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Biomedical subjects

K Green

Publications and source records attributed to K Green.

At least 19 recordsLinked to original sources
PubMed1998

Marijuana smoking vs cannabinoids for glaucoma therapy.

OBJECTIVE: To discuss the clinical effects, including toxicological data, of marijuana and its many constituent compounds on the eye and the remainder of the body. A perspective is given on the use of marijuana and the cannabinoids in the treatment of glaucoma. RESULTS: Although it is undisputed that smoking of marijuana plant material causes a fall in intraocular pressure (IOP) in 60% to 65% of users, continued use at a rate needed to control glaucomatous IOP would lead to substantial systemic toxic effects revealed as pathological changes. CONCLUSIONS: Development of drugs based on the cannabinoid molecule or its agonists for use as topical or oral antiglaucoma medications seems to be worthy of further pursuit. Among the latter chemicals, some have no known adverse psychoactive side effects. Smoking of marijuana plant material for the reduction of elevated IOP in glaucoma is ill-advised, given its toxicological profile.

Cannabinoids↗
PubMed1998

Proteolysis of connexin43-containing gap junctions in normal and heat-stressed cardiac myocytes.

OBJECTIVE: The present studies were performed to examine the degradation of connexin43-containing gap junctions by the lysosome or the proteasome in normal and heat-stressed cultures of neonatal rat ventricular myocytes. METHODS: Primary cultures were prepared from neonatal rat ventricular myocytes. Connexin43 was detected by immunoblotting, immunofluorescence, or immunoprecipitation. Gap junction profiles were detected by transmission electron microscopy. RESULTS: Immunoblots of whole cell lysates demonstrated increased levels of connexin43 in cultures treated with lysosomal inhibitors (chloroquine, leupeptin, E-64, or ammonium chloride) or proteasomal inhibitors (lactacystin or ALLN). Pulse-chase experiments showed that the half-life of connexin43 was 1.4 h in control cultures, but was prolonged to 2.0 or 2.8 h in cultures treated with chloroquine or lactacystin, respectively. Immunofluorescence and electron microscopy showed a significant increase in the number of gap junction profiles in myocytes treated with either chloroquine or lactacystin. Heat treatment of cultures (43.5 degrees C for 30 min) produced a rapid loss of connexin43 as detected by immunoblotting or immunofluorescence. Heat-induced connexin43 degradation was prevented by simultaneous treatment with lactacystin, ALLN, or chloroquine. Connexin43 levels and distribution returned to normal by 3 h following a heat shock and were resistant to a subsequent repeat heat stress. The heat shock also led to production of HSP70 as detected by immunoblotting. CONCLUSIONS: These data suggest that Cx43 gap junctions in myocytes are degraded by the proteasome and the lysosome, that this proteolysis can be augmented by heat stress, and that inducible factors such as HSP70 may protect against Cx43 degradation.

Acetylcysteine↗
PubMed1998

A minimal avian retroviral packaging sequence has a complex structure.

We have defined a 160-nucleotide region, Mpsi, from the 5' leader region of the Rous sarcoma virus genome that is sufficient to direct the packaging of a heterologous RNA. Mpsi contains the putative O3 stem structure that has previously been shown, and that has been confirmed in this study, to be important for the efficient packaging of avian leukosis-sarcoma virus RNA. Analyses of several O3 stem mutants revealed that other regions within Mpsi can interfere with the proper folding of altered sequences which are predicted to form a wild-type O3 stem.

Avian Sarcoma Viruses↗
PubMed1998

Adiposity and serum leptin increase in fatty (fa/fa) BNZ neonates without decreased VMH serotonergic activity.

Decreased ventromedial hypothalamic (VMH) serotonergic activity occurs in genetic and diet-induced animal models of obesity. We previously found that this activity was lower in adult and in 12-day-old Zucker fa/fa vs. Fa/Fa pups, the fa/fa animals being identified by their greater adiposity. In the present study, we evaluated fa/fa rats (Brown Norway-Zucker hybrids) at ages 2, 4, 7, and 12 days to test the hypothesis that lower VMH serotonergic activity occurs before increased adiposity and/or attenuated energy expenditure. Our results negate this hypothesis. VMH serotonergic activity showed no consistent genotype differences even at 12 days of age. In contrast, by day 7, fa/fa vs. Fa/Fa pups had higher serum leptin concentrations, greater percent body fat, lower resting and cold-induced energy expenditure, and lower activity of brown fat thyroxine 5'-deiodinase, an enzyme that converts thyroxine to triiodothyronine. We conclude that the onset of increased adiposity induced by the fa gene does not require decreased VMH serotonergic activity and that the lower serotonergic activity seen in older fa/fa pups may be secondary to metabolic consequences of the disruption of the leptin regulatory pathway.

Adipose Tissue↗
PubMed1998

Kinetics of fluid delivery from methylcellulose sponges.

