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Biomedical subjects

K McCarthy

Publications and source records attributed to K McCarthy.

At least 127 records · Page 7Linked to original sources

Pathogenic factors in bronchopulmonary dysplasia.

Serum factors related to oxygen exposure were studied in 56 full-term cord blood samples and in 69 newborn infants of varying gestational age (GA). Serum malondialdehyde (MDA), which reflects membrane lipid peroxidation, was elevated during the first 2 d of life and rose to a peak at 3-5 d of life. This peak value was unrelated to GA or to assisted ventilation. The serum antioxidant, vitamin E, showed a significant rise by 6-10 d, and came into the adult range after d 11. Vitamin E levels did not correlate with GA, assisted ventilation, or the development of bronchopulmonary dysplasia (BPD). Serum ceruloplasmin, another antioxidant, was measured both by activity assay and by protein concentration assay. Little activity was found in cord blood. Ceruloplasmin activity increased during the first 48 h of life, and both activity and protein concentration correlated with GA at that time. Infants who subsequently developed BPD had a less active protein than infants on ventilators who did not develop BPD. In addition, activity and protein levels on 3-5 d were lower in infants on ventilators than in those not requiring assisted ventilation. Serum levels of alpha-1-AP activity and protein concentration were also correlated with GA during the first 48 h of life. The less mature infants had levels of activity and protein which were significantly less than the more mature infants and significantly less than the full-term cord values. The proportion of active protein correlated with GA at 3-5 d, indicating that the less mature infants had a lower proportion of active protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Proteins↗

Early alcoholism treatment: the Emmanuel Movement and Richard Peabody.

The history of alcoholism treatment in the early twentieth century is outlined. The methods of the Emmanuel Movement and of Richard Peabody are described, biographical details of their main practitioners are given, the populations treated are described, and the predecessors and successors of the two methods are discussed. In addition, the two methods are compared with each other and with the methods of Alcoholics Anonymous and Freudian psychoanalysis. The founder of the E. Movement was a clergyman, Dr. Elwood Worcester, whose method was designed to treat a variety of neurotic disorders. He felt that all diseases, including alcoholism, had physical, mental and spiritual components. His principal techniques of relaxation therapy and suggestion (including autosuggestion) were used to reach the unconscious. Worcester felt that alcoholics could be helped by redirecting their attention away from their problems to a life of service and spirituality. Prayer, group support and self-help were important. Worcester tried to reduce patients' guilt and rejected temperance preaching. He felt that recovery must come from surrender to external forces and to the healing capacities of the unconscious. One patient of his, Courtenay Baylor, began to work with him at the E. Church. Like Worcester, Baylor believed that alcohol, and not one's life history, caused alcoholism. Baylor believed that alcoholism resulted from mental and physical "tenseness" and, like Worcester, he used relaxation therapy. He believed in giving a longer period of treatment than did Worcester and in providing more treatment for the families of alcoholics. One of Baylor's most famous patients was Peabody. Peabody had no credentials but he refined and professionalized the E. treatment method. He was a strong believer in the control of one's feelings and in increased efficiency--his patients were told to follow detailed time plans. He believed that early family history caused alcoholism. Like the E. Movement, he felt that relaxation, suggestion and catharsis were important. Unlike the E. Movement, he regarded the unconscious as an obstacle. His method was also less spiritual. His philosophy seemed to have been derived from the mind-cure movement, including New Thought; he was not interested in the body. The fact that the practitioners of the Emmanuel and Peabody methods were not physicians is discussed. The treatment success of both methods is unclear.

Alcoholism↗

Alterations in glomerular anionic sites in autologous immune complex nephritis.

In the present study in Munich-Wistar rats during the initial stages of autologous immune complex nephritis (protein excretion 3 to 50 mg/24 hours) we examined the sequential changes in binding of cationized ferritin to anionic sites, as well as alterations in staining with colloidal iron of podocyte membrane sialoglycoprotein and correlated these with changes in glomerular basement membrane permeability to native ferritin. The results are compared with those obtained from rats with advanced autologous immune complex nephritis (protein excretion 100 to 350 mg/24 hours) and with normal control rats. The formation of the smallest detectable immune complex deposits was associated with a concomitant decrease in binding of cationized ferritin to anionic sites in the lamina rara externa in the area of the deposits. This was accompanied by a diminution in staining by colloidal iron of the epithelial cell coat overlying the deposits. The staining of the remainder of the epithelial cell glycocalyx, however, remained unaltered even in the presence of severe proteinuria. Alterations in the permeability of the glomerular basement membrane to native ferritin could not be documented until protein excretion exceeded 10 mg/24 hours. The gradual loss of staining of the epithelial cell glycocalyx adjacent to immune complexes supports the concept that, as immune complexes are formed in situ by the interaction of antibodies with a glycoprotein present on the epithelial cell surface, they are shed and gradually accumulate in the lamina rara externa. Furthermore, as the immune complex deposits enlarge they destroy and/or mask the heparan sulfate anionic sites in the lamina rara externa resulting in a decreased number of anionic binding sites for cationized ferritin.

