摘要:

This report gives a more complete description of pathologic and enzymologic findings in the feline Maroteaux-Lamy Syndrome based on additional studies in the cat originally described, three other affected Siamese cats from two additional families and an affected kitten produced by an experimental mating between obligate heterozygotes from two independently ascertained families.All affected animals had facial dysmorphia with a small head and broad, shortened maxilla. None had hepatosplenomegaly. All had a diffuse ground glass appearance of all layers of the cornea.All long bones had multiple severe exostoses with epiphyseal dysplasia and irregular articular surfaces.There was no indication in these cats of any deficit comparable to what is defined in man as mental retardation.The electrophoretic patterns obtained showed that the primary glycosaminoglycan (GAG) excreted in the urine by the affected cats was dermatan sulfate.In two human mucopolysaccharidoses (MPS) VI patients and all five affected cats, 90–100% of the circulating polymorphonu-clear (PMN) leukocytes contained, by light microscopy, excessive coarse granulations in the cytoplasm. In the human MPS VI patients, most PMN leukocytes contained, by electron microscopy, small (0.2–0.5u) round membrane bound inclusions, a majority of which contained an amorphous to granular electron dense material. The predominant inclusion type in the cat varied among families: lamellar, granular, and crystalloid, but all three inclusion types were present in some cells of all affected individuals.The data indicate that the detection of normals, heterozygotes, and homozygotes for the mutant gene was possible using an assay for arylsulfatase B (ASB) in peripheral blood leukocytes. The existence of an obligate heterozygote which has very low ASB activity with the nitrocatechol sulfate assay indicates that clinical criteria must be combined with assays of enzyme activity before an individual can be defined as affected.Pedigree information in the three independently ascertained families of cats is consistent with autosomal recessive inheritance. An experimental mating between obligate heterozygotes in families 2 and 3 produced a kitten with characteristic signs and enzymatic deficiency of the syndrome, indicating that the same locus, and in all probability the same mutant allele, is involved in these two families.SpeculationThis feline model of mucopolysaccharidosis VI (Maroteaux-Lamy Syndrome) can be produced by experimental mating and should allow advances in the understanding of the pathogenesis and approaches to therapy for this and related genetic storage diseases.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

It has been well established that heterologous antisera against whole rat kidney homogenate when injected into pregnant rats during the embryonic organogenetic period may induce abnormal embryonic development. Attempts were made to isolate the active components from soluble rat kidney extract by ammonium sulfate precipitation, anion-exchange chromatography, and concanavalin A-Sepharose 4B affinity chromatography. The glycoproteins isolated were capable of stimulating the production of potent rabbit antisera. When injected ip into the 9th day pregnant rats, these antisera induced embryonic death, congenital abnormalities, and fetal growth retardation. Eighty-four surviving fetuses were examined, all of them were malformed. The most frequently observed congenital defects were anophthalmia and microphthalmia. Attempts were made to analyze the glycoprotein fraction by discontinuous and sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. The results indicate that the glycoproteins were of high molecular weight and could be dissociated by SDS into a multitude of molecules or subunits. Although double immunodif-fusion indicated that there were one major and two minor antigens in the glycoprotein fraction, attempts to identify the antigens as to their size by analytical gel electrophoresis have not been successful. Electron microscopic study seemed to suggest that the glycoproteins might tend to aggregate to form particulates. The underlying mechanism whereby the antisera to these glycoproteins induce abnormal embryonic development is not understood. The hypotheses to explain the possible sites of teratogenic antibody interaction are discussed.SpeculationHeterologous antibodies are known to be transmitted from the mother to the fetus. The data indicate that the antigens which stimulate the production of teratogenic antibodies are glycoproteins. Recently, it has been demonstrated by other developmental biologists that each tissue contains a specific aggregation factor that ligates cells of that particular tissue. These aggregation factors are glycoproteins. It is possible that a population of heterologous antibodies directed against rat kidney glycoproteins may crossreact with some aggregation factors and, thus, interfere with cell-cell interaction at the time of histogenesis resulting in abnormal embryonic development.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

The regional distribution of acetylcholinesterase in the right atrium was determined by quantitative chemical measurements on hearts obtained from 14 infant and 9 adult humans at autopsy, and 9 adult dogs after termination of acute animal experiments. The atrium and interatrial septum were dissected, and the appendage was cut along its fold from the ventricular border to the superior vena cava. The atrium was cut into 20 consecutive sections. Homogenates (10% w/v) were prepared, centrifuged, and the supernatants were used for the enzyme assay by the method of Ellman. The acetylcholinesterase concentration [AChE] was mapped by section, or the sections were grouped into areas and mapped. The results show that: 1) in the dog, [AChE] is significantly higher in the nodal regions as compared to the appendicular areas, which contain the lowest [AChE]; 2) in the human, the [AChE] distribution pattern is qualitatively similar between the adult and infant, and in contrast to the dog, the appendicular areas contain the highest [AChE]; 3) for all areas studied, human infant [AChE] levels are significantly higher than human adult levels for corresponding areas. It is concluded that there is a distinct species difference between the regional distribution of the [AChE] in human and canine right atrium. Also, within humans, there is an age-related difference in the quantitative [AChE| levels. These species and age-related differences may reflect a varying pattern of distribution of the vagus nerve between the two species studied.SpeculationThis study presents quantitative data about the regional distribution of AChE concentration within the right atria of adult dog, and adult and infant human hearts. Significant species and age-related differences were observed. Because a close correlation is known to exist between the concentration of acetylcholine, acetylcholinesterase, and choline acetylase in various regions of the peripheral and central nervous system, it is speculated that the differences in the distribution of acetylcholinesterase within the right atrium reported here reflect a difference in the pattern of cholinergic innervation between species.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

