摘要:

SummaryCystinotic fibroblasts contain highly elevated amounts of intraellular non-protein cystine within lysosomes compared to normal fibroblasts. Both the rate of cystine reaccumulation by cystin-delepleted cystinotic fibroblasts and the steady-state cystine content of nondepleted cystinotic fibroblasts can be modulated by the addition of bovine scrum albumin to the culture medium. This effect is not seen in cultures of normal and cystinotic heterozygote fibroblasts. The cystinotic homozygote cells accumulate cystine under these conditions from proteolysis of the albumin. An increased rate of pinocytosis or proteolysis of albumin does not account for the observed cystine accumulation by the cystinotic fibroblasts. Comparison of the amount of cystine accumulated to the amount of albumin degraded shows that less than one percent of the cystine moieties released by proteolysis is retained within these cells.SpeculationThe metabolic defect leading to cystine storage in cystinosis remains to be identified. Study of the relationship between the rate of cystine accumulation and the cystine and cysteine content of proteins degraded by cystinotic fibroblasts may help to determine if the defect is related to an abnormality of lysosomal disulfide reduction.

ISSN:0031-3998    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

SummaryThe protective value of pooled human gamma globulin (GG) and a group B streptococcal immune globulin (GBSIG) was studied in a chick embryo and a murine model of group B streptococcal (GBS) infection. Chick embryos were protected by the IV administration of 0.4 to 0.8 mg of GG from three manufacturers against IV challenge with type Ia GBS. Two of three GG preparations at doses of 0.4 to 1.65 mg protected chick embryos against type III, but 1.65 mg of all three preparations failed to protect against GBS types Ib and II. Mice were protected from lethal IP challenges with types Ia and Ib by the prior IM inoculation of three and two of the three GG preparations at doses of 0.5 to 1.0 mg, respectively. Administration IM of 1 mg of GG failed to protect mice against types II and III.The IV administration of 0.2 mg of GBSIG protected chick embryos against IV inoculation with GBS types Ia, Ib, II, and III. Administration IM of 0.5 mg of GBSIG protected mice against IP challenges with types Ia, Ib, and II, but not with type III. The IP administration of 0.25 mg of GBSIG simultaneously with type III GBS protected mice, whereas GG was not protective. GBSIG should undergo clinical trials for the prevention of GBS infections and their recurrences and as a possible adjunct to antibiotic and supportive therapy of severe GBS infections.SpeculationSome human sera contain antibody which protects animals against infection with group B streptococcus. If passive immunization with human gamma globulin or group B streptococcal immune globulin is effective in animal models, it may be potentially useful in preventing neonatal group B streptococcal infections, and clinical trials would be indicated.

ISSN:0031-3998    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

SummaryThe present study was designed to investigate glucose metabolism in the postmature fetus and newborn. In the fetus, the decreased hepatic glycogen content together with the decrease by the same percentage of total hepatic glycogen radioactivity from directly injected [6-3H]glucose demonstrate that fetal glycogenolysis occurs during prolonged gestation. Moreover, fetal glycogen synthesis as tested byin vivo[6-3H]glucose incorporation experiments is inhibited.In vivoexperiments with [14C]lactate are consistent with gluconeogenesis, being inactive in the postmature fetus as well as in the normal-term fetus. During the first hr after delivery, ourin vivodata about conversion of [14C]lactate to glucose show that the gluconeogenic pathway is not functioning in spite of very high phosphoenolpyruvate carboxykinase activity in the postmature. By 3 hr postpartum, the phosphoenolpyruvate carboxykinase activity, the blood lactate level, the percentage of conversion, and the rate of gluconeogenesis are very elevated in the postmatures as compared to the term neonates. By 6 hr postpartum, despite maintained phosphoenolpyruvate carboxykinase activity, gluconeogenic rate becomes very weak in postmatures kept fasting. This is the time characterized by a profound hypoglycemia. In contrast, fed postmature neonates exhibit normal blood glucose levels by 6 and 12 hr postpartum as a result of sustained rate of gluconeogenesis.SpeculationIn utero hepatic glycogenolysis of the postmature rat leads to impaired capacity to cope with neonatal fasting. Gluconeogenic pathway, as measured under normal blood oxygenation of the mother, is not operating in the postmature as well as in the term fetus.