Animals↗

Studies of herpes virus latency in the sensory spinal ganglia of rabbits.

Experimental latent herpes infection of rabbit dorsal root ganglia (DRG) is reported. The simian herpes virus used was derived from fatal natural infection in owl monkeys and has limited neurotropism in the rabbit. Following intradermal injection of the flank it causes a local lesion followed only by dorsal root ganglionitis; segmental paraesthesia and/or sensory loss going on to clinical recovery. Methods were developed for mapping sensory losses. Virus could be immediately re-isolated from skin or DRG homogenates in the acute (first week) stage but from 8-550 days by DRG organ culture only. Spontaneous recurrence does not occur but reactivation can be provoked. The system provides an improved analogue model for the study of the pathogenesis and symptomatic treatment of herpes zoster.

Animals↗

Protein synthesis-dependent and protein synthesis-independent secretion of lysosomal hydrolases from rabbit and human macrophages.

Rabbit alveolar macrophages and human monocyte-derived macrophages released lysosomal enzymes in response to a variety of stimuli. The release of these enzyme appeared to be under the control of at least two distinct mechanisms. The first involved a rapid release of preformed granule constituents in response to a phagocytic load. This release reaction was concentration- and time-dependent, was not affected by the protein synthesis inhibitors cycloheximide and puromycin, and resulted in a concomitant loss in intracellular enzyme levels. The second mechanism involved a prolonged secretion in response to lower concentration of stimuli, which increased with time, and was inhibited by cycloheximide and puromycin. The secretion did not result in the loss of intracellular enzyme stores; rather an induction of enzyme was seen following such stimulation, which resulted in increases in the total concentration within the cultures. This protein synthesis-dependent secretion of acid hydrolases from human macrophages varied for each lysosomal hydrolase and each stimulus. beta-Glucosaminidase synthesis and secretion was induced by low-dose opsonized zymosan, by latex particles, and by formaldehyde-treated SRBC. However, only the last mentioned stimulus caused release of acid phosphates although all three particles induced synthesis of the enzyme. None of the stimuli at these concentrations (10:1 particle to cell ratio) caused the release of beta-glucoronidase, although the enzyme was releasable if higher stimulus concentrations were used. In addition the enzyme was not inducible under these conditions. It is concluded that each of the acid hydrolases studied may be under different control in the human macrophage and that the cells may respond in a qualitatively different way to different types of phagocytosable stimuli.

Animals↗

A differential effect of C5a and C5a des Arg in the induction of pulmonary inflammation.

Earlier studies have shown that C5 fragments induce an inflammatory reaction when instilled into the rabbit lung. Because C5a is rapidly converted to C5a des Arg in vivo, experiments were performed to determine which fragment was most effective in producing pulmonary inflammation in this animal model. C5a des Arg consistently produced marked inflammation. This was characterized by neutrophil accumulation, edema, hemorrhage, fibrin formation, and damage to alveolar epithelium. The time course of the inflammatory reaction initiated by C5a des Arg showed pulmonary vascular sequestration of neutrophils with no intra-alveolar migration at 30 minutes after injection. By 2 hours, interstitial and alveolar neutrophils were numerous, with the accumulation of neutrophils in the alveoli increasing to a maximum at 6 hours. At 24 and 48 hours, the predominant cells were mononuclear (macrophages). By 120 hours, the lesions were resolving. In contrast, at all doses examined, a similar instillation of C5a induced either no inflammation or a milder, more focal response than C5a des Arg. This inability of C5a to initiate inflammation was not apparently due to the generation of inhibitors, since mixtures of C5a and C5a des Arg were phlogistic. A prolonged, intrapulmonary infusion of C5a (20 minutes), in contrast to a bolus instillation (1 minute), did initiate an inflammatory response, which may reflect the conversion of the C5a to C5a des Arg in the lung. This study points out the inflammatory potential of products of complement activation, particularly of the C5 fragment C5a des Arg, when applied to the airway side of the lungs. This inflammatory response raises the possibility that cleavage of intrapulmonary C5 may play an important role in the initiation of pulmonary inflammation.

Anaphylatoxins↗

Complement fragments, alveolar macrophages, and alveolitis.

