摘要:

SummaryUsing a piglet model of neonatal sepsis, we have determined that Group B streptococcal (GBS) bacteremia is associated with a state of vascular hyper‐resistance in both the pulmonary and systemic circulations. This elevated vascular resistance is accompanied by a significant fall in cardiac output despite the assurance of constant intravascular fluid volume. Pulmonary artery pressure rises extensively while systemic blood pressure remains essentially unchanged during this GBS infusion protocol.We report here our attempts to relieve the vascular hyperresistance of GBS infusion by administration of an &agr;‐sympathetic antagonist, tolazoline (Tz). We found that Tz, in a dose‐related fashion, decreased both systemic and pulmonary vascular resistance over the entire range from 2 to 25 mg/kg. Further, at all doses tested, the resistance‐reducing effect of Tz was equal in the systemic and pulmonary vascular beds. No selective pulmonary or systemic vasodilatory effect was demonstrated by Tz in this model of neonatal pulmonary hypertension.The reduction of systemic vascular resistance was accompanied by a significant elevation in total body cardiac output at all Tz doses. Compared to pre‐Tz values, cardiac output rose by 24, 55, and 55% after Tz at 2, 8.3, and 25 mg/kg respectively. In addition, administration of Tz to septic normovolemic piglets reliably produced a transient decrease of systemic blood pressure. For Tz doses of 2 and 8.3 mg/kg, steady state systemic blood pressure returned to pre‐Tz levels within 10 min. However, after Tz at 25 mg/kg, steady state systemic blood pressure remained significantly below pre‐Tz levels.AbbreviationsAOP, aortic pressurePAP, pulmonary artery pressureLAP, left atrial pressureCVP, central venous pressurePVR, pulmonary vascular resistanceSVR, systemic vascular resistanceGBS, Group B streptococciTz, tolazoline

ISSN:0031-3998    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

SummaryResistance of 5‐ to 8‐day‐old neonatal rabbits to dermal lesion development after intradermal inoculation ofTreponema pallidumwas demonstrated. Clinical evidence of infection following inoculation of 1 × 106Treponema pallidumat each of two sites was either minimal or absent. Atypical, nonprogressive, nonulcerative lesions occurred in 59% of the inoculated neonates and at 45% of inoculated sites. Differences in incubation periods, duration, and maximum diameters of lesions among adult controlsversusneonatal rabbits were significant. The age of waning resistance was determined by inoculating groups of neonates ranging from 1 to 7 weeks of age. Five‐week‐old (31‐36 days) neonates demonstrated waning resistance by the appearance of typically ulcerative, progressive lesions, though their parameters (duration, size) were not yet those of adult control lesions. The resistance demonstrated by neonates may be due in part to group housing (nesting) which could create unfavorable temperatures forT. pallidumsurvival; comparison of lesion development between nesting and individually housed neonates, 31 to 46 days of age, revealed a greater percentage of typical lesions developing among those individually housed (95versus52%). However, these differences may reflect the variability of typical lesion development found among animals of this age when resistance begins to wane. In both groups, the duration of typical lesions was significantly shorter than for adult controls. A heat‐stable serum factor(s) was demonstrated in 19 of 20 basal sera from neonates 4 to 6 days of age; this presented another possible mechanism of resistance. The neutralizing serum factor(s) was not demonstrable in the sera of does either before mating, during gestation, or shortly after kindling. The relationship of temperature, serum factors, and nutritional factors to neonatal resistance following intradermal inoculation withT. pallidumis discussed.AbbreviationsVDRL, Venereal Disease Research LaboratoryNRS, nonimmune rabbit serumIRS, immune rabbit serumMicro‐NZ, microneutralization

