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Biomedical subjects

C Hall

Publications and source records attributed to C Hall.

At least 307 records · Page 17Linked to original sources
PubMed1987

The effect of mitoxantrone treatment in beagle dogs previously treated with minimally cardiotoxic doses of doxorubicin.

Low-grade chronic cardiotoxicity as determined by myocardial biopsy specimens was induced in beagle dogs after four courses of doxorubicin hydrochloride (1.64 mg/kg, 34.0 mg/sq m) given intravenously once every 3 weeks. After this initial treatment, these dogs were separated into three groups. Two groups received six courses of mitoxantrone (0.25 mg/kg, 5 mg/sq m) commencing at 7 weeks or 19 weeks after the final doxorubicin treatment. The third group was treated with six additional courses of doxorubicin after an interval of 7 weeks. Up to seven sequential endomyocardial biopsies were performed to monitor the myocardial changes which were observed after the initial doxorubicin treatment. The low-grade cardiotoxic changes progressed for at least 7-11 weeks without any additional doxorubicin treatment, and stabilized or even partially reversed after 19 weeks of a treatment-free period. Dogs that received additional doxorubicin demonstrated progressive cardiotoxicity, associated with clinical signs, that resulted in death after a total of seven to ten courses of treatment (12-16 mg/kg, 238-340 mg/sq m cumulative dose). In dogs treated with doxorubicin followed by mitoxantrone after a 19-week treatment-free period, myocardial changes were shown to have stabilized and/or partially regressed. This study indicated that in beagle dogs four courses of doxorubicin (7 mg/kg, 136 mg/sq m cumulative dose) are the threshold dose at which non-life-threatening cardiotoxicity occurs. Residual toxic effects of doxorubicin may be erroneously interpreted as adverse findings attributable to other agents given subsequently during the susceptible period, ie, prior to stabilization of the myocardium. Mitoxantrone given after stabilization of doxorubicin-induced low-grade myocardial changes did not show additive or synergistic effects.

Animals↗
PubMed1986

Immunological effects of recombinant interferon alfa-2a in patients with disseminated melanoma.

Twenty patients with disseminated melanoma were treated with interferon alfa-2a, given by intramuscular (IM) injection three times a week in escalating doses from 15 to 50 X 10(6) U/m2. Of 18 patients considered evaluable, two had complete remission and in two others the disease was stabilized. Laboratory tests 6 hours after injection of interferon alfa-2a indicated a marked lymphopenia and a reduction in natural killer (NK) cell activity. Sequential changes (measured before injection of interferon alfa-2a on days 3, 10, and 31) consisted of neutropenia, thrombocytopenia, and a slight increase in OKT4 positive T cells compared with OKT8 positive T cells. NK activity against the K562 target cells was increased in most patients during the first week of treatment, returning to near or below pretreatment levels thereafter. This response contrasted with a delayed increase against melanoma target cells in 10 patients. The latter correlated with an increase in mitogen-stimulated interleukin-2 (IL2) production, and may indicate that the cytotoxic activity resulted from lymphokine-activated killer (LAK) cells. Changes in cortisol levels may explain some effects on the immune system, such as depression of IL2 and immunoglobulin production in vitro, and the differences noted in clinical responses during the present study compared with those observed with interferon alfa-2b given by intravenous (IV) injection in 5-day cycles. These results suggest that interferon alfa-2a has antitumor activity in certain melanoma patients, in particular those with metastases to pulmonary or subcutaneous sites. Assays of IL2 production and LAK activity may assist in the selection of patients who respond to interferon alfa-2a and help to optimize treatment regimens.

Adult↗
PubMed1986

Plasma concentrations of angiotensin II and aldosterone during acute left ventricular failure in the dog. Effect of converting enzyme inhibition.

Acute left ventricular failure was induced in anesthetized dogs by left coronary embolization. Treatment with the converting enzyme inhibitor enalaprilat (MK-422) was then given. Hemodynamic registrations confirmed the development of left ventricular failure. Plasma concentrations of angiotensin II and aldosterone rose significantly. Treatment with enalaprilat was accompanied by significant reductions in heart preload and afterload and in plasma hormone concentrations.

