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Biomedical subjects

B Woodward

Publications and source records attributed to B Woodward.

At least 73 records · Page 4Linked to original sources

Long-term results of mastoid cavities grafted with cultured epithelium prepared from autologus epidermal cells to prevent chronic otorrhea.

Chronic otorrhea and recurrent infection from open mastoid cavities are common and troublesome clinical problems for which there is no very satisfactory treatment. The authors have previously described a simple procedure to solve this problem, using autologous cultured keratinocyte layers grafted onto the unepithelialized open mastoid cavities. All procedures are carried out on an outpatient basis without anesthesia, except for local anesthesia for the skin biopsy. Twenty-six patients with 28 "difficult" mastoids, in which otorrhea had been present from 2 to 32 years, have been grafted with a follow-up period varying from 10 to 18 months. Seventeen mastoid cavities became symptom-free as a result of this technique. There were 4 failures, and partial success was shown in 7 cavities as judged by both the patient and by clinical examination.

Adolescent↗

Dietary arginine requirement of young rainbow trout (Oncorhynchus mykiss).

1. Two growth trials were conducted with young rainbow trout (Oncorhynchus mykiss) to determine the dietary arginine requirement under conditions of rapid weight gain at 15 degrees C. 2. The growth requirement does not exceed 4.2 g arginine/16 g dietary nitrogen and, thus, is much lower than the value of 6.0 g arginine/16 g dietary nitrogen presently listed by the NRC for Chinook salmon and widely applied to all Salmonids. 3. Comparison of the present results with the arginine requirement of the chick reveals remarkable similarity despite the phylogenetic distance between the two species, and demonstrates the need to re-evaluate, as anomalously high, the presently-accepted value for Chinook salmon.

Animal Nutritional Physiological Phenomena↗

Hematological profiles in dairy cows treated with recombinant bovine somatotropin.

Recombinant bovine somatotropin (bST) was administered at 0, 10.3, or 20.6 mg per cow per day to 32 Holsteins for 38 wk. Fifteen currently treated cows had been treated in the previous lactation. Eighteen hematological variables and blood concentration of insulin-like growth factor I (IGF-I) were measured at five sample periods. The objectives of the study were to test the effects of bST treatments on hematological profiles and to relate blood IGF-I concentration to these variables. Results indicated little influence (P greater than .10) of previous bST treatments on hematological profiles measured in the current lactation. Current bST treatments, however, altered hematocrits (P = .10), mean corpuscular volume (P = .03), mean corpuscular hemoglobin (P = .009), and fraction of blood lymphocytes (P = .09). A week x bST treatment interaction also contributed to variation in hematocrit (P = .09), mean corpuscular hemoglobin (P = .05), fraction of neutrophils (P = .02), and fraction of lymphocytes (P = .04). Blood IGF-I concentration influenced fractions and counts of neutrophils (P = .06, .09), lymphocytes (P = .04, .02), and monocytes (P = .08, .05). Further in vivo and in vitro studies are warranted because this preliminary evidence suggests that bST and(or) IGF-I contribute to regulation of hematopoiesis in mature dairy cows.

Analysis of Variance↗

Contact sensitivity and systemic antibody responses in dairy cows treated with recombinant bovine somatotropin.

Effects of exogenous bST on humoral and cell-mediated immune responses in lactating dairy cows were determined. The systemic antibody response to human erythrocytes and the cutaneous sensitivity response induced by dinitrochlorobenzene were the immune responses investigated. Cows were treated with either 0, 10.3, or 20.6 mg of bST/d for 266 d starting between wk 4 and 5 of lactation. Systemic immunizations and contact sensitivity were initiated during midlactation, 22 wk after bST treatments began. Hemagglutinating antibody titers and areas under the response profiles were not statistically different for bST-treated versus control cows. The cutaneous sensitivity response was similarly not affected by bST administration. Present antibody titer results agreed with our previous observations that bST did not affect serum IgM concentrations, but the cutaneous sensitivity results were in contrast with our finding of augmented proliferative responsiveness of mitogen-stimulated peripheral blood lymphocytes in bST-treated versus control cows. It is possible that exogenous bST affects some immune processes and lymphocyte subsets and not others. Further research is required to determine the practical significance of the variable immunomodulation elicited by exogenous bST.