PURPOSE: The authors quantitatively evaluate the kinetics of fluid transfer from microsurgical sponges in a laboratory model to understand the kinetics of mitomycin C (MMC) delivery. METHODS: The amount of fluid transferred from soaked methylcellulose (Weck-cel, Weck Inc., Durham, NC, U.S.A.) sponges to small pieces of hydrated or dry filter paper used to simulate episcleral tissue and Tenon fascia was measured as a function of time, sponge size, hydration status of the filter paper, and technique of sponge application. RESULTS: The time course of fluid delivery from methylcellulose sponges to filter paper was nonlinear and characterized by a rapid delivery phase over the first 15 to 30 seconds, followed by a slow phase extending to at least 5 minutes. Sponge size and baseline hydration of the paper significantly influenced the rate and amount of fluid delivered, as did replacing the sponge every minute with a new sponge. CONCLUSION: The transfer of fluid from a microsurgical sponge displays nonlinear kinetics, with the majority of delivery occurring in the first 15 to 30 seconds. Sponge size, hydration of the recipient tissue, and technique of sponge application are significant variables influencing the amount of fluid, and therefore mitomycin C, delivered.

Antibiotics, Antineoplastic↗
PubMed1997

Population-based surveillance for group A streptococcal necrotizing fasciitis: Clinical features, prognostic indicators, and microbiologic analysis of seventy-seven cases. Ontario Group A Streptococcal Study.

PURPOSE: To determine the incidence of group A streptococcal necrotizing fasciitis in Ontario, Canada, and to describe the clinical features, outcome, and microbiologic characteristics of this infection. PATIENTS AND METHODS: Prospective, population-based surveillance for invasive group A streptococcal infections was conducted in Ontario from November 1991 to May 1995. All 77 patients meeting clinical and/or histopathologic criteria for streptococcal necrotizing fasciitis were included. Demographic and clinical information was obtained by patient interviews and chart review. Group A streptococci were characterized by M-protein and T-agglutination typing, and polymerase chain reaction (PCR) detection of streptococcal pyrogenic exotoxin genes A and C (speA; speC). RESULTS: The incidence of group A streptococcal necrotizing fasciitis increased during the study from 0.085 per 100,000 population in the first year to 0.40 per 100,000 population in the last year (P < 0.001). The median age of cases was 57.5 years and the rate of disease increased with increasing age. Seventy-nine percent of cases were community-acquired, 11% were nosocomial, and 10% were acquired in a nursing home. Forty-seven percent of cases were associated with the presence of streptococcal toxic shock syndrome (Strep TSS) and 46% were bacteremic. Thirty-four percent of cases died and mortality was correlated with increasing age (P = 0.006), presence of hypotension (P = 0.01), and bacteremia (P = 0.03). The most common streptococcal serotypes were M1 (35%) and M3 (25%). Forty-one percent of strains possessed the speA gene and 30% the speC gene. Outcome was not correlated with M-type or the presence of spe genes. CONCLUSIONS: The incidence of necrotizing fasciitis caused by group A streptococcus increased in Ontario between 1992 and 1995. Elderly individuals were more likely to acquire the disease and to die from it. Mortality because of streptococcal necrotizing fasciitis was also associated with the presence of hypotension, Strep TSS, or bacteremia, but not with M-type or the presence of pyrogenic exotoxin genes.

Aged↗
PubMed1997

Perceptual adjustment to highly compressed speech: effects of talker and rate changes.

This study investigated the perceptual adjustments that occur when listeners recognize highly compressed speech. In Experiment 1, adjustment was examined as a function of the amount of exposure to compressed speech by use of 2 different speakers and compression rates. The results demonstrated that adjustment takes place over a number of sentences, depending on the compression rate. Lower compression rates required less experience before full adjustment occurred. In Experiment 2, the impact of an abrupt change in talker characteristics was investigated; in Experiment 3, the impact of an abrupt change in compression rate was studied. The results of these 2 experiments indicated that sudden changes in talker characteristics or compression rate had little impact on the adjustment process. The findings are discussed with respect to the level of speech processing at which such adjustment might occur.

Female↗
PubMed1997

Evidence against cannabinoid receptor involvement in intraocular pressure effects of cannabinoids in rabbits.

Cannabinoid receptor involvement in the intraocular-pressure (IOP)-lowering effect of the cannabinoids has not been determined. These receptors bind four structural classes of agonists: the classical and the nonclassical cannabinoids, the aminoalkylindoles and the arachidonylethanolamides (the endogenous ligands). We examined the IOP effect in normotensive rabbits after systemic administration of an aminoalkylindole, WIN-55,212-2, and of (R)-(+)-methanandamine, a hydrolysis-resistant endogenous ligand derivative. The decrease in IOP for 6 animals treated with WIN-55,212-2 was marginal and for 6 animals treated with (R)-(+)-methanandamide was negligible compared to animals treated with vehicle alone. These studies suggest that the IOP-lowering effects of cannabinoids are not mediated by a cannabinoid receptor in rabbits.

Animals↗
PubMed1996

Invasive group A streptococcal infections in Ontario, Canada. Ontario Group A Streptococcal Study Group.

