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Biomedical subjects

L Wallace

Publications and source records attributed to L Wallace.

At least 55 records · Page 3Linked to original sources
PubMed1996

Slow nocturnal home hemodialysis (SNHHD)--one year later.

High costs and overcrowding of dialysis centres are leading to a global crisis in health care provision. We are developing slow nocturnal home hemodialysis (SNHHD) in which patients dialyze for eight to 10 hours during sleep five to seven nights per week. Vascular access is by means of the Cook silastic jugular catheter. Special precautions are taken to prevent accidental disconnection and air embolism. Dialysis functions are remotely monitored on computer via a modem by trained staff. Five patients have completed five to seven weeks of training and have been successfully performing SNHHD single-handedly (three out of five patients live alone) for 14, 14, 11, 10 and four months respectively. All have discontinued their phosphate binders and increased dietary phosphate intake. Compared with conventional hemodialysis (CHD) results, average pre-dialysis urea and creatinine levels are remarkably reduced to 9.6 mmol/l and 486 umol/l respectively. The average cumulative weekly Kt/V for CHD is 5.0 as compared to 7.7 while on SNHHD. Four out of five patients report sleeping soundly and experience greatly increased energy and stamina. Their days are entirely free. Repeated in-situ re-use of the dialyzer and blood lines will reduce the patient's work and make SNHHD a very inexpensive modality. SNHHD appears to be a widely applicable treatment with many advantages to both the patient and the health care system.

Adult↗
PubMed1996

Spontaneous and drug-stimulated locomotor activity after the administration of pertussis toxin into the ventral tegmental area.

Pertussis toxin (PTX) injected into the ventral tegmental area (VTA) produces an enhanced locomotor response to amphetamine. In the present study, we have evaluated the role of dopamine receptors on spontaneous locomotor activity and the enhanced locomotor response to dopaminergic agonists after the administration of PTX into the VTA. PTX injected into the VTA of rats produced a delayed increase in spontaneous locomotor activity with a latency of 4 d. This activity was markedly increased by day 6 and remained elevated for at least 28 d after PTX treatment. This increased spontaneous locomotor activity of PTX-treated animals was antagonized by the administration of the D1 receptor antagonist SCH23390 (0.03 and 0.1 mg/kg sc), but not by the D2 receptor antagonist eticlopride (0.1 and 0.3 mg/kg sc). After adaptation to the locomotor cages, the animals showed a markedly enhanced motor response to amphetamine (0.5 mg/kg ip) and apomorphine (5 mg/kg sc). The heightened locomotor responses to these dopaminergic agonists could be elicited for at least 2 mo after PTX administration. The enhanced response to amphetamine was antagonized by the administration of SCH23390 (0.03 and 0.1 mg/kg sc), but not by eticlopride (0.1 mg/kg). The increased response to apomorphine in PTX-treated animals was inhibited by SCH23390 (0.1 mg/kg sc) and partially inhibited by eticlopride (0.1 mg/kg sc). Both of these antagonists inhibited the spontaneous and the drug-induced locomotor responses in vehicle-treated control animals. These results suggest that the administration of PTX into the VTA leads to an increase in spontaneous and drug-induced locomotor activity in which D1 receptors seem to play an important role.

Animals↗
PubMed1995

Fulminant reactivation of hepatitis B due to envelope protein mutant that escaped detection by monoclonal HBsAg ELISA.

The detection of a fatal case of reactivation of hepatitis B, in a previously vaccinated Indonesian patient after withdrawal of chemotherapy for lymphoma, was delayed because HBsAg was negative in a widely used monoclonal-antibody-based ELISA. The serum was later found to be strongly reactive for HBsAg by the polyclonal radioimmunoassay and for HBV DNA. PCR sequencing revealed a substitution of arginine for glycine at position 145 of HBsAg in the major neutralising epitope cluster, the a determinant, as well as a 2-aminoacid insertion of asparagine and threonine between positions 122 and 123, immediately upstream of this determinant.

Amino Acid Sequence↗
PubMed1995

Water on the sun.

High-resolution infrared spectra of sunspot umbrae have been recorded with the 1-meter Fourier transform spectrometer on Kitt Peak. The spectra contain a very large number of water absorption features originating on the sun. These lines have been assigned to the pure rotation and the vibration-rotation transitions of hot water by comparison with high-temperature laboratory emission spectra.

Solar System↗
PubMed1995

A district general hospital pain management programme. First year experiences and outcomes.

