Biomedical subjects

M Gibson

Publications and source records attributed to M Gibson.

At least 109 records · Page 6Linked to original sources

PubMed1992

Interleukin 4 induces the maturation of idiotype-specific regulatory B cell populations.

CD5+ B cells have been shown to be disproportionately associated with autoimmune diseases and transformation. In many cases, their apparent ability to bypass self-tolerance is manifested by the production of autoantibodies. These observations, plus the hypothesis that CD5+ B cells represent a distinct B cell lineage, encourage studies into the conditions and factors that influence their development. In the present study, we employed a well-established assay for murine CD5+ B cell function, i.e., their ability to augment the responses of IgHb-linked idiotypic determinants on anti-(4-hydroxy-3-nitrophenyl) acetyl (NP) antibody (Nbb) idiotype-bearing CD5- B cells to a T-independent antigen, together with multiple methods of cell surface phenotyping, to evaluate the potential for interleukin (IL) 4 to effect maturation of CD5+ B cells, CD5+, IgM+, Thy-1-, and NPb idiotype-specific cells panned on antibody-coated petri dishes or sorted by flow cytometry from spleen were capable of augmenting NPb idiotypic responses of NP-KLH-primed responder cells to NP-Ficoll. Splenic B cell populations depleted of CD5+ B cells failed to affect idiotype expression even after 2 days in culture, a time when a small percentage of CD5+ B cells appeared to be regenerated. However, idiotype-specific regulatory activity could be restored in CD5- splenic B cell populations by culture for 2 days with recombinant IL-4. Cells responsible for idiotype-specific regulatory activity after culture with IL-4 were in fact CD5+, IgM+, and Thy-1.2- B cells, demonstrating that IL-4 can drive the functional, if not the phenotypic, maturation of splenic B cells associated with the CD5+ B cell lineage. The results illustrate one possible mechanism by which T cells could control the maturation of cells belonging to the CD5+ B cell lineage.

Animals↗

PubMed1992

Investigation and treatment of poor drains of dialysate fluid associated with anterior abdominal wall leaks in patients on chronic ambulatory peritoneal dialysis.

Reduced dialysate fluid volume and genital and abdominal-wall oedema occurring many months after initiation of continuous ambulatory peritoneal dialysis (CAPD) has been investigated in 20 patients using computed tomographic peritoneography. Leaks into the anterior abdominal wall at the site of insertion of the Tenckhoff catheter have been demonstrated in a series of 14 patients. Nocturnal peritoneal dialysis alone led to resolution of leaks in four of the nine patients who underwent this mode of treatment. Four of the failures plus a further four patients successfully underwent either resuture of the peritoneum or replacement of the catheter. A policy for management of proven anterior abdominal-wall leaks in CAPD patients is described, consisting of nocturnal peritoneal dialysis for 2 weeks followed by surgical intervention if the former is unsuccessful.

Abdominal Muscles↗

PubMed1992

Fetal ascitic fluid: a new source of lymphocytes for rapid chromosomal analysis.

BACKGROUND: The cells found in ascites can be processed like amniotic fluid for fetal karyotyping. We have characterized these cells and used them for a rapid cytogenetic result. CASES: Three patients presented with massive fetal ascites detected by sonography. Samples of ascitic fluid were obtained at fetal paracentesis. Cells from the fluid were cultured using standard methods for fetal blood, and were compared with fetal blood lymphocytes and amniocytes. The length of time in culture, chromosome morphology, and mitotic index of ascitic fluid cells were equivalent to those of fetal blood. In the third case, we performed immunophenotyping on the ascitic fluid cells. CONCLUSION: Ascitic fluid contains lymphocytes that permit rapid chromosomal analysis within 96 hours.

Adult↗

PubMed1992

CA-125 levels in human uterine fluid.

