Search PubMed⌕ Search

Biomedical subjects

C Berry

Publications and source records attributed to C Berry.

At least 109 records · Page 6Linked to original sources
PubMed1995

Population and family studies of three disease-related polymorphic genes in systemic lupus erythematosus.

The contribution to systemic lupus erythematosus (SLE) of three lupus-associated polymorphisms (involving the C4A2 complement component, Humhv3005 and the T cell antigen receptor alpha chain gene) are investigated in 81 individuals from 14 multiplex SLE families, 41 unrelated lupus patients, and 88 unrelated healthy controls. The results show a strong association between C4A deletion and SLE in these families. While the current study confirms the previously reported association between hv3005 deletion and sporadic SLE, the study fails to support this association in familial SLE patients. Moreover, no correlation is detected between the occurrence of hv3005 deletion and C4A null alleles in lupus patients, suggesting that the effects of these genetic polymorphisms on predisposition to lupus are independent. The previously reported lupus-associated T cell receptor (TCR) alpha chain polymorphism is not detected in any of the individuals studied here. The combined data suggest that C4A null alleles predispose strongly to development of lupus, whereas the influence of hv3005 deletion is relatively weak. The results also suggest that contributions of weak susceptibility genes such as hv3005 to disease predisposition may be obscured by the effects of stronger genetic factors and thus need to be examined in patients lacking these factors.

Base Sequence↗
PubMed1995

Characteristics of repeat trauma patients, San Diego County.

Data on 22,312 admissions to the San Diego County Trauma System were used to identify 185 trauma patients admitted repeatedly to trauma units. These patients were compared with the entire group of nonrepeating trauma patients admitted during the 80-month period of the study. In comparison with nonrepeaters, the repeaters were younger, were more often men, were more often Black, and were much more frequently victims of assault. Forty-eight percent of the repeaters were injured by the same general mechanism on both admissions.

California↗
PubMed1995

Renal ultrasonography as a tool for detecting dynamic changes in blood pressure.

Renal ultrasonography has been used to assess renal blood flow under pathological conditions. We attempted to determine if sonographically derived renal resistive index measurements would be affected by subtle changes in flow as a consequence of transiently induced mild increases in blood pressure in persons with normal renal functioning. Nine subjects free of structural renal disease were studied with duplex Doppler ultrasonography. Main renal artery resistive indices were determined under resting baseline conditions and in response to graded infusions of phenylephrine sufficient to increase blood pressure by approximately 13/5 mm Hg. Change in blood pressure correlated with the change in main renal artery resistive index (r = 0.254, P < 0.05). Thus, the resistive index varies in association with transient increases in blood pressure and may reflect concurrent alterations in distal resistance under physiologic conditions.

Blood Pressure↗
PubMed1995

A rapid indirect method to determine the plasma concentrations of neutral endopeptidase inhibitors.

The selection of therapeutic agents for clinical development is principally based upon pharmacodynamic and pharmacokinetic criteria. Although many compounds are routinely tested in pharmacologic assays, direct pharmacokinetic assessment is difficult and not applicable to a large number of agents. Therefore, we have developed a rapid indirect method based on enzyme inhibition for determining the unbound concentration of NEP 24.11 inhibitors in rat plasma. In the present study, drug levels of compounds from three different classes of NEP 24.11 inhibitors: mercaptoalkyl, carboxyalkyl and aminophosphonates were compared. Studies were carried out in conscious, unrestrained rats. Arterial blood samples were obtained 10, 30, 60, 120, and 240 min after drug administration at 10 mg/kg i.v. or 30 mg/kg p.o. The blood was collected in EDTA and plasma prepared immediately. Protein bound NEP inhibitor was separated from plasma by centrifugation through an ultrafiltration membrane. Following acidification and serial dilution, the concentration of unbound inhibitor was determined in the plasma ultrafiltrate using the in vitro assay for NEP 24.11 inhibition. The results of this study indicated that the mercaptoalkyl inhibitor thiorphan was cleared rapidly from plasma, whereas, the plasma concentrations of the carboxyalkyl inhibitor CGS 23880A (UK-69,578), and the plasma concentrations of the aminophosphonate, CGS 24128, were maintained at high levels for at least 4 hours. Furthermore, the ratio of the NEP inhibitor concentration/IC50 value correlated well with the pharmacologic activity of these compounds.