A pain management programme was set up in a large District General Hospital to improve the management of the many patients with chronic non-malignant pain who do not respond to interventional medicine. Outcome measures studied were depression, anxiety, disability, pain locus of control, illness behaviour and patient satisfaction with the programme. The first five of these measures showed statistically significant improvements whilst patient satisfaction with the programme was high at both assessments. In addition, there were marked decreases in the consumption of analgesics and sedative drugs. We conclude that a multidisciplinary pain management programme is a cost effective and constructive way of treating patients whose pain does not respond to interventional management.

Adult↗
PubMed1995

Hepatic distribution of E2 component of pyruvate dehydrogenase complex after transplantation.

We have examined the distribution of the E2 component of pyruvate dehydrogenase complex in the liver of patients with native primary biliary cirrhosis (PBC), and after transplantation, using affinity-purified anti-E2 antibodies. In the posttransplantation group, we studied biopsy specimens from patients grafted for conditions other than PBC (n = 6) and those grafted for PBC with (n = 6) and without (n = 5) histological features suggestive of PBC recurrence. Features suggestive of PBC recurrence included portal tract granulomas, bile duct damage, ductopenia, and lymphoid aggregates. In the native liver from patients with PBC, there was increased staining of E2 on the biliary epithelial cells compared with hepatocytes, as previously described. However, in liver biopsy specimens from patients after transplantation, the pattern of staining of E2 was similar to that of normal, control liver in all three groups studied. These findings suggest that E2 overexpression on bile duct cells may not be important in the perpetuation of the bile duct damage in PCB, that expression in the allograft may be modified by immunosuppression, or that PBC does not recur in the allograft.

Biopsy↗
PubMed1995

Characterization of biliary epithelial cells isolated from needle biopsies of human liver in the presence of hepatocyte growth factor.

Current methods for the isolation of intrahepatic biliary epithelial cells from human liver rely upon relatively large segments of tissue, thereby limiting studies to cells isolated from patients with end-stage disease. To investigate a greater range of diseases and those at an earlier stage, we have developed a method to isolate biliary epithelial cells from biopsy-sized fragments of human liver. Tissue explants are cultured for > 4 weeks, and, in approximately 50% of samples incubated with medium containing hepatocyte growth factor, biliary epithelial cells begin to migrate from the fragments and proliferate. With time they form confluent pavements of cells that express cytokeratin 19 and gamma-glutamyl transpeptidase and are negative for markers of non-biliary cell phenotype. After subculturing, cells can be expanded, yielding substantial numbers for subsequent study in vitro. Cells can be isolated with a similar degree of success from adult normal liver, from a variety of liver diseases, and from post-transplant liver biopsies. Overall, pediatric tissue yielded cells less frequently than adult tissue. This novel technique is likely to have a major impact on the study of biliary pathophysiology, as small fragments of tissue removed from biopsies taken for diagnostic purposes can be used.

Adolescent↗
PubMed1994

Inhibition of cathepsin L-like cysteine proteases by cytotoxic T-lymphocyte antigen-2 beta.

The protein sequence of cytotoxic T-lymphocyte antigen-2 beta (CTLA-2 beta) is 36% identical to the proregion of mouse cathepsin L (Denizot, F., Brunet, J.F., Roustan, P., Harper, K., Suzan, M., Luciani, M. F., Mattei, M. G., and Goldstein, P. (1989) Eur. J. Immunol. 19, 631-635). Here we report the expression, purification, and characterization of recombinant murine CTLA-2 beta. The protein was purified by consecutive gel-filtration, anion-exchange, and reverse-phase (C4) chromatography. Purified CTLA-2 beta exists in solution primarily as a dimer but also as a disulfide-linked tetramer as judged by size exclusion chromatography. Circular dichroism studies suggest that the dimeric form of the protein contains 8% alpha-helix, 67% beta-sheet, and 21% random coil and also indicates that there is a conformational change upon formation of the tetramer. The protein is a competitive inhibitor of certain cysteine proteases including papain (Ki = 25 nM), cathepsins L (Ki = 24 nM) and H (IC50 = 67 nM) but not cathepsin B. CTLA-2 beta forms a noncovalent complex with cathepsin L and has a stoichiometry of binding to papain of 1 mol of CTLA-2 beta/mol of papain. There is no homology between CTLA-2 beta and any of the known cysteine protease inhibitors, including the kininogens and cystatins. Therefore, CTLA-2 beta represents a novel class of cysteine protease inhibitor that is specific for the cathepsin L family of proteases.