OBJECTIVE: To measure uterine fluid CA-125 concentration and to determine if any menstrual cycle phase dependent changes exist in its level. Serum levels are measured for comparison. DESIGN: CA-125 levels in uterine fluid were measured during the follicular and luteal phases of the menstrual cycle. In a sequential study, paired uterine fluid and serum samples were obtained once in both midfollicular and midluteal phases of the same menstrual cycle. RESULTS: CA-125 in uterine fluid during the follicular phase (n = 14) ranged from 16.4 x 10(3) to 616.5 x 10(3) U/mL, and from 6.2 x 10(3) to 567.3 x 10(3) U/mL in the luteal phase (n = 11). In the paired sequential uterine fluid and serum samples, (1) the means (+/- SEM) CA-125 in uterine fluid were 81.5 x 10(3) +/- 37.9 x 10(3) U/mL and 91.4 x 10(3) +/- 56.8 x 10(3) U/mL in the midfollicular and midluteal phases, respectively (P = 0.75); (2) the CA-125 levels in serum increased in the midluteal phase (P less than 0.05); and (3) compared with serum, uterine fluid levels were greater with a wider range. CONCLUSIONS: When compared with serum CA-125, uterine fluid contains high concentrations varying over a wide range without fluctuation between the follicular and luteal phases of the menstrual cycle.

Adult↗

PubMed1991

Studies on the stability of trimelamol, a carbinolamine-containing antitumor drug.

The stability of trimelamol (N2,N4,N6-trimethylol-N2,N4,N6-trimethylmelamine) a synthetic carbinolamine-containing antitumor drug, has been studied. Two major degradation pathways have been characterized and a unified mechanism proposed to rationalize the chemistry involved. One degradation pathway involves the consecutive loss of hydroxymethylene units by elimination of formaldehyde until the parent trimethylmelamine (4) results. An HPLC method was used to obtain kinetic data for the loss of trimelamol and to monitor the order of appearance of three degradation products. This pathway was shown to follow first-order kinetics at all pH values studied at both 18 and 37 degrees C. The second pathway involves the coupling of two trimelamol molecules via a methylene bridge to form bis(trimelamol) (6) which had been previously referred to in the literature as a "polymer". This reaction is acid catalyzed and temperature dependent. Bis(trimelamol) is virtually water insoluble and adheres strongly to glass surfaces. Finally, t1/2 values have been determined for trimelamol in aqueous solution at different temperatures, and the kinetics of formation of degradation products has been studied over a period of 30 h under a variety of conditions of pH and temperature. The data reported here are relevant to both the formulation and clinical administration of trimelamol, and may contribute to an understanding of mechanism of action and future analogue development studies.

Chromatography, High Pressure Liquid↗

PubMed1991

Estrogen receptor stereochemistry: ligand binding and hormonal responsiveness.

Estrogen stimulation of the uterus produces a spectrum of biochemical responses that are customarily linked together. This report is an overview of a series of studies by our laboratory investigating the role of different ligand structures in eliciting hormonal responses. Diethylstilbestrol (DES) and certain structural analogs, indenestrol A (IA), indenestrol B (IB), and pseudo-DES, were used as probes to segregate various genomic responses previously considered interrelated, most notably the events of specific protein synthesis and DNA synthesis. These compounds have weak uterotrophic activity; however, they interact with high affinity specifically with mouse uterine estrogen receptors (ERs). All of them produce stoichiometrically similar amounts of ER complex in the nucleus. Indenestrol A and IB possess a single chiral carbon atom and exist as a mixture of enantiomers (ENTs). Competitive binding assays of pure ENTs and cytosolic ERs demonstrated a stereochemical chiral preference for the IA isomer but not IB. This preference was also evident from nuclear ER occupancy experiments. Biologic activity of the IA ENTs also demonstrated differences as seen by receptor binding. Ornithine decarboxylase (ODC) activity was stimulated 600% by DES and partially by IA (rac). All of the ODC activity produced by IA (rac) was due to the IA(C3)-S ENT. Uterine DNA synthesis was measured after treatment with the IA compounds. Indenestrol A (rac) increased DNA synthesis to 40% of the level seen with DES. The weak ENTs showed no activity and the active ENTs were weaker than the IA racemic. These compounds should be useful probes for studying the individual responses involved in estrogen-induced uterine growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Error in histologic dating of secretory endometrium: variance component analysis.

OBJECTIVE: To characterize the extent and sources of imprecision in histologic dating of the endometrial biopsy. DESIGN: Duplicate endometrial biopsies from 25 women were dated by five evaluators on two separate occasions to evaluate the overall precision of the measure. Using variance component analysis, estimates of intrauterine, intraevaluator, and interevaluator variability were determined. SETTING: Samples were obtained during outpatient fertility testing. Evaluators were colleagues at the same institution. PATIENTS, PARTICIPANTS: Women presenting with infertility undergoing routine evaluation. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Variability in histologic dating of the endometrium. RESULTS: Inconsistencies between evaluators accounted for 65% of the observed variability, whereas 27% was because of inconsistencies in duplicate readings by the same evaluator. Regional differences in the uterus accounted for only 8% of the total variability. CONCLUSIONS: The overall error from these sources have the potential to result in a substantial false-positive rate for diagnosis of luteal phase defect.

