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Biomedical subjects

J Goodman

Publications and source records attributed to J Goodman.

At least 91 records · Page 5Linked to original sources

Membrane protein band 3 alteration associated with neurologic disease and tissue-reactive antibodies.

Immunological analogues of band 3, the anion transporter, have been identified in all cells that have been studied, including both isolated neurons and neurons of the central nervous system. We studied band 3 structural/functional relationships in a family in which the proposita has a serious, progressive, genetic neurologic disorder with acanthocytosis (choreoacanthocytosis). Biochemical studies of erythrocytes from the proposita, her mother and brother revealed that maximal sulfate transport velocity (Vmax) and sodium transport were increased, glucose efflux was decreased. Ankyrin binding was normal. Immunologic studies revealed increased IgG binding to middle-aged cells of the proposita and her brother, binding of antibodies to aged band 3 to a distinct region of band 3 in erythrocyte membranes in immunoblots, and binding of choreoacanthocytosis sera IgG to erythroid and brain band 3 and synthetic peptides of band 3 in immunoblots. Antibodies to neural and, to a lesser extent, renal tissue were observed in choreoacanthocytosis sera. These antibodies appear to have a band 3 specificity. Monoclonal antibodies to 150 residues of the carboxyl terminus of band 3 stained two band 3 fragments in immunoblots of chymotrypsin-digested membranes that are not present in control cells. This suggests that band 3 is altered in this autosomal recessive neurologic disorder. In addition, these monoclonal antibodies stained five band 3 breakdown products in membranes of untreated red cells in both control and choreoacanthocytosis cells. The possibility that a disturbance of some function of band 3 may contribute to the neurologic abnormalities in affected individuals is intriguing. This is the first evidence for abnormalities of membrane transport in the neurologic disorder known as choreoacanthocytosis.

Acanthocytes↗

Derivatives of tamoxifen. Dependence of antiestrogenicity on the 4-substituent.

A range of tamoxifen derivatives substituted in the 4-position of the 1-phenyl ring are described. The key steps in the synthesis of 4-iodo-, 4-bromo-, and 4-(methylthio)tamoxifen were reactions of 1,2-diarylbutanones with the (4-halogenophenyl)lithium or [4-(methylthio)phenyl]magnesium bromide. Oxidized precursors of 4-(methylthio)tamoxifen were used to prepare the methylsulfinyl and methylsulfonyl derivatives. Further derivatives (formyl, hydroxymethyl, oxirane, mercapto) were prepared from 4-bromotamoxifen via the 4-lithio derivative. Several of the derivatives (Br, I, SMe, SOMe, SO2Me, oxirane, CHO, CH2OH) displayed a higher affinity for estrogen receptors (ER) of calf uterine cytosol than did tamoxifen, but there was no relationship between affinity to ER and the ability to inhibit the growth of the MCF-7 breast cancer cell line in vitro.

Animals↗

Maximal aerobic exercise following prolonged sleep deprivation.

The effect of 60 h without sleep upon maximal oxygen intake was examined in 12 young women, using a cycle ergometer protocol. The arousal of the subjects was maintained by requiring the performance of a sequence of cognitive tasks throughout the experimental period. Well-defined oxygen intake plateaus were obtained both before and after sleep deprivation, and no change of maximal oxygen intake was observed immediately following sleep deprivation. The endurance time for exhausting exercise also remained unchanged, as did such markers of aerobic performance as peak exercise ventilation, peak heart rate, peak respiratory gas exchange ratio, and peak blood lactate. However, as in an earlier study of sleep deprivation with male subjects (in which a decrease of treadmill maximal oxygen intake was observed), the formula of Dill and Costill (4) indicated the development of a substantial (11.6%) increase of estimated plasma volume percentage with corresponding decreases in hematocrit and red cell count. Possible factors sustaining maximal oxygen intake under the conditions of the present experiment include (1) maintained arousal of the subjects with no decrease in peak exercise ventilation or the related respiratory work and (2) use of a cycle ergometer rather than a treadmill test with possible concurrent differences in the impact of hematocrit levels and plasma volume expansion upon peak cardiac output and thus oxygen delivery to the working muscles.

Adult↗

Alteration in membrane protein band 3 associated with accelerated erythrocyte aging.

