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Biomedical subjects

K Green

Publications and source records attributed to K Green.

At least 73 records · Page 4Linked to original sources
PubMed1996

An outbreak of fatal nosocomial infections due to group A streptococcus on a medical ward.

Group A streptococcus is an uncommon but important cause of nosocomial infections. Outbreaks of infection most often have occurred in surgical or obstetrical patients. We describe an outbreak of severe group A streptococcal infections that occurred on a medical unit of a community hospital. Within an 8-day period, three patients developed fatal nosocomial skin and soft-tissue infection due to group A streptococcus. Three nurses who had provided care to one or more of these patients subsequently developed streptococcal pharyngitis, and three other nurses were treated with antibiotics for pharyngitis (cultures not obtained). Patient isolates were serotype M-nontypeable, T-11, opacity factor-positive, and shared identical DNA profiles when typed by pulsed-field gel electrophoresis; staff isolates were not available for typing. To prevent further spread of infection, the ward was closed to new admissions, and symptomatic staff were treated with antibiotics and relieved of patient-care duties. This outbreak demonstrates the ability of group A streptococcus to spread rapidly in a hospital setting and to cause severe life threatening disease in hospitalized patients.

Cluster Analysis↗
PubMed1996

Association of maternal drug use during pregnancy with maternal HIV culture positivity and perinatal HIV transmission.

OBJECTIVE: To evaluate the relationship of drug use with maternal HIV culture positivity at delivery and perinatal HIV transmission. DESIGN: Multicenter prospective cohort study. SETTING: Obstetric and pediatric clinics in five cities in the United States. PARTICIPANTS: Five hundred and thirty HIV-infected pregnant women and their infants. MAIN OUTCOME MEASURES: Multivariate logistic regression was used to evaluate the association of 'hard drug' use (one or more of the following: cocaine, heroin/opiates, methadone, injecting drug use) assessed by self-report and urine toxicology with positive maternal HIV culture at delivery and perinatal HIV transmission. RESULTS: Forty-two per cent of women used hard drugs during pregnancy. Increased probability of a positive maternal delivery HIV culture was significantly associated with prenatal hard drug use [odds ratio (OR), 3.08] and maternal cocaine use (OR, 2.98) among HIV-infected women with > 29% CD4+ lymphocytes. After adjusting for maternal culture positivity at delivery, CD4+ lymphocyte percentage and gestational age, significantly greater transmission risk was observed with hard drug use among women with membrane rupture > 4 h. CONCLUSIONS: On the basis of self-report and urine toxicology, overall maternal hard drug use and cocaine use in the WITS cohort were associated with maternal HIV culture positivity at delivery, and maternal hard drug use was associated with perinatal transmission.

Alcohol Drinking↗
PubMed1996

Scheimpflug densitometric analysis of cataracts in diabetic rats: correlation with glycation.

Glycation has been implicated in cataract formation. Our earlier studies showed that crystallin glycation enhances oxidation and aggregation, whereas MIP26 glycation affects the membrane permeability. Scheimpflug densitometric analysis has been used to quantify the lens opacification. In this study, we measured the progressive changes in lens opacification and correlated them with protein glycation in streptozotocin-induced diabetic rats. The lens opacification progressed in a biphasic manner: an initial slow increase between 0 and 60 days, followed by a steep increase between 60 and 90 days of diabetes. There was a strong correlation between lens opacification and lens crystallin and MIP26 glycation. The correlation was relatively weak with plasma glucose. This study suggests that glycation of lens crystallin and MIP26 plays a significant role in the development of lens opacification in diabetic rats.

Animals↗
PubMed1995

CDR walking mutagenesis for the affinity maturation of a potent human anti-HIV-1 antibody into the picomolar range.

We describe the investigation of methodologies for the creation of very high affinity human antibodies. The high affinity human antibody b4/12 was optimized for its affinity to the human envelope glycoprotein gp120 of human immunodeficiency virus type 1 (HIV-1). Five libraries of b4/12 were constructed by saturation mutagenesis of complementarity-determining regions (CDRs). Libraries of antibody Fab fragments were displayed on the surface of filamentous phage and selected in vitro for binding to immobilized gp120. Sequential and parallel optimization strategies of CDRs were examined. The sequential CDR walking strategy consistently yielded b4/12 variants of improved affinity in each of the four different optimization sequences examined. This resulted in a 96-fold improvement in affinity. Additivity effects in the antibody combining site were explored by combining independently optimized CDRs in the parallel optimization strategy. Six variants containing optimized CDRs were constructed. Improvement of affinity based on additivity effects proved to be unpredictable but did lead to a modest improvement in affinity. Indeed, only one of the six combinations demonstrated additivity. The highest affinity Fab prepared using this strategy was improved 420-fold in affinity. The affinity of this Fab was 15 pM as compared to 6.3 nM for b4/12. Examination of the kinetics of Fab binding to gp120 revealed that improvements in affinity were dominated by a slowing of the off-rate of the Fab. The methodology presented here provides a route for the improvement of the affinities of antibodies typical of tertiary immune responses into the picomolar range. Such improvements may have profound effects on the utility of antibodies as therapeutic and prophylactic agents.