The biosynthetic activities of protein and collagen from the patient of kinky hair disease, were reduced to 70 and 50%, respectively, compared with control.In tissue cultures, fast-green FCF staining coarse granules were found in the cytoplasm of skin fibroblasts from the patient.Ultrastructurally, collagen fibrils by iliac cartilage biopsy were irregular in width. Ruthenium red staining granules, presumed to be proteoglycans in the cartilage matrix, were relatively small in size and few in number. Chondrocytes showed poor development of organelles and relatively small glycogen accumulation.SpeculationThe metabolic disorder of copper may play a role in the reduced biosynthetic of collagen. There is a possibility that fast-green FCF staining coarse granules in the cytoplasm of skin fibroblast, may be a precursor material of collagen. The appearance of huge collagen fibrils in the cartilage matrix may be related to the decreased number of proteoglycan granules which are considered to play a role in fiber formation.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

The effect of eight branched-chain amino acid metabolites, four metabolites from the β-oxidation, and the unphysiologic acid 4-pentenoic acid on the oxygen consumption rate of liver mitochondria oxidizing pyruvate, 2-oxo-glutarate, and L-palmitoylcarnitine has been investigated. The 12 metabolites are: propionic, isobu-tyric, 2-Me-butyric, isovaleric, acrylic, Me-acrylic, tiglic, Me-crotonic, butyric, hexanoic, crotonic, and 2-hexenoic acids. The oxidation rate of pyruvate was strongly inhibited by propionic, 4-pentenoic, and isovaleric acids at 0.1, 0.1, and 1.0 mM, respectively. With 2-oxo-glutarate as substrate, the oxygen consumption rate was strongly inhibited at 0.1 mM of propionic, 4-pentenoic, and isovaleric acids. The L-palmitoyl-carnitine oxidation rate was very strongly inhibited by 0.1 mM 4-pentenoic acid, whereas butyric and hexanoic acids exerted a moderate inhibition at 0.1 mM. Propionic acid inhibited L-palmitoylcarnitine oxidation slightly at 1.0 mM. It is argued that propionyl-CoA and isovaleryl-CoA inhibit pyruvate and 2-oxo-glutarate dehydrogenases directly, and the significance of the results for ketotic episodes in organic acidurias is discussed.SpeculationThe significant inhibition of energy metabolism by propionic and isovaleric acids compared to the other monocarboxylic acids suggests a direct inhibition of pyruvate and 2-oxo-glutarate dehydrogenases in mitochondria incubated with propionic or isovaleric acids. It may be speculated that the inhibition of the pyruvate metabolism in the intact cell, may cause an accumulation of pyruvate and lactate, and that the inhibition of the 2-oxo-glutarate oxidation may be ketogenetic by lowering the cellular oxaloacetate concentration. The excessive excretion and accumulation of propionic and/or isovaleric acid in acute episodes and the terminal phases of some organic acidurias is consistent with the hypothesis that these acids contribute to the pathophysiology of the acute disease states.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

In order to identify the fetal features in neonatal erythrocytes, cord blood was separated into seven fractions of varying specific density. Cell age in the single fractions was ascertained by means of reticulocyte count, glutamic-oxalacetic transaminase activity, and hemoglobin F concentration. The same procedures were used with blood of adults. With the exception of the fraction of neonatal blood with the highest specific density, the blood from neonates and adults correlated well for cell age and specific density. The highest specific density fraction of neonatal blood was found to contain a higher proportion of younger cells.The comparison of enzyme activities in the single fractions between neonates and adults showed that a high activity of glucose-6-phosphatedehydrogenase and enolase and a low activity of phosphofructokinase are typical fetal signs of neonatal cells.SpeculationThe changing constitution of red blood cells (RBC), which were observed during the first months of life may be a part of the differentiation process. Due to their good accessibility and their relatively simple metabolism, erythrocytes from neonates can serve as a goodin vivomodel that helps to clarify the process of differentiation.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

Levamisole (Ketrax), an anthelmintic drug commonly used in the tropics, has been found to restore the impaired spontaneous rosette-forming lymphocytes and delayed cutaneous hypersensitiv-ity reactions in experimentally malnourished rats. It, however, has no effects on plaque-forming cells.The drug was also found to reconstitute the histologic integrity of the thymus in malnutrition.SpeculationDue to the diminished immune response in malnutrition, mortality usually occurs as a result of superimposed infections like diarrhea and bronchopneumonia. It is speculated that levamisole that potentiates cellular immunity in malnutrition may aid the recovery of children with kwashiorkor and marasmus, particularly those with gastroenteritis and bronchopneumonia.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

