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Biomedical subjects

J Smith

Publications and source records attributed to J Smith.

At least 649 records · Page 36Linked to original sources
PubMed1994

Acidic and basic fibroblast growth factors in human breast tissue.

Previously we have reported changes in fibroblast growth factors (FGF) in conditioned medium (CM) derived from rat mammary tumours undergoing remission. We have used a similar approach to assay for the presence of FGFs in human breast tissue and cell lines. The majority of cancer tissues (35/50), benign tissues (8/9) and all cancer adjacent normal tissues (20/20) released heat labile, NR6 transforming activity which coeluted from heparin with acidic FGF (aFGF) at 0.9-1.1 M NaCl and was neutralised by antibodies to aFGF. The conclusion that the majority of breast cancers contain active aFGF was supported by immunoblotting. The CM of a minority (15/50) of cancers and one benign tissue had highly transforming activity for NR6 cells, and was mitogenic for a breast cancer cell line, was heat labile, and strongly heparin binding, eluting at 1.5-2.0 M salt. It was not immunoreactive with antibodies to aFGF, basic FGF (bFGF) or Kaposi's FGF (kFGF) and its activity was reduced by the presence of aFGF, suggesting competition for the same receptor. Very little aFGF was observed in the CM of these tumours, and neither aFGF nor other FGF activity was detected in CM of breast cell lines.

Breast↗
PubMed1994

Oestrogen modulation with parturition in the human placenta.

An initial group of term (36-41 6/7 weeks), preterm (less than 36 weeks), and post-term (42 or more weeks) placentae were collected from women at delivery to determine the placental levels of important steroids and steroidogenic enzymes involved in the oestrogen synthesis pathway as a function of gestational age. A second group of placentae were obtained from women delivering at term before and after the onset of labour. Placentae were evaluated individually for cytosolic steroid hormone levels and microsomal steroidogenic enzyme activities. Oestradiol (E2), oestrone (E1), progesterone (P), and delta-4-androstenedione (A) were measured by radioimmunoassay in placental cytosols. Aromatase (AR), sulphatase (S), and 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta HSD) activities were assayed in placental microsomes. Cytosolic concentrations of E1, E2, P, and A did not differ with respect to gestational age. Correspondingly, the microsomal enzyme activities of 3 beta HSD, S, and AR did not vary as a function of gestational age. However, when patients at term who were in labour prior to delivery were compared to those who were not, the placental cytosolic level of E1 was found to be threefold higher in the non-labouring group (4572 versus 1427 pg/mg cytosolic protein, P < 0.025). Additionally, microsomal aromatase activity was also significantly higher in the non-labouring patients (46 versus 19 pM/min/mg protein, P < 0.025), while the E2 to P ratio in the labouring patients was twice that of the non-labouring group, a difference which was significant at the P < 0.025 level (Wilcoxon rank sum test). These data suggest that at term, prior to labour, the placental production of E1 by AR is high, and that AR activity and E1 levels fall significantly after the onset of labour. Also, the placental cytosolic concentration of the more active oestrogen, E2, demonstrates stable to rising levels with a significant increase in E2/P after the onset of labour. We theorize that in the term pregnancy prior to labour, E1 may represent a large but relatively inactive intracellular oestrogen pool which is maintained by high AR activity, and may function to protect the pregnant local uterine environment from the more oxytocic effects of E2.

3-Hydroxysteroid Dehydrogenases↗
PubMed1994

Laser scanning confocal examination and comparison of nidogen (entactin) with laminin in term human amniochorion.

Indirect immunofluorescence confocal microscopy was used to compare the distribution of nidogen (entactin) and laminin in term human amniochorion. Rabbit antiserum raised against recombinant mouse nidogen was immunoreactive with components of the amniotic epithelial basement membrane, chorion laeve basement membrane and maternally derived capillary basement membranes. Overall anti-nidogen immunoreactivity co-distributes with laminin except in the extracellular matrix of the maternally derived decidua, the embryonically derived trophoblast and the apical surfaces of the amniotic epithelia. These differences lead us to suggest that nidogen and laminin may be independently expressed and are not always complexed together. Original observations include dramatic parallel nidogen rich striations in the decidual layer, the fact that the trophoblastic basement membrane appears to extend inwards forming a boundary layer to degenerate chorionic villi and the finding that the recently discovered collagen type IV rich microtrabeculae of the fibroblast layer also contain nidogen and laminin.

Amnion↗
PubMed1994

Neuroendocrine and clinical effects of electroconvulsive therapy and their relationship to treatment outcome.