Antigens↗
PubMed1994

Screening for anxiety and depression in cancer patients: the effects of disease and treatment.

The General Health Questionnaire 28 (GHQ 28), Hospital Anxiety and Depression Scale (HADS), and Rotterdam Symptom Checklist (RSCL) seemed promising in their ability to detect anxiety and depression in cancer patients. To compare their screening performance, 513 patients were recruited from four cancer centres, and visited at home by a trained interviewer. Paired combinations of questionnaires (GHQ 28 + HADS, GHQ 28 + RSCL or RSCL+HADS) were used, and then the Psychiatric Assessment Schedule was administered to enable a psychiatric diagnosis to be made using DSM III diagnostic criteria. A receiver operating characteristics curve was drawn by plotting the true positive rate (sensitivity) against the false positive rate (1-specificity) for each possible score on each questionnaire. In the overall sample, the HADS and RSCL performed well comparably. The HADS did best in those free of disease and when the disease was judged to be stable. Only the RSCL performed well in those with progressive disease. Both the HADS and RSCL were effective in those on treatment. The GHQ was superior to the RSCL in those off treatment. The choice of questionnaire and threshold score should take disease and treatment status into account, but all three questionnaires have a definite role in screening out anxiety and depression.

Adolescent↗
PubMed1994

Vasoactive intestinal polypeptide: a transmitter in submucous neurons mediating secretion in guinea pig distal colon.

The aim of the study was to investigate the role of vasoactive intestinal polypeptide (VIP) as a transmitter in regulation of epithelial function. Submucosa/mucosa segments from guinea pig distal colon were mounted in flux chambers and increases in short-circuit current were used as an index of secretion. Serosal addition of VIP, peptide histidine isoleucine, helodermin and pituitary adenylate cyclase-activating peptide caused an increase in short-circuit current. Tissues were less responsive to peptide histidine isoleucine, helodermin and pituitary adenylate cyclase-activating peptide than to VIP. In tissues without neurogenic tone, VIP(10-28), but not tetrodotoxin, reduced the response to exogenous VIP. The secretory response to VIP was attenuated by tetrodotoxin and atropine only in tissues with ongoing neural activity influencing basal rates of transport. In the presence of muscarinic blockade, neural stimulation evoked an increase in short-circuit current which was attenuated by VIP(10-28). High extracellular potassium concentrations or carbachol evoked release of endogenous VIP. VIP and VIP (10-28) displaced the binding of [125I]VIP to epithelial receptors. These results provide evidence that VIP is a neurotransmitter within the submucous plexus involved in regulation of epithelial transport in the guinea pig colon.

Animals↗
PubMed1993

In vivo inhibition of insulin-like growth factor I gene expression by tamoxifen.

Tamoxifen, a partial antagonist to the estrogen receptor, is widely used in the treatment of breast cancer and is currently being evaluated as a breast cancer preventative agent in large-scale clinical trials. Recent clinical research has demonstrated that tamoxifen administration is associated with a reduction of serum insulin-like growth factor I (IGF-I) concentration. We demonstrate here that tamoxifen, when administered in an in vivo experimental system previously used to demonstrate its cytostatic effect on breast cancer cell proliferation, inhibits the expression of the IGF-I gene in common target organs for breast cancer metastasis. Furthermore, while our prior experimental studies have demonstrated an inhibitory effect of tamoxifen on growth hormone output, we show here for the first time that the suppression of IGF-I gene expression associated with tamoxifen administration is in part a consequence of a pituitary-independent action of the drug. Because IGF-I is a potent mitogen for breast cancer cells, this newly described activity of tamoxifen may contribute to its antineoplastic properties, particularly with regard to inhibition of metastasis seen both in animal models and clinically.

Animals↗
PubMed1993

Interaction of AZA analogs of chlorpromazine with the dopamine D2 receptor.

1. Permanently charged AZA analogs of chlorpromazine inhibited the binding of [3H]spiperone and antagonized the apomorphine-induced inhibition of the potassium evoked release of [3H]acetylcholine. 2. The AZA analogs were more potent in binding affinity and antagonist activity than the trimethylammonium analog of chlorpromazine but less potent than chlorpromazine. 3. These results suggest that it is possible to enhance the binding of the permanently charged trimethylammonium analog of chlorpromazine by the addition of a functional group near the quaternary nitrogen which is capable of forming a hydrogen bond with the D2 dopamine receptor. 4. However, it appears that for optimal binding, as achieved with chlorpromazine, the hydrogen-bonding proton should be on the charged nitrogen.