Animals↗
PubMed1994

High level expression and characterisation of Plasmepsin II, an aspartic proteinase from Plasmodium falciparum.

DNA encoding the last 48 residues of the propart and the whole mature sequence of Plasmepsin II was inserted into the T7 dependent vector pET 3a for expression in E. coli. The resultant product was insoluble but accumulated at approximately 20 mg/l of cell culture. Following solubilisation with urea, the zymogen was refolded and, after purification by ion-exchange chromatography, was autoactivated to generate mature Plasmepsin II. The ability of this enzyme to hydrolyse several chromogenic peptide substrates was examined; despite an overall identity of approximately 35% to human renin, Plasmepsin II was not inhibited significantly by renin inhibitors.

Amino Acid Sequence↗
PubMed1994

N-Phosphonomethyl dipeptides and their phosphonate prodrugs, a new generation of neutral endopeptidase (NEP, EC 3.4.24.11) inhibitors.

Inhibitors of the zinc protease neutral endopeptidase (NEP, EC 3.4.24.11) offer significant therapeutic interest as antihypertensives due to their ability to potentiate the biological action of the circulating natriuretic hormone ANF (atrial natriuretic factor). N-Phosphonomethyl dipeptides bearing a central (4-phenyl)phenylalanine residue have been designed to exert potent and selective NEP inhibition. In particular, (S)-3-[N-[2- [(phosphonomethyl)amino]-3-(4-biphenylyl)propionyl]amino]propionic acid (10a) (CGS 24592) displayed high inhibitory potency in vitro (IC50 = 1.9 +/- 0.1 nM) and a long plasma half-life in rats but lacked oral bioavailability. This drawback was overcome by using esterase-sensitive (acyloxy)alkyl phosphonates. More remarkable, several diaryl phosphonate derivatives of 10a also performed as effective prodrugs. Specifically, the structurally simple diphenyl phosphonate 18 (CGS 25462) induced potent inhibition of NEP ex vivo for at least 8 h after oral administration to rats (30 mg/kg). Its antihypertensive effect was demonstrated in DOCA-salt rats. At 30 mg/kg orally, 18 caused a significant reduction in mean arterial pressure measuring -35 +/- 7 mmHg at 5-h postdosing. The alpha-aminomethyl phosphonate 18 represents a new generation of selective NEP inhibitors that combine high potency, long duration of action, and oral bioavailability. Therefore, it holds promise as a novel therapeutic agent for the treatment of human hypertension and congestive heart failure.

Animals↗
PubMed1994

Sequence, expression and modeled structure of an aspartic proteinase from the human malaria parasite Plasmodium falciparum.

A clone encoding the aspartic proteinase (PFAPD) from Plasmodium falciparum strain HB3 was obtained during the course of a project designed to sequence and identify the protein coding regions of the parasite's genome. The protein encoded by the clone contains a sequence identical to the N-terminal sequence determined for an aspartic proteinase isolated from the digestive vacuole of P. falciparum and demonstrated to participate in the hemoglobin digestive pathway (D. Goldberg, personal communication). The translated polypeptide sequence encompasses a number of features characteristic of aspartic proteinases, having > 30% identity and > 50% similarity overall to human cathepsin D, cathepsin E and renin. A model of the three-dimensional structure of PFAPD was constructed using rule-based procedures. This confirms that the primary sequence may be folded as a single chain into a three dimensional structure closely resembling those of other known aspartic proteinases. It includes a lengthy prosegment, two typical-hydrophobic-hydrophobic-Asp-Thr/Ser-Gly motifs and a tyrosine residue positioned in a beta-hairpin loop. The distribution of hydrophobic residues throughout the active site cleft is indicative of a likely preference for hydrophobic polypeptide substrates. The recombinant form of this enzyme expressed using the pGEX2T vector in Escherichia coli is active in digesting hemoglobin at acidic pH and in hydrolyzing a synthetic peptide corresponding to the putative initial cleavage site in hemoglobin. Activity is inhibited completely by pepstatin, confirming the identity of PFAPD as a member of the aspartic proteinase family. Specific mRNA for PFAPD is expressed in the erythrocytic stages of the life cycle.