Analysis of Variance↗

PubMed1991

Pathophysiology of luteal-phase deficiency in human reproduction.

There are numerous probable mechanisms for the clinical occurrence of a luteal-phase deficiency. Defects may occur in either the proliferative, luteal, or luteal-rescue stage of a menstrual cycle. In each of these three domains, alterations in the trophic stimulation or the response at either the ovarian or endometrial level further subdivide the etiologies for luteal-phase deficiency. Additional development of new concepts in the areas of intraovarian signaling, the possible role of growth factors, and the measurement of newly discovered luteal products will enable us to expand our thought process. With a better understanding of the pathophysiology of luteal-phase deficiency, it is anticipated that new treatments will be devised to address precisely a given specific etiologic factor.

Corpus Luteum↗

PubMed1991

The provision of ophthalmic services for a rehabilitation day care centre population with multiple physical handicaps.

The provision of the wide variety of support services necessary for patients with multiple handicaps is often poorly coordinated. In this study a group of 108 adults, aged from 19 to 90 years, who suffered from multiple physical handicaps and attended a rehabilitation day care centre, had their visual functions and requirements assessed by a multidisciplinary team. The programme consisted of five stages. Each patient was initially screened and subsequently referred for more detailed optometric, ophthalmological, low vision or rehabilitation assessments, where appropriate. Results indicated that many of the patients had not been receiving regular ocular assessments and would benefit from the provision of an optical appliance or ophthalmological treatment. The survey provided staff at the rehabilitation centre with information on the visual status of individual patients and enhanced general eye-care awareness.

Adult↗

PubMed1991

Short-term modulation of gonadotropin secretion by progesterone during the luteal phase.

Progesterone (P) levels were acutely augmented by intravenous (IV) infusion in seven women in the midluteal phase to ascertain if short-term changes in P levels have an effect on gonadotropin secretion. During four 6-hour intervals of alternating control and IV P infusion, each subject underwent blood sampling for luteinizing hormone (LH), follicle-stimulating hormone (FSH), and P every 20 minutes for 24 hours. As a result of the P infusions, mean (+/- SE) P levels rose 72% from a control level of 26.24 +/- 2.13 to 45.22 +/- 3.47 nmol/L, whereas mean LH levels were reduced by 20% from a control level of 4.82 +/- 0.67 to 3.85 +/- 0.66 IU/L. During P infusions, mean LH pulse amplitude was reduced by 33% from 3.33 +/- 0.37 to 2.23 +/- 0.28 IU/L. The mean LH interpulse interval increased by 93% (2.56 +/- 0.14 to 4.92 +/- 0.15/h) when the interval between pulses was interdicted by the onset of P infusion. The infusion of P reduced mean FSH levels by 10% from 3.34 +/- 0.41 to 3.01 +/- 0.35 IU/L. These findings suggest that acute elevations in P levels within the physiological range have a short-term inhibitory effect on gonadotropin secretion during the midluteal phase.

Adult↗

PubMed1991

Endometrial histology after first trimester spontaneous abortion.

The endometrial histology after spontaneous abortion was investigated by performing an endometrial biopsy in the two menstrual cycles subsequent to miscarriage in 12 women. In the first cycle, 66% (8/12) of the biopsies had the following abnormalities: (1) proliferative endometrium (n = 4), (2) proliferative glands and decidualized stroma (n = 1), (3) endometritis (n = 1), and (4) luteal insufficiency (n = 2). In the second cycle, 20% (2/10) of the biopsies demonstrated luteal insufficiency. Forty-five percent (10/22) of the first two cycles after spontaneous abortion demonstrated abnormal endometrial histology, with the first appearing more abnormal than the second (P = 0.06). Two conceptions occurred during the study period; both were uneventful term pregnancies. These findings suggest that a large proportion of the first two menstrual cycles after spontaneous abortion and curettage are abnormal, with the first cycle being more frequently abnormal than the second.

Abortion, Spontaneous↗

PubMed1991

Progesterone production in early pregnancy.

