Biomedical subjects

K Green

Publications and source records attributed to K Green.

At least 91 records · Page 5Linked to original sources

PubMed1993

The effects of X monosomy on brain development: monozygotic twins discordant for Turner's syndrome.

Monosomy for the X chromosome is the most frequent cause of Turner's syndrome, a common clinical syndrome associated with particular physical and neurobehavioral features. The results from comprehensive assessment of prepubertal monozygotic female twins discordant for X monosomy are presented. Zygosity was established with DNA Fingerprinting and no evidence of chromosomal mosaicism was seen in either child. Physical features in the affected twin were relatively mild with respect to the full spectrum of physical malformations and disabilities associated with Turner's syndrome. The neurobehavioral phenotypes of the twins were compared. Although both sisters scored in the superior range of intelligence, the affected twin's Performance IQ was 18 points less than her sister, whereas Verbal IQ showed only a 3-point difference between the sisters. Other relative differences were noted within the executive, visuospatial, and visuomotor domains of function. Behavioral evaluation indicated greater problems with attention, hyperactivity, and anxiety in the affected twin. Quantitative analysis of brain anatomy revealed evidence of both general and regional effects of X monosomy on neurodevelopment. Cerebrospinal fluid volume was increased by 25% in the affected twin compared with her sister with a corresponding decrease in gray matter volume. The right frontal, right parietal-occipital, and left parietal-perisylvian regions showed the greatest discrepancy between the sisters with respect to increased cerebrospinal fluid and decreased gray matter volumes in twin with X monosomy. Differences in the posterior fossa were also noted with a 50% relative increase in the volumes of the fourth ventricle and cisterna magna and a 10 to 15% relative reduction in size of the cerebellar vermis, pons, and medulla in the affected twin. The association between the neurobehavioral and neuroanatomical findings in the affected twin is discussed. The unique nature of the naturally occurring genetic phenomenon seen in this twin pair provides an opportunity to more fully elucidate the neurobehavioral phenotype associated with X monosomy and Turner's syndrome.

Brain↗

PubMed1993

A cluster of surgical wound infections due to unrelated strains of group A streptococci.

Group A streptococci account for less than 1% of all surgical wound infections but are an important cause of nosocomial outbreaks. We report here a cluster of four group A streptococcal infections that occurred within an 11-day period on a single surgical service. The index case presented with toxic shock-like syndrome. Epidemiologic investigation did not identify any relationship between infections. Restriction endonuclease analysis and M and T typing found the four isolates to be unrelated. Restriction endonuclease analysis is a useful tool for determining relatedness of nosocomial isolates of group A streptococci.

Cluster Analysis↗

PubMed1993

Blood-ocular barrier permeability and electroretinogram after intravitreal silicone oils of varying composition.

Silicone oils, used as long-term retinal tamponades, cause retinal toxicity that may be related to certain ingredients. Specific additives, proven to increase corneal endothelial permeability, were added to a purified oil, and placed into the vitreous of rabbits to assess their effects on the retina. Oils were exchanged for vitreous at constant intraocular pressure to 1 ml oil volume. Blood-ocular barrier permeability was measured with fluorophotometry after intravenous dye, and retinal function was measured using dark-adapted electroretinography (ERG). Each parameter was determined at eight week intervals: this periodicity was chosen to allow any toxicity to develop based upon prior data in the literature. The fluorescein concentration in different ocular compartments indicated an increased aqueous humor fluorescein concentration after pure oil (a non-statistically significant 50% increase) or oil plus long chain additive (a significant 240% increase). After oil plus a linear series of compounds both aqueous humor (2000%) and anterior vitreous fluorescence (8000%) was statistically significantly increased, indicating a breakdown of the blood-aqueous barrier. The height of the b-wave of the ERG was unaffected by any oil in the presence or absence of additive. Overt changes were minimal with oil alone, increased with oil containing linear chain additive, and were extensive with oil with long chain additive.

Animals↗

PubMed1993

Rabbit corneal endothelial cell membrane potential.