Mechanisms of neutrophil infiltration into the rabbit alveolus have been investigated. Complement activation in the circulation induced pulmonary vascular margination but not a significant level of alveolar infiltration. Instillation of C5 fragments into the airways, however, attracted neutrophils into the alveolar airspaces. The anaphylatoxin-inactive fragment of C5, C5a des Arg, was found to be much more active in this regard than C5a. Furthermore, these fragments were shown to induce the production of a neutrophil-directed chemoctactic factor from pulmonary macrophages, raising the question of whether the C5a des Arg was acting directly to attract neutrophils or indirectly via the macrophage. To substantiate a possible role for C5 and C5 fragments in alveolitis, active C5 was demonstrated in lavage fluids, and macrophage-derived C5 cleaving enzymes have been described. Finally, a route of neutrophil infiltration via migration through the alveolar capillary wall into the interstitium is proposed, and subsequent penetration of the alveolar epithelium out into the airspace. (Am J Pathol 97:93--110, 1979).

Alveolitis, Extrinsic Allergic↗

Induction of lysosomal enzyme secretion by alveolar macrophages in response to the purified complement fragments C5a and C5a des-arg.

Purified C5a and its "inactive" form, C5a des-arg, were shown to induce secretion of acid hydrolases from rabbit alveolar macrophages (AM) in a concentration-dependent manner. Secretion increased with time to 5 times above controls by 72 hr. Concentrations of these enzymes in the cell lysates did not decrease during the incubation, suggesting that synthesis of new enzyme was occurring. The lysosomal enzyme secretion was accompanied by increased pinocytosis and release of proteolytic enzymes from the macrophages. At no time was significant lactic dehydrogenase liberated, indicating that secretion was selective and not due to cell death. Data presented also suggest that C5a des-arg induced secretion from the macrophages of a chemotactic factor for neutrophils. It was concluded that C5a and C5a des-arg may play a role in lung injury by interactions with AM, inducing the secretion of acid hydrolases and proteolytic enzymes that can cause tissue damage, and by regulating the influx of other inflammatory cells into the interstitium and air spaces.

Anaphylatoxins↗

Observations on the effects of formaldehyde on cockroaches and their flora: I. Survival of vaccinia virus-infected cockroaches during fumigation with formaldehyde.

In these studies it is shown that the common "British" and "American" adult cockroaches can survive exposure to formaldehyde fumigation carried out at double the strength and for four times as long as is recommended for disinfection of rooms. It is further reported that vaccinia virus ingested prior to the fumigation survives in the cockroach gut and may be excreted up to 5 days later. Since cockroaches are ubiquitous and are to be found in most hospitals, laboratories and animal houses, these findings should be considered whenever fumigation is called for.

Animals↗

Observations on the effects of formaldehyde on cockroaches and their flora: II. Prolonged survival of cockroaches drinking formaldehyde or glutaraldehyde solutions.

Adult cockroaches were found to survive up to 22 weeks when provided with 1% Formalin (0.4% formaldehyde) in lieu of drinking water. Given 4% Formalin or 2% glutaraldehyde they survived up to 41 days. During the experiments eggs were laid and hatched and the offspring continued to grow. Combined with surface disinfection, this may hold out a simple method of rendering adult cockroaches gnotobiotic or even axenic.

Animals↗

Observations of the effects of formaldehyde on cockroaches and their flora: III. The effect of formaldehyde in eliminating the normal gut flora.

The normal flora of cockroaches (Periplaneta americana) was determined over a period of 24 days prior to substituting water with 1% Formalin for drinking water. During the first 4 days of treatment the normal flora was significantly reduced and by the fifth day, when the cockroaches became diarrhoeic, no bacteria, fungi, or viruses could be detected by the methods used.

Animals↗

Adolescent breast masses.

A retrospective experience with breast masses in 143 female and 22 male adolescents is reviewed: 104 females (71.7 per cent) had fibroadenomas and 1 (0.7 per cent) adenocarcinoma; all 22 males had gynecomastia. The significance of these findings is related to surgical therapy.

Adenofibroma↗

Hazards from simian herpes viruses: reactivation of skin lesions with virus shedding.

A new simian herpes virus with biological properties similar to herpes simplex and to simian "B" virus has been used as a model system for studying virus latency in dorsal root spinal sensory ganglia. Following intradermal injection, virus is present in the skin lesions and corresponding ganglia only, during the acute stage of the disease. By organ-culture techniques, latent virus was rescued from ganglia up to 2 years later. No latent virus was ever found in skin organ cultures of the primary site. Treatment with cortisone up to 18 months later reactivated virus latent in the ganglia, and virus returned to the skin where it produced small but typical herpes lesions which shed virus. Reactivation of Herpesvirus tamarinus was achieved after 28 months. This is believed to be the first report of a model system for the study of herpes latency in which skin lesions are found to recur, and provides an opportunity for more detailed investigations of the mechanisms of virus latency in man. The presumption that reactivation of skin lesions will also be possible in rhesus monkeys seropositive for "B" virus points to a possibly grave and largely unsuspected hazard for those engaged in primate research.

Animals↗