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Biomedical subjects

J Bigelow

Publications and source records attributed to J Bigelow.

17 recordsLinked to original sources
PubMed2004

A picture of amputees and the prosthetic situation in Haiti.

PURPOSE: The purpose of this study is to present the situation of Haitian amputees and to outline some of the major barriers in Haiti that prevent people from receiving prosthetic treatment. METHOD: Interviews were conducted with amputees throughout Haiti using a 42-question questionnaire. Additionally, interviews were conducted with traditional healers, health care workers, and leaders of handicap associations. Each interview was manuscripted and the data were subsequently coded and analysed in the USA. RESULTS: There are three full-time prosthetic shops and two part-time prosthetic shops in Haiti, all of which are severely limited in the scope of services they are able to provide amputees due to insufficient supplies and inadequately trained personnel. Only 25% of the 164 amputees interviewed had ever had a prosthetic limb. Typically prosthetic treatment is inaccessible and unaffordable for amputees, which prevents many from seeking treatment. The most common cause of amputation in Haiti is infection, followed by motor vehicle accidents. CONCLUSION: There must be additional cooperation between Haitian patients, doctors, traditional healers, prosthetists, and government officials in order to provide more adequate prosthetic care. Prosthetic treatment in Haiti can be successful with cooperation of different entities, proper rehabilitation therapy, adequately trained personnel, and development of culturally appropriate limbs.

Adolescent↗
PubMed1998

Inhibition of in vitro and in vivo HIV replication by a distamycin analogue that interferes with chemokine receptor function: a candidate for chemotherapeutic and microbicidal application.

Select chemokine receptors act as coreceptors for HIV-1 entry into human cells and represent targets for antiviral therapy. In this report we describe a distamycin analogue, 2,2'-[4, 4'-[[aminocarbonyl]amino]bis[N,4'-di[pryrrole-2-carboxamide- 1, 1'-dimethyl]]-6,8-naphthalenedisulfonic acid]hexasodium salt (NSC 651016), that selectively inhibited chemokine binding to CCR5, CCR3, CCR1, and CXCR4, but not to CXCR2 or CCR2b, and blocked chemokine-induced calcium flux. Inhibition was not due to nonspecific charge interactions at the cell surface, but was based on a specific competition for the ligand receptor interaction sites since the inhibitory effect was specific for some but not all chemoattractant receptors. NSC 651016 inhibited in vitro replication of a wide range of HIV-1 isolates, as well as HIV-2 and SIV, and exhibited in vivo anti-HIV-1 activity in a murine model. In contrast, a distamycin analogue with similar structure and charge and the monomeric form of NSC 651016 demonstrated no inhibitory effects. These data demonstrate that molecules which interfere with HIV-1 entry into cells by targeting specific chemokine coreceptors can provide a viable approach to anti-HIV-1 therapy. NSC 651016 represents an attractive candidate for the chemotherapeutic treatment of HIV-1 infection and as a microbicide to prevent the sexual transmisssion of HIV-1. Moreover, NSC 651016 can serve as a template for medicinal chemical modifications leading to more effective antivirals.

Administration, Cutaneous↗
PubMed1997

Nonphosphorylated peptide ligands for the Grb2 Src homology 2 domain.

Critical intracellular signals in normal and malignant cells are transmitted by the adaptor protein Grb2 by means of its Src homology 2 (SH2) domain, which binds to phosphotyrosyl (pTyr) residues generated by the activation of tyrosine kinases. To understand this important control point and to design inhibitors, previous investigations have focused on the molecular mechanisms by which the Grb2 SH2 domain selectively binds pTyr containing peptides. In the current study, we demonstrate that the Grb2 SH2 domain can also bind in a pTyr independent manner. Using phage display, an 11-amino acid cyclic peptide, G1, has been identified that binds to the Grb2 SH2 domain but not the src SH2 domain. Synthetic G1 peptide blocks Grb2 SH2 domain association (IC50 10-25 microM) with a 9-amino acid pTyr-containing peptide derived from the SHC protein (pTyr317). These data and amino acid substitution analysis indicate that G1 interacts in the phosphopeptide binding site. G1 peptide requires a YXN sequence similar to that found in natural pTyr-containing ligands, and phosphorylation of the tyrosine increases G1 inhibitory activity. G1 also requires an internal disulfide bond to maintain the active binding conformation. Since the G1 peptide does not contain pTyr, it defines a new type of SH2 domain binding motif that may advance the design of Grb2 antagonists.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Controlled trial of 4-ASA in ulcerative colitis.