Membrane potential of rabbit corneal endothelial cells measured using microelectrodes was -29.3 +/- 0.8 mV, n = 45, (mean +/- SEM). Histological location of Lucifer Yellow dye iontophoresed out of the microelectrode confirmed that the microelectrode was located intracellularly. The Lucifer Yellow diffused five to six cell diameters away from the impaled cell indicating endothelial cell coupling. Depolarization by ouabain (10(-4) M) and high extracellular potassium (potassium for sodium substitution) showed the cells to be responsive to changes in the bathing solution whilst impaled, that the cell membrane is more permeable to potassium than sodium and that membrane bound Na(+)-K(+)-ATPase activity generates the transmembrane electrolyte gradients.

Animals↗

PubMed1993

Perfluorocarbon effects on rabbit blood-retinal barrier permeability.

Studies have been made of the effects of intravitreal perfluoro-n-octane on the permeability to fluorescein of the blood-retinal barrier in rabbits. At day 1 after injection, there is increased aqueous humor fluorescence that reflects the physical disturbance to the eye following injection. From that time through 7 weeks, there is no evidence of any overt toxicity to the blood-retinal barrier. The retention in the vitreous of a small volume of perfluoro-n-octane following its intraoperative use would not be expected to induce a toxic response. Some effect on an already compromised retina cannot, however, be excluded.

Animals↗

PubMed1993

Recombinant human insulin-like growth factor binding proteins 4, 5, and 6: biological and physiochemical characterization.

We have recently cloned cDNAs encoding human insulin-like growth factor binding proteins (IGFBP)-4, -5 and -6 and have now expressed these BPs in yeast as ubiquitin (Ub)-IGFBP fusion proteins. Western ligand blotting with 125I-IGF II under nonreducing conditions of recombinant human (rh) IGFBP-containing yeast lysates revealed specific binding bands for IGFBP-4, -5, and -6 at apparent molecular masses of 24-26, 30-32, and 24-26 kDa, respectively, indicating expression and processing of the fusion proteins. HPLC purified rhIGFBPs had virtually the same amino acid composition, amino acid number, and NH2-terminal sequences as the native BPs. Rabbit antiserum directed against each rhIGFBP-4, -5 and -6 reacted specifically with the respective rhIGFBP as well as with the native human counterpart and displayed very low cross-reactivity with other IGFBPs. Except for the affinity of rhIGFBP-6 for IGF I (Ka = 8.5 x 10(8) M-1), the affinity constants of the three IGFBPs for IGF I and II lie between 1.7 and 3.3 x 10(10) M-1. When present in excess, rhIGFBP-4, -5, and -6 inhibited IGF I- and II-stimulated DNA and glycogen synthesis in human osteoblastic cells, although rh-IGFBP-6 had only a weak inhibitory effect on IGF I in agreement with its relatively lower IGF I affinity constant.

Amino Acid Sequence↗

PubMed1992

Characterization of recombinant human insulin-like growth factor binding proteins 4, 5, and 6 produced in yeast.

The insulin-like growth factor binding protein (IGFBP) family comprises six structurally distinct, but highly homologous proteins. They have been identified in serum and other biological fluids, tissue extracts, and cell culture media. We have recently cloned cDNAs encoding human IGFBP-4, -5, and -6 and have now expressed these BPs in yeast as ubiquitin (Ub)-IGFBP fusion proteins. Western ligand blotting with 125I-IGF II under nonreducing conditions of recombinant human (rh) IGFBP-containing yeast lysates revealed specific binding bands for IGFBP-4, -5, and -6 at apparent molecular masses of 24-26, 30-32, and 24-26 kDa, respectively, indicating processing of the fusion proteins. High-performance liquid chromatography-purified rhIGFBPs had virually the same amino acid composition, amino acid number, and NH2-terminal sequences as the native BPs. Except for the affinity of rhIGFBP-6 for IGF I (Ka = 8.5 x 10(8) M-1), the affinity constants of the three IGFBPs for IGF I and II lie between 1.7 and 3.3 x 10(10) M-1, i.e. 25-100 times higher than the IGF I and II affinities of the type I IGF receptor. When present in excess, rhIGFBP-4, -5, and -6 inhibited IGF I- and II-stimulated DNA and glycogen synthesis in human osteoblastic cells, but rhIGFBP-6 had only a weak inhibitory effect on IGF I in agreement with its relatively lower IGF I affinity constant. The results of this study show that the primary effect of the three rhIGFBPs is the attenuation of IGF activity and suggest that IGFBPs contribute to the control of IGF-mediated cell growth and metabolism.

