Inherited platelet delta-storage pool disease in dogs causing severe bleeding: an animal model for a specific ADP deficiency.

The nature of a disorder producing moderate to severe bleeding after minor trauma, venipuncture, and surgery was studied in 3 families of American cocker spaniel dogs. In the 5 affected dogs tested, platelet counts and measurements of plasma coagulant function and von Willebrand factor were normal. However, bleeding times were prolonged in 4 of the 5 affected dogs tested, and platelet aggregation in response to ADP and collagen was consistently abnormal in 3, suggesting that the bleeding disorder was due to abnormal platelet function. Measurements of 14C-serotonin uptake and retention by the affected platelets were normal. However, their ADP content was decreased, while their ATP content was normal, resulting in a mean ATP/ADP ratio of 8.32, compared to a mean ratio of 1.9 in normal canine platelets. Electron microscopy revealed that the number and appearance of the dense granules in the affected platelets were indistinguishable from those of normal controls. These studies suggest that this bleeding disorder results from a deficient delta-granule storage pool of ADP; given the normal serotonin uptake and retention by affected platelets and the apparently normal number of dense granules, the ADP deficiency may be the consequence of a selective defect in delta-granule ADP transport. Additional studies of this unique platelet disorder will provide an opportunity to understand the mechanism of adenine nucleotide storage in platelet delta-granules.

Intracytoplasmic lumina in bladder carcinomas.

Intracytoplasmic lumina were identified in neoplastic cells from four human and three canine "spontaneous" bladder carcinomas. They were also found in N-[4-(5-nitro-2-furyl)-2-thiazoly] formamide induced bladder carcinomas in rats as well as in cultured tumor cell lines derived from these experimental tumors. Intracytoplasmic lumina were readily recognized in 5 micrometer. paraffin embedded and 1 micrometer. epoxy embedded sections. Histochemically, intracytoplasmic lumina were strongly positive with PAS and alcian blue-PAS; mucicarmine stain was positive as unevenly distributed droplets. Ultrastructurally lumina were defined by a symmetric unit membrane; they displayed abundant pleomorphic microvilli, which contained prominent cytoskeletal elements. Step section electron microscopic study revealed continuity between intracytoplasmic lumina and the extracellular space in only one case of experimental bladder carcinoma; otherwise they appeared to be entirely encompassed within the cytoplasm. No instance of exocytosis in relation to intracytoplasmic lumina was found. Our observations suggest that intracytoplasmic lumina may be rather frequent in several forms of urothelial carcinoma. They appear to be predominantly but not invariably intracytoplasmic. The mechanism that may determine the development of continuity between intracytoplasmic lumina and the extracellular space and the adduced relationship between intracytoplasmic lumina and the process of secretion remain undetermined.

A comparison of Pacific Islander and European stillbirths.

From 1967-1978, there were 26,688 births at St Helens Hospital, Auckland. A comparison was made between the Pacific Island stillbirths, and 65 matched European stillbirths. The stillbirth rate for the European group was only 6.6 per 1000 births, despite the increased prevalence of the following adverse factors: preterm 42 percent, toxaemia 38 percent, and lethal congenital abnormalities 20 percent. There was a significantly increased incidence of neural tube defects in the European group. In contrast the Pacific Island stillbirth rate was 11.1 per 1000 births, and the important factors were: unknown gestation 17 percent, post-term delivery 17 percent, no antenatal care 8 percent, or born before arrival in 3 percent. Intrauterine anoxia was the major cause of stillbirths, especially in the Pacific Island group where 68 percent of the infants were 37 weeks gestation or more. Community education stressing the importance of good antenatal care beginning in early pregnancy is needed for the Pacific Island mothers, with the avoidance of postmaturity and intrauterine anoxia by appropriate obstetric treatment.

Digital manipulation in scientific images: some ethical considerations.

Images play a vital role in the publication and presentation of scientific research. Large proportions of these images today are produced digitally, and these images as well as elements within these images, can be easily enhanced or manipulated using electronic darkroom software. This article examines some of the ethical issues associated with digital manipulation and offers some suggestions on how to deal with them.

Automated spatially scanning ellipsometer for retardation measurements of transparent materials.

A highly sensitive and automated technique has been developed for measuring the birefringence in transparent optical materials. The spatially scanning modulated transmission ellipsometer maps the birefringence of a transparent material by probing it with a polarization-modulated He-Ne laser beam. Computer-controlled voltage biasing of a Pockels cell permits self-calibration and background subtraction of the system retardance. The technique is capable of resolving differential retardances as small as 0.1 nm (λ/6328) through a range of ±λ/2, where λ = 632.8 nm. Samples typically range in size from 50 µm to 10 cm in diameter within the sample plane and as much as 400 mm along the optical axis.

The effects of treatment with indomethacin on the cerebral vasculature of newborn piglets before and during hemorrhagic hypotension.

