) genes, and surfactant was isolated from alveolar lavage fluid. Surfactant was analyzed for the composition of proteins and phospholipids and for its surface properties. We found, over the 8 days of exposure, that an alveolitis composed of polymorphonuclear leukocytes (PMNs) and alveolar macrophages, accompanied by exudation of edema fluid, appeared in the alveolar spaces. The steady-state levels of SP mRNAs declined after 8 days of exposure to 100% oxygen, but the patterns indicated individual genetic control. SP-A was elevated early in the course of the hyperoxic exposure but decreased significantly by day 8; SP-B decreased continuously; SP-C was unchanged (or slightly elevated) through day 2 and then declined. The amounts of recoverable lavage surfactant increased by greater than threefold, and the phospholipid composition showed increasing percentages of disaturated phosphatidylcholine. All surfactants lowered surface tension to less than 10 dyn/cm, but the adsorption rates decreased as exposure progressed. The results indicate that lung injury induced by 100% oxygen is accompanied by altered patterns of surfactant metabolism, possibly because of a changing type II cell phenotype or alterations in Clara cell-derived surfactant. These changes may result in perturbed physiological function contributing to decreased lung compliance.

Animals↗
PubMed1992

Pathophysiologic, morphometric, and biochemical studies of the premature baboon with bronchopulmonary dysplasia.

Pathophysiologic, morphometric, and biochemical (surfactant and coagulation-fibrinolytic parameters) features were studied in premature baboons with and without bronchopulmonary dysplasia (BPD). A total of 22 baboons were delivered by hysterotomy at 75% of gestation and randomized into two groups. Group 1 (PRN) animals were ventilated with high-frequency oscillation for 48 to 72 h and then changed to positive-pressure ventilation (PPV) while maintained on clinically appropriate oxygen for the 21-day experimental period. Group 2 (BPD) animals were ventilated with PPV and 1.0 FlO2 for 7 days followed by 0.8 FlO2 for 14 days. Group 3 (control) animals were delivered and immediately killed at 140 days gestation. Group 1 animals showed no significant airway or saccular lesions, and alveolarization of the saccules was present. Group 2 animals showed metaplastic or hyperplastic epithelial lesions in airways and an alternating pattern of atelectatic but more normal appearing saccules and alveoli interposed between foci of thickened overexpanded saccular walls with no alveolarization. Differences within and between the three study groups were analyzed morphometrically. When numerical densities were examined by comparing control, PRN, BPD-atelectatic areas, and BPD-overexpanded areas. Type II cells were significantly increased in the BPD-overexpanded sites above those of control and PRN values. The interstitial cells were significantly more numerous in the BPD-atelectatic blocks compared with control and BPD-overexpanded blocks. Endothelial cell numerical densities were significantly decreased in the overexpanded sites of the BPD animals compared with the control, PRN, and BPD-atelectatic values. Volume density data showed that the interstitial compartment of the BPD group was significantly larger than those of the control and PRN groups. This was seen as significant increases in the cellular, noncellular, and connective tissue fiber components. Vascular endothelium or lumen volume densities were not different between the BPD and PRN animals, but did differ from those of the 140-day gestation controls. Comparable levels of lavage plasminogen-dependent fibrinolytic activity, were detectable at the 21-day study interval. The phospholipid composition of pulmonary surfactant, including disaturated PC and total PG, was similar between BPD and PRN groups at 21 days. The pathologic, morphometric, and biochemical patterns in this study probably represent those seen in human neonates with mild to moderate clinical BPD who survive. At this time, it is not known if the destructive endothelial lesion and the lack of alveolarization in the overexpanded and fibrotic lesions will resolve over time in long-term BPD survivors.

Animals↗
PubMed1992

Progression from steroid sensitive to insensitive state in breast tumours.

Progression from a hormone sensitive to insensitive tumour can take place by several independent pathways, some of which involve loss of receptor, whereas, others may be due to the presence of abnormal receptors. Examples now exist of insensitivity despite seemingly normal receptors, such cells being generated either by spontaneous changes or by steroid deprivation. Breast cancer is a multifactorial set of diseases with steroids being only one component of the jigsaw; it is likely that further mechanisms of response loss will be identified when experimental systems are refined and additional parts of the jigsaw identified.

Animals↗
PubMed1991

Biology of female sex hormone action in relation to contraceptive agents and neoplasia.

This article will present an overview of estrogen and progestin action at a cellular level, with emphasis on points that are relevant to neoplasia. In breast, endometrium and ovary, these two classes of hormone are clearly implicated in carcinogenesis, but their involvement with cancers of the liver, cervix and other tissues is more problematic. In the latter situations, I will highlight the major points to be considered if the hormones are involved without wishing to judge whether there actually is a causal involvement.