A six-week placebo-controlled trial of the efficacy and safety of 6 g per day of 4-aminosalicylic acid (4-ASA) was conducted in 30 subjects with mild to moderately severe ulcerative colitis. Subjects were stratified into groups having distal (< 60 cm) or more extensive (> 60 cm) disease. Diarrhea, bleeding, sigmoidoscopic and biopsy appearance, and physician global assessment were scored to judge efficacy. Safety was evaluated by monitoring untoward symptoms and laboratory values. Median percent improvement was significantly greater (P < 0.05) in the 4-ASA > 60-cm group (42.7%) than in the placebo > 60-cm group (21.2%), but 4-ASA was not better than placebo for the < 60-cm group or the total study group. Severe dyspepsia (one subject), abnormal AST (transient in five, persistent in one) and elevated lipase without pancreatitis (six subjects) were noted. Thus 6 g 4-ASA for six weeks was more effective than placebo in mild to moderate ulcerative colitis extending more than 60 cm above the anus, but not in distal disease, and the drug was generally well tolerated.

Aminosalicylic Acid↗
PubMed1995

Monocyte chemoattractant activity associated with human colon mucosal cells.

Mucosal epithelial cell preparations from 18 disease-free segments of human colon resections and 7 cell lines were examined for chemoattractant properties. Mucosal cells were dissociated from lamina propria by sequential incubations in ethylenediaminetetraacetic acid, harvested at 1.5 x 10(6) cells/ml, and lysed. Lysates were tested for chemoattractant activity for monocytes and neutrophils. Chemoattractant preparations were further purified by gel filtration chromatography, and amino acid analysis was performed on selected chemoattractant fractions. Mucosa from normal bowel exhibited significant chemoattractant properties for monocytes, up to 15 times greater than for neutrophils. Checkerboard analysis indicated chemotaxis rather than chemokinesis. Neither cell culture nor lamina propria cell lysates exhibited statistically significant chemoattraction, although activity was evident in certain preparations of isolated cell cultures. Chromatography of human mucosal chemoattractant preparations consistently gave peaks of activity in the 2000 dalton range. These yielded consistent amino acid profiles, with aspartic acid, glutamic acid, glycine, alanine, and lysine being dominant in all preparations. This peptide is apparently different from other known chemotactic agents and could play a role in recruitment of mononuclear phagocytes to the mucosa of the human colon.

Amino Acids↗
PubMed1990

Luminal concentrations of orally ingested 4-aminosalicylic acid as determined by in-vivo equilibrium dialysis.

We measured 4-aminosalicylic acid (4-ASA) levels in faecal water by in-vivo equilibrium dialysis during oral ingestion of drug by two different dose protocols (A and B). In Protocol A, 5 normal subjects ingested 3 g of 4-ASA as the free acid and 20 mg of metaclopromide per day. On Day 5, small dialysis sacs filled with dextran 40 were ingested and the oral drug was continued until the sacs were retrieved from the stool. Protocol B followed the same format except that 3 g of 4-ASA was ingested twice daily and metaclopromide was omitted. In both protocols concentrations of 4-ASA and N-acetylated 4-ASA in sac contents were measured by HPLC. In-vitro dialysis studies showed bi-directional equilibrium was reached within 120 min. During Protocol A, intraluminal concentrations of total 4-ASA ranged from 14.0 to 32.2 mmol/L with a mean of 20.6 mmol/L. With Protocol B, total 4-ASA levels ranged from 20.1 to 41.3 mmol/L with a mean of 33.9 mmol/L. From 90 to 99% of the drug in the dialysates was N-acetylated. These concentrations of total 4-ASA are similar to those of 5-ASA after ingestion of therapeutic doses of sulphasalazine or absorption-resistant formulations of 5-ASA. Thus, oral 4-ASA could have a role in the treatment of inflammatory bowel disease.

Acetylation↗
PubMed1986

Mechanism of binding of a benzomorphan opiate to the acetylcholine receptor from Torpedo electroplaque.