Amino Acid Sequence↗
PubMed1995

Pelizaeus-Merzbacher disease caused by a de novo mutation that originated in exon 2 of the maternal great-grandfather of the propositus.

Pelizaeus-Merzbacher disease (PMD) is an X-linked dysmyelinating disorder of the central nervous system. Many cases of PMD can be attributed to defects in the proteolipid protein gene (PLP). To date, with one exception, each family has had either no or a unique mutation in one of the seven exons of PLP. We describe a new missense mutation in exon 2 of the PLP gene of an affected individual. This mutation codes for Ile instead of Thr at codon 42. The point mutation originated in the X chromosome of the maternal great-grandfather of the propositus. This was determined from the pattern of inheritance of the AhaII polymorphism and a series of microsatellite markers that are localized near PLP at Xq22.

Adult↗
PubMed1995

Computer-simulated eye surgery. A novel teaching method for residents and practitioners.

PURPOSE: To describe an eye surgery simulator that uses a computerized graphic display to allow ophthalmic surgeons of all experience levels to enhance their surgical skills. METHODS: The eye surgery simulation environment consists of a high-speed computer graphics workstation, a stereo operating system, a wrist rest, and a position tracking stylus connected to force feedback motors. The surgeon views computer-generated images of the eye and surgical instruments through the stereo operating system and controls the position and orientation of the chosen surgical instrument by moving the stylus. During the simulated instrument-tissue interactions, three feedback motors generate component force feedback along three orthogonal axes connected by thin rigid bars to the tip of the stylus. RESULTS: The current proof-of-concept system provides a method for rapid learning experiences in a living eye simulation. Procedures can be recorded for playback and analysis, as well as for examination of techniques from different viewpoints (e.g., from inside the eye). Four simulated surgical instruments are available for use (scalpel, forceps, scissors, and phacoemulsifier). CONCLUSION: Eye surgery simulation offers both beginning and experienced ophthalmic surgeons an opportunity to learn new techniques and skills and achieve a satisfactory level of proficiency before use of that procedure in the operating room. When fully developed, this system should shorten the learning curve for new surgeons (i.e., residents) and offer an opportunity for practice before doing a difficult case or development of new techniques by experienced surgeons. The goal of replacement of current standard training methods for surgeons awaits further refinement and adjustment of the model.

Computer Simulation↗
PubMed1995

Tear flow in cyclosporine recipients.

PURPOSE: To measure tear flow in renal allograft recipients who received oral cyclosporine as immunosuppressive therapy. PATIENTS: Control subjects were from the staff of various clinics, dialysis patients were recruited, and one group of kidney transplant recipients took oral cyclosporine, whereas another group took azathioprine. Written informed consent was obtained for an institutionally approved protocol. METHODS: A 4-minute Schirmer test with topical anesthetic was performed in both eyes of each person, and the average score was used in calculations. RESULTS: The tear flow rate was 10.6 mm/4 minutes in the control subjects, 13.6 mm/4 minutes in the dialysis patients, 10.4 mm/4 minutes in kidney transplant recipients taking azathioprine, and 19.0 mm/4 minutes in kidney transplant recipients taking cyclosporine. Kidney transplant recipients taking cyclosporine had significantly increased tear flow compared with the other three groups (P < 0.05); dialysis patients, kidney transplant recipients taking azathioprine, and control subjects showed statistically indistinguishable tear flow. Within-group comparisons (male versus female, black versus white, and all combinations) showed no statistically significant differences. CONCLUSION: Medications used by dialysis patients or the azathioprine group did not significantly increase tear flow compared with control subjects. The addition of cyclosporine (plus prednisone) enhanced tear flow in kidney transplant recipients compared with all other groups. Systemic cyclosporine appears to increase tear flow even when no lacrimal autoimmune disease exists.