Amino Acid Sequence↗

PubMed1992

Structural characteristics of cyclodextrins in the solid state.

A comparison of alpha-, beta-, and gamma-cyclodextrins in the solid state is made. Monomeric features analyzed include orientations of primary hydroxyl groups and pyran ring pucker. Macromolecular features examined include planarity of the oligomer, tilting of pyran rings, and, deviation from Cn symmetry where n = number of monomers. The mean values and standard deviations of these shape descriptors are given for cyclodextrins with and without guests embedded in their interiors. Molecular mechanics calculations using the MM2, AMBER, and CHARMM force fields show that most solid state cyclodextrins are trapped in high-energy conformations relative to the most stable forms found in this study.

Chemical Phenomena↗

PubMed1992

Platelet activation and prostacyclin release in essential hypertension.

To evaluate platelet activation thromboxane A2 (TxA2) and beta-thromboglobulin (beta TG) were used as markers and in addition we studied the biosynthesis of prostacyclin. Synthesis of TxA2 and prostacyclin was assessed by measurement of urinary metabolites. Fifteen untreated hypertensive patients (HT) and 15 age-matched normotensive controls (NT) were investigated at rest, during and after exercise. HT patients were re-examined after 3 months on enalapril. During basal conditions there was no difference in the excretion of Tx-M, PGI-M or beta TG between the groups. During strenuous exercise HT exhibit a significantly higher increase in prostacyclin synthesis (162%) compared to NT (76%). The levels of beta TG increased with 82% in the HT and 24% in the NT group, Tx-M increased with 27% and 23% respectively. Treatment with the ACE-inhibitor enalapril did not significantly alter these findings. These results indicate that there is no evidence of basal platelet activation in early essential hypertension. Strenuous exercise leads to some increase in Tx-M in both groups, with no pronounced differences between the groups. Hypertensive patients exhibit a significantly increased prostacyclin response to exercise which could be due to differences in vessel-wall reactivity. Enalapril seems to exert no effect on platelet activation or on prostacyclin biosynthesis.

Adult↗

PubMed1992

Drug interaction with intraocular lenses of different materials.

The uptake and washout kinetics of four drugs representing different classes of ophthalmic medications were measured in intraocular lenses of different materials. The materials ranged from hydrogel lenses to poly(methyl methacrylate) (PMMA), Acrysof (acrylic/methacrylic), and two types of silicone lenses (Chiroflex and AMO SI-18NB). Uptake was determined after seven days of immersion in a large volume of Ringer's solution containing drug concentrations that equaled those found in aqueous humor 30 minutes to one hour after topical administration. Washout was determined after placing lenses in 1 ml of 0.9% saline for 24 hours. Only hydrogel lenses could be digested in acid to measure lens uptake directly. The PMMA, Acrysof, and silicone lenses behaved similarly toward gentamicin and dexamethasone--low uptake (less than 3.5 ng/mg lens) and low washout (less than 4.0%). Their uptake of norepinephrine was lower (less than 0.7 ng/mg lens) but the washout varied from 29% (AMO silicone) to 100% (PMMA and Acrysof). The pilocarpine uptake was the lowest of drugs tested (less than 0.03 ng/mg lens) and the washout varied from 1.5% (acrylic) to 100% (PMMA and Chiroflex silicone). Hydrogel lenses took up the most drug in the following order: dexamethasone greater than pilocarpine greater than gentamicin greater than norepinephrine. Washout was high, ranging from 83% to 98%. Despite the greater uptake and washout, the maximum drug uptake would only provide one-tenth of the greatest aqueous humor concentration that occurs after topical drug administration. Intraocular lenses of the materials tested did not interfere with the intraocular drug pharmacokinetics, nor did the data indicate that presoaking intraocular lenses of these materials in drugs would enhance post-surgical intraocular drug concentrations.

Absorption↗

PubMed1992

Leukotrienes and sensory innervation in blood-aqueous barrier disruption in the dog.