ISSN:0031-3998    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

SummaryThe immunological competence of neonatal rabbits inoculated intradermally withTreponema pallidumwas examined. Both cellular responses and the production of humoral antibody to specificT. pallidumantigens and to nonspecific antigens or mitogens were investigated. In blast transformation assays, splenic and popliteal lymph node lymphocytes from neonates inoculated with virulentT. pallidumresponsed toT. pallidumantigens in a manner similar to or greater than inoculated adult rabbits. Splenic and popliteal lymph node lymphocytes from both uninoculated andT. pallidum‐inoculated neonate and adult animals showed consistent and similar responses to concanavalin A. Both neonate and adult animals inoculated with heat‐killedT. pallidumalso responded but to a significantly lesser degree. Immunofluorescent examination of skin sections from the site of inoculation of adult and neonatal animals revealed 1) that the early infiltrate was composed predominntly of T cells, 2) diffuse antibody staining with rare B cells, and 3) fewer treponemes with significant fragmentation in neonates as compared to adult controls. Antibody production by neonates inoculated with virulentT. pallidumwas delayed 4 to 6 weeks postinoculation as measured by the fluorescent Treponemal antibody absorption and Venereal Disease Research Laboratory (VDRL) test procedures, respectively. Antibody was not detected among neonates inoculated with heat‐killed treponemes during a 6‐week observation period and only low levels of VDRL antibody were detected in a few adult control animals.Evidence for incomplete resistance of neonatal rabbits to the intradermal inoculation ofTreponema pallidumwas provided. Twenty‐two of 23 neonatal rabbits resistant to symptomatic infection upon initial inoculation with treponemes were also resistant to homologous challenge 3 to 5 months later, thus indicating a refractive state. Additional evidence was provided by the appearance of generalized lesions among seven of 29 neonates.AbbreviationsVDRL, Venereal Disease Research LaboratoryFTA‐ABS, fluorescent treponemal antibody absorptionCon A, concanavalin Ales(+), lesion positiveATS, anti‐rabbit thymocyte serumdil, dilutant

ISSN:0031-3998    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

SummaryThis report describes a third mucopolysaccharidosis in animals: canine mucopolysaccharidosis VII. The affected dog was the offspring of a father‐daughter mating. Weakness in the rear legs was evident at 8 weeks of age and became progressively worse. He had a large head, a shortened maxilla, and corneal granularities. Most joints were extremely lax, easily subluxated, with joint capsules that were swollen and fluctuant.The dog was alert and had apparently normal pain perception. At 13 months of age, there was radiographic evidence of extensive skeletal disease including bilateral femoral head luxation, abnormalities in the shape and density of the carpal and tarsal bones, radiolucent lesions of the epiphyseal regions of most long bones, and cervical vertebral dysplasia and platyspondylia. The electrophoretic pattern of precipitated glycosaminoglycans indicated a predominance of chondroitin sulfate.The animal died suddenly from gastric dilatation. There was generalized hepatomegaly, thickening of the atrioventricular heart valves, and generalized polyarthropathy. Vacuolated cytoplasm was observed in hepatocytes, keratocytes, fibroblasts, chondrocytes and cells of the synovial membrane, retinal pigment epithelium, and cardiac valves. Neurons had cytoplasmic vacuoles. Electron microscopy demonstrated membrane‐bound cytoplasmic inclusions in polymorphonuclear leukocytes, hepatocytes, synovium, heart valves and spleen.The activities of 12 lysosomal hydrolases were determined in liver from the affected and control dogs: &bgr;‐glucuronidase (EC 3.2.1.31), &bgr;‐hexosaminidases A and B (EC 3.2.1.30), &agr;‐hexosaminidase (EC 3.2.1.‐), &agr;‐L‐iduronidase (EC 3.2.1.76), &agr;‐galactosidase A (EC 3.2.1.22), &bgr;‐galactosidase (EC 3.2.1.23), arylsulfatases A and B (EC 3.1.6.1), acid &agr;‐mannosidase (EC 3.2.1.24), acid &bgr;‐mannosidase (EC 3.2.1.25), andN‐acetyl‐D‐galactosamine‐6‐sulfate sulfatase (EC 3.1.6.‐). The activity of &bgr;‐glucuronidase was reduced to less than 2% of the normal mean value of normal controls.AbbreviationsMPS, mucopolysaccharidosesGAG, glycosaminoglycanEM, electron microscopy

ISSN:0031-3998    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

SummaryMicrovillus membranes (MVM) were isolated from newborn and adult New Zealand rabbit small intestine. The isolation procedure provided a mean enrichment of 25 ± 4 for sucrase activity in adult preparations and of 27 ± 3 for lactase activity in newborn preparations. These purified MVM were incubated with increasing concentrations of125I‐labeled cholera toxin (CT).125I‐CT binding to adult MVM reached saturation at 6.4 × 10−9M; in contrast125I‐CT binding to newborn MVM did not reach saturation but instead continued to increase with increasing125I‐CT concentrations. Scatchard plot analysis of adult data supported the existence of a single binding site (Kd= 1.2 ± 0.2 × 10−9M); analysis of newborn data, however, suggested the existence of additional binding sites, as125I‐CT binding to newborn MVM was inhibited by preincubation with unlabeled CT. These results show that CT binding to both preparations is quantitatively different and is higher in newborn preparations. This difference may be accounted for by the existence of additional binding sites in newborn MVM preparations in contrast to the presence of only the unique receptor previously reported in adult MVM preparations.AbbreviationsMVM, microvillus membraneCT, cholera toxinHepes, 4‐(2‐hydroxyethyl)‐1‐piperazineethanesulfonic acid

