Assessment of adult skeletons to detect prenatal exposure to trypan blue in mice

A Skeletal Variant Assay System (SVAS) consisting of a group of 88 spontaneously occurring qualitative variations of the adult mouse skeleton was studied in CD-1 mice which had been exposed in utero by way of three daily ip injections of their dams on days 7-9 of gestation with trypan blue. Treatment groups received daily doses of 0.25 cc of 0, .037, .075, .15, or .30% trypan blue dissolved in 0.9% NaCl. Two separate series of experiments were performed, and skeletons were examined at 62 +/- 2 days postnatal. Sixty-six and 58 of the variants occurred in the two series, respectively. Frequencies of occurrence of substantial numbers of variants differed from Untreated (UNTD) and Vehicle-Treated (VEH) values in a dose-related manner for both series. At the high dose 18 and 22 variants occurred with significantly different (P less than .01) frequencies from UNTD in the two series. Contrasting high-dose animals with vehicle controls revealed significant differences in 24 and 17 variants. There were 13 and 14 variants in the two series, respectively, which differed from both UNTD and VEH. If one considers differences at P less than .01 in one comparison and P less than .05 in the other, then 22 and 18 variants qualify as being significantly different from both controls in the two series. Agreement between the two series was excellent regarding which variants were affected. Several differed significantly from both UNTD and VEH in both series of experiments. Among these were a number which appeared more or less specific to trypan blue exposure. They include Dyssymphysis of the Atlas, Carpal Fusions, and Tarsal Fusions. Although increased frequency of an Interfrontal bone is seen with several treatments, the magnitude of the response and the low doses at which it is elicited are unique to trypan blue exposure. Numerous low-dose effects are striking in this set of experiments, making the SVAS a very sensitive indicator of trypan blue exposure. In addition to the variants mentioned, a large cluster of cervical (C) vertebrae variants, including dyssymphyses, fusions, imperfect transverse foramina of C1 and C2, and accessory transverse foramina of C3-C6, as well as vertebral fusions at various levels (especially cervical, sacral, and caudal), appear to be the principal effects of exposure to this compound. In addition, rib malformations at the high dose level, and increased frequency of occurrence of 27-presacral vertebrae at all dose levels, were important effects.(ABSTRACT TRUNCATED AT 400 WORDS)     

国人颈椎横突孔的形态观察与测量

本文作者用精密度为0.02毫米的游标卡尺对东北地区出土的100副成套颈椎,1200个颈椎横突孔的诸径进行了测量,得到了一系列数据,并对颈椎横突孔的形状(将它分为五型)及一些特异颈椎进行了观察,根据这些材料探讨了横突孔与椎动脉的关系。     

Prenatal ossification as an indicator of exposure to toxic agents

Following exposure to bromodeoxyuridine (BUDR), acetazolamide (ACZM), trypan blue (TRBL), cortisone (CORT), or diphenylhydantoin (DPH), alizarin-stained, cleared fetuses were examined at 18 days postcoitus for unossified cervical vertebral centra; number of ossified caudal vertebrae; number of ribs; and ossification of sternebrae, metatarsals, metacarpals, and phalangeal rows. At all teratogenic doses, in no vehicle-treated groups, and rarely in lower-dose groups, there were significant increases in frequency of unossified cervical centra, the first vertebra (C1) being most often affected, and C7 least often affected. In the high-dose CORT group, there was a significant correlation between unossified C1 and cleft palate. No association between abnormality and reduced ossification of cervical vertebrae was seen in other series examined, nor was there any correlation between litter size and abnormality. With minor complications, the number of ossified caudal vertebrae was significantly reduced after exposure at teratogenic dose levels to all compounds except DPH. Although caudal and cervical ossification were correlated with each other in those series examined, neither was correlated with abnormality. Frequency of 14 ribs was increased in BUDR, ACZM, and TRBL but not CORT or DPH. Other parameters were essentially unaffected. Significantly increased frequency of abnormality, when contrasted with untreated or vehicle-treated groups, was seen at high-dose levels in all but DPH treatments, and mortality was increased in ACZM D9-11, TRBL, and CORT. These studies show that reduced ossification of cervical centra is an excellent indicator of prenatal exposure to noxious substances, and caudal vertebrae appear to be useful as well. Increased frequency of 14 ribs occurred for all strong teratogens utilized if they were administered on day 7 or day 8 postcoitus.     