We report a human band 3 alteration that is associated with anemia as determined by a reticulocyte count of 20%. Erythrocyte defects included increased IgG binding, increased breakdown products of band 3, and altered anion- and glucose-transport activity in middle-aged cells. These changes were observed during normal erythrocyte aging in situ. Binding of ankyrin to band 3 was normal. Serum/cell crossover studies indicated that a neoantigen appears on the propositus' erythrocytes to which IgG from both propositus and control serum binds as measured with a protein A binding assay. IgG eluted from the propositus' erythrocytes appeared to have a specificity for senescent cell antigen as determined by a phagocytosis inhibition assay. Immunoelectron microscopy showed that antibodies to band 3, which do not normally bind to intact erythrocytes, bound to the propositus' erythrocytes. Antibody 980 binds to normal old cells but not young or middle-aged cells. It also binds to a distinct region of band 3 in immunoblots of membranes from the propositus' middle-aged cells. Cells from both of the propositus' parents exhibited increased IgG binding and altered anion and glucose transport. The results of these studies suggest that (i) band 3 is aging prematurely in erythrocytes from the propositus, (ii) senescent cell antigen appears on the propositus' middle-aged red cells, and (iii) band 3 alterations observed in the propositus may have a genetic component.

Anion Exchange Protein 1, Erythrocyte↗

Pulmonary rapidly adapting receptors reflexly increase airway secretion in dogs.

We attempted to determine whether stimulation of pulmonary rapidly adapting receptors (RARs) increase tracheal submucosal gland secretion in anesthetized open-chest dogs. Electroneurographic studies of pulmonary afferents established that RARs but not lung C-fibers were stimulated by intermittent lung collapse during deflation, collapse being produced by removing positive end-expiratory pressure (PEEP, 4 cmH2O) or by applying negative end-expiratory pressure (NEEP, -4 cmH2O). We measured tracheal secretion by the "hillocks" method. Removing PEEP or applying NEEP for 1 min increased secretion from a base line of 6.0 +/- 1.1 to 11.8 +/- 1.7 and 22.0 +/- 2.8 hillocks.cm-2.min-1, respectively (P less than 0.005). After PEEP was restored, dynamic lung compliance (Cdyn) was 37% below control, and secretion remained elevated (P less than 0.05). A decrease in Cdyn stimulates RARs but not other pulmonary afferents. Hyperinflation, which restored Cdyn and RAR activity to control, returned secretion rate to base line. Secretory responses to lung collapse were abolished by vagal cooling (6 degrees C), by pulmonary vagal section, or by atropine. We conclude that RAR stimulation reflexly increases airway secretion. We cannot exclude the possibility that reduced input from slowly adapting stretch receptors contributed to the secretory response.

Afferent Pathways↗

LL-E19020 alpha and beta, animal growth promoting antibiotics: taxonomy, fermentation and biological activity.

Antibacterial antibiotics LL-E19020 alpha and beta were isolated from the fermentation broth of an actinomycete strain. Based on cultural and physiological characteristics, culture LL-E19020 was identified as a new subspecies of Streptomyces lydicus. The LL-E19020 alpha and beta antibiotics were found to possess a very narrow antibacterial spectrum against human pathogens. In studies in chickens, LL-E19020 alpha demonstrated excellent growth promoting activity.

Aminoglycosides↗

LL-E19085 alpha, a novel antibiotic from Micromonospora citrea: taxonomy, fermentation and biological activity.

A new antibacterial antibiotic, designated LL-E19085 alpha, was isolated from the fermentation broth of an actinomycete strain. Based on cultural, physiological, morphological and chemical characteristics, culture LL-E19085 was identified as a new subspecies of Micromonospora citrea. Antibiotic LL-E19085 alpha demonstrated potent activity against a spectrum of Gram-positive aerobic and anaerobic bacteria.

Animals↗

Palinopsia as a presenting manifestation of Creutzfeldt-Jakob disease.

A 70-year-old man developed a syndrome of progressive nondominant parietal and occipital dysfunction including palinopsia and a visual field defect. Despite the marked focality of his clinical findings, radiologic studies were normal. Myoclonus and ataxia began 6 weeks after onset of his illness at which time brain biopsy confirmed Creutzfeldt-Jakob disease (CJD). This is the first reported case of palinopsia due to CJD.

Aged↗

Thrombolytic therapy in catheter-related subclavian venous thrombosis.

A 57-year-old woman presented with swelling of her left arm. She had had an indwelling Hickman infusion catheter for five months. Venography demonstrated subclavian vein thrombosis which was successfully treated using a low-dose streptokinase infusion into the involved catheter over a 20-hour period. No complications related to embolic disease were observed during the treatment period or during six months of follow-up.

Catheters, Indwelling↗