Animals↗
PubMed1991

MMPI measures of impulsivity and depression correlate with CSF 5-HIAA and HVA in depression but not schizophrenia.

Recent studies have linked impulsivity with CSF concentrations of both 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA). One work found a negative correlation between the MMPI psychopathic deviate (Pd) scale and 5-HIAA in personality disordered men (Brown et al., 1982). We found that the 5-HIAA/Pd correlation extends (P less than 0.05) to unmedicated depressed patients (n = 21). A trend was found between HVA and Pd in depression. There was no relationship between either metabolite and the Pd scale in unmedicated schizophrenics (n = 24). A significant inverse correlation was found between the MMPI depression scale and CSF HVA but not 5-HIAA in the depressed patients.

Adult↗
PubMed1991

Presence of an oestradiol receptor-related protein in the skin: changes during the normal menstrual cycle.

OBJECTIVE: To investigate the presence of an oestradiol receptor-related protein (P29) in skin and skin organelles, and to assess changes in its content during the normal menstrual cycle. DESIGN: An observational study. SETTING: King's College School of Medicine and Dentistry, London. SUBJECTS: Twenty-one premenopausal women with regular menstrual cycles undergoing gynaecological surgery. They were allocated to proliferative or secretory phases of the menstrual cycle on the basis of menstrual dating and histological examination of an endometrial sample. INTERVENTIONS: Small full thickness sections of skin (about 5 mm in depth) taken from the anterior abdominal wall at hysterectomy or laparoscopic sterilization. MAIN OUTCOME MEASURES: The concentration of the oestradiol receptor-related protein in skin and its organelles was assessed semi-quantitatively, using a monoclonal antibody technique. The intensity of staining was compared between the proliferative and secretory phases of the cycle. RESULTS: The receptor-related protein was consistently observed in epidermis, sebaceous glands, hair follicles and sweat ducts; there was no significant difference in its concentration between the proliferative and secretory phases of the menstrual cycle. The protein was not present in dermis and sweat ducts. CONCLUSIONS: Epidermis and some skin organelles contain an oestradiol receptor-related protein and must be considered as oestrogen target tissues. However, the content of this protein does not appear to change significantly during the normal menstrual cycle.

Adult↗
PubMed1991

Assay for detection and enumeration of genetically engineered microorganisms which is based on the activity of a deregulated 2,4-dichlorophenoxyacetate monooxygenase.

An assay system was developed for the enumeration of genetically engineered microorganisms expressing a deregulated 2,4-dichlorophenoxyacetate (TFD) monooxygenase, which converts phenoxyacetate (PAA) to phenol. In PAA-amended cultures of Pseudomonas aeruginosa PAO1C(pRO103) and Pseudomonas putida PPO301(pRO103), strains which express a deregulated TFD monooxygenase, phenol production was proportional to cell number. Phenol was reacted, under specific conditions, with a 4-aminoantipyrine dye to form an intensely colored dye-phenol complex (AAPPC), which when measured spectrophotometrically could detect as few as 10(3) cells per ml. This assay was corroborated by monitoring the disappearance of PAA and the accumulation of phenol by high-performance liquid chromatography and gas chromatography. The AAPPC assay was modified for use with plate cultures and clearly distinguished colonies of PPO301(pRO103) and PAO1C(pRO103) from a strain expressing a regulated TFD monooxygenase. Colonies of P. putida PPO301(pRO101) remained cream colored, while colonies of PPO301(pRO103) and PAO1C(pRO103) turned a distinct red.

Ampyrone↗
PubMed1991

Alterations in surfactant protein gene expression associated with premature birth and exposure to hyperoxia.

Steady-state levels of mRNAs for the three surfactant-associated proteins, SP-A, SP-B, and SP-C, were measured in a primate model of premature birth and survival. These values were determined by Northern and quantitative slot blot analyses of total lung RNA during both in utero and extrauterine development of the fetus as well as in response to hyperoxic exposure. The composition and surface properties of surfactant were also analyzed to determine the effect of differential expression of the surfactant proteins on the overall composition and function of surfactant. The data clearly demonstrate that the regulation of surfactant mRNA levels in the premature fetus is under complex physiological control. Interruption of in utero development by premature birth results in increased levels of all three surfactant mRNAs, presumably in response to precocious initiation of air breathing. Within the first 24 h after parturition both SP-B and SP-C mRNA levels are increased beyond the levels found in the full-term fetal controls. Expression of mRNA for these genes peaks on day 2 and thereafter drops to levels below that found on day 1. However, response of the SP-A gene to premature birth is slow and transcripts from this gene lag considerably behind values found in the full-term fetus. Furthermore, exposure of the premature fetus to hyperoxia results in an increase in the steady-state levels of SP-B and SP-C mRNA without significant changes in SP-A. Defects in the ability of the SP-A gene to respond to extrauterine exposure and hyperoxia may be contributing to development of bronchopulmonary dysplasia, a common clinical complication of premature birth in humans.

