Morphological evidence of vestibular pathology in long-term experimental diabetes mellitus. I. Microvascular changes

The influence of long-term experimental diabetes on the microvasculature of the saccule and utricle was investigated using quantitative light and electron microscopic techniques. Basal lamina thickening or reduplication, typically seen in diabetic microangiopathy, were not observed. However, morphometric analysis did reveal a statistically significant increase in capillary diameters along with an increased vascularization of both the saccule and utricle. Both of these microvascular abnormalities may have been caused by the hemodynamic alterations known to occur in diabetes. These alterations include decreased deformability of red blood cells and increased blood viscosity. Either of these factors can lead to a greater stress on the capillary wall and possibly to a reduced oxygen delivery to the tissues.     

Characteristics of human surfactant-associated glycoproteins A

Surfactant-associated glycoprotein A [molecular weight (Mr) = 34,000, isoelectric point (pI) 4.6-5.0] and its sulfhydryl dependent oligomers were purified and partially characterized from surfactant obtained from human alveolar lavage. Two major forms of the protein were identified by silver stain and immunoblot analysis of surfactant using human surfactant-associated glycoprotein A antisera: glycoprotein A2, Mr = 34,000 and glycoprotein A1, Mr = 28,000. The larger form was reduced to Mr = 28,000 by treatment with endoglycosidase F, indicating the presence of complex N-linked oligosaccharide on the molecule. Charge heterogeneity was decreased and the isoelectric point increased by treatment with neuroaminidase, supporting the presence of sialic acid. Homology between the proteins Mr = 34,000 and 28,000 was confirmed by analysis of two-dimensional tryptic and chymotryptic peptides of 125I-iodo-glycoproteins A1 and A2 which were identical. The protein was very rich in glycine and its amino acid composition was similar to that of glycoprotein A previously reported for the dog and rat. Treatment of glycoproteins A with bacterial collagenase resulted in the generation of highly glycosylated peptides Mr = 20,000-22,000, pI 4.6-5.0, which no longer formed sulfhydryl-dependent oligomers, supporting the presence of significant collagen-like region in the molecule. In the absence of reducing agents, glycoprotein A from surfactant was present as sulfhydryl-dependent dimers and larger oligomers. Higher molecular weight aggregates of glycoproteins A were also present in lavage material even after sulfhydryl reduction. Glycoproteins A were identified in surfactant from amniotic fluid, normal adult lung lavage, human cadaver lung lavage, and material obtained from lung lavage from a patient with alveolar proteinosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects on plasma glucose concentration of light-for-date infants and infants of diabetic mothers of feeds supplemented with a glucose polymer

Serial plasma glucose estimations were performed in 44 light-for-date infants and 17 infants of diabetic mothers fed 2, 3 or 4-hourly with feeds containing 10% additional carbohydrate in the form of a glucose polymer (Caloreen). In the infants fed 2 and 3-hourly, plasma glucose was higher following the high carbohydrate feeds, particularly immediately before the next feed was due. Given 4-hourly, the high carbohydrate feed had little effect in most light-for-date infants, and in one light-for-date infant and two infants of diabetic mothers the plasma glucose was lower at the end of 4 hours than following normal formula. It is concluded that the addition of glucose polymer to feeds given 2 and 3 hourly has a potentially useful effect in neonates at risk of developing hypoglycaemia, but it cannot be used to increase the feed interval to 4 hours.     

Sex chromosome fragment in a phenotypically normal female. Significance of occult Y-related material

The authors report a 15-year-old short, nonvirilized, prepubertal female whose peripheral karyotype revealed a mosaicism in which 62 percent of the cells had a karyotype of 45X, and the other 38 percent had a karyotype of 46X plus a small unidentified marker chromosome. Since the authors were unable to determine from the karyotype whether this marker was derived from an X or a Y chromosome and because of the high risk for neoplasia in abnormal gonads containing Y material, she underwent surgical exploration, with removal of gonadal tissue. Microscopic examination of the streak gonads revealed a mixture of dysgenetic ovarian and testicular type tissues. The presence of testicular-like tubules strongly implied the presence of Y material in the genotype. Review of the literature reveals at least 19 similar cases in which presumed sex chromosomal markers or fragments were found in phenotypically normal females. Because of the risk of gonadal neoplasia in patients with occult Y chromosomal material, gonadectomy is indicated when the origin of the marker chromosome is uncertain.     

Morphological evidence for parallel processing of information in rat macula

Study of montages, tracings and reconstructions prepared from a series of 570 consecutive ultrathin sections shows that rat maculas are morphologically organized for parallel processing of linear acceleratory information. Type II cells of one terminal field distribute information to neighboring terminals as well. The findings are examined in light of physiological data which indicate that macular receptor fields have a preferred directional vector, and are interpreted by analogy to a computer technology known as an information network.     