ISSN:0031-3998    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

SummaryHuman serum specimens containing respiratory syncytial virus (RSV)‐specific neutralizing antibody were found to prevent the formation of syncytia when applied to HEp‐2 tissue culture monolayers which had been infected with RSV 12 h previously. This was evidenced by the demonstration of RSV‐infected cells without any syncytia formation in the monolayers treated with RSV antibody‐positive serum. On the other hand, widespread syncytia formation was observed with antibody‐negative control serum. The inhibitory effects of RSV antibody progressively declined when applied beyond 12 h after infection. Protection of the monolayer against syncytia formation occurred only in the presence of antibody and was quickly lost after the serum was removed. The titer of antisyncytial antibody correlated with the titer of neurtralization antibody.AbbreviationsRSV, respiratory syncytial virusCPE, cytopathologic effectsPBS, phosphate‐buffered salineMEM, minimal essential mediumTCID50, 50% tissue culture infectious dose

ISSN:0031-3998    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

SummaryWe have studied a 17‐year‐old girl with lactic acidosis (3‐18 mEq/liter) and progressive muscle weakness since 9 years of age. Morphological findings in muscle were of a typical ragged red myopathy with multiple collections of bizarre mitochondria, some containing paracrystalline inclusions.The carnitine content of serum and muscle was normal, as were the activities of carnitine palmitoyltransferase, carnitine octanoyltransferase, and carnitine acetyltransferase in the patient's muscle. Measurement of the enzymes of oxidative phosphorylation in both crude muscle homogenates and mitochondrial fractions showed close to normal activities of cytochromecoxidase, succinate dehydrogenase, and ATPase. In contrast, succinate cytochromecreductase activity was greatly reduced in the patient, being 0.035 &mgr;mol/min/g tissue in whole muscle (controls 1.16 ± 0.47 &mgr;mol/min/g tissue) and 8 nmol/min/mg protein in the mitochondria (control, 340 nmol/min/mg protein). Rotenonesensitive NADH‐cytochromecreductase was also undetectable in the patient's mitochondria. Spectral analysis of cytochromes showed decrease of reducible cytochromebto 16% of the control. These results indicate a defect of ubiquinol‐cytochromecreductase or the cytochromebc1segment (complex III) of the electron transport chain. Antibody‐binding studies of the individual components of complex III showed additional deficiencies of core proteins I and II and peptide VI, indicating a more widespread defect of complex III than was evident from spectral analysis and enzyme activity measurements alone.Urine organic acid analysis after fasting and following a medium chain triglyceride load showed unusually high levels of lactate and 3‐hydroxybutyrate, lower than expected levels of acetoacetate and dicarboxylic acids, and the presence of several other metabolites suggesting a disturbed citric acid cycle and redox state. Thus, the defect in this patient may be more widespread than is apparent from the clinical presentation.AbbreviationsCNS, central nervous systemCK, creatine kinaseEMG, electromyogramECG, electrocardiogramMCT, medium chain triglycerideSDS, sodium dodecyl sulfateDCIP, 2,6‐dichloroindophenol

ISSN:0031-3998    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

Summary&agr;2‐Macroglobulin (&agr;2M) is a major plasma protease inhibitor that has been studied because of its suggested role in the pathology of cystic fibrosis (CF). A panel of monoclonal antibodies specific for human &agr;2M were produced and screened for their ability to bind to a number of human &agr;2M samples. We have used these antibodies to characterize individual antigenic sites in this protein. &agr;2M was purified from plasma by polyethylene glycol precipitation followed by zinc chelate chromatography. A total of 23 &agr;2M samples in the native configuration, as well as the nucleophile‐treated configuration, were screened by the panel of 18 monoclonal antibodies in an enzyme‐linked immunosorbent assay procedure. Five of the samples tested were from individuals with cystic fibrosis. &agr;2M from family members of two of these patients was subsequently tested for reactivity with the monoclonal antibodies. One antibody, SAM94, exhibited a significant difference in binding to &agr;2M obtained from CF patients as compared with control individuals. This difference was particularly apparent in the binding of SAM94 to the nucleophile‐treated CF &agr;2M; SAM94 showed significantly reduced binding to four of five unrelated CF individuals (p< 0.005) and three of four cystic fibrosis obligate heterozygotes (p< 0.005).Abbreviations&agr;2M, &agr;2‐macroglobulinCF, cystic fibrosisELISA, enzyme‐linked immunosorbent assayPEG, polyethylene glycolPBS, phosphate‐buffered salinePMSF, phenylmethylsulfonyl fluorideSBTI, soybean trypsin inhibitorTEMED,N,N,N',N'‐tetramethylethylenediamine