Animals↗
PubMed1991

Comparative phenomenology of early-onset versus late-onset panic attacks: a pilot survey.

Studies of panic attacks in older adults are virtually nonexistent. The authors surveyed 520 adults with panic attacks; 445 were younger than age 55, 57 were 55 years old or older but had their first panic attack before age 55, and 18 were 55 years old or older and had their first panic attack at age 55 or later. The respondents with late-onset panic attacks reported fewer symptoms during their attacks and were less avoidant than both groups of respondents with early-onset panic attacks.

Age Factors↗
PubMed1991

Biochemical changes in endometrial carcinoma and their correlation to clinical outcome and prognosis.

Four biochemical parameters, soluble oestradiol (REC) progesterone (RP) receptors, 17B oestradiol and isocitric dehydrogenase enzymes were studied to evaluate hormone sensitivity in 51 patients with endometrial carcinoma. Samples of tumours were taken before and after 7 to 14 days of oral medroxyprogesterone acetate (MPA) treatment for histological and biochemical analysis. Hormone sensitivity assessed by a decrease in receptor concentration after MPA in REC rich (p less than 0.005) and RP rich (p less than 0.02) tumours was 65% and 63% respectively. Induction of isocitric dehydrogenase enzyme with MPA was highly significant in REC rich (p less than 0.0001) and RP rich (p less than 0.001) tumours, as was the induction of 17B oestradiol dehydrogenase in REC rich (p less than 0.01) and RP rich (p less than 0.005), confirming progestogen sensitivity. Post MPA dehydrogenase enzyme levels predicted survival more accurately than pre MPA receptor status of the tumours.

Adenocarcinoma↗
PubMed1990

5-HIAA in cerebrospinal fluid and deficit schizophrenic characteristics.

Higher CSF 5-HIAA concentrations and lower CSF HVA concentrations have been associated with various measures of slowed motor behaviour and communication in schizophrenic patients. To derive a single, reliable measure of deficit characteristics in schizophrenic patients, we entered four items of the BPRS reflecting negative symptoms, a work history measure derived from the Strauss-Carpenter scale, and three subscale scores of the WAIS-R into a principal-components analysis to derive a single factor score. The CSF 5-HIAA concentrations were within the normal range of values, and correlated directly with this factor score, but CSF HVA concentrations were not associated with the deficit factor score. These findings add support to the hypothesis that brain serotonin function is associated with deficit schizophrenic characteristics.

Adult↗
PubMed1979

Physicochemical properties of dipalmitoyl phosphatidylcholine after interaction with an apolipoprotein of pulmonary surfactant.

We studied the interaction between an apolipoprotein of pulmonary surfactant and the principal lipid found in this material, dipalmitoyl phosphatidylcholine. The apolipoprotein was extracted from canine surfactant and purified to greater than 90% homogeneity. The apolipoprotein was mixed for 16 h at room temperature with dipalmitoyl phosphatidylcholine dispersed in a buffer containing 0.1 M NaCl and 3mM CaCl2. Unbound lipid, unbound protein, and recombinants of lipid and protein were separated by density gradient centrifugation. 71% of the apolipoprotein was found associated with dipalmitoyl phosphatidylcholine. In comparable experiments using bovine plasma albumin about 13% of the albumin was recovered with the lipid. The physicochemical state of the lipid in the apolipoprotein-lipid complex was modified after binding of the protein. A distinct phase transition at 42 degrees C could no longer be detected, and the rate of adsorption to an air-liquid interface of the apolipoprotein-lipid complex was greater than that of the lipid alone. Surface tension vs. surface area isotherms of the dipalmitoyl phosphatidylcholine-apolipoprotein materials, however, were similar to those exhibited by pure dipalmitoyl phosphatidylcholine. The results suggest a physiological role for this apolipoprotein. It may bind to dipalmitoyl phosphatidylcholine under conditions expected in vivo, and may modify the physical properties of the aggregated dipalmitoyl phosphatidylcholine to form domains of lipid in a liquid-crystalline array. The complex dipalmitoyl phosphatidylcholine and apolipoprotein would have the physical properties necessary for its physiological function, allowing it to absorb to the alveolar interface and reduce its surface tension to less than 10 dynes/cm. Dipalmitoyl phosphatidylcholine, by itself, is in a gel-crystalline array below its phase transition temperature (42 degrees C) and would be incapable of effecting these actions.

Animals↗