Amino Acid Sequence↗
PubMed1994

Blood cell deformability in horses with intestinal colic.

Hematologic and rheologic variables were examined in a group of 13 horses with intestinal colic and a control group of 6 horses. All horses had been recently transported to the veterinary teaching hospital, and blood samples were obtained during initial examination. There were no significant differences in blood neutrophil count or plasma fibrinogen concentration between the groups, and PCV was significantly increased in horses with intestinal colic. Cell filterability was measured by passing uniform concentrations of blood, erythrocytes, and neutrophils through micropore filters. There were no significant differences between the control and intestinal colic groups in filterability of erythrocytes. Significant (P < 0.05) prolongation in filterability of blood and neutrophils was observed in the group of horses with intestinal colic, compared with the control group. This neutrophil change, indicative of decreased neutrophil deformability, corresponded with severity of the illness. Horses that failed to survive the intestinal colic episode had significantly (P < 0.05) prolonged blood and neutrophil filterability, compared with horses that survived intestinal colic. These findings indicate that deformability of neutrophils decreases in horses with intestinal colic, possibly a result of endotoxin-induced activation. This change can further impede microvascular blood flow that is altered in association with intestinal ischemia.

Analysis of Variance↗
PubMed1993

Risk factors for development of rhegmatogenous retinal detachment in patients with cytomegalovirus retinitis.

We studied 259 patients to determine the time-dependent risk and risk factors for the development of retinal detachment in patients with cytomegalovirus retinitis. The six-month and one-year retinal detachment rates (by eye) were 11% and 24%, respectively. Increasing retinal surface involvement outside of the posterior pole and the presence of retinitis activity were found to be the two covariates that best predicted retinal detachment. Eyes with peripheral involvement greater than 25% had a fivefold risk for detachment, compared to eyes with 10% involvement. If there was retinitis activity and more than 25% peripheral (external to major vascular arcades) involvement, the risk increased to 24-fold. The presence of a fellow eye with retinal detachment was not an independent risk factor. These observations should help in the design of a prophylactic trial intended to prevent retinal detachment and should also help ophthalmologists counsel patients with cytomegalovirus retinitis.

AIDS-Related Opportunistic Infections↗
PubMed1993

Fatal disseminated intravascular coagulation complicating dental extraction.

A case is reported of fatal disseminated intravascular coagulation occurring 8 h after routine extraction of wisdom teeth in a 24-year-old woman. Since all bacteriological specimens taken were sterile and no other precipitant was found, we believe this case represents an example of the generalised Shwartzman reaction to the local trauma of dental extraction leading to fatal initiation of the coagulation system.

Adult↗
PubMed1993

Genetic determinants of host ranges of Bacillus sphaericus mosquito larvicidal toxins.

The 51.4-kDa-41.9-kDa binary toxin produced by different strains of Bacillus sphaericus shows differential activity toward Culex quinquefasciatus, Aedes atropalpus, and Aedes aegypti mosquito larvae. The patterns of larvicidal activity toward all three mosquito species and growth retardation in A. aegypti have been shown to be due to the 41.9-kDa protein. By using mutant toxins expressed in Escherichia coli, insecticidal activity and growth retardation correlated with amino acids centered around position 100 of the 41.9-kDa protein. In its response to these toxins, A. atropalpus resembled C. quinquefasciatus rather than its congener, A. aegypti.

Aedes↗
PubMed1993

Cytotoxicity and ADP-ribosylating activity of the mosquitocidal toxin from Bacillus sphaericus SSII-1: possible roles of the 27- and 70-kilodalton peptides.

