Search PubMed⌕ Search

Biomedical subjects

D Johnson

Publications and source records attributed to D Johnson.

At least 451 records · Page 25Linked to original sources
PubMed1991

Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer.

BACKGROUND: Neutropenia and infection are major dose-limiting side effects of chemotherapy. Previous studies have suggested that recombinant methionyl granulocyte colony-stimulating factor (G-CSF) can reduce chemotherapy-related neutropenia in patients with cancer. We conducted a randomized clinical trial to test this hypothesis and the clinical implications. METHODS: Patients with small-cell lung cancer were enrolled in a multicenter, randomized, double-blind, placebo-controlled trial of recombinant methionyl G-CSF to study the incidence of infection as manifested by fever with neutropenia (absolute neutrophil count, less than 1.0 x 10(9) per liter, with a temperature greater than or equal to 38.2 degrees C) resulting from up to six cycles of chemotherapy with cyclophosphamide, doxorubicin, and etoposide. The patients were randomly assigned to receive either placebo or G-CSF, with treatment beginning on day 4 and continuing through day 17 of a 21-day cycle. RESULTS: The safety of the study treatment could be evaluated in 207 of the 211 patients assigned to either drug, and its efficacy in 199. At least one episode of fever with neutropenia occurred in 77 percent of the placebo group, as compared with 40 percent of the G-CSF group (P less than 0.001). Over all cycles of chemotherapy, the median duration of grade IV neutropenia (absolute neutrophil count, less than 0.5 x 10(9) per liter) was six days with placebo as compared with one day with G-CSF. During cycles of blinded treatment, the number of days of treatment with intravenous antibiotics, the number of days of hospitalization, and the incidence of confirmed infections were reduced by approximately 50 percent when G-CSF was given, as compared with placebo. Mild-to-moderate medullary bone pain occurred in 20 percent of the patients receiving G-CSF. CONCLUSIONS: The use of G-CSF as an adjunct to chemotherapy in patients with small-cell cancer of the lung was well tolerated and led to reductions in the incidence of fever with neutropenia and culture-confirmed infections; in the incidence, duration, and severity of grade IV neutropenia; and in the total number of days of treatment with intravenous antibiotics and days of hospitalization.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Protease nexin-1 activity in cultured Schwann cells.

We report that protease nexin-1 (PN-1), a serine protease inhibitor known to have neurite-promoting effects, is made by Schwann cells in tissue culture. Three modalities have been used to demonstrate the presence of PN-1 in Schwann cell cultures. Immunostaining of the cultures with anti-PN-1 antibody gives positive staining over cells and matrix. Western blots of Schwann cell conditioned medium (CM) using anti-PN-1 antibody show a band that co-migrates with the PN-1 standard at 45 kDa. Biochemical assay for protease inhibitory activity shows that CM inhibits thrombin activity in a calorimetric assay. The CM-mediated inhibition of thrombin is reversed if the CM is pre-incubated with anti-PN-1 antibody.

Amyloid beta-Protein Precursor↗
PubMed1991

Evidence from dwarf rats that growth hormone may not regulate the sexual differentiation of liver cytochrome P450 enzymes and steroid 5 alpha-reductase.

Differences in the pattern of growth hormone (GH) secretion in mature rats (i.e., "continuous" secretion in females versus "pulsatile" secretion in males) are thought to be the underlying cause of sex-dependent differences in a subpopulation of liver microsomal P450 enzymes and steroid 5 alpha-reductase. A new strain of dwarf rats (NIMR/AS) has recently been shown to have low or undetectable levels of circulating GH due to a selective defect in pituitary GH synthesis. We have measured the levels and/or activity of IIA1 (P450a), IIA2 (P450m), IIC11 (P450h), IIC12 (P450i), IIIA2 (a P450p isozyme), and steroid 5 alpha-reductase in liver microsomes from male and female dwarf rats, to test the hypothesis that the expression of these sexually dimorphic enzymes is regulated by GH. In mature rats, the levels of liver microsomal IIA2, IIC11, and IIIA2 were higher in male than in female dwarf rats, whereas the levels of activity of IIA1, IIC12, and steroid 5 alpha-reductase were greater in female than in male dwarf rats. These sex differences resulted from age-related changes in either male dwarf rats (i.e., an increase in IIC11 and IIA2 and a decrease in IIA1) or female dwarf rats (i.e., an increase in IIC12 and 5 alpha-reductase and a decrease in IIIA2). The magnitudes of these sex-dependent, age-related changes were essentially indistinguishable from those observed in normal rats. These unexpected results suggest that GH is not the pituitary factor responsible for regulating the levels of sexually dimorphic, steroid-metabolizing enzymes in rat liver. Alternatively, it is possible that these enzymes are regulated by extremely low levels of GH. In either case, the current model of how steroid-metabolizing enzymes are regulated in rats must be revised to account for the normal sexual differentiation of these enzymes in dwarf rats.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1991

The Drosophila Hrb87F gene encodes a new member of the A and B hnRNP protein group.