Two groups of variables, endocrine and clinical, have been reported to have predictive value in determining response to electroconvulsive therapy (ECT) in depressed patients. Baseline levels of oxytocin associated neurophysin (OAN) and peak OAN response to ECT may predict clinical outcome, while the presence of delusional symptoms may indicate favourable initial response to ECT. The purpose of this study was to examine the relationship between these variables on initial and longer term response over a course of ECT, using a direct measure of plasma oxytocin concentrations. A substantial and immediate increase in oxytocin was seen after the first ECT, with significantly attenuated responses after the third and fifth ECTs. Increased plasma vasopressin concentrations were seen after all ECT treatments, each response being of similar magnitude. No associations were found between either endocrine baseline levels or peak responses, and clinical outcome. Only clinical variables predicted outcome, as patients with psychotic symptoms had more rapid initial response to ECT, and patients who had relapsed 2 months after the end of ECT had significantly higher depression ratings at day 14 of treatment than treatment responders.

Aged↗
PubMed1994

Occupational settings facilitating wisdom-related knowledge: the sample case of clinical psychologists.

Wisdom can be defined as expert knowledge in the fundamental pragmatics of life. Examined here is whether clinical practice may facilitate access to and acquisition of such knowledge. Spontaneous think-aloud responses to 2 wisdom-related dilemmas from young (M = 32 years) and older (M = 70 years) clinicians were compared with responses obtained from other professionals. Raters judged clinicians' responses as higher on 5 criteria of wisdom: factual knowledge, procedural knowledge, life-span contextualism, value relativism, and management of uncertainty. Contrary to most studies of cognitive aging, young and older adults did not differ. Rather, each age-cohort group received highest ratings when responding to a life dilemma matched to their own life phase. Discussed is the application of a wisdom framework to assessing therapeutic treatment goals and therapist interventions as well as global changes in client's beliefs during therapy.

Adult↗
PubMed1994

Empirical prediction of physiological response to prolonged work in encapsulating protective clothing.

Work in moderate or hotter environments while wearing encapsulating protective clothing (PC) results in heat storage and substantial diminution of work productivity, as well as being a potential health risk. An ability to predict the responses of workers using PC would be very useful. Predictions were made of work times at 21 degrees C of 15 subjects performing prolonged hard work (450 W gross) while wearing PC, based upon prior measures of short-duration bench stepping in PC and heart rate responses. A simple model was derived that shows good potential for predicting work time in moderate temperatures in PC; Total Time = 7.2 (bench step duration) - 34 (bench comfort) + 4 (height); R2 = 0.83, C.V. = 13. Unexpectedly, models that incorporated recovery heart rate as a variable were not as effective. With further refinement, the prediction approach tested in this study would be immediately useful for managing military and civilian personnel working in PC. Additionally, it could be utilized at minimal cost during routine training.

Adult↗
PubMed1994

Presence of multiple genetic subtypes of human immunodeficiency virus type 1 proviruses in Uganda.

DNA sequences encoding the C2-V3 regions or the C2-V5 regions of the surface glycoprotein gp120 of the human immunodeficiency virus type 1 (HIV-1) were amplified by the polymerase chain reaction (PCR) from peripheral blood mononuclear cells obtained in 1990/1992 from 20 infected Ugandans. The PCR-amplified DNA was cloned into a phagemid vector and between 1 and 12 clones from each provirus were sequenced. The Ugandan proviruses were aligned into four subtypes (A, B, C, and D) by phylogenetic analysis of consensus nucleotide sequences for the C2-V3 regions. Analysis of the deduced amino acid sequences of the C2-V3 regions by a maximum parsimony program gave a similar phylogenetic relationship. The data indicated that phylogenetic analysis of nucleotide and/or amino acid sequences from the C2-V3 regions is a reliable method of subtype determination. The consensus amino acid sequence of the subtype A and D proviruses were almost identical to those of the Albert et al. group B and group A proviruses, respectively. The deduced amino acid sequences of the C2-V5 regions of six of these proviruses showed considerable diversity both between patients and within patients. The region varied in length between 234 and 243 amino acids and included deletions and repetitions, particularly in the V4 region.

Adult↗
PubMed1994

Systemic delivery of secreted protein by grafts of epidermal keratinocytes: prospects for keratinocyte gene therapy.

Grafts of autologous keratinocytes genetically altered to secrete a new gene product are a potential vehicle for gene therapy. To consider the feasibility of such an approach, we have examined the ability of keratinocytes to secrete and deliver apolipoprotein E (apoE) to the circulation of mice bearing grafts of human keratinocytes. The grafted keratinocytes secreted two forms of apoE, an endogenous apoE encoded in the genome and a recombinant apoE encoded in a transfected gene construct. In vitro studies showed that endogenous apoE was secreted from basal keratinocytes whereas recombinant apoE was secreted from basal as well as suprabasal cells. On the basis of amounts of recombinant apoE present in the serum of grafted mice, we estimate that a graft occupying 2% of the surface area of an adult human would deliver 6.5-8.3 mg of recombinant apoE protein per day.