Acetylcholine↗
PubMed1993

A decade of studies of human exposure: what have we learned?

All four TEAM Studies operated on the basis concepts of probability sampling and direct measurement of exposure. These concepts made possible the discovery that, for nearly all of the 50 or so targeted pollutants, personal exposures exceeded outdoor levels by large margins. The conclusion, corroborated in part by other studies around the world, is that the major sources of exposure are personal activities and consumer products. This result is at odds with most existing environmental legislation, which generally does not deal with products or with indoor air in homes, in favor of regulating "major" stationary and mobile sources. These sources, however, provide only between 2-25% of personal exposure to most of the two dozen or so toxic and carcinogenic VOCs and pesticides included in the TEAM Studies. Several official publications have accepted this point, finding that funding priorities are skewed, with lower-risk problems receiving more funding than higher-risk problems such as indoor air pollution. However, just as exposures are due to small nearby sources, control of exposures can often be instituted by small individual actions. Among these are stopping smoking, reducing or eliminating the use of moth balls and bathroom deodorizers containing p-dichlorobenzene, reducing or eliminating the use of dry-cleaned clothes or airing them out for a day, and maintaining dust-free homes.

Air Pollutants↗
PubMed1993

Scanning electron-microscopic and magnetic resonance-imaging studies of injuries to the patellofemoral joint after acute transarticular loading.

To examine the effects of transarticular loading on articular cartilage and subchondral bone, we used a canine model that we had developed previously, in which a standardized load of approximately 2000 newtons is delivered across the patellofemoral joint. The purpose of the study was to define and describe the initial changes, as seen on histopathological and magnetic resonance-imaging studies, that occur in the early stages after injury to the joint by transarticular loading. Scanning electron microscopy was used to define the extent and characteristics of the fractures produced in the subchondral bone of four patellae that were examined on the day of loading. We found multiple, extensive fractures through the zone of calcified cartilage and the subchondral bone, frequently with step-off displacement, and with little or no change in the gross appearance of the articular cartilage. Specimens from four patellae were examined histologically two weeks after loading, and the observed changes were correlated with those that had been demonstrated by scanning electron microscopy. Fractures through the zone of calcified cartilage and the subchondral bone, with step-off displacement, were prominent. Clefts were present in the surface of the articular cartilage and, in some areas, there was a focal loss of proteoglycan from the extracellular matrix, as indicated by the complete absence of staining with safranin O. Six dogs were examined one year after loading. There was healing of the subchondral fractures and restoration of proteoglycan in the extracellular matrix. However, superficial clefts and fissures were still present in the articular cartilage. Sequential magnetic resonance-imaging studies were also carried out on these six dogs, at two, eight, sixteen, thirty-six, and fifty-two weeks after loading. Two weeks after loading, all knees had soft-tissue swelling, effusion, and a decreased marrow signal in the medullary cavity of the patella. The decreased marrow signal and effusion were still present eight weeks after the impact, and then the findings gradually returned to normal. One year after loading, it was found that the histopathological changes had not been progressive; in fact, they had been ameliorated and, to some extent, reversed by repair processes. The early, severe magnetic resonance-imaging changes had also been reversed, so that this study demonstrated normal findings by one year after loading.

Animals↗
PubMed1992

Purification and characterization of Epstein-Barr virus gp340/220 produced by a bovine papillomavirus virus expression vector system.

Our initial results with a bovine papilloma virus (BPV) vector expression system indicated that we could produce significant amounts of Epstein-Barr virus (EBV) gp340/220 in the supernatant of a mouse fibroblast cell line. We have now extended these findings to show that the truncated version of gp340/220, where the membrane anchor sequence is deleted, is produced even after extended passage of the cells, at a level of approximately 1 mg/4 x 10(8) cells. A simple purification protocol using Sephacryl S300HR and gelatin agarose gives a product which is greater than 90% pure. This product is recognized by anti-gp340 monoclonal antibodies from five different epitope groups and induces antibody that recognizes the authentic gp340/220 and neutralizes EBV in vitro. The purified gp340/220 can be used in ELISA and stimulates the proliferation of T-cell clones specific for gp340/220. These characteristics, together with the fact that BPV-transformed lines have been utilized for the production of pharmaceuticals for use in humans, suggest that this gp340/220 is suitable as a source of antigen for vaccination to prevent EBV infection and related diseases.

Animals↗