Aldosterone↗
PubMed1986

The brain 68-kilodalton microtubule-associated protein is a cognate form of the 70-kilodalton mammalian heat-shock protein and is present as a specific isoform in synaptosomal membranes.

The relationship between the 68-kilodalton microtubule-associated protein (68KMAP) and the major heat-induced protein (HSP70) in rat and human cells was investigated by comparison of their heat induction properties and by tryptic and Cleveland peptide mapping procedures. HSP70 synthesis was induced by heat shock of rat and human cells, whereas 68KMAP was a major synthesised protein in the absence of heat shock, with its synthesis being only slightly increased on heat shock. Tryptic peptide mapping, however, indicated strong peptide homology between the two proteins. These data, therefore, confirm that 68KMAP represents a constitutively expressed, heat-shock cognate gene. Two-dimensional gel electrophoretic analysis of subcellular fractions of rat brain, combined with peptide mapping procedures, indicated that 68KMAP exists as at least two isoforms separable by isofocussing, the more acidic of which (alpha 68KMAP) is present in fractions enriched in microtubules, cytosol, microsomes, synaptosomal plasma membranes, and synaptic vesicles, and the more basic of which (beta 68KMAP) is present predominantly in fractions enriched in synaptic vesicles and synaptosomal plasma membranes. These two forms are distinguishable in terms of changes in Cleveland peptide maps, and we conclude that alpha- and beta 68KMAP, therefore, represent distinct forms. The significance of these findings to the molecular pathogenesis of Down's syndrome in the human brain is discussed.

Animals↗
PubMed1986

Autosomal dominant thoracolaryngopelvic dysplasia: Barnes syndrome.

We review a family in which a mother and two of her three children suffered a distinct syndrome of thoracic dystrophy with small chest volume, laryngeal stenosis, normal stature with variable asymmetry, asthenic build, and a small pelvis. In addition to the different inheritance pattern, this syndrome is distinguished from the better known Jeune syndrome by the differing thoracic and pelvic configuration.

Abnormalities, Multiple↗
PubMed1986

Demonstration of calcitonin and calmodulin by immunoperoxidase in the cystic fibrosis lung.

In this investigation, the presence of calcitonin and calmodulin has been demonstrated in immunoperoxidase formalin-fixed, paraffin-embedded sections of lung from autopsy tissues of four patients who died as a result of complications resulting from their cystic fibrosis disease. Immunoreactive calcitonin has been stained and quantitated in solitary endocrine cells which are increased in number and staining intensity in cystic fibrosis lung when compared to COPD and normal lungs. Immunoreactive calmodulin has been demonstrated to be increased in cystic fibrosis lung when compared to COPD and normal lungs. Previously, increased calcitonin and calmodulin were identified in sputum from cystic fibrosis patients utilizing radioimmunoassay. The calcitonin and calmodulin may be associated with increased calcium in pulmonary secretions leading to selective colonization of the lung by a limited number of pathogenic bacteria and enhanced pulmonary infection.

Calcitonin↗
PubMed1986

A histochemical evaluation of experimentally reinnervated canine laryngeal muscles.

Sixteen dogs underwent different types of experimental reinnervation procedures of the posterior cricoarytenoid (PCA) muscle - reinnervation by the recurrent nerve itself (self-reinnervation) (n = 6), by the ansa cervicalis nerve (n = 5) or by the phrenic nerve (n = 5). After functional evaluation the normal left and the reinnervated right PCA muscles were removed for histochemical analysis. Cryostat sections were incubated for actomyosin ATPase, NADH-TR and alpha-GPDH. All muscles showed microscopical evidence of successful reinnervation. There was a slight change in the muscle fiber type composition in the reinnervated muscle as compared to the normal side. Incubations for the NADH-TR and alpha-GPDH showed less staining intensity in the reinnervated muscles. The histochemical differences between normal and reinnervated muscles were small, however, and probably of minor importance with regard to the function of the muscles.