Animals↗
PubMed1994

Post-circumcision analgesia: comparison of topical analgesia with dorsal nerve block using the midline and lateral approaches.

Forty-five patients undergoing circumcision were allocated randomly to one of three study groups to compare topical analgesia with dorsal nerve block using the midline or lateral approach. Pain scores, side effects and analgesic requirements were recorded after surgery. Patients who received topical analgesia required significantly more fentanyl and had higher pain scores at the 15-min observation period after operation. Fentanyl requirements and pain scores were similar in patients who received a dorsal nerve block using either the midline or lateral approach. The incidence of side effects after surgery was similar in all three groups.

Administration, Topical↗
PubMed1994

Resistance of Candida albicans to fluconazole during treatment of oropharyngeal candidiasis in a patient with AIDS: documentation by in vitro susceptibility testing and DNA subtype analysis.

We describe a patient with recurrent episodes of oropharyngeal candidiasis who required progressively higher doses of fluconazole to control and infection. The patient was treated for 14 infections over a 2-year period with doses of fluconazole that ranged from 100 to 800 mg per day. Clinical response, two methods of in vitro susceptibility testing, and molecular epidemiologic techniques were evaluated for 12 of the 14 episodes. Ultimately, the patient became unresponsive clinically to a dose of 800 mg of fluconazole per day. In vitro susceptibility testing of isolates obtained during these successive episodes of infection revealed the development of resistance to fluconazole, and molecular epidemiologic techniques confirmed the persistence of the same Candida albicans strain throughout all 12 episodes.

AIDS-Related Opportunistic Infections↗
PubMed1994

Bactericidal/permeability-increasing protein inhibits induction of macrophage nitric oxide production by lipopolysaccharide.

A recombinant (r) NH2-terminal fragment of bactericidal/permeability-increasing protein, rBPI23, was shown to inhibit murine macrophage nitric oxide (NO) production elicited by lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma). Normal mouse plasma amplified NO synthesis (measured as NO2- release) at LPS concentrations of 1-10 ng/mL, and antibody to the plasma LPS-binding protein (LBP) partially inhibited NO2- release in the presence of normal mouse plasma. rBPI23 (1 microgram/mL) effectively inhibited LPS-dependent NO2- release in the presence or absence of normal mouse plasma. Fifty percent inhibition of IFN-gamma/LPS-elicited NO2- production or of binding of fluoresceinated LPS was obtained with approximately 0.2 microgram/mL rBPI23. These results provide a basis for studies of rBPI23 effects on NO synthase activity in murine models of gram-negative sepsis.

Animals↗
PubMed1994

Autologous peripheral blood cell transplantation in the treatment of advanced neuroblastoma.

PURPOSE: We review the experience with autologous peripheral blood cell transplantation (APBCT) in children with neuroblastoma at the University of Minnesota. PATIENTS AND METHODS: Aspects of peripheral blood cell collection and use in nine patients who had advanced neuroblastoma (eight Evans stage IV, 1 stage III), who were median age 4 years (range 10 months-22 years) and who were treated with high-dose chemotherapy without total body irradiation and APBCT between September 1987 and December 1989 are reviewed. RESULTS: A median of 4.8 x 10(8) (range 3.3-8.9) mononuclear cells per kilogram of body weight were obtained by a median of six (range four-eight) collections. In vitro assay of granulocyte-monocyte colony-forming cells (CFU-GM) demonstrated a median of 3.6 x 10(4) (range 0.7-7.8) CFU-GM/kg of body weight. After APBCT, granulocyte recovery (absolute neutrophil count > 500 x 10(6)/L) occurred at a median of 28 days (range 14-72) and platelet recovery (> 150 x 10(9)/L) occurred at a median of 34 days (range 19-202). All patients but one, who had progressive disease, were transplanted with residual disease. Immunocytological analysis of peripheral blood stem cell harvest showed the presence of circulating neuroblastoma cells in three of nine patients, all of whom had minimal marrow residual disease by biopsy. One patient is still alive with no evidence of disease after 5 years. The others died of recurrent neuroblastoma a median of 14 months (range 3-29) after transplant. CONCLUSION: APBCT is safe and effective for hematopoietic reconstitution after high-dose chemotherapy, and may be useful when a bone marrow harvest cannot be performed because of prior pelvic radiation or minimal residual bone marrow metastasis. Immunocytological methods to ensure that the product is free of tumor contamination should be performed.

Adolescent↗
PubMed1994

Pituitary stone: two cases of densely calcified thyrotrophin-secreting pituitary adenomas.