The mechanism of binding of the benzomorphan opiate, (-)-N-allylnormetazocine [(-)-ANMC], to Torpedo acetylcholine receptor (AcChR)-rich membranes was investigated. Using a centrifugation assay, two equilibrium binding affinities were observed with KD values of 0.4 and 2 microM. The KD and the apparent Bmax of the higher affinity component were decreased by cholinergic agonists and antagonists but not by alpha-bungarotoxin alone. The high affinity binding site (KD = 0.4 microM) was found to be distinct from the binding site for tetracaine, a noncompetitive blocker. The apparent association rate constant was essentially independent of receptor concentration both in the presence and absence of the cholinergic agonist, carbamoylcholine. When carbamoylcholine was equilibrated with the AcChR prior to (-)-[3H]ANMC addition, the association rate constant was 2- to 3-fold greater than in the absence of cholinergic effectors. When carbamoylcholine and (-)-[3H]ANMC were added simultaneously to AcChR-rich membranes, association was too rapid to resolve manually and binding measured at 5 sec was greater than the equilibrium level both in the presence and absence of carbamoylcholine. Binding decreased as a function of time, reaching its equilibrium level with a time constant of approximately 1 min. This effect appeared to be agonist specific since it was not observed when the antagonist, d-tubocurarine, replaced carbamoylcholine. In the absence of cholinergic ligands, dissociation of (-)-ANMC was biphasic (t1/2 values of less than 5 sec and approximately 2.5 min) and, in the presence of cholinergic ligands, was monophasic (t1/2 of 40 sec). The simultaneous addition of carbamoylcholine and (-)-[3H]ANMC to the membranes initially results in a biphasic dissociation (t1/2 of 5 and 30 sec) which becomes monophasic with increasing times of incubation. A mechanism is proposed involving an isomerization of the receptor-ligand complex which agrees quantitatively and qualitatively with the data.

Affinity Labels↗
PubMed1983

Male mouse (Mus musculus) ultrasonic vocalizations to female urine: why is heterosexual experience necessary?

Previous research was consistent with the hypothesis that urinary chemosignals from female mice (Mus musculus) serve as a conditioned stimulus (CS) for the elicitation of male ultrasonic courtship vocalizations while some other unknown aspect of the female serves as an unconditioned stimulus (US). According to this hypothesis adult heterosexual experience is necessary for males to pair the urinary CS with the US. Three experiments further examined this hypothesis. Experiment 1 demonstrated that the hypothesized US was not female behavior. Experience with anesthesized males and females was just as effective as experience with awake conspecifics. Experiments 2 and 3, however, question the primacy of the Classical Conditioning hypothesis. In both experiments sexually naive males were allowed contact with either normal females or female surrogates. The female surrogates were neonatally castrated males (Experiment 2) or hypophysectomized females (Experiment 3), both of which appeared to possess the hypothesized US but not the urinary CS on the basis of previous research. While exposure to normal females caused the highest level of vocalization to urine from normal females, exposure to the two classes of female surrogates also resulted in vocalizations to the urine of normal females. Thus under some circumstances, males do not require experience with a normal female to emit ultrasounds to urine from normal females. Factors in addition to Classical Conditioning must be operating to account fully for the role of adult heterosexual experience in causing female urine to come to elicit male courtship vocalization.

Animals↗
PubMed1982

Evaluation of the MICUR system for quantitative antimicrobial susceptibility testing: a multiphasic comparison with reference methods.

Four laboratories participated in a three-phase study to evaluate the MICUR antimicrobial broth microdilution system (Boehringer Mannheim Diagnostics, Inc., Houston, Tex.). The dried-antimicrobial agent MICUR system was compared with a reference broth microdilution method (National Committee for Clinical Laboratory Standards) by using 304 recently isolated clinical strains and two collections of stock or challenge organisms. Of 7,092 minimum inhibitory concentration (MIC) datum pairs derived from the clinical isolates, 96.6% were within an acceptable (+/- 1 log2 dilution) range. MICUR MICs agreed with the reference broth microdilution method MICs in 95.3% of 6,840 MIC pair determinations performed on stock or challenge cultures. The MICUR intralaboratory reproducibility within +/- 1 log2 dilution step for the clinical isolates was 98.4%. The MICUR intralaboratory and interlaboratory reproducibilities for 26 stock cultures were 98.4 and 95.1%, respectively. For 180 challenge cultures (4,199 MIC pairs) which were included in the MICUR testing to provide a wide variety of antimicrobial susceptibility and resistance patterns, the results for 92.5% were in close agreement with the reference broth microdilution results. No specific resistance mechanism went unrecognized by this new commercial system. The MICUR system gives comparable MIC results when evaluated against the reference broth microdilution method, and it would be acceptable for use in clinical microbiology laboratories.

Anti-Bacterial Agents↗
PubMed1980

Kallikrein content of rat pancreatic acinar cells or islets by direct radioimmunoassay.

Recent reports have suggested that kallikreins may enzymatically convert proinsulin to insulin. The quantity of rat pancreatic kallikrein in isolated Islets of Langerhans, acinar cells and in whole pancreatic extracts was measured by direct radioimmunoassay and bioassay. Immunoreactive kallikrein content in acinar cells was 813 +/- 111 ng/mg protein (mean +/- S.E.M.). In whole pancreatic homogenates, it was 1303 +/- 213 ng/mg protein. Appreciable quantities of the enzyme were not detected in islets. Kallikrein activity as measured with a rat uterine bioassay had similar distribution. Because of the localization of kallikrein, it is unlikely that the enzyme is involved in the in vivo conversion of proinsulin to insulin.

Animals↗