BACKGROUND: Several reports suggest that the incidence of invasive group A streptococcal infections, including streptococcal toxic shock syndrome and necrotizing fasciitis, is increasing. METHODS: During 1992 and 1993 we conducted prospective, population-based surveillance of invasive group A streptococcal disease in Ontario, Canada. We reviewed clinical and laboratory records, searched for secondary cases of invasive disease, and cultured specimens from household contacts. RESULTS: We identified 323 patients with invasive group A streptococcal infections, for an annual incidence of 1.5 cases per 100,000 population. The rates were highest in young children and the elderly. Fifty-six percent of the patients had underlying chronic illness. Risk factors for disease included infection with the human immunodeficiency virus, cancer, diabetes, alcohol abuse, and chickenpox. The most common clinical presentations were soft-tissue infection (48 percent), bacteremia with no septic focus (14 percent), and pneumonia (11 percent). Necrotizing fasciitis occurred in 6 percent of patients, and toxic shock in 13 percent. The mortality rate was 15 percent overall, but it was 29 percent among those over 64 years of age (P<0.001) and 81 percent among those with toxic shock (P<0.001). Fourteen percent of the cases were nosocomial, and 4 percent occurred in nursing home residents, often in association with disease outbreaks. Invasive disease occurred in 2 household contacts of patients with infection, for an estimated risk of 3.2 per 1000 household contacts (95 percent confidence interval, 0.39 to 12 per 1000). CONCLUSIONS: The elderly and those with underlying medical conditions are at greatest risk for invasive group A streptococcal disease, toxic shock, and necrotizing fasciitis. Invasive steptococcal infection is associated with a substantial risk of transmission in households and health care institutions.

Adolescent↗
PubMed1996

Inhibition of cataracts in moderately diabetic rats by aminoguanidine.

The effect of aminoguanidine (AG), an inhibitor of advanced glycation, on the development of cataracts was studied in diabetic rats. Rats were made diabetic with streptozotocin, and based on the level of plasma glucose they were grouped as moderately (< 350 mg dl-1 plasma glucose) and severely (> 350 mg dl-1 plasma glucose) diabetic. One half of the animals in each group received AG (25 mg kg-1 body weight each day), intraperitoneally, starting from the day of streptozotocin injection. Progression of lens opacification was recorded using Fundus and Scheimpflug photography at regular time intervals. On the ninetieth day all the rats were killed and the levels of advanced glycation end products (AGE) was determined by measuring the non-tryptophan fluorescence of the lens soluble and insoluble fractions. Densitometric analysis of Scheimpflug images showed that in diabetic rats lens opacification progressed in a biphasic manner, an initial slow progression for the first 60 days, followed by a steep increase during next 30 days. Moderately and severely diabetic rats developed lens opacities more or less at the same time. AGE fluorescence in the lens soluble fractions increased three-fold and seven-fold in the moderately and severely diabetic rats, respectively; whereas in insoluble fractions there was a 30% and three-fold increase in the moderately and severely diabetic rats, respectively. Although AG treatment inhibited the AGE fluorescence of lens soluble and insoluble fractions by about 56% and 75% in moderately diabetic and by 19% and 52% severely diabetic rats, respectively, the development of cataracts was delayed only in the moderately diabetic rats. These results thus suggest that the effect of AG is indeed inhibition of the formation of AGEs. However, in the severely diabetic rats the beneficial effect of AG is overwhelmed by the excessive accumulation of AGEs.

Animals↗
PubMed1996

Longitudinal tear study after cyclosporine in kidney transplant recipients.

PURPOSE: To determine Schirmer wetting (tear flow) in patients before and after kidney transplantation where systemic cyclosporine was used as an immunosuppressive. METHODS: Patients with end-stage renal disease who received living donor or cadaveric kidney transplants and simultaneous systemic cyclosporine were recruited. A 4-minute Schirmer test with topical anesthetic was performed in both eyes of each person before cyclosporine was initiated and three times after transplantation. The tear flow values from both eyes were averaged before analysis. RESULTS: Tear flow increased significantly from precyclosporine levels of 19.4 +/- 1.5 mm/4 minutes (mean +/- standard error of the mean, n = 7; readings at 1 to 3 days before cyclosporine was begun) to 28.4 +/- 2.4 mm/4 minutes at 1 to 2 months after cyclosporine (P < 0.01), 26.4 +/- 2.0 mm/4 minutes at 3 to 5 months (P < 0.05), and 24.4 +/- 2.1 mm/4 minutes at 9 to 18 months (P < 0.05) after initiation of cyclosporine therapy. No relation existed between tear flow and systemic cyclosporine concentration. CONCLUSION: Tear flow was significantly enhanced by systemic cyclosporine when given to renal allograft recipients as an immunosuppressive. The increased flow rate was sustained over the maximum follow-up of 18 months and indicates an unexpected, beneficial side effect of cyclosporine, even in the absence of a deficit in baseline tear production.

Adult↗
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↗