Calcification is a well recognized but relatively uncommon feature of prolactin-secreting, growth hormone-secreting and non-functional pituitary tumours. It varies in extent, but rarely exceeds a tiny amount histologically or radiologically. Thyrotroph adenomas are the rarest of the secretory pituitary tumours, accounting for less than 1% of cases, and partial calcification of such lesions has been reported in only three cases. We describe two patients in whom the clinical and biochemical features indicated the presence of a TSH-secreting adenoma and radiology demonstrated a large 'pituitary stone'. One patient, a 59-year-old female, initially presented with hyperthyroidism, aged 18, and was rendered euthyroid by two subtotal thyroidectomies before a pituitary lesion was suspected, over 20 years later. Autonomous secretion of thyrotrophin was demonstrated by dynamic tests, and the failure of exogenous T3 to reduce the serum TSH. In the absence of tumour expansion and compressive symptoms, pituitary surgery was not undertaken. At the age of 56, she developed symptoms of intermittent ataxia and diplopia, culminating in a focal seizure, and was found on CT scan to have, in addition to the pituitary lesion, a parasagittal meningioma. This was successfully removed at craniotomy. In the second patient, a 42-year-old male, the finding of hyperthyroidism in association with an elevated TSH concentration led to the discovery of a pituitary stone which was removed transethmoidally, together with surrounding adenomatous tissue which stained positively for TSH on immunocytochemistry.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1994

Evaluation of different antimicrobial agents used as selective supplements for isolation and recovery of Yersinia enterocolitica.

Seventeen antimicrobial agents were evaluated separately or in combination for their efficiency as selective supplements in a broth medium against six different serotypes of Yersinia enterocolitica and 20 selected strains of different Gram-negative bacteria. Irgasan (DP300, 5-chloro-2-(2,4- dichlorophenoxy) phenol) at a concentration of 4 micrograms ml-1 inhibited the growth of most Gram-negative bacteria with the exceptions of Aeromonas hydrophila, Morganella morganii, Pseudomonas aeruginosa and Serratia liquefaciens. Other antimicrobial agents incorporated in the growth medium, separately or in combination with Irgasan, either inhibited some strains of Y. enterocolitica or did not inhibit the growth of Irgasan-resistant Gram-negative bacteria.

Anti-Infective Agents, Local↗
PubMed1994

Stability of caffeine oral formulations for neonatal use.

The stability of an oral formulation of 10 mg/ml caffeine citrate (equivalent to 5.03 mg/ml caffeine free base), which was preserved with potassium sorbate, was assessed at a range of temperatures. There was no appreciable change in pH or caffeine content over 1 year, even at storage temperatures of 32 degrees C and 45 degrees C. A batch-to-batch difference in the stability of potassium sorbate was detected, with losses over 1 year of 2% and 11% for two batches at 25 degrees C and 10% and 30%, respectively, at 45 degrees C. The formulation complied with the Antimicrobial Preservative Efficacy test of the British Pharmacopoeia throughout a period of storage at 25 degrees C for 1 year. There was no detectable benefit to preservative efficacy by adding 20% w/v sorbitol as an osmotic agent. The formula with no sorbitol may be preferable due to the potential for sorbitol to cause gastrointestinal upset. A shelf-life of 1 year at room temperature is feasible. The additional precaution of limiting the in-use storage life to 1 month after opening is recommended to ensure acceptable microbiological quality.

Administration, Oral↗
PubMed1994

Hepatitis C in liver transplantation: preliminary study of prognostic factors.

At the University of Miami liver transplantation for chronic liver disease in HCV-positive patients has shown good results, with a 92% patients survival rate (follow up 8 to 57 months, median 21). None the less, we found that a large number of patients are expected to develop serious histological graft damage and may need retransplantation, which may place a further strain on the already scarce donor resources. We have conducted a preliminary investigation on the importance of parameters which may correlate with the prognosis of HCV grafts. We found no impact of HLA match or typing. An interesting hypothesis, which deserves further investigation, is that some HCV strains could be more virulent than others and play a role as an independent risk factor. We have identified six strains among our patients and the BK serotype shows a trend to be associated with a worse outcome. We have found that patients developing and maintaining higher liver enzyme levels (ALT and GGT) after transplant and those with higher levels of viremia may be at risk to develop serious damage to their grafts.

Adolescent↗
PubMed1994

A self-report Insight Scale for psychosis: reliability, validity and sensitivity to change.

Lack of insight is a frequent concomitant of psychosis and has traditionally been viewed as a binary, all or none phenomenon. Recent conceptualization has formulated insight as a continuum representing the juxtaposition of 3 factors--awareness of illness, need for treatment and attribution of symptoms. Measurement of insight has been exclusively based on interview; this method does not easily lend itself to frequent repeated measurement and requires interrater reliability to be established. A self-report Insight Scale is presented, and evidence in support of its reliability, validity and sensitivity is provided that includes a sample of 30 patients monitored during recovery from an acute psychosis. The scale is a quick and acceptable measure that may find application in investigations of acute care, cognitive therapy of psychotic symptoms and as a method of augmenting clinical judgements of insight.

Adult↗