Some experimental data in human jejunum suggest a Na dependence for glucose absorption and a glucose dependence for Na absorption. However, the relationship between these two transport processes is not yet known. Na+and D-glucose absorptions were, therefore, measured simultaneously,in vitro, in isolated jejunal mucosa of children. The results are as follows: 1) the steady-state accumulation of D-glucose (C/M glucose) is a function of the Na concentration gradient between cell and medium (C/M Na). In Ringer solution, C/M glucose = 3.97 and C/M Na = 0.29; in the presence of 10-4M ouabain, C/M glucose = 1.63 and C/M Na = 0.60, and in Na free solution, C/M glucose = 0.99. In the presence of phloridzin, C/M Na is not statistically different from that in Ringer, but C/M glucose is significantly decreased. 2) The influx of D-glucose at the luminal membrane is a function of Na concentration in the bathing solution; it has the value of 4.41 /μmole/hr cm2in the presence of Na and of 1.65 μmole/hr cm2in absence of Na. 3) The short-circuit current is a saturable function of D-glucose and of 3-o-D-methylglucose. The Ktfor glucose is 8.01 mM. These results support the concept of a coupling between Na and D-glucose absorptions at the luminal membrane of jejunal mucosa of children.SpeculationThesein vitroresults might help to understand the stimulation of Na absorption by glucosein vivo. They might be useful in a physiologic approach of treatment of acute diarrhea in children.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

Bone marrow (BM) karyotypes from 16 consecutive children presenting with nonlymphocytic leukemia were established with the use of banding techniques, before therapy. The two patients with chronic myeloid leukemia (CML) showed the Philadelphia (PhI) translocation (9q+;22q-). Five of the 14 patients with an acute nonlymphocytic leukemia (ANLL) presented no acquired cytogenetic abnormalities, but one of these five showed a high level of hypodiploidy. One patient with AML evidenced a variant of the Ph1chromosome originated as a translocation (12p+;22q-). Nonrandom abnormalities (-7; 7q-; +8; t(8;21); −21) were found in six patients, isolated or in association with other aberrations. Among the random abnormalities, apparently balanced transloca-tions and chromosomal deletions were observed.In ANLL, no correlation could be found between morphologic diagnosis and cytogenetic findings. On the other hand, the presence of BM cells with a normal karyotype at diagnosis was associated with an improved remission rate and survival time. Followup studies were performed in four ANLL patients with an abnormal cell clone at diagnosis. Three of them achieved hema-tologic remission; their BM karyotype was found to be normal at that stage. In the 4th patient, generalization of the abnormal karyotype in BM cells was seen in the terminal phase of the disease.SpeculationChromosome identification techniques have greatly improved our knowledge of acquired BM aneuploidy found in leukemia. Nonrandom patterns of abnormalities have been found. Analyses of larger series of patients using advanced banding techniques and systematic followup studies will ascertain the significance of these cytogenetic abnormalities for diagnosis, prognosis, and neoplastic transformation.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

A peptic-tryptic-cotazym (PTC) digest of a crude wheat gliadin preparation was obtained under experimental conditions simulatingin vivoprotein digestion and then fractionated into 10 peaks by ion-exchange chromatography. PTC-gliadin digest and one of its subfractions (coded as fraction 9 according to its elution pattern) were very active in inhibitingin vitrodevelopment and morphogenesis of small intestine from 17− and 18-day-old rat fetuses, whereas they were harmless for the culture of jejunum from 21-day-old fetuses. PTC-digest also induced extensive tissue degeneration and necrosis ofin vitrocultured small intestinal mucosa from patients with active celiac disease (gluten-induced entheropathy), but did not cause any detectable effect on histolog-ically normal human small intestinal mucosa. Some wheat albumin and gliadin fractions were also tested onin vitrodeveloping small intestine from 17-day-old rat fetus. Among all the tested protein fractions, only one gliadin fraction (coded as αio-gliadin from its gel electrophoretic mobility) exhibited a toxic effect; morphologic alterations induced by αio-gliadin were similar to those induced by PTC-digest and fraction 9.SpeculationPeptides obtained from wheat gliadins underin vitroconditions simulating protein digestion by humans as well as whole wheat gliadin are very active in damagingin vitrodeveloping jejunum from 17− and 18-day-old rat fetuses, but have no toxic effect on the culture of jejunum from 21-day-old rat fetus. The transient character of such an effect is suggestive of a protective mechanism against the toxic protein components from wheat, associated with the age-dependent maturation of rat intestinal mucosa. It is speculated that also human normal intestine develops with maturation similar specific detoxifying mechanisms and that wheat gliadin and gliadin-derived peptides might exert a toxic action when human intestinal mucosa is not yet fully mature (i.e., during early extrauterine life) or when adult human mucosa regresses towards immature steps of development (i.e., in intestinal diseases with mucosal atrophy).

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID