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Biomedical subjects

D Jackson

Publications and source records attributed to D Jackson.

At least 145 records · Page 8Linked to original sources

Massive splenomegaly in sarcoidosis.

We have presented a case of massive splenomegaly. Our patient was initially thought to have lymphoma, but at operation she was found to have sarcoidosis with splenic involvement. At 2250 g, the spleen was one of the largest recorded in the literature on sarcoidosis. Although the spleen is frequently involved in sarcoidosis, a review of 6074 cases showed that the incidence of actual splenomegaly is only 10%. In 628 of these cases the authors described various degrees of splenomegaly, but the incidence of massive splenomegaly was only 3%. We conclude that sarcoidosis must be considered in the differential diagnosis of splenomegaly.

Adult↗

In vivo neurochemical evaluation of striatal serotonergic hyperinnervation in rats depleted of dopamine at infancy.

Destruction of nigrostriatal dopamine (DA) neurons with 6-hydroxydopamine (6-OHDA) early in development results in hyperinnervation of striatum by the serotonergic afferents deriving from the dorsal raphe nucleus. We have used in vivo microdialysis to investigate the degree to which serotonergic neurotransmission in striatum is altered by this increase in the density of serotonin (5-HT) terminals. The effects of several manipulations known to influence 5-HT function on extracellular 5-HT and 5-hydroxyindoleacetic acid in striatum were compared in adult rats treated neonatally with 6-OHDA and in intact adult rats. Basal levels of 5-HT in extracellular fluid (ECF) of striatum were similar in neonatally DA-depleted rats and in intact rats. Perfusion with the 5-HT reuptake blocker, fluoxetine (100 microM), increased 5-HT in striatal ECF of neonatally DA-depleted rats to levels that were threefold greater than those achieved in intact rats. Likewise, K(+)-depolarization of the 5-HT terminals (100 mM in perfusate) or systemic administration of the 5-HT releaser, (+/-)-fenfluramine (10 mg/kg i.p.), increased the concentration of 5-HT in striatal ECF of neonatally DA-depleted rats to levels approximately threefold greater than those observed in striatum of intact rats. These findings indicate that the 5-HT hyperinnervation of striatum that takes place in rats depleted of DA at infancy is associated with an increased capacity for neurotransmitter release in this system. Concomitant increased in high-affinity 5-HT uptake may prevent the occurrence of any measurable changes in the resting concentration of 5-HT in striatal ECF.

Animals↗

Rapid diagnosis of Brucella melitensis in blood: some operational characteristics of the BACT/ALERT.

A clinical isolate of Brucella melitensis was detected in a blood culture with the BACT/ALERT after an incubation period of 2.8 days. Dilution studies revealed an inverse linear relationship between the log of the initial concentration of the organism and the time to detection of a positive result. Reproducibility studies demonstrated a mean detection time of 48 +/- 1 h in 8 of 10 replicates seeded with a stock containing 10(2) CFU/ml.

Adult↗

Cellular kinetics of transforming growth factor-beta induced hemoglobin accumulation in the HEL erythroleukemia cell line.

Transforming growth factor-beta 1 (TGF beta 1) can induce hemoglobin accumulation in a clone of the human HEL erythroleukemia cell line. This clone has previously been designated as HEL-T. The effect of TGF beta 1 was reversible and it had to be continuously present for the maximal number of cells to become positive for hemoglobin. The TGF beta 1 effect was blocked by phorbol ester and partially blocked by the calmodulin antagonist W-7, but not by dexamethasone. Simultaneous exposure to gamma-interferon, IL-1, IL-6, IL-3 and GM-CSF had no significant effect on TGF beta induced hemoglobin accumulation. However, when TGF beta was combined with TNF alpha, it was observed that there was approximately a 10-15% reduction in benzidine-positive cells. Cell-cycle analysis revealed no significant long-term alterations in any of the compartments. Analysis of the TGF beta 1 effect on 10 different HEL-T-derived clones revealed that the number of benzidine-positive cells ranged from 12 to 70% after 5 days of continuous exposure. Cell proliferation was similarly differentially affected. Another HEL cell line, designated as W-HEL, did not accumulate hemoglobin in the presence of TGF beta 1, but did have an increase in alpha-globin RNA expression.

Cell Cycle↗

The synergistic effect of hemin and transforming growth factor-beta on hemoglobin accumulation in HEL erythroleukemia cells.

Transforming growth factor-beta (TGF beta) and hemin can both independently induce hemoglobin accumulation in the human HEL erythroleukemia cell line. The combination of these two agents resulted in a synergistic effect in the production of hemoglobin. On day 1, following exposure to both hemin and TGF beta, approximately 35% of the cells had accumulated hemoglobin, as evidenced, by benzidine staining. Whereas, when treated alone with either agent, the percentage of benzidine-positive cells was less than 10%. By day 5, approximately 70-80% on the cells treated with the combination were benzidine-positive. Cell surface analysis showed that the combination of TGF beta and hemin increased the expression of CD34, CD64, glycophorin A, and GPIIb-IIIa(CDW41). Cell proliferation was decreased by the combination.

Antigens, Surface↗

Expression patterns of myb genes from Antirrhinum flowers.

Six genes that contain sequence encoding the DNA binding domain of the Myb oncoproteins have been isolated from a cDNA library prepared from Antirrhinum majus (snapdragon) flowers using oligonucleotide probes directed against part of this domain. The derived amino acid sequences of these genes reveal acidic domains in their carboxy termini, suggesting that they might act as transcriptional activators. Analysis of their expression patterns with respect to organ specificity, floral differentiation, and response to light suggests that these genes are not involved in controlling anthocyanin biosynthesis, unlike the characterized myb-related genes C1 and Pl from maize. One of the genes is expressed mainly in the nectary and the transmitting tract of the style, two major secretory tissues of the flower, suggesting that the function of this gene is related to active carbohydrate secretion. We conclude that plants contain a number of myb-related transcriptional activators involved in a diversity of gene regulation.

Amino Acid Sequence↗

The Chiang Mai lactation project: study design and implementation.

The Chiang Mai lactation project is a longitudinal field study of human lactation carried out among northern Thai women living in the Sanpatong area of Chiang Mai Province. Its aim was to measure the volume and composition of breast milk transferred from mothers to their infants in the first year postpartum, and to relate it to predictors of milk production, and to the growth of the child. Breast milk and supplementary food intake, and nursing patterns, were recorded over two consecutive 24-hour periods six times during the first year. Samples of breast milk and of supplementary foods were analysed for energy and protein. Supplementary foods were also analysed for bacterial contamination. The growth of the child was measured, and health assessed using a combination of health diaries and examination by a physician. Recruitment to the study was excellent. After recruitment, two subjects left the study area, but otherwise only two dropped out, so complete sets of data covering these variables are available for 58 of the 62 recruited subjects.

Body Weight↗

Basic medical physiology: the whole is more than the sum of its parts.

In this article we examine the role of basic medical physiology in medical school education. We discuss the historical background, courses in this subject, and methods of teaching it. We conclude that the teaching of medical physiology should emphasize the study of organ systems and of the intact body. The techniques should emphasize meticulous observation, the posing of hypotheses, and the subsequent testing of the hypotheses, i.e., the use of the method used successfully in research. Students should learn the power of the experimental approach and to appreciate the immense variability possible in responses in complex organisms. They should also learn that principles of statistical probability applied logically can detect important differences in data that may be obscured by this variability. They should learn that there are no rigid answers when studying an individual and that they must continue to learn throughout their lives.

Animals↗

Evolution of beta-lactamase inhibitors.

After the introduction of penicillin G into therapeutics, bacteria became increasingly resistant to this penicillin and subsequent beta-lactam antibiotics. The major cause of this resistance is beta-lactamase, an enzyme produced by the bacterium, that destroys the antibiotic before it reaches its target within the bacterial cell. One of the ways to combat this resistance has been the use of beta-lactamase inhibitors, which protect the antibiotic by inactivating the destructive enzyme before the antibiotic reaches the infection site. At present, at least two beta-lactamase inhibitors are in clinical use, clavulanic acid and sulbactam, that are effective against most beta-lactamases, although relatively inactive against class I beta-lactamases, the cephalosporinases. Newly developed beta-lactamase inhibitors, however, especially BRL-42715, show some promise against these enzymes.

Anti-Bacterial Agents↗

Use of site-directed mutagenesis to identify valine-573 in the S'1 binding site of rat neutral endopeptidase 24.11 (enkephalinase).

On the basis of the identity of a segment of the amino acid sequence within the active site of the bacterial enzyme thermolysin and the mammalian enzyme neutral endopeptidase 24.11, the possible involvement of valine-573 of neutral endopeptidase 24.11 in substrate binding was investigated. Valine-573 was changed to leucine and to alanine by site-directed mutagenesis. The effect of these mutations on inhibitor binding and substrate catalysis was examined with a series of compounds containing variable P'1 residues. With a small P'1 residue such as alanine, both mutant enzymes exhibited kinetic properties essentially the same as the wild-type enzyme. However, with larger P'1 residues such as phenylalanine, tyrosine, and leucine, the Val573Leu mutant showed a 24-100-fold decrease in inhibitor affinity. Similarly substrates containing bulky P'1 residues showed a 10-40-fold decrease in Vmax with little change in Km. In contrast, the Val573Ala mutant showed only modest changes in terms of inhibitor binding or substrate turnover. These results support the proposed role of valine-573 as a part of the hydrophobic binding pocket, S'1 binding subsite, of neutral endopeptidase 24.11.

Amino Acid Sequence↗

Fine-needle aspiration biopsy diagnosis of endodermal sinus tumor: histologic and ultrastructural correlations.

Fine-needle aspiration biopsies from five patients with endodermal sinus tumors (ESTs) were reviewed, and the findings were correlated with histologic and ultrastructural appearances. In the aspiration smears, two types of tumor cells were seen, forming clusters of variable sizes. Type A cells had distinct cell borders, and their cytoplasm contained only occasional vacuoles. Type B cells had ill-defined cell borders and formed syncytial clusters; their cytoplasm was characterized by large numbers of rounded vacuoles. The background contained patches of mucoid material and macrophages with foamy cytoplasm. Eosinophilic hyaline cytoplasmic bodies and irregular deposits of intercellular basement membrane-like material were recognized easily in aspiration smears. These features correlated well with histologic and ultrastructural appearances. The significance of these findings in the fine-needle aspiration biopsy diagnosis of EST and its distinction from other germ-cell and non-germ-cell tumors is discussed.

Adult↗

High- versus standard-dose megestrol acetate in women with advanced breast cancer: a phase III trial of the Piedmont Oncology Association.

One hundred seventy-two patients with advanced breast cancer were randomized to receive oral standard-dose megestrol acetate (MA), 160 mg/d or high-dose MA, 800 mg/d. All but two patients had one prior trial of tamoxifen therapy for either metastatic disease (74%) or as adjuvant treatment (26%). Pretreatment characteristics were similar for both arms. High-dose MA resulted in a superior complete plus partial response rate (27% v 10%, P = .005), time to treatment failure (median, 8.0 v 3.2 months, P = .019), and survival (median, 22.4 v 16.5 months, P = .04) when compared with standard-dose therapy. These differences remained significant after adjustment for other covariates. Thirty-four patients were given high-dose MA after failure of standard-dose MA treatment, and none responded. Weight gain was the most distressing side effect, with 13% of standard-dose and 43% of high-dose patients gaining more than 20 lbs. Four major cardiovascular events occurred in patients receiving high-dose treatment and one in patients given standard doses. Other toxicity was modest. High-dose MA may represent a significant improvement in secondary endocrine therapy for advanced breast cancer patients refractory to initial endocrine treatment, but its use on a regular basis should be reserved until these results are confirmed by other clinical trials.

Adult↗

Phase II study of fluorouracil and recombinant interferon alfa-2a in previously untreated advanced colorectal carcinoma.

We conducted a phase II clinical trial of fluorouracil (5FU) and recombinant interferon alfa-2a (rIFN alpha-2a) in 52 previously untreated patients with bidimensionally measurable metastatic colorectal cancer. During week 1, 5FU was administered as a continuous intravenous infusion, 750 mg/m2/d for 5 consecutive days. Intravenous bolus administration of 5FU 750 mg/m2 was given weekly for 7 weeks starting on day 12. rIFN alpha-2a (Roferon; Hoffman-LaRoche, Nutley, NJ), 9 x 10(6) U, was administered subcutaneously three times weekly during weeks 1 to 8. Patients were evaluated for response on week 9. Of 52 patients enrolled in the study, 51 were assessable for toxicity, and 45 were assessable for response. Fifteen patients experienced partial response, and one patient achieved a clinical complete response for an overall response rate of 35% (95% confidence interval [CI], 22%, 50%). Median duration of response is 7.5 months (range, 4 to 11 months). Seventy percent of patients entered on the study are alive with a median follow-up duration of 7 months. Twenty-five percent of patients developed grade 4 toxicity, and 82% developed grade 3 toxicity. One drug-related death in the presence of sepsis was reported, and two treatment-related seizures occurred. Our experience with this schedule produced a lower response rate with greater toxicity than previously reported. Current randomized trials comparing this schedule of 5FU with rIFN alpha-2a to 5FU plus folinic acid (leucovorin) or single-agent 5FU may determine its role in the treatment of advanced colorectal carcinomas.

Colorectal Neoplasms↗

The role of the community psychiatric nurse.

The community psychiatric nurse is an essential element in a comprehensive mental health service. At present each nurse is expected to be a trained counsellor and psychotherapist, a skilled behaviour therapist and an expert assessor of clinical status. This superhuman role is unrealistic; a more appropriate one is outlined.

Behavior Therapy↗