ISSN:0031-3998    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

SummaryThe ontogeny of single nephron flitration distribution was studied in 29 canine puppies two hr to 42 days old using the [14C] ferrocyanide method as modified by Coehlo (9). The ratio of14Counts in outer cortical nephrons (OC) to counts in juxtamedullary nephrons (JM) were plotted against age for each puppy. This ratio (OC:JM) provided an index for comparing the single nephron mlomerular filtration between regions. A four-fold increase in OC:JM occurred from two days to four wk. The youngest puppy, two or old, showed a ratio of zero because no counts were detected in OC at that age.The most rapid increase occurred in the first 8 days of life. By the fourth wk, the mean OC:JM ratio was 0.72 ± 0.06, approaching values reported by other laboratories for adult dogs. In contrast to age-related changes in OC:JM ratio, the ratio of middle cortical to JM counts showed no age-related increase. Cortical blood flow distribution was determined by the microsphere method. The ratio of blood flow to outer and inner cortex increased from 0.43 at one-half a day to a mean of 2.93 after one wk. The ratio of OC:JM single nephron nitration to OC/inner cortical nephron renal blood low was 0.36 from 3 days to 26 days (n= 12) and did not change significantly with age, indicating that changes in zonal filtration matched the alterations in cortical blood flow distribution.SpeculationThese studies suggest that although systemic arterial pressure changes probably play a role in the increasing single nephron filtration in the outer cortex of the maturing puppy, it is likely that plasma flow is a governing factor.

ISSN:0031-3998    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

SummarySuckling mice infected with reovirus type 3 were examined for changes in the epithelial brush border of the small intestine. After 3 days of infection with reovirus type 3, no significant changes were found in intestinal morphology or activity of any enzymes tested. After 6 days, villi were shortened and blunted with lymphangiectatic lesions and mild mononuclear infiltration in the lamina propria. In addition, there was a significant decrease in lactase (P< 0.001) and enterokinase activity (P< 0.05). However, there were no significant changes in the activities of alkaline phosphatase. In contrast, maltase (P< 0.001) and leucine amino-peptidase (P< 0.05) activities in the infected mice were significantly increased. These data suggest that brush border enzymes are affected differently by reovirus infection.SpeculationThe decrease in lactase activity and increase in maltase and leucine aminopeptidase in infant mice infected with reovirus type 3 can be a reflection of accelerated maturation subsequent to an increased turnover of the epithelial cells of the crypt and villi or to an induction of specific enzymes. In addition, it is possible that the severe decrease of lactase activity in comparison to other brush border enzyme changes is due to the fact that lactase is more vulnerable than are other enzymes to mucosal injury and the possibility that lactase is a receptor for the virus.

ISSN:0031-3998    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

SummaryThe availibility of neutrophils is an important factor in host resistance to bacterial infection. Therefore, circulating and storage neutrophil quantification was carried out on groups of neonatal rats intranasally inoculated with type II group B streptococci. The dose of type II group B streptococci used produced 56% mortality in 48 neonatal rats with death being due to pneumonia and sepsis. Neutropenia (1300 ± 150/mm3versus2300 ± 170/mm3; mean ± S.D.;P< 0.01) and an elevation in band/polymorphonuclear ratio (0.98 ± 0.04versus0.30 ± 0.04:P< 0.01) were observed in infected neonatal rats 24 hr following inoculation. Femoral marrow as well as splenic and hepatic neutrophil storage compartment quantification revealed dimunition of postmitotic (polymorphonuclear, band, and metamyelocyte) neutrophils in the infected group (P< 0.01) with sparing of the proliferative neutrophils (myeloblasts, promyelocytes, and myelocytes). Repletion of the myeloid but not the splenic or hepatic neutrophil storage compartments with normalization of the neutrophil count and band/polymorphonuclear ratio occurred in animals surviving 72 hr. These studies establish that neutropenia and neutrophil storage pool depletion are prominent features of experimental type II group B streptococci infection in neonates.SpeculationAlthough neutrophil storage pool depletion is rare in infected adult animals or humans, its presence can be correlated with an increased mortality. It appears that neutrophil storage pool depletion is a prominent feature of experimental neonatal type II group B streptococci infection. The resulting deficiency of phagocytic cell supply probably represents diminution in the already compromised host defense mechanism of the neonate. Thus, it is postulated that neutrophil storage pool depletion represents a pathophysiologic factor contributing to the high mortality rate observed in neonatal type II group B streptococci infection.