Before and after elective abortion, progesterone (P) and human chorionic gonadotropin (hCG) levels were determined to describe the origin of P and to investigate the relationship between levels of hCG and luteal steroidogenesis. After abortion, P levels initially fell rapidly, followed by a slower decline. The initial fall in P levels and the remaining level of P 3 hours after abortion were taken to represent the removal of P that originated from the trophoblast and the continuing P contribution by the corpus luteum (CL), respectively. Using this analysis, we conclude: (1) P production by the CL is sustained well into the second trimester of pregnancy and (2) increasing trophoblastic production of P allows the pregnancy progressive independence from the CL.

Adult↗

PubMed1990

Dispersed cell suspensions of fetal SCN restore circadian rhythmicity in SCN-lesioned adult hamsters.

Overt circadian rhythms are permanently disrupted following lesions of the suprachiasmatic nucleus (SCN) in hamsters. It has previously been demonstrated that whole tissue grafts which include the fetal SCN restore circadian locomotor rhythms to hamsters previously made arrhythmic by SCN lesions. In the present study, we ask whether the intrinsic peptidergic organization of the SCN is a prerequisite for functional recovery of circadian rhythms of locomotor activity. To this end, dispersed cell suspensions of [3H]thymidine-labelled fetal anterior hypothalamic tissue which contains the SCN, were injected stereotaxically into the brain of adult hamsters. Dispersed cell suspensions restored free-running locomotor rhythms, but not entrainment or gonadal regression. The period of the restored free-running rhythms following injections of SCN cell suspensions was shorter than 24 h, in contrast to intact hamsters and SCN-lesioned hamsters whose rhythms are restored by whole tissue grafts. In animals with restored rhythms, a majority of [3H]thymidine-labelled cells were located within nuclei of the midline thalamus and zona incerta. In a few individuals, donor cells were also deposited along the injection tract as far ventrally as the medial hypothalamus. Restoration of free-running locomotor rhythmicity was correlated with the presence of small numbers of isolated VIP cells along with small plexuses of VIP fibers. In animals which did not recover locomotor rhythmicity, grafts were identical in location and size to those in recovered hamsters, but did not contain peptidergic cells characteristic of the SCN. The results suggest that structural integrity of the fetal SCN is not necessary for restoration of rhythmicity after grafting.

Animals↗

PubMed1990

Characterization of a B cell helper factor(s) derived from CD5+ B cell hybridomas.

Work from our laboratory suggests that the selective advantage of frequently autoreactive CD5+ B cells is to provide activation signals to CD5- antigen-specific B cells. This hypothesis is supported by the observation that supernatants from CD5+ B cell hybridomas replace CD5+ B cell populations in helping idiotypic B cell subsets respond to antigen plus anti-idiotype antibody. The present study was designed to initiate the characterization of CD5+ B hybridoma-derived helper factor(s) (BHF) and to compare BHF to previously described cytokines. Elution of BHF from a lectin column enabled significant enrichment of the apparently glycosylated helper factor(s) from serum-free hybridoma supernatant. Gel filtration of this enriched activity revealed two significant peaks of helper activity, one at approximately 19-22 kDa and a second at 29-32 kDa. BHF activity in each fraction was sensitive to protease treatment. To determine if some previously described cytokines of approximately the same molecular weights were responsible for BHF activity, BHF fractions were tested for cytokine activity in respective bioassays. At least 2000 units of BHF did not contain detectable levels of IL-1, IL-2, IL-3, IL-4, IL-6, GM-CSF, G-CSF, or IFN-gamma activity. Furthermore, three hybridomas which produced BHF did not transcribe detectable levels of mRNAs specific for IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, GM-CSF, or IFN-gamma. The results suggest that CD5+ B cell hybridomas produce a lymphokine(s) distinct from cytokines commonly associated with B cell activation. The potential roles of this lymphokine in immunity and disease are discussed.

Animals↗

PubMed1990

Diagnosis and treatment of cornual obstruction using a flexible tip guidewire.