Analysis of Variance↗

Borrowed proteins in bacterial bioluminescence.

A library of Photobacterium phosphoreum DNA was screened in lambda 2001 for the lumazine protein gene, using two degenerate 17-mer oligonucleotide probes that were deduced from a partial protein primary sequence. The lumazine protein gene was localized to a 3.4-kilobase BamHI/EcoRI fragment in one clone. The fragment contained an open reading frame, encoding a 189-residue protein, that had a predicted amino acid sequence that concurred with the partial sequence determined for lumazine protein. Considerable sequence similarity was detected between lumazine protein, the yellow fluorescence protein from Vibrio fischeri, and the alpha subunit of riboflavin synthetase (EC 2.5.1.9). A highly conserved sequence in lumazine protein corresponds to the proposed lumazine binding sites in the alpha subunit of riboflavin synthetase. Several secondary structure programs predict the conformation of this site in lumazine protein to be a beta-sheet. A minimal model with three interactions between the ligand and this beta-sheet structure is proposed, which is consistent with the results of NMR and ligand binding studies.

Amino Acid Sequence↗

Treatment of chronic mastoiditis by grafting of mastoid cavities with autologous epithelial layers generated by in vitro culture of buccal epithelium.

Autologous cultured epithelial layers were established from biopsies from the mucosa of the cheek, a non-keratinizing region of the oral cavity. These were grafted to the unepithelialized mastoid cavities of nine patients with chronic mastoiditis and severe otorrhoea varying from two to 30 years' duration. All procedures were performed on an out-patient basis, with no anaesthesia except for topical anaesthesia for the mucosal biopsy. In seven of the patients the grafts took well, with complete resolution of the otorrhoea for a minimum follow-up period of eight months. In one patient there was a partial take of the graft with substantial improvement in the rate of discharge. The mastoid cavities of two patients were biopsied five months after grafting, and demonstrated a stratified squamous epithelium, with keratinization of the epithelium clearly evident.

Adult↗

Effects of bradykinin in the rat isolated perfused heart: role of kinin receptors and endothelium-derived relaxing factor.

1. The effects of bradykinin (BK) in the microcirculation of the isolated perfused heart of the rat were examined. The kinin receptors mediating the effects of BK were characterized and the role of endothelium-derived relaxation factor (EDRF) and prostacyclin investigated. 2. The dose-related vasodilator responses elicited by bolus doses of BK (0.001-10.0 nmol) were competitively blocked by the selective kinin B2 receptor antagonist [D-Arg0,Hyp3, Thi5.8,D-Phe7]-bradykinin (pA2 = 6.8). Des-Arg9-bradykinin, a selective kinin B1 receptor agonist had no vasodilator activity at doses of up to 10 nmol. 3. L-NG-nitro arginine (100 microM; L-NOArg), an inhibitor of endothelium-dependent vasodilatation, reduced the duration but not the magnitude of the BK vasodilator response. This action of L-NOArg was not reversed by L-arginine (100 microM). 4. Superoxide dismutase (10 units ml-1), haemoglobin (10 microM) and methylene blue (MB; 1 microM), all known to modify EDRF-mediated responses, failed to alter the vasodilator action of BK. 5. Gossypol (1-15 microM), a presumed inhibitor of EDRF biosynthesis, caused a marked drop in perfusion pressure followed by vasoconstriction. These changes in coronary tone were accompanied by an irreversible depression of cardiac contractility and heart rate. Over the same concentration range gossypol abolished the vasodilator action of BK (1.0 nmol), however it also blocked the endothelium-independent vasodilator response to sodium nitroprusside (30 nmol) and the vasoconstrictor effect of endothelin-1 (10 pmol) which suggests non-specific toxic actions of gossypol. 6. Bolus injections of BK (0.001-1.Onmol) failed to elevate basal levels of prostacyclin (PGI2) as shown by assaying for its stable metabolite 6-keto-PGF<,,. In addition, BK-induced vasodilatation was not blocked by flurbiprofen (2 microM) or BW755C (7.5 microM) which are inhibitors of the arachidonic acid pathway. When added with L-NOArg (100 microM), flurbiprofe(10 microM) did not potentiate the inhibitory action of L-NOArg on the BK response. 7. These results show that the vasodilator action of BK in the rat heart is dependent on the activation of the kinin B2 receptors but independent of PGI2 release. Although a conclusive role for EDRF could not be established, this study has questioned the suitability of several agents commonly used as inhibitors of EDRF-mediated responses.