The effect of a specific 5-lipoxygenase inhibitor, PF5901 (5% in corn oil), on disruption of the blood-aqueous barrier (BAB) in the dog was investigated using a unilateral mild paracentesis model. BAB breakdown was quantitated using anterior chamber fluorophotometry. Fluorescence in the eyes of the PF5901 group was not statistically significantly different (P greater than 0.05) from that in the vehicle group. A tendency towards greater fluorescein concentrations was noted in the PF5901 treated eyes. It was concluded that leukotrienes are not important mediators of BAB disruption in this model and that leukotriene inhibitors may actually exacerbate disruption due to shunting of arachidonate metabolism towards the cyclooxygenase and/or epoxygenase pathways. In a second experiment, the effects of proparacaine and flurbiprofen were evaluated on blood-aqueous barrier disruption and pupil size following a more severe paracentesis. Flurbiprofen dampened both barrier disruption and the miotic response but proparacaine suppressed neither reaction, suggesting that, in the dog, prostaglandins are more important mediators of the ocular irritative response than are sensory neuropeptides.

Animals↗

PubMed1992

Impact of the Los Angeles County Trauma System on the survival of seriously injured patients.

We compared the survival of 658 seriously injured patients treated in Los Angeles County in the Fall of 1982 (prior to the activation of the trauma system) with that of 766 such patients treated in the Fall of 1984 (when the system was young and composed of essentially a full complement of trauma centers). We demonstrated a statistically significant improvement in the adjusted odds of survival for 1984 over 1982 with regard to victims of motor vehicle collisions who sustained multiple serious injuries (1980 Injury Severity Score: 26-50) (p = 0.042). For the data set as a whole, although an improvement in survivorship over this period was suggested by the data, statistical significance could not be demonstrated.

Adolescent↗

PubMed1992

Intracellular pH regulation by a Na+/H+ exchanger in cultured bovine trabecular cells.

Intracellular pH (pHi) of cultured bovine trabecular cells was measured using video-imaging techniques with a pH-sensitive intracellular fluorescent dye, BCECF. In bicarbonate-rich Ringer at pH 7.4, pHi was 7.29 +/- 0.03 (+/- SEM, n = 12 monolayers, 120 cells sampled). Exposure to 20 mM NH4Cl immediately alkalinized pHi: replacement with a Na(+)-rich solution acidified pHi before recovery to resting levels. When NH4Cl was replaced by a low Na+ solution, acidification was sustained but pHi recovery occurred after Na(+)-rich solution. A pHi of 7.11 +/- 0.02 (n = 2 monolayers, 20 cells) occurred in pH 6.8 and pHi was 7.72 +/- 0.03 (n = 2 monolayers, 20 cells) in pH 8.0. Amiloride (1 mM) acidified pHi but DIDS (1 mM) treatment, HCO3(-)-free condition, 1 mM ouabain, 50 mM K+, and 2 mM BaCl2 failed to change pHi. Hydrogen peroxide (1 mM) acidified pHi but no change occurred with 50 microM. Trabecular cells possess an Na+/H+ exchanger similar to that in other cell types.

Ammonium Chloride↗

PubMed1992

Optimal pupil diameter for Scheimpflug slit image photography of the lens in man.

Densitometric analysis of Scheimpflug photography of the lens has been examined as a function of pupil diameter in normal volunteers. On the basis of both the length of the lens waveform and the integral area under the curve of the lens waveform, there is a critical pupil diameter above which the waveform is unchanged. Below this critical diameter the waveform becomes distorted by shortening and a change in shape. The critical pupil diameter is between 6 and 6.5 mm. This result is of importance either in longitudinal studies, where the pupil diameter may not be reproducible, or in studies where other drugs are used which may prevent full pupil dilatation.

Adult↗

PubMed1992

Comparative studies of furosemide effects on membrane potential and intracellular chloride activity in human and rabbit ciliary epithelium.

Furosemide (1 mM), a potent loop diuretic, caused a 10-mV (n = 14) depolarization of the intracellular potential difference (PDI) of isolated rabbit ciliary epithelium (CE), but produced a 9-mV (n = 5) hyperpolarization of PDI of isolated human CE. In rabbit CE, furosemide consistently depolarized PDI by 13, 7 and 8 mV in HCO3(-)-free Ringer, Na(+)-free Ringer and after BaCl2 treatment, respectively. The depolarization of PDI was reduced to 2 mV (n = 11) in Cl(-)-free conditions. A hyperpolarization of PDI caused by furosemide that was quantitatively similar to that seen in normal Ringer also occurred in human CE during immersion in HCO3(-)-free Ringer, Na(+)-free Ringer and after BaCl2 treatment. There was a small hyperpolarization (3 mV) of PDI in Cl(-)-free conditions. Human or rabbit tissue-cultured nonpigmented ciliary epithelial cells were loaded with the Cl(-)-sensitive fluorophore 6-methoxy-N-(3-sulfopropyl) quinolinium (SPQ) in hypotonic solution (145 mosm) for 4 min at 37 degrees C. Furosemide decreased intracellular Cl- fluorescence activity of both human and rabbit ciliary epithelial cells by 30 +/- 5 (n = 8) and 25 +/- 7% (n = 13), respectively, when the cells were immersed in Cl(-)-rich solution. It is suggested that a furosemide-sensitive Cl- movement exists in both rabbit and human CE, although the mode of Cl- movement to the aqueous across CE may differ between these species.