Adenosine Triphosphatases↗
PubMed1986

Comparative study on the effects of recombinant alpha-2 interferon on immune function in patients with disseminated melanoma.

Fifteen patients with disseminated melanoma were treated by intravenous administration of recombinant alpha-2 interferon (rIFN-alpha 2) on 5 consecutive days every 2 weeks. Immunological studies on approximately 50% of the patients revealed no significant changes in lymphocyte numbers or T-cell subsets. Natural killer (NK) activity against the K562 target cell and a melanoma cell was increased in the first treatment cycle, but in subsequent treatment cycles it tended to decrease against the melanoma cell and to show either no change or moderate increases against the K562 target cell. Interleukin-2 (IL-2) production from mitogen-stimulated lymphocytes was decreased in most patients in each treatment cycle. This also applied to immunoglobulin production in vitro from pokeweed mitogen (PWM)-stimulated B and T cells. The latter was not due to the induction of radiation-sensitive suppressor T cells and may reflect effects on B cells or helper T cells. The repeated inhibition of IL-2 production with each cycle of treatment and the decrease in NK activity against the melanoma target cells after the first treatment cycle contrasted with the return to at or above pretreatment values of these tests when rIFN-alpha A was given intramuscularly on an alternate-day basis. It is suggested that these effects may be due to the relatively greater increase in endogenous cortisol production at the beginning of each treatment cycle in patients given rIFN-alpha 2 intravenously compared to that observed in patients treated with rIFN-alpha A on alternate days intramuscularly. Immunosuppression resulting from the increase in cortisol production may be one of the factors accounting for the low tumor response rate of patients in this study and may emphasize the possible importance of the schedule of rIFN-alpha administration for obtaining optimal antitumor responses.

Adult↗
PubMed1986

Functional results after experimental reinnervation of the posterior cricoarytenoid muscle in dogs.

The purpose of the present investigation was to test and compare three different types of experimental posterior cricoarytenoid (PCA) muscle reinnervation. Dogs were subjected to reinnervation by the recurrent nerve itself (self-reinnervation) (n = 6), by the ansa cervicalis nerve (n = 5) or by the phrenic nerve (n = 5). In all but three of the self-reinnervation cases the adductor branch of the nerve was cut and ligated. Three to seven months postoperatively--depending upon the experimental approach--the animals were anesthetized and the function of the vocal cords was tested, visually evaluated and photographed. In the self--reinnervated larynges there were no observable movements on the reinnervated side during quiet inspiration, while during forced inspiration there were small but inconsistent movements. In the larynges reinnervated by the ansa cervicalis nerve no movements could be observed on the reinnervated side during either quiet or forced respiration. In four out of five larynges reinnervated by the phrenic nerve there were larger excursions on the reinnervated side as compared to the normal side during quiet respiration. During forced inspiration the excursions increased on both sides, but relatively more on the normal side. In all experiments indirect electrical stimulation gave large excursions on the experimental side indicating successful reinnervation. It is concluded that the phrenic nerve appears to be the best alternative if reinnervation of the PCA muscle in paralyzed larynges is attempted.

Animals↗
PubMed1985

A simple one-step procedure for the separation of calpain I, calpain II and calpastatin.

The soluble fraction from rabbit brain was adsorbed on a column of phenyl-Sepharose. By applying a linear gradient with decreasing salt concentration and increasing pH, it was possible to separate calpain I and calpain II from each other and from the endogenous inhibitor calpastatin. Both enzymes were capable of degrading endogenously labelled neuronal proteins, including slowly axonally transported soluble proteins and rapidly transported membrane-bound proteins, as well as casein.

Calcium↗
PubMed1985

Identification of the principal receptor responsible for adsorptive endocytosis of a fucose-specific lectin from Aleuria aurantia in the rabbit retina.