Nascent premessenger RNA transcripts are packaged into heterogeneous nuclear ribonucleoprotein (hnRNP) complexes containing specific nuclear proteins, the hnRNP proteins. The A and B group proteins constitute a major class of small basic proteins found in mammalian hnRNP complexes. We have previously characterized the Drosophila melanogaster Hrb98DE gene, which is alternatively spliced to encode four protein isoforms closely related to the A and B proteins. We report here that the Drosophila genome contains a family of genes related to the Hrb98DE gene. One member of the family, Hrb87F, is very homologous to Hrb98DE in both sequence and structure. The Hrb87F transcripts (1.7 and 2.2 kb) utilize two alternative polyadenylation sites, are abundant in ovaries and early embryos, and are present in lesser amounts throughout development. In one wildtype strain of Drosophila there is a naturally-occurring polymorphism in this gene due to the insertion of a 412 transposable element in the 3' untranslated region. The larger transcript is not produced in these files and thus is not required for viability. Sequence identities among the Drosophila Hrb proteins and the vertebrate A and B hnRNP proteins suggest that these proteins may form a distinct subfamily within the larger family of related RNA binding proteins.

Amino Acid Sequence↗
PubMed1991

Dermal absorption of niclosamide in rats and minipigs.

The dermal absorption of niclosamide, a drug shown to prevent Schistosomiasis by blocking the dermal penetration of cercariae, has been examined in Sinclair minipigs and rats. Radioactivity in the urine and feces collected daily for 7 days after application of 14C-niclosamide accounted for less than 2 per cent and 10 per cent of the labelled compound applied to pig and rat skin, respectively. Approximately 20 per cent of the radioactivity from the dose solution was recovered on the skin excised from the area of application in both minipigs and rats. No radioactivity was detected in organs removed from the pig 7 days after application of radiolabelled drug while less than 6 per cent of the dose could be accounted for in the rat organs/carcass. Radioactivity in swine blood, removed 0.5, 1, 2, 4 and at 24 h intervals after dosing, was at or below three times background in all of the samples. Total recovery of the applied radioactivity was 78 per cent in pigs and 57 per cent in rats. These studies indicate that niclosamide is very poorly absorbed after dermal application. The results are consistent with earlier comparative studies showing that dermal penetration of xenobiotics in rats is generally higher than in swine.

Administration, Cutaneous↗
PubMed1991

Directional coronary atherectomy for failed angioplasty due to occlusive coronary dissection.

We describe a case in which coronary balloon angioplasty failed to improve sequential lesions and resulted in a long area of dissection between the stenoses. Directional coronary atherectomy of the occlusive dissection produced excellent angiographic improvement to achieve a successful result and avoid the need for urgent coronary bypass surgery. Directional coronary atherectomy represents a potentially useful treatment for PTCA-induced coronary dissection.

Angioplasty, Balloon, Coronary↗
PubMed1991

Lymphoepithelioma-like carcinoma of the lung.

Historically lymphoepithelioma was a term used to describe an undifferentiated mucosal carcinoma with a lymphocytic component arising only from the nasopharynx, although recently, lymphoepithelioma-like carcinoma has been found to occur as a primary tumor of the lung. Thus far, five patients have been documented as having this rare anatomical presentation. The patient that is being presented is the latest case of lymphoepithelioma-like carcinoma of the lung and will be compared clinically and histologically with the other four cases. The case is presented in order to discuss optimal methods of diagnoses and treatment for this condition.

Aged↗
PubMed1991

Maturation-related changes in mass and elemental contents of secretory granules as measured by electron-microprobe.

The relationship between granule density, protein content, and Ca and S contents were studied in two secretory granule fractions, from parotid glands of the rat, previously shown to constitute different stages in granule maturation. The density of the lighter fraction was between 1.133 and 1.142 g/ml, while that of the heavier fraction was greater than 1.142 g/ml. The mean protein content of the denser granules was 12% greater than that of the lighter granules (P less than 0.03), while the dry-mass elemental concentrations in the two granule fractions were unchanged. These results indicate that protein is added to granules during the maturation process (presumably by vesicular traffic), and that the resulting increase in granule density is not driven simply by decrease in water content and/or increased concentrations of inorganic Ca or S in the granules. The elemental concentration values also indicate that the diffusible elements permeate the granule membrane during the fractionation procedures.

Animals↗
PubMed1991

Diurnal variation of methotrexate disposition in children with acute leukaemia.