ISSN:0031-3998    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

SummaryEighteen normal infants were studied in the first 2 wk of life during sleep and subsequently at their monthly birthdays for the first 4 months of life. The R-R interval was measured with an accuracy of 0.2 msec. Sleep staging was performed visually using electroencephalogram, electrooculogram, and electromyogram, and behavioral criteria. Our results show that the R-R interval and the beat-to-beat variability are, in general, smaller in rapid eye movement than in quiet sleep. The two sleep states, however, are best differentiated by the overall variability which is characteristically higher in rapid eye movement sleep. The R-R interval as well as the overall and the beat-to-beat variability show minimal values at 1 month and maximal rates of increase between 2 and 3 months of age, indicating that the R-R interval and R-R variability are not simple linear functions of age.SpeculationWe suspect that the large variability in the R-R interval in rapid eye movement sleep is attributable to the wide fluctuations in the activity of the sympathetic and parasympathetic nervous system characteristic of this sleep state. Because peripheral vasodilatation is known to occur in rapid eye movement sleep, we speculate further that the decrease in R-R interval in rapid eye movement sleep may be an adjustment to maintain the cardiac output and blood pressure.

ISSN:0031-3998    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

SummaryPeptidase activities have been investigated in the brush border of human proximal jejunum by using dipeptides and tripeptides and β-naphthylamides of glycyl-L-proline and amino acids as substrates. The activities hydrolyzing glycyl-L-leucine, L-phenylalanyl-L-alanine, and L-leucylglycylglycine in the brush border were found to be only 1.5, 15, and 16% of the total peptidase activities present in the intestinal mucosa, but the specific activities for the hydrolysis of these substrates appeared in the brush border to be as high as or higher than that of sucrase. The enzyme(s) hydrolyzing L-phenylalanyl-L-alanine in the brush border showed different properties from the enzyme(s) hydrolyzing the same substrate in the cytosol, the former being completely resistant top-hydroxymercuribenzoate, partially resistant to heating, and inhibited by puromycin by about 50%. On the other hand, the enzymatic activities hydrolyzing the β-naphthylamides of glycyl-L-proline, L-leucine, and α-L-glutamic acid as well asN-carbobenzoxy-L-prolyl-L-alanine were shown to be almost totally localized in the brush border. All the peptidase and β-naphthylamidase activities studied were well solubilized by papain from the brush border membrane with the only exception being the activity hydrolyzing glycyl-L-leucine. By acrylamide gel electrophoresis, three enzymatic activities were clearly separated from each other as well as from the oligoaminopeptidase- (EC 3.4.11.2) splitting L-leucyl-β-naphthylamide: (1) the aminopeptidase A (EC 3.4.11.7) hydrolyzing α-L-glutamyl-β-naphthylamide; (2) the dipeptidylaminopeptidase IV (EC 3.4.14.-) liberating glycyl-L-proline from glycyl-L-prolyl-β-naphthylamide; and (3) a carboxypeptidase hydrolyzingN-carbobenzoxy-L-prolyl-L-alanine (EC 3.4.12.-).Brush border peptidases (oligoaminopeptidase, aminopeptidase A, dipeptidylaminopeptidase IV, and carboxypeptidase) and cytosol dipeptidase and tripeptidase activities were measured in intestinal biopsies of celiac patients utilizing specific substrates.These enzymatic activities were normal in eight children with celiac disease in histologic remission, with only aminopeptidase A being reduced to 70% of control values. On the contrary, in the atrophic mucosa of 12 children with active celiac disease, these were all significantly but not equally reduced.SpeculationThe identification of the above-mentioned peptidases in the intestinal brush border demonstrates the importance of this sub-cellular organelle in the digestion of protein and peptides complementary to intraluminal and intracellular digestion. Brush border peptidases are probably involved in the digestion of gliadin, which is very rich in glutamic acid and proline residues; as these activities are lowered in the atrophic celiac mucosa, digestibility of gliadin peptides might be reduced during active celiac disease.