Adult↗
PubMed1995

Sudden death in individuals in hobble restraints during paramedic transport.

For patient and personnel safety, agitated and violent individuals are sometime physically restrained during out-of-hospital ambulance transport. We report two cases of unexpected death in restrained, agitated individuals while they were being trans-ported by advanced life support ambulance. Both patients had been placed in hobble restraints by law enforcement. At autopsy, toxicologic analysis revealed nonlethal levels of amphetamines in one patient and nonlethal levels of ethanol, cocaine, and amphetamines in the other. In both cases the cause of death was determined to be positional asphyxiation during restraint for excited delirium. Physicians and emergency service personnel should be aware of the potential complications of using physical restraints for control of agitated patients.

Adult↗
PubMed1995

Gap junction protein phenotypes of the human heart and conduction system.

INTRODUCTION: Gap junction channels are major determinants of intercellular resistance to current flow between cardiac myocytes. Alterations in gap junctions may contribute to development of arrhythmia substrates in patients. However, there is significant interspecies variation in the types and amounts of gap junction subunit proteins (connexins) expressed in disparate regions of mammalian hearts. To elucidate determinants of conduction properties in the human heart, we characterized connexin phenotypes of specific human cardiac tissues with different conduction properties. METHODS AND RESULTS: The distribution and relative abundance of Cx37, Cx40, Cx43, Cx45, and Cx46 were studied immunohistochemically using monospecific antibodies and frozen sections of the sinoatrial node and adjacent atria. AV node and His bundle, the bundle branches, and the left and right ventricular walls. Patterns of expression of these connexins in the human heart differed from those in previous animal studies. Sinus node gap junctions were small and sparse and contained Cx45 and apparently smaller amounts of Cx40 but no Cx43. AV node gap junctions were also small and contained mainly Cx45 and Cx40 but, unlike the sinus node, also expressed Cx43. Atrial gap junctions were larger than nodal junctions and contained moderate amounts of Cx40, Cx43, and Cx45. Junctions in the bundle branches were the largest in size and contained abundant amounts of Cx40, Cx43, and Cx45. Gap junctions in ventricular myocardium contained mainly Cx43 and Cx45; only a very small and amount of ventricular Cx40 was detected in subendocardial myocyte junctions and endothelial cells of small to medium sized intramural coronary arteries. Minimal Cx37 and Cx46 immunoreactivity was detected between occasional atrial or ventricular myocytes. CONCLUSIONS: The relative amounts of individual connexins and the number and size of gap junctions vary greatly in specific regions of the human heart with different conduction properties. These differences likely play a role in regulating cardiac conduction velocity. Differences in the connexin phenotypes of specific regions of the human heart and experimental animal hearts must be considered in future experimental or modeling studies of cardiac conduction.

Adult↗
PubMed1995

Free radicals and aging of anterior segment tissues of the eye: a hypothesis.

A hypothesis is proposed that aging processes in the eye occur as a consequence of degradation of enzymes that normally metabolize and detoxify hydrogen peroxide and other free radicals. The loss of enzyme activity allows hydrogen peroxide, which normally occurs within eye fluids, and free radicals to induce irreversible deleterious effects on different eye tissues. These processes may lead to cataract formation in the lens, loss of corneal endothelial cells, modification of the glycosaminoglycan secretory patterns of the cells of the trabecular meshwork, and other changes associated with ocular aging. These processes may be exacerbated during inflammation when oxidation products increase. Considerable circumstantial evidence points towards hydrogen peroxide as one of the major chemicals involved in the induction of these changes. Much remains to be determined to definitively identify this chemical or free radicals as the primary inducers of tissue alterations that occur in aging eyes.

Aging↗
PubMed1994

Nitric oxide formation is involved in vagal inhibition of the stomach of the trout (Salmo gairdneri).

Stimulation of the vagus nerves to isolated stomach preparations from trout (Salmo gairdneri) caused both excitation and inhibition of smooth muscle activity. Excitatory responses were partly reduced by atropine, suggesting that cholinergic neurons are involved. The atropine-resistant excitation could not readily be ascribed to a 'rebound' from preceding inhibition, to the production of prostaglandins, or to the activation of either adrenergic or capsaicin-sensitive fibres. Inhibitory responses were reduced by the nicotinic antagonist d-tubocurarine and more profoundly reduced by an inhibitor of nitric oxide synthase, NG-nitro-L-arginine. The latter effect was reversed by excess L-arginine. The nitric oxide donors sodium nitroprusside and nitroglycerine caused inhibition of the muscle. It is concluded that the vagal inhibitory postganglionic neurons are nitergic in this tissue.