Chickenpox increasingly affects preschool children

Between 1983 and 1998, age specific incidences of chickenpox derived from consultations with general practitioners taking part in the Royal College of General Practitioners Weekly Returns Service doubled in children aged 0 to 4 years, halved in children aged 5 to 14 years, and fell by almost a third in adults aged 15 to 44 years. This downward shift in age of contracting chickenpox may be a result of increased social contact between preschool children.     

Maternal exposure to potential inhibitors of DNA topoisomerase II and infant leukemia (United States): A report from the Children's Cancer Group

Nearly 80 percent of infant leukemias present with an abnormality involving the MLL gene at 11q23. Moreover, secondary acute myeloid leukemias (AML) that occur as the result of chemotherapy agents, which are known to inhibit DNA topoisomerase II, often manifest the same MLL abnormalities. It has been hypothesized that de novo infant leukemias may occur as a result of maternal exposure to agents in diet and medications that inhibit DNA topoisomerase II. Three epidemiologic studies of childhood leukemia with similar methodologies were conducted in the United States and Canada over the past 10 years by the Children's Cancer Group (CCG). Of the total 771 mothers of infants diagnosed at one year of age or less (<12.5 months) who originally were interviewed (303 infant cases and 468 matched controls) across the three studies, follow-up questionnaire data on maternal exposure to potential DNA topoisomerase II inhibitors during pregnancy were available on 84 cases and 97 matched controls in the US. For maternal diet, a composite variable was created that consisted of 10 foods identified a priori as containing DNA topoisomerase II inhibitors. There were no significant trends with increasing maternal consumption for either the overall group, or the acute lymphoblastic leukemia (ALL) stratum. However, within the AML stratum, there was a statistically significant positive association (P trend=0.04) with increasing consumption of DNA topoisomerase II-inhibitor containing foods (odds ratio [OR]=9.8, 95 percent confidence interval [CI]=1.1–84.8; OR=10.2, CI=1.1–96.4; for medium and high consumption, respectively). Other potential topoisomerase II inhibitors were explored; no significant findings were found. Results of this preliminary study, in combination with molecular data, should be used in future investigations of childhood leukemia (particularly, infant) to justify the incorporation of a detailed dietary history.Drs Ross and Robison are with the Division of Pediatric Epidemiology and Clinical Research, University of Minnesota, Minneapolis, MN, USA. Dr Potter is with the Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Dr Reaman is with the Department of Pediatric Hematology-Oncology, Children's National Medical Center, Washington, DC. Dr Pendergrass is with the Department of Pediatric Hematology-Oncology, Children's Hospital and Medical Center, Seattle, WA. Address correspondence to Dr Ross, Children's Cancer Group, P.O. Box 60012, Arcadia, CA 91066-6012, USA. This research was supported in part by the University of Minnesota Children's Cancer Research Fund, NIH training grant T32 09607, and NCI grants CA42479, CA49450, CA58051 from the United States Department of Health and Human Services. Participating Children's Cancer Group investigators, institutions, and grant numbers (Division of Cancer Treatment, National Cancer Institute) are provided in the appendix.     

Benzo[b]fluoranthene: tumorigenicity in strain A/J mouse lungs, DNA adducts and mutations in the Ki-ras oncogene

The polycyclic aromatic hydrocarbon benzo[b]fluoranthene (B[b]F)is a pervasive constituent of environmental combustion products.We sought to examine the lung tumorigenic activity of B[b]Fin strain A/J mice, to study the relationship between formationand decay of B[b]F-DNA adducts and to examine mutations in theKi-ras proto-oncogene in DNA from B[b]F-induced tumors. Micewere given i.p. injections of 0, 10, 50, 100 or 200 mg/kg bodywt and lung adenomas were scored after 8 months. B[b]F inducedsignificant numbers of mouse lung adenomas in a dose-relatedfashion, with the highest dose (200 mg/kg) yielding 6.95 adenomas/mouse, with 100% of the mice exhibiting an adenoma. In micegiven tricaprylin, the vehicle control, there were 0.60 adenomas/mouse,with 55% of the mice exhibiting an adenoma. Based on dose, B[b]Fwas less active than benzo[     

Inhibitation of pro-inflammatory cytokine gene expression and papilloma growth during murine multistage carcinogenesis by pentoxifylline

Topical application of 12-O-tetradecanoylphorbol-13-acetate(TPA) to the dorsal epidermis of Sencar mice induces synthesisof pro-inflammatory cytokines, including interleukin-1     

Gene expression and cellular sources of inducible nitric oxide synthase during tumor promotion

The present studies examined the temporal sequence of induciblenitric oxide synthase (iNOS) gene expression and the cellularsources of iNOS protein and of 3-nitrotyrosine, as a markerof production of nitric oxide-derived reactive nitrogen intermediatesduring murine multi-stage carcino-genesis. Levels of iNOS mRNAin dorsal skin isolated from acetone-treated female Sencar micewere 2.5-fold higher than iNOS gene expression detected in cutaneoustissue isolated from Sencar mice at 1,3,6,10,16 and 22 weeksafter exposure to a single topical application of 25 nmol 7,12-dimethylbenz[