Proximal tubal obstruction, either unilateral or bilateral, is a frequent finding on hysterosalpingogram (HSG). Approximately two-thirds of the fallopian tubes resected for proximal tubal obstruction reveal an absence of luminal occlusion. The distinction between true pathologic occlusion and either spasm or plugging is crucial in determining therapy. We combined hysteroscopic cannulation of the proximal fallopian tube with laparoscopy in 11 patients with proximal tubal obstruction diagnosed by HSG and confirmed at laparoscopy. Hysteroscopic cannulation was able to be performed in 72% of the fallopian tubes attempted, and there was a postcannulation patency rate by HSG of 73%. Six of the 11 patients became pregnant after tubal cannulation and adjunctive distal tubal surgery. Hysteroscopic cannulation of the fallopian tube is a safe diagnostic procedure that can be used to identify those patients with true proximal occlusion, and may also serve as a therapeutic procedure in some of these patients.

Adult↗

PubMed1990

CA-125 secretion by luteal phase endometrium in vitro.

The source of CA-125 in normal women and the mechanisms which control CA-125 production remain to be defined. This study was initiated to examine the pattern of secretion of CA-125 from luteal phase endometrium. Endometrial samples were obtained during the early luteal phase (histological days 16-18) and late luteal phase (histological days 25-27) from ovulatory women with a laparoscopically normal pelvis. The tissue was maintained in explant culture using Trowell's T-8 medium with either no additions (NA), progesterone (P), oestradiol (E2), or E2 + P. The concentration of CA-125 in spent media from the second day in culture was determined by immunoradiometric assay. In early luteal endometrium, the concentration of CA-125 in spent media from the NA treated wells was significantly higher than when the endometrium was exposed to either P or E2 + P. Similar differences were noted between treatments for the late luteal endometrium. Within each treatment, there was a higher concentration of CA-125 in the spent media from the late versus the early luteal endometrium. We conclude that the endometrium is a potential source of serum CA-125 and that endometrial CA-125 is suppressed by P in both the early and the late luteal phase. Further, there appears to be an increase in endometrial CA-125 secretion from the early to the late luteal phase.

Antigens, Tumor-Associated, Carbohydrate↗

PubMed1990

The application of basic science concepts to clinical problem-solving.

This study looks at the relationship between anatomical concepts held by medical students and their clinical application, and develops a testable model of how students use basic science concepts for clinical problem-solving. According to the model, the essential prerequisites to solve a clinical problem using basic science information include the appropriate basic science knowledge, the ability to collect and interpret clinical information, with the key concept being the link that must then be made between clinical data and basic science. A detailed analysis of the individual components of the model should help to clarify and resolve some of the debate about the nature and balance of basic science and clinical education. A neurological diagnostic problem was used to test the assumptions of the model in a group of medical students who had minimal clinical experiences. There was no demonstrable relationship between anatomical knowledge as assessed by conventional tests and the diagnosis. There was a powerful relationship between measures of organization of knowledge and diagnosis, suggesting that the organization and development of concepts is the key to correct diagnosis. The findings have significant implications for assessment purposes and suggest that standard methods as generally practised may not measure the appropriate conceptual development and are not congruent with curricular objectives. Through the examination of its different learning outcome measures, the model may also be used to provide a profile of individual students or classes, which should help teachers and students deal with difficulties that may be experienced in learning to link clinical and basic science concepts.

Clinical Competence↗

PubMed1990

Effects of vasopressin on insulin secretion and inositol phosphate production in a hamster beta cell line (HIT).

The recent isolation of vasopressin (VP) from the rat and human pancreas led us to investigate the effects of VP on insulin secretion. In the SV 40-transformed hamster beta cell line (HIT), 0.1-1.0 nM VP caused rapid stimulation of insulin secretion. Slight but significant inhibition of insulin secretion was observed in the presence of 10 pM VP. These effects of VP on insulin secretion were paralleled by dose-dependent changes in inositol phosphate (IP) production, indicating mediation by V1-type VP receptors. VP stimulated IP3 production at 30 sec and production of IP1 by 60 sec. VP (0.1 nM to 1 microM) failed to stimulate the release or cellular content of cAMP, whereas forskolin was an effective stimulus. Forskolin and VP together caused at least additive stimulation of insulin secretion. Taken together, these observations indicate that VP is not acting via V2-mediated pathways. However, VP-induced stimulation of insulin and IP production were only slightly inhibited by a V1a pressor antagonist in 100- or 1,000-fold excess, indicating that VP effects are not mediated by V1a receptors. The V1 receptor involved may represent a V1b or a novel type of VP receptor. These observations suggest a potential physiological role of VP in regulating insulin secretion.

Animals↗