ISSN:0031-3998    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

SummaryWe present the study of a black family in which the proband suffered from a severe neonatal hemolytic anemia with poikilocytosis. Both the parents, sister's, and brother's proband were clinically normal. The presence of poikilocytes in proband led to a search for a red cell membrane skeleton defect. Owing to recent improvements in the erythrocyte membrane knowledge, it is now possible to approach the diagnosis by means of biochemical evaluation of both parents, even if they are asymptomatic. So, the first time discovery of a spectrin self‐association defect in both parents allowed us to suspect double inheritance of this abnormality in the proband. A complete morphological and biochemical evaluation of the family allowed us to propound the diagnosis of heterozygous type I hereditary elliptocytosis (HE) for both parents and the sister and the diagnosis of homozygous type I HE for the proband owing to the following reasons: slight ovalocytosis was present in both parents and the sister; cell deformability ektacytometric studies gave the same profiles of curve as those observed in patients with HE. Defective spectrin dimer self‐association found in both parents was also observed in the sister and proband, associated with the same abnormal spectrin digest pattern, namely a decrease in the amount of a 80,000‐dalton peptide and a corresponding increase in a 74,000‐dalton peptide. However, clinical presentation of the proband was consistent either with hereditary pyropoikilocytosis or homozygous hereditary elliptocytosis; erythrocyte thermal sensitivity studies in the proband could not be conclusive because of the presence of transfused cells. Both these diagnoses are discussed in detail. Other modifications of spectrin tryptic patterns were detectable and were not related to the functional defect of spectrin since the proband's normal brother appeared homozygous for these modifications.AbbreviationsHPP, hereditary pyropoikilocytosisHE, hereditary elliptocytosisPMSF, phenylmethylsulfonyl fluorideSDS, sodium dodecyl sulfateBME, &bgr;‐mercaptoethanol

ISSN:0031-3998    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

SummaryWeanling rabbits were fed a purified diet with or without vitamin E supplementation to evaluate the abnormal sequestration of iron in skeletal muscle associated with vitamin E deficiency. A severe myopathy developed in unsupplemented rabbits within 3 to 4 weeks. At this time, the concentration of soluble nonheme iron in biceps femoris muscles had increased from 2.1 ± 0.4 &mgr;g/g wet weight (mean ± SD) for six control rabbits to 4.3 ± 1.4 for 10 vitamin E‐deficient rabbits, and total nonheme iron had increased from 5.0 ± 1.2 to 8.4 ± 3.3. Soleus muscles had even greater increases in total and soluble nonheme iron concentrations. Intramuscular injection of iron‐dextran caused large increases in total and soluble nonheme iron in noninjected muscle of vitamin E‐deficient rabbits, which further exaggerated the difference between the two groups. By radioimmunoassay using an antibody to rabbit liver ferritin, the concentration of ferritin in biceps femoris muscles increased from 0.47 ± 0.18 &mgr;g/g wet weight for seven control rabbits to 6.34 ± 1.70 for 14 vitamin E‐deficient rabbits. Uptake of intravenously injected transferrinbound iron into muscle of vitamin E‐deficient rabbits was not increased in a short term experiment (6 h), but radioiron did accumulate in muscle in a long term experiment (6 days). There was no trapping of heat‐damaged erythrocytes, no phagocytosis of intravenously injected carbon particles, and no erythrophagocytosis in muscle. An immunohistological staining method designed to detect ferritin in tissue sections stained muscle from normal rabbits very scantily but intensely stained macrophages in the muscle of vitamin E‐deficient rabbits. We conclude that macrophages in skeletal muscle of vitamin E‐deficient rabbits take up iron from transferrin and incorporate it into ferritin, in which form it is relatively unavailable for erythropoiesis because of slow release.

ISSN:0031-3998    

出版商:OVID    

年代:1984

数据来源: OVID