New postcranial elements of the Thalassodrominae (Pterodactyloidea,Tapejaridae) from the Romualdo Formation (Aptian–Albian), Santana Group,Araripe Basin,Brazil

Tapejarids are edentate pterosaurs recovered mainly from Early Cretaceous deposits. They are diagnosed by five synapomorphies, among which only one is postcranial: a broad and well‐developed tubercle at the ventroposterior margin of the coracoid. Regarding the clade Thalassodrominae, most phylogenetic studies are based on cranial elements, as postcranial skeletons of these pterosaurs are rare. Here, new postcranial material from the Romualdo Formation (Aptian–Albian) from the Araripe Basin is described. The material comprises the three posteriormost cervical vertebrae, the first seven dorsal vertebrae (fused into a notarium), both scapulocoracoids, a fragment of a sternum, a partial right humerus, a small fragment of a 4th phalanx of the wing finger, a distal extremity of the right femur and the proximal portions of both tibia and fibula. Comparisons with other specimens and morphological features examined in a phylogenetic context, such as the presence of three foramina lateral and dorsal to the neural canal of the cervical vertebrae, the presence of a notarium and a pneumatic foramen on the ventral side of the proximal portion of the humerus, allow the assignment of this specimen as Thalassodrominae indet. Regarding palaeobiogeographical aspects, to date, this clade is exclusively found in the Romualdo Formation. It is the most complete postcranial material assigned to the Thalassodrominae described so far.     

Meander tail: a recessive mutant located in chromosome 4 of the mouse

A variable kinked-tail mutant was found in 1974 in a moderately inbred stock of mice at Iowa State University, Ames. It was named meander tail and was shown to be completely recessive. Study 8 alizarin-stained skeletons showed all degrees of ankylosis or fusions of tail vertebrae and occasionally other vertebrae. Extreme examples had great reduction in number of tail vertebrae. Affected mice over 2 weeks old commonly also show some unsteadiness, presumably a pleiotropic effect of the mutant. Less commonly, one or both hind legs showed some paralysis. Linkage tests of the mutant, symbolized mea, place it fairly close to brown, b, in chromosome 4, and apparently in the small segment between Ps and Pt.     

Narrow axis: an inherited anomaly of the second cervical vertebra in the rabbit

Narrow axis, an inherited anomaly resulting in a marked narrowing of the second cervical vertebra, has been observed in strain X/J rabbits. This condition is first recognizable on X rays at 32-33 days gestation. For size comparisons 21 measurements of the first five cervical vertebrae were taken on the skeletons of each of 14 strain X/J animals (7 normal and 7 with narrow axis) and 14 IIIC/J animals for control at two months of age and 27 strain X/J (11 normal and 16 narrow axis) and 14 strain IIIC/J at seven months of age. The primary effect appeared to be a premature fusion of the centrum with its neural arches. Expression is variable. The effect on the posterior articulation of the atlas appeared to be secondary and adaptive. The other cervical vertebrae and the foramen magnum were relatively unaffected. In the 20-year period encompassed in this report, X rays of 3244 rabbits were used for genetic analysis. Inheritance appears to be due to a single autosomal recessive gene with incomplete penetrance. The condition is neither sex-linked nor sex-limited. We propose the symbol nx for the gene responsible for narrow axis in the rabbit.     

Spinal nerves and their bearing on,salamander phylogeny

Examination of the vertebral columns of representatives of all families of salamanders revealed that, in contrast to the condition found in most other vertebrates, salamander spinal nerves often pass through foramina in the vertebrae. Two kinds of spinal nerve foramina were found: those in the anterior halves of vertebrae, and those in the posterior halves. In addition, many salamanders retain intervertebral nerves. However, within each family or, in a few cases, subfamily there is a characteristic pattern of spinal nerve-vertebral relationships. The first spinal nerve of all salamanders exits through a foramen in the anterior half of the atlas. All more posterior nerves are intervertebral in the families Cryptobranchidae, Hynobiidae and Proteidae. The posterior caudal nerves exit through the posterior halves of the caudal vertebrae in the family Amphiumidae, while in the subfamilies Dicamptodontinae and Rhyacotritoninae all post-sacral nerves exit through the posterior halves of the vertebrae. All but the first three nerves exit through posterior foramina in the family Plethodontidae and the subfamily Ambystomatinae, while all but the first two nerves pass through posterior foramina in the families Salamandridae and Sirenidae. Several fossil salamanders were also examined. These showed that the amphiumid and dicamptodontine-rhyacotritonine nerve patterns had evolved by the Late Cretaceous, and the sirenid pattern had probably evolved by that time. Other Cretaceous genera associated with the Ambystomatoidea still possessed the primitive intervertebral pattern. Using spinal nerve patterns and several other previously described morphological characters, a new hypothesis of the phylogeny of recent and fossil salamanders is presented and compared to earlier proposed phylogenies of the group. A new classification of salamander families is presented.     