Substantial physiologic data point to a significant role for dilator prostanoids in the regulation of cerebral vascular tone in newborn pigs. This study begins to address the hypothesis that multiple dilator systems, including prostanoids, can provide for the initiation and maintenance of cerebral vasodilation in response to hypotension. Piglets were anesthetized, and cranial windows were implanted. Hypotension was achieved by hemorrhage to 50% of the control arterial pressure and maintained for 10 min. Each piglet served as its own control by the induction of hypotension and return to normotension before treatment. Pial arterioles dilated (38 +/- 5% increase in diameter) in response to hypotension. Pretreatment with indomethacin (5 mg/kg i.v.) at 20 min and immediately before hypotension did not block this response (28 +/- 7% and 23 +/- 9% increase in diameter, respectively). In contrast, when indomethacin was administered 10 min into the hypotensive period, the dilated arterioles (106 +/- 6 microns) constricted to the normotensive diameter (75 +/- 5 microns) and remained constricted for the duration of the observation. These findings suggest that compensatory mechanisms provide for cerebral vasodilation when prostanoid synthesis and prostacyclin receptors are blocked before hemorrhagic hypotension. However, removal of prostanoids after vasodilation is established in response to hypotension causes constriction without compensation from alternative mechanisms. Awareness of these findings may be important when considering giving indomethacin to sick preterm infants during periods of cardiac instability.

Hepatic storage of glycosaminoglycans in feline and canine models of mucopolysaccharidoses I, VI, and VII.

Livers from normal cats and dogs, cats with mucopolysaccharidoses (MPS) I and VI, and dogs with MPS VII were analyzed biochemically and morphometrically to determine the lysosomal storage of glycosaminoglycans (GAG) in these animal models of human genetic disease. Analyses were performed on liver samples from seven normal cats ranging in age from 13 weeks to 15 months; six MPS I-affected cats ranging in age from 10 weeks to 26 months; four MPS VI-affected cats ranging in age from 9 months to 32 months; four normal dogs ranging in age from 1 month to 47 months; and three MPS VII-affected dogs, 5 days, 11 days, and 14 months of age. All of the animals were from the breeding colony at the University of Pennsylvania School of Veterinary Medicine and were maintained in accordance with national standards for the care and use of laboratory animals. Each GAG subclass was quantitated, and total GAG concentration was determined. Liver from cats with MPS I had the highest total GAG concentration (5.7 times that of the control), followed by liver from dogs with MPS VII (1.8 times) and cats with MPS VI (1.5 times). These data were very closely correlated (R2 = 0.982) with the results of the morphometric analyses of hepatocyte and Kupffer cell vacuolation associated with lysosomal storage and support the validity of both methods. This is particularly important for the quantification of total and individual GAG concentrations in tissue preparations. The values obtained should prove useful in future assessments of therapeutic regimes, such as enzyme replacement, bone marrow transplantation, and gene therapy, for these genetic diseases.

GenBank.

The GenBank nucleotide sequence database now contains sequence data and associated annotation corresponding to 56,000,000 nucleotides in 45,000 entries. The input stream of data coming into the database has largely been shifted to direct submissions from the scientific community on electronic media. The data have been installed in a relational database management system and are made available in this form through on-line access, and through various network and off-line computer-readable media. In addition, GenBank provides the U.S. distribution center for the BIOSCI electronic bulletin board service.

GenBank.

The GenBank nucleotide sequence database now contains sequence data and associated annotation corresponding to 85,000,000 nucleotides in 67,000 entries from a total of 3,000 organisms. The input stream of data coming into the database is primarily as direct submissions from the scientific community on electronic media, with little or no data being keyboarded from the printed page by the databank staff. The data are maintained in a relational database management system and are made available in flatfile form through on-line access, and through various network and off-line computer-readable media. The data are also distributed in relational form through satellite copies at a number of institutions in the U.S. and elsewhere. In addition, GenBank provides the U.S. distribution center for the BIOSCI electronic bulletin board service.

Extreme elevation of maternal serum alpha-fetoprotein associated with mosaic trisomy 8 in a liveborn.

Constitutional mosaic trisomy 8 has been associated with syndromic dysmorphology, corneal opacities, leukemias, and trophoblastic disease. However, abnormal maternal serum alpha-fetoprotein (MSAFP) has not been reported in association with mosaic trisomy 8. Our case first presented for evaluation of an extremely elevated MSAFP with mild elevation of MShCG in an otherwise normal pregnancy: MSAFP 13.89 MoM, MShCG 3.57 MoM, and MSuE3 1.04 MoM. Fetal dysmorphism was limited to bilateral pyelectasis and a prominent third ventricle. Spontaneous labor at 38 weeks resulted in the birth of a 3,570-gram AGA male with APGARs 7(1)/8(5). The neonate had facial asymmetry, 5th finger clinodactyly, 2-3 toe syndactyly, undescended testicle, abnormal prepuce, and mild pyelectasis. CT scan revealed hypoplasia of the corpus callosum, while echocardiography demonstrated bicuspid aortic valve, and the neonatal karyotype (blood) returned 46,XY/47,XY+8. Evaluation at 3 months revealed more prominent facial asymmetry, plagiocephaly, plantar creases, descent of the testis, and mild developmental delay. Review of the literature does not include any previously reported maternal serum alpha-fetoprotein aberrations in mosaic trisomy 8.