Amino Acid Oxidoreductases↗
PubMed1994

Factor analytic structure and stability of the separation-individuation test of adolescence.

The present study was undertaken to examine internal structural properties of the Separation-Individuation Test Adolescence (SITA; Levine, Green, & Millon, 1986). In 1990, 131 late adolescent undergraduate university students received the SITA; 2 years later, 79 of these same subjects were reassessed. Principal components analyses were conducted for the 1990 and 1992 samples, and internal consistency reliabilities (Cronbach's alpha) were calculated for each subscale. The internal structural properties converged moderately to strongly for the following scales: Practicing Mirroring, Engulfment Anxiety, Dependency Denial, Nurturance Seeking, and Teacher Enmeshment. These findings parallel those of Levine (in press). The developmental impact of the late adolescent separation-individuation process may explain in part some different clusterings of scale items over time.

Adolescent↗
PubMed1994

Ca(2+)-transporting ATPase, phospholamban, and calsequestrin levels in nonfailing and failing human myocardium.

BACKGROUND: Observations of abnormalities in the diastolic components of intracellular Ca2+ transients in failing human left ventricular myocardium have raised the possibility that reductions in the level or function of sarcoplasmic reticulum proteins involved in Ca2+ transport contribute to the pathophysiology of dilated cardiomyopathy in humans. Functional assays, however, have revealed no differences in ATP-dependent Ca2+ transport or its modulation by phospholamban in sarcoplasmic reticulum-enriched microsomes prepared from nonfailing and failing human left ventricular myocardium. The purpose of the present study was to quantify protein levels of Ca(2+)-transporting ATPase, phospholamban, and calsequestrin directly in nonfailing and failing human left ventricular myocardium. METHOD AND RESULTS: Total protein extracts were prepared from nonfailing left ventricular myocardium from the hearts of unmatched organ donors with normal left ventricular contractility (n = 6) and from failing left ventricular myocardium from the excised hearts of transplant recipients with class IV heart failure resulting from idiopathic dilated cardiomyopathy (n = 6). Ca(2+)-transporting ATPase, phospholamban, and calsequestrin contents were determined by quantitative immunoblotting with monoclonal and affinity-purified polyclonal antibodies. The levels of the three proteins were identical in nonfailing and failing human left ventricular myocardium. CONCLUSIONS: These results indicate that protein levels of Ca(2+)-transporting ATPase, phospholamban, and calsequestrin are not diminished in failing human left ventricular myocardium and that downregulation of the Ca(2+)-transporting ATPase and phospholamban is not part of the molecular pathophysiology of dilated cardiomyopathy in humans.

Adenosine Triphosphatases↗
PubMed1994

Effects of calcium channel blockers on rabbit corneal endothelial function.

The effects of calcium channel antagonists and agents that alter intracellular Ca2+ mobilization on corneal endothelial function have been examined. All experiments, except where specifically designated, were performed in the continuous presence of extracellular Ca2+. Verapamil (at 50 microM) increased the swelling rate of corneas bathed in normal Ringer solution whereas nifedipine and diltiazem (both up to 100 microM) were without effect. The nifedipine analog nisoldipine caused corneal swelling at 10 microM and 50 microM but nimodipine was without effect. When briefly exposed to a Ca(2+)-free solution corneal swelling was enhanced after subsequent exposure to 50 microM verapamil in normal Ringer but not after 50 microM diltiazem in normal Ringer, indicating that Ca2+ entry from the bathing solution into the cell was important and was apparently impeded by verapamil. Cadmium (0.6 and 1 mM) but not nickel (up to 250 microM) caused swelling of corneas bathed in normal Ringer. A Ca2+ channel agonist, BAY-K-8644, alone did not influence corneal thickness but when presented to the endothelium with 50 microM verapamil the swelling rate was much reduced compared to verapamil alone. The agonist, therefore, presumably maintained some Ca2+ channels open in face of the Ca2+ channel blocker. An agent that inhibited the release of intracellular Ca2+ stores (TMB-8) caused an initial corneal swelling over the first 1.5 hr of perfusion but thereafter had no effect on corneal thickness. In the presence of continued extracellular Ca2+ one explanation for the results is that modulation of intracellular Ca2+ by agents that alter plasma membrane transfer of Ca2+ influences apical junction permeability.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