There is recent evidence that survival is improved when maintenance therapy for acute lymphocytic leukaemia in children is given at night. We have examined the possibility that diurnal variation in methotrexate pharmacokinetics may contribute to this improvement. In 6 children with leukaemia there was a significant fall in methotrexate plasma clearance at night (from 5.6 to 4.7 ml.kg-1.min-1). Renal clearance of methotrexate tended to fall at night and unbound renal clearance fell significantly (from 17.5 to 8.5 ml.min-1.kg-1 P less than 0.05). Creatinine clearance did not exhibit diurnal variation, whereas there was a significant fall in the non-glomerular clearance of methotrexate (from 14.8 to 6 ml.min-1.kg-1). Since methotrexate is a weak organic acid, its tubular secretion depends on urinary pH. At night urinary pH is more acidic, and this may result in more reabsorption and hence reduced renal clearance.

Acute Disease↗
PubMed1991

Behavioural profile of partial D2 dopamine receptor agonists. 1. Atypical inhibition of d-amphetamine-induced locomotor hyperactivity and stereotypy.

The effects of partial D2 dopamine (DA) receptor agonists on the behavioural activation produced by 1.5 and 8.0 mg/kg d-amphetamine were compared with the changes produced by the classical DA antagonist haloperidol. Alterations in behaviour were assessed in standard activity monitoring cages by direct observation of the rats using a rapid time sampling procedure. Haloperidol blocked d-amphetamine (1.5 mg/kg)-induced increases in photocell counts, ambulation, rearing and sniffing up, and after the highest dose of the DA antagonist the animals were mainly inactive. The partial D2 DA agonist SDZ 208-911 was equipotent to haloperidol in blocking the increase in photocell counts and rearing produced by d-amphetamine. However, even high doses of the drug did not reduce the incidence of sniffing or induce inactivity, but qualitative changes in the form of sniffing did occur. Although considerably less potent, preclamol exerted similar effects to SDZ 208-911. The profiles of SDZ 208-912 and terguride were intermediary to those of SDZ 208-911 and haloperidol. All compounds blocked the repetitive sniffing down produced by 8.0 mg/kg d-amphetamine. After a low dose of haloperidol, these stereotyped behaviours were replaced by a behavioural syndrome similar to that observed with low dose d-amphetamine, but inactivity was observed following a further small increase in antagonist dose. The blockade of stereotypy by SDZ 208-911, preclamol and terguride was accompanied only by the low dose d-amphetamine behavioural syndrome; no inhibition of sniffing or induction of inactivity occurred. SDZ 208-912 exhibited a profile with features very similar to that noted with haloperidol. These findings suggest that partial D2 agonists exert similar, but not identical, behavioural effects to classical DA antagonists when dopaminergic function in increased by d-amphetamine. The differences in behavioural profile are discussed in relation to variations in the intrinsic efficacy of the dopaminergic compounds and to differences in the response capability of D2 receptor populations underlying the different behaviours produced by d-amphetamine.

Animals↗
PubMed1991

Anterior sternal retraction for reoperative median sternotomy.

The incidence of reoperative median sternotomy for repeat cardiac surgery is increasing. Reoperative median sternotomy is associated with a higher morbidity and mortality than first-time cardiac surgery. A portion of this morbidity and mortality may be due to direct injury to the heart and great vessels in the process of reopening the sternum. We report a new technique utilizing anterior sternal retraction that allows division of adhesions between the undersurface of the sternum and the heart and great vessels under direct vision. This technique enables the surgeon to minimize the risk of serious injury to these underlying structures during reoperative cardiac surgery.

Cardiac Surgical Procedures↗
PubMed1991

Comparison of elemental concentrations in the acinar cells of the human labial salivary gland.

Two types of acinar cells were observed in human labial glands by conventional and analytical electron microscopic and light microscopic techniques. The predominant type contained large and prominent secretory granules that were strongly mucicarmine and PAS (with and without diastase) positive. The second type contained small, lacy, secretory granules, and these cells were faintly positive with these stains. The elemental contents of the two types of granules were measured by analytical electron microscopy using digital mapping and spot analysis applied to freeze-dried cryosections prepared from gland slices incubated in vitro under non-stimulated conditions. The large secretory granules had significantly higher Ca, S and Mg concentrations and significantly lower Cl and K concentrations than the small granules. The difference in elemental contents probably reflects differences in the content of secretory macromolecules. Specifically, the S content is thought to reflect the anionic properties of the secretory macromolecules, while the levels of divalent cations are thought to be determined by electroneutrality requirements for macromolecular folding and storage. No differences were found in nuclear or cytoplasmic elemental concentrations between the two cell types.

Adult↗