中国人肱骨滑车上孔的调查

本文应用Martin方法,对在西安地区坟墓中收集的213副(男122,女91)中国成人肱骨滑车上孔的出现率、形状、数目和径线进行了调查。结果表明:滑车上孔出现率为11％,女性大于男性,其出现率女性与男性之比为2.29:1。通过比较得知,中国人滑车上孔出现率与日本人、朝鲜人相近,较白种人为高,而比黑种人低。滑车上孔之形状大部分(78.72％)为横椭圆形;在一个肱骨上出现一个滑车上孔者占97.87％。本文还对该孔出现的原因进行了探讨。     

Atrial septation: I. Scanning electron microscopy in the chick

Chick hearts were prepared for scanning electron microscopy by standard methods, the purpose being to investigate the surface morphology of the developing atrial septal region. By Day 3, the atrial septum primum appeared as a sickle-shaped structure. During Day 4, the first representation of the foramina secunda occurred in the mid-dorsal portion of the septum. During Day 5, the septum primum fused with the atrioventricular endocardial cushions, thereby occluding the foramen primum. From Days 5 through 8, the secondary perforations (foramina secunda) multiplied and increased in size. The endocardial-covered cords of cells comprising the septum thickened from Days 9 through 15. This resulted in a marked reduction in the dimensions of the perforations from Day 16 to hatching. The atrial septum at hatching occasionally contained a small single orifice. At 3 days posthatching, the atrial septum was a solid sheet covered with flattened endocardial cells. All interatrial communications were occluded. During Days 5 through 9, two distinct cell types became apparent on the endocardial-covered cords. Simultaneously, fenestrations were observed on the cords surrounding the foramina secunda and on the ventral portion of the atrial septum. The integral role which the fenestrations and cellular types play in the development of the formina secunda is discussed.     

Susceptible period of nitrous oxide teratogenicity in Sprague-Dawley rats

The susceptible period of nitrous oxide (N2O) teratogenicity was studied in 170 Sprague-Dawley rats. Seven groups of 20 timed-pregnant rats were exposed to 60% N2O for 24 hours on each of days 6-12 of gestation; a control group of 30 timed-pregnant rats was exposed to air on day 9. On day 20 of gestation, dams were killed and reproductive indices were determined; their fetuses were subsequently examined for external, skeletal, and visceral abnormalities. There were no differences among the groups in the number of implantations and live fetuses, mean fetal weight, and sex ratio. The incidence of fetal wastage was higher than control in N2O-treated groups exposed on days 8 and 11 of gestation. Skeletal malformations of the ribs and vertebrae were increased following exposure on day 9 of gestation. However, the specific minor anomaly, cervical rib, was increased only following exposure on day 8 of gestation. The incidences of right-sided aortic arch and left-sided umbilical artery, abnormalities indicative of altered laterality, were increased following exposure on day 8 of gestation. Nitrous oxide administration during organogenesis causes several reproductive defects by mechanisms which remain to be determined.     

Effects of PGE1 or PGE2 and/or acetazolamide on expulsion of Nippostrongylus brasiliensis from rats

PGE1 and PGE2 have been reported to enhance natural expulsion of Nippostrongylus brasiliensis, a nematode parasite, from the intestine of the rat. Mucus production may also be a key element of worm rejection. Our study attempts to determine if 1) PGE1 or PGE2 alter the normal course of infection with N. brasiliensis in rats, 2) a known mucous enhancing drug, acetazolamide, can augment the rate of worm expulsion, and 3) combinations of prostaglandins and acetazolamide affect N. brasiliensis in the rat. Rats were inoculated with approximately 1,000 infective larvae of N. brasiliensis. Animals were administered, intraduodenally, one of the following: 0.2 ml 0.9% NaCl; 0.2 ml 100% ethanol; 250 micrograms PGE1/0.2 ml 100% ethanol; 250 micrograms PGE2/0.2 ml 100% ethanol; 250 micrograms acetazolamide/0.2 ml 100% ethanol; 250 micrograms PGE1 or PGE2 + 250 micrograms acetazolamide/0.2 ml 100% ethanol. These solutions were given in a single bolus on day 6 postinoculation (PI) or twice daily on days 6-9 PI. Following these treatments the number of parasite ova per gram feces per day for days 6-10 PI and numbers of worms present at necropsy on day 10 PI were determined. Treatment with prostaglandins or acetazolamide or both failed to adversely affect egg deposition by adult female worms or the number of worms in the small intestine. These results do not support the involvement of prostaglandins in the expulsion of N. brasiliensis from the host intestine.     