The retinal uptake of the fucose-specific lectin from Aleuria aurantia was investigated in rabbit. Following intraocular injections of Aleuria lectin, the probe was taken up by retinal ganglion cells and rapidly transported at two distinct rates in the optic pathway, to reach the nerve terminals in the lateral geniculate body and superior colliculus [3]. In this study, it was found that adsorptive endocytosis of Aleuria lectin was mediated mainly by a glycoprotein of Mr 275,000.

Adsorption↗
PubMed1985

The fate of tendon healing after restoration of the integrity of the tendon sheath with autogenous vein grafts.

This experimental study in the chicken model compares the results of sheath closure during primary tendon surgery. Sheath closure after tendon grafting was accomplished by trapdoor of the original sheath, vein patch, and vein conduit. After casting in flexion for 14 days, the operated foot and digits were taken through a full passive range of motion every 3 days. At the 28th postoperative day, all immobilization was removed and free active range of motion and daily perching began. Active flexion was measured after death by continuous traction on the proximal profundus tendon: simulated active flexion. The unoperated contralateral foot served as the control. All operated middle toes achieved significantly greater functional return when the sheath was restored either with trap-door closure, vein conduit, or vein patch compared with simple excision of the sheath. The results indicate the efficacy of sheath closure as well as the possibility of utilizing vein patches or conduits during primary tendon repair.

Animals↗
PubMed1985

Effects of prolonged supratentorial mass expansion on regional blood flow and cardiovascular parameters during the Cushing response.

To clarify the central nervous and the cardiovascular mechanisms mediating the Cushing response (CR) during intracranial hypertension, the effects of continuous and prolonged expansion of an epidural supratentorial balloon was studied in six dogs. Regional cerebral blood flow, cardiac output, extracerebral tissue blood flow and regional vascular resistance were measured with radioactive microspheres before and during the CR while heart rate, arterial blood pressure and ECG were continuously recorded. The results showed that balloon expansion led progressively to cerebrospinal ischemia beginning in the cerebrum and progressing to the pons, medulla oblongata and spinal cord in an orderly rostro-caudal fashion. This progressing ischemia was closely associated with patterned and stereotyped changes in cardiovascular indices. Thus, respiration ceased, heart rate decreased, blood pressure increased and cardiac output fell when the ischemia appeared in the lower pons. Further advancement of the ischemic front to the lower medulla oblongata led to an abrupt switch-over from bradycardia to tachycardia, which persisted until the experiment was terminated. Since bradycardia disappeared when ischemia reached the vagal cardiomotor nucleus, the initial bradycardia appeared to be the result of increased vagal discharge. When ischemia reached the pons, the mean arterial pressure rose to a maximum of 245 mm Hg (+/- 45) but then fell progressively when the ischemia reached the spinal cord. The decrease in cardiac output persisted throughout the CR and was associated with decreased flow in most extracerebral organs. Exceptions were the heart muscle and the adrenal medulla in which blood flow increased considerably. Changes in regional vascular resistance reciprocated the changes in flow. These results suggest that the vasomotor component of the CR is brought about entirely by peripheral vasoconstriction.

Animals↗
PubMed1985

Assembly-controlled autogenous modulation of bacteriophage P22 scaffolding protein gene expression.

In the assembly of bacteriophage P22, precursor particles containing two major proteins, the gene 5 coat protein and the gene 8 scaffolding protein, package the DNA molecule. During the encapsidation reaction all of the scaffolding protein molecules are released intact and subsequently participate in further rounds of DNA encapsidation. We have previously shown that even though it lies in the center of the late region of the genetic map, the scaffolding protein gene is not always expressed coordinately with the remainder of the late proteins and that some feature of the phage assembly process affects its expression. We present here in vivo experiments which show that there is an inverse correlation between the amount of unassembled scaffolding protein and the rate of scaffolding protein synthesis and that long amber fragments of the scaffolding protein can turn down the synthesis of intact scaffolding protein in trans. These results support a model for scaffolding protein regulation in which the feature of the assembly process which modulates the rate of scaffolding protein synthesis is the amount of unassembled scaffolding protein itself.

Capsid↗