6-Ketoprostaglandin F1 alpha↗

The synthesis, and structure-activity relationships of some long chain acyl carnitine esters on the coronary circulation of the rat isolated heart.

The synthesis of the isopropyl ester of carnitine and a series of fatty acid derivatives with fatty acid lengths C8-C30 is described. Bolus doses of these compounds (0.03-300 nmol) showed coronary vasodilator activity in the rat isolated heart. Increasing fatty acid chain length from C8 to C16 resulted in an increased vasodilator potency. Longer lasting vasodilation was observed with the C20 compound. Increasing fatty acid chain length to C30 was associated with a small dilator response preceded by vasoconstriction.

Animals↗

Underdiagnosis of alcohol dependence in psychiatric inpatients.

Alcoholism is prevalent among psychiatric inpatients, and accurately diagnosing alcohol problems is a critical step in treatment planning. The authors diagnosed alcohol dependence in 35 psychiatric inpatients by blind review of interview protocols and hospital records. They then examined the frequency with which admitting and attending clinicians diagnosed alcohol abuse and dependence in these patients. Alcoholism was underdiagnosed; 24% of the clinicians' diagnoses included no alcoholism diagnosis, 39% were alcohol abuse, and only 37% were alcohol dependence. Underdiagnosis was strongly associated with the presence of a comorbid psychosis, as well as with patients' denial of alcoholism and with less severe alcoholism. The authors discuss the patient and clinician variables which may contribute to underdiagnosing alcoholism and recommend educational and administrative measures to improve clinicians' diagnostic sensitivity.

Adolescent↗

Influence of exogenous bovine somatotropin on the responsiveness of peripheral blood lymphocytes to mitogen.

Our objectives were to determine the effects of exogenous bovine somatotropin on peripheral blood lymphocyte responsiveness to mitogen and on concentrations of serum insulin-like growth factor-I and to determine whether a statistical relationship exists between these two variables. The cows on trial were treated with 0, 10.3, or 20.6 mg/d somatotropin, starting between wk 4 and 5 of lactation and continuing for 266 consecutive d. Lymphocyte proliferation (counts per minute) and concentration of insulin-like growth factor-I (nanograms per milliliter) were recorded from blood sampled at wk 3, 10, 26, 35, and 46 of lactation. The results showed that lymphocytes from the blood of treated cows responded to mitogen with higher proliferative responsiveness than cells from control cows, but that this effect required long-term treatment and adequate mitogen concentrations to be detected. The blood of treated cows also had elevated concentrations of insulin-like growth factor-I relative to that of control cows, but these were not statistically associated with the proliferative responsiveness of the peripheral blood lymphocytes to mitogen. Our results suggest that somatotropin has a role in the immune system of cows, but its mode of action and target tissues must be determined. Bovine somatotropin, injected at doses that increase milk yield, can augment cow immunity as judged by the proliferative responsiveness of peripheral blood lymphocytes in culture.

Analysis of Variance↗

Serum immunoglobulin profiles of dairy cows chronically treated with recombinant bovine somatotropin.