Clones expressing regions of the 100-kDa Bacillus sphaericus SSII-1 mosquitocidal toxin (Mtx) as fusion proteins with glutathione S-transferase were constructed, and the toxin-derived peptides were purified. The in vitro ADP-ribosylation activities of these peptides and their effects on larvae and cells in culture were studied. Mtx25 (amino acids 30 to 493) was found to ADP-ribosylate two proteins with molecular masses of 38 and 42 kDa, respectively, in Culex quinquefasciatus (G7) cell extracts, in addition to ADP-ribosylating itself. Mtx21 (amino acids 30 to 870; or a combination of Mtx25 and Mtx26 (amino acids 259 to 870) caused mortality in C. quinquefasciatus larvae. Mtx25, Mtx26, or Mtx24 (amino acids 30 to 276) alone and Mtx24 in combination with Mtx26 were not toxic to larvae. Mtx21 and Mtx26 produced marked morphological changes in G7 cells and to a lesser extent in Aedes aegypti cells but had no effect on Anopheles gambiae or HeLa cells. Thus, a domain in the N-terminal region of the Mtx protein is sufficient for ADP-ribosylation of C. quinquefasciatus cell protein, and a domain in the C-terminal region is sufficient for toxicity to cultured C. quinquefasciatus cells; however, both regions are necessary for toxicity to mosquito larvae.

Adenosine Diphosphate Ribose↗
PubMed1993

Disposition of thiorphan in DOCA-salt and spontaneously hypertensive rats.

Thiorphan was administered intravenously (i.v.) at 10 mg/kg to conscious rats in two different models of hypertension to allow a comparison of pharmacokinetics. The two models were: 1) Deoxycorticosterone acetate (DOCA)-salt uninephrectomized rats; 2) Spontaneously hypertensive rats (SHR), and their respective normotensive controls; 3) Sprague-Dawley (SD) rats; and 4) Wistar-Kyoto rats (WKY). Pharmacokinetic parameters were calculated for total and unbound thiorphan in plasma. In normotensive SD and WKY rats, the volume of distribution, clearance and plasma protein binding of thiorphan were not significantly different. Furthermore, the apparent elimination half-life was not significantly different for total or unbound thiorphan amongst all models. The volume of distribution and plasma clearance for both unbound and total thiorphan, however, were lower in DOCA-salt rats when compared to normotensive control rats by 61-66% and 46-51%, respectively. In contrast, pharmacokinetic parameters for both unbound and total thiorphan were not significantly different between SHR and WKY rats. These results indicate that reduced clearance of thiorphan in DOCA-salt rats may be due to the co-administration of DOCA-salt or altered renal function of the hypertrophic remaining kidney and not solely due to hypertension.

Animals↗
PubMed1993

Association between neonatal care practices and efficacy of exogenous human surfactant: results of a bicenter randomized trial.

The purpose of this study was to analyze the impact of neonatal care practices on the efficacy of exogenous human surfactant. Two hundred newborns (gestational age 24.0 to 29.9 weeks, lecithin-sphingomyelin ratio less than 2 or absent phosphatidylglycerol, and requirement of mechanical ventilation at birth) participated in a randomized bicenter trial of human surfactant substitution. In only one of the two sites (site 2) surfactant substitution decreased the severity of respiratory failure and increased neonatal survival without bronchopulmonary dysplasia. For analysis of three-way association, continuous variables describing patient characteristics and treatment were dichotomized at the median. The following variables were significantly associated with good outcome in site 1 and 2 and with surfactant substitution in site 2: low oxygen requirement during first three neonatal days, low mean airway pressure during second and third day, low PaCO2 during first two neonatal days, and no ligation of ductus arteriosus. Low fluid intake during the first three days and low colloid intake during the first two days of life were associated with good outcome in both sites. The ratio between mean airway pressure and the oxygen requirement was higher in site 2 than in site 1 during the first day of life. Fluid intake and ventilatory management may influence the efficacy of exogenous surfactant.

Humans↗