ISSN:0031-3998    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

SummaryLittle information is available regarding the time, rhythm, number, and appropriate dosage of human chorionic gonadotropin (HCG) for adequate testing of testicular function in human. The time course of the effect of two, three, or seven HCG injections at intervals of one, five, and two days, respectively, on the plasma levels of testosterone was studied in 11 boys. The first injection induced a progressive and modest rise of T. The second given one day later had little additive effect, maximal values being seen 72 to 120 hr later. In the prepubertal boys to whom several HCG injections were given, testosterone levels reached comparable levels after four injections every five days or seven injections every other day. Although the number of subjects studied was relatively small, these results give some rational basis for the following HCG test: two or four injections at four-day intervals.SpeculationIn adult men or rats, human chorionic gonadotropin induces a rapid increase in testosterone biosynthesis, followed by a steroidogenic desensitization phenomenon and a trophic effect. The recruitment of new functioning Leydig cells probably occurs parallel to the steroidogenic refractoriness of the cells when gonadotropic stimulation reaches a certain level.During pubertal development, luteinizing hormone also induces the differentiation of existing nonsteroidogenic interstitial cells into Leydig cells. Meanwhile, circulating levels of testosterone progressively increase. Assuming that endogenous luteinizing hormone has the same actions as human chorionic gonadotropin, it is speculated that if a possible induction of refractoriness of the Leydig cells is present at this stage, it might “modulate” the testicular response to the increasing levels of luteinizing hormone and partially explain the relatively slow achievement of a fully active testicular secretion in humans.

ISSN:0031-3998    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

SummaryActivities of phosphoribosyltransferase for hypoxanthine and adenine were investigated in erythrocytes and human tissues of fetuses and adults as well as in cultivated fibroblasts and amniotic fluid cells. Kinetic characteristics of these enzymes were also studied in patients with the Lesch-Nyhan syndrome and with partial deficiency for hypoxanthine phosphoribosyltransferase (HGPRTase), and their obligate heterozygotes. The affinity of HGPRTase for both substrates in partial deficiency decreased to 13 to 20% of normal and by a less degree in its heterozygotes (50 to 65% of normal). A slight decrease in the Kmfor phosphoribosylpyrophosphate was observed in the case of heterozygotes for the Lesch-Nyhan syndrome.Elevated erythrocytic adenine phosphoribosyltransferase (APRTase) activity was found in fetuses, patients with the Lesch-Nyhan syndrome or with partial deficiency, and in some heterozygotes as well. However, the Kmof APRTase for hypoxanthine in these subjects was the same as that in the normal adults. The HGPRTase activity in liver increased almost 4 times during the developmental period, whereas the APRTase activity remained approximately the same. In fetal liver, the APRTase activity was almost two times higher than the HGPRTase activity, whereas in fetal brain the HGPRTase activity was higher. The Kmof HGPRTase for hypoxanthine in cultivated cells and human tissues were similar to that in erythrocytes and leukocytes. On the other hand, the HGPRTase affinity for phosphoribosylpyrophosphate in these cells was considerably larger than in erythrocytes or in leukocytes.SpeculationAberration in active sites of hypoxanthine phosphoribosyltransferase may be one of the causes for the decrease in enzyme activity in patients with partial deficiency. Phosphoribosylpyrophosphate may stabilize adenine phosphoribosyltransferase but not affect the stability of hypoxanthine phosphoribosyltransferase. Residual activity is often observed in cultivated cells and liver of patients with the Leach-Nyhan syndrome but rarely in their erythrocytes. This may be either due to the lower affinity of erythrocytic enzyme for phosphoribosylpyrophosphate or to the existence of a quite different enzyme in erythrocytes and leukocytes to that in cultivated cells and liver.

ISSN:0031-3998    

出版商:OVID    

年代:1980

数据来源: OVID