The objective of this study was to determine the effects of exogenous somatotropin on blood profiles of the major bovine Ig isotypes. Holsteins were treated with either 0, 10.3, or 20.6 mg recombinant bST/d. Subcutaneous injections were started between wk 4 and 5 of lactation and continued for 266 d. Blood samples were collected by coccygeal venipuncture throughout lactation for serum IgG, G1, G2, A, and M concentration determination. Cows treated with 10.3 mg of bST/d exhibited modest increases in mean blood concentrations of IgG (12.4%) and IgG2 (18.4%) relative to the other groups of cows. In addition, treated cows had 10.1% higher average concentration of IgA than controls. Somatotropin did not influence average lactational concentrations of IgG1 or IgM, although the group receiving 10.3 mg/d had higher late lactation concentrations of IgG1 than did the other two groups. However, treatment mean isotype concentrations were always within normal ranges, except for IgG2 from the 10.3 mg/d group, which were higher. The practical significance of elevated serum Ig concentrations observed in the present study is not known. However, the present data do show that bST administered at doses that increased milk yield had no apparent detrimental effect on humoral immunity as measured by blood concentrations of Ig.

Analysis of Variance↗

Isoproterenol and the genesis of reperfusion-induced arrhythmias in isolated rat heart: adrenoceptor or free radical-mediated mechanisms?

In the isolated rat heart, reperfusion-induced arrhythmias were exacerbated by isoproterenol (0.01-1.0 microM). The proarrhythmic action of isoproterenol was primarily the result of a beta 1-receptor-mediated tachycardia rather than via a free radical-mediated process, since it was prevented competitively by the beta 1-receptor antagonist metoprolol, but not by the free radical scavengers mannitol, superoxide dismutase, and catalase. If heart rate was maintained by electrical pacing, the protective action of metoprolol against the isoproterenol-induced arrhythmias was lost. At high concentrations (5 and 50 microM), metoprolol alone produced a bradycardia that was probably not related to beta 1 blockade, and this resulted in some nonspecific antiarrhythmic activity. The data provide evidence that, in this model, heart rate during ischaemia is an important determinant of reperfusion-induced arrhythmias, and that free radical formation from the oxidation of high levels of exogenous isoproterenol present at the time of reperfusion does not contribute in a major way to the detrimental action of isoproterenol.

Animals↗

Vasodilator action of endothelin-1 in the perfused rat heart.

The effects of bolus injections of porcine endothelin (ET-1, 1-100 pmol) on the coronary microvasculature of isolated perfused rat heart were examined. Results show that ET-1 possesses dose-dependent vasodilator as well as vasoconstrictor properties. The vasodilator effect was transient and preceded its more pronounced and persistent vasoconstrictor action. ET-1-induced vasodilation in rat heart was not associated with release of prostacyclin (PGI2), as shown by radioimmunoassay (RIA) analysis of cardiac effluent and was not blocked by the cyclooxygenase inhibitors flurbiprofen (2 microM) or BW755c (7.5 microM). Neither was the dilatory response to ET-1 inhibited by haemoglobin (10 microM) or potentiated by superoxide dismutase (20 U/ml) but it was abolished by methylene blue (20 microM). However, methylene blue itself caused coronary dilation which could mask the vasodilator action of ET-1. These results show that in isolated perfused rat heart ET-1 possesses a vasodilator action that is not mediated by PGI2 and that may also be independent of release of endothelium-derived relaxing factor (EDRF).

6-Ketoprostaglandin F1 alpha↗

The effects of novel vasodilator long chain acyl carnitine esters in the isolated perfused heart of the rat.

1. The effects of palmitoyl carnitine (PC) and novel derivatives were examined on the isolated Langendorff perfused heart of the rat. 2. Bolus injections of PC (1-300 nmol) produced coronary constriction accompanied by a cumulative irreversible depression of contractility. 3. Prior storage of PC in chloroform containing 2% ethanol in heat-sealed ampoules resulted in production of the ethyl ester of the compound (PCE). This compound was isolated and also synthesized (P1E). In contrast to PC, both PCE and P1E exhibited potent vasodilator activity. 4. Increasing the fatty acid chain length from palmitoyl to stearoyl resulted in a significant reduction in coronary dilator activity of the ester compound, whereas different ester groups did not affect the vasodilator action appreciably. Complete removal of the fatty acid chain abolished all vascular effects at the doses used. 5. The vasodilatation produced by these acyl carnitine esters was comparable to that produced by several known vasodilator drugs including verapamil, cromakalim, amyl nitrate and iloprost; however, the duration of the vasodilator response was more prolonged with the carnitate derivatives.

Animals↗