Animals↗

PubMed1992

Tear potassium contributes to maintenance of corneal thickness.

Isolated rabbit corneas were bathed on their endothelial surfaces with normal Krebs bicarbonate Ringer solution, while the epithelial surfaces were bathed in a basic tear solution containing sodium and potassium. When bathed in basic tear solution alone, corneal swelling occurred at an average of 12 microns/h over a 3-hour period. Corneal swelling occurred at a rate of about 21 microns/h when the epithelial solution was switched from normal basic tear solution to an iso-osmotic K(+)-free basic tear solution. Corneal swelling then slowed, and in the final hour of a 3-hour exposure to K(+)-free tear solution, the corneas deswelled at about 10 microns/h. The data indicate that potassium is a necessary solute for the maintenance of normal corneal thickness. The results suggest that a lacrimal dysfunction that would cause a decrease in the potassium content of tears may influence corneal thickness and also suggest that the inclusion of potassium in artificial tears is important.

Animals↗

PubMed1992

Subconjunctival gentamicin induction of extraocular toxic muscle myopathy.

Subconjunctival injection of commercially available gentamicin, delivered in one of several protocols, caused an acute toxic reaction myopathy of the extraocular muscles. The response began as a small focal infiltrate of polymorphonuclear leukocytes, and as the lesion progressed it assumed a mononuclear cell predominance accompanied by muscle fiber degeneration. The injection of individual components of the commercial preparation (gentamicin, methylparaben, ethylenediaminetetraacetic acid (EDTA) and sodium bisulfite), each at the same concentration as in the parent solution, gave no response except for gentamicin alone. Gentamicin caused acute toxic myopathy when injected away from the muscles and when given as an isotonic solution in saline compared to the hypotonic commercial solution. Solutions at acidic pH not containing gentamicin did not initiate myopathy. Several factors that have been inferred as participating in the toxic response to gentamicin have been eliminated. Gentamicin alone is responsible for the induction of the extraocular muscle myopathy.

Animals↗

PubMed1992

Intracellular pH of tissue-cultured bovine corneal endothelial cells.

Intracellular pH (pHi) of bovine tissue-cultured corneal endothelial cells has been measured under several experimental conditions. Determinations were made on individual cells using video-imaging techniques that allowed assessment of 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein fluorescence at 440 and 490 nm. Each experiment had a calibration performed on a cell monolayer: this was performed using a high K(+)-nigericin solution. Resting pHi was 7.25 +/- 0.03 (n = 18) in bicarbonate solution at pH 7.4. Amiloride (1 mM) caused an acidification of approximately 0.2 U within 2 min: replacement with normal Ringer allowed a return to normal pHi after an alkali overshoot. Exposure to 20 mM NH4Cl caused alkalinization that became acidic upon washout of NH4Cl. In Na(+)-rich solution pHi returned to normal after acidification but pHi remained low in Na(+)-free solution until substituted by Na(+)-rich solution. Removal of HCO3- from the bathing solution caused a nonsignificant acidification of pHi by 0.1 U at 2 and 4 min, and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS; 1 mM) acidified pHi by 0.14 U at 2 min and 0.24 U at 4 min. Addition of DIDS (1 mM) in a HCO3(-)-free solution had no effect on pHi. Hydrogen peroxide acidified pHi by 0.3 U at 50 microM and 1 mM. These results indicate that a Na+:H+ antiport exists that regulates pHi even at normal ambient pH in the presence of bicarbonate: this process becomes highly activated after an acid load. There is a DIDS-sensitive HCO3- movement that is probably coupled to Na+ or Cl-.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