SB-236057: Critical window of sensitivity study and embryopathy of a potent musculoskeletal teratogen

BACKGROUND: SB-236057 is a potent skeletal teratogen in rodents and rabbits. The study objective was to identify the critical developmental window of compound sensitivity and to characterize the early onset of SB-236057 embryopathy. METHODS: SB-236057 was orally administered to Sprague Dawley dams at 100 mg/kg/day on days 6-7, 8-11, 12-14, or 15-17 postcoitus (pc). The critical window of sensitivity was identified to occur between days 8-11 pc. Dams were then dosed on days 8-11 pc and embryos were evaluated by histochemical procedures on days 11, 13, or 15 pc. RESULTS: Axial malformations were evident by day 11 pc. Analysis of the cartilaginous skeleton revealed missing posterior axial skeletal elements. However, only about one-third of the malformed fetuses exhibited obvious rib and vertebrae abnormalities, and none of the affected fetuses exhibited abnormal appendicular skeletal elements. Expression pattern of sonic hedgehog in the notochord and floor plate was not affected, suggesting ventral midline signaling was not disrupted. Histological analysis demonstrated hypoplastic and/or missing musculature in proximity to the ribs and vertebrae. Caspase 3 analysis revealed no increases in apoptotic cells in the musculature. Confocal analysis of the limbs demonstrated truncated peripheral nerve formation and shortening of the appendicular musculature. CONCLUSIONS: SB-236057 is speculated to alter paraxial mesoderm programming. Many of the skeletal malformations may be caused secondarily from musculature abnormalities, suggesting that the myotome may be particularly sensitive to the compound. Furthermore, the finding that peripheral nerve trajectories were altered along the axis and in the limb suggests that SB-236057 may alter early embryonic signaling pathways necessary for neuronal differentiation/axonal guidance that occur subsequently in embryo-fetal development.     

颅底孔在多层CT三维重建中的测量研究

探讨颅底MSCT三维重建图像效果及主要孔的正常值,采用多层螺旋CT(MSCT),对200名正常成人(男100名,女100名)进行颅脑扫描,利用电子计算机三维重建程序立体地显示颅底外面的卵圆孔、棘孔、颈动脉管外口、破裂孔、茎乳孔、枕骨大孔,并观察其形态和测出其内径及其性差。     

Oral Acetazolamide after Boston Keratoprosthesis in Stevens Johnson Syndrome

ABSTRACT: BACKGROUND: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare but severe and sometimes fatal condition associated with exposure to medications; sulfamethoxazole is among the most common causes. We sought to address the safety of acetazolamide, a chemically related compound, in patients with prior SJS/TEN and glaucoma. A retrospective case series is described of patients at the Massachusetts Eye and Ear Infirmary who underwent keratoprosthesis surgery for corneal blindness from SJS/TEN, and later required oral acetazolamide for elevated intraocular pressure. FINDINGS: Over the last 10 years, 17 patients with SJS/TEN received a Boston keratoprosthesis. Of these, 11 developed elevated intraocular pressure that required administration of oral acetazolamide. One of 11 developed a mild allergic reaction, but no patient experienced a recurrence of SJS/TEN or any severe adverse reaction. CONCLUSION: Although an increase in the rate of recurrent SJS/TEN due to oral acetazolamide would not necessarily be apparent after treating only 11 patients, in our series, acetazolamide administration was well tolerated without serious sequela.     

The circumorbital foramina in primates

This paper documents the diversity and variation in the circumorbital foramina in extant primates. A qualitative and quantitative analysis of the circumorbital foramina, comprising the supraorbital foramen, the infraorbital foramen, and the malar foramen, was carried out using representative species from nine extant families of primates. The information obtained from the study is used to reconstruct ancestral morphotypes, and to make inferences about evolutionary changes that may have taken place in the major primate lineages. In addition, the analysis provides useful comparative data for interpretation of the phylogenetic significance and paleobiological implications of the circumorbital foramina in fossil primates.     

Thyroid hormone suppresses the differentiation of osteoprogenitor cells to osteoblasts,but enhances functional activities of mature osteoblasts in cultured rat calvaria cells

The effects of thyroid hormone on osteoblastic differentiation and activity were studied in fetal rat calvaria (RC) cells cultured for up to 30 days in medium supplemented with thyroid hormone-depleted serum. In this condition, the cells proliferated and differentiated to form mineralized bone nodules (BN) and expressed osteoblastic markers such as alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). The continuous presence of triiodothyronine (T3) at 10^-9-10^-8 M in the medium inhibited the osteoblastic differentiation: 34% decrease in ALP activity on day 12 and 60% decrease in BN formation on day 15 at 10^-8 M. T3 at these doses had no effect on the DNA content of RC cells at confluence (day 6). Short-term (48-h) exposure of T3 at 10^-9 M or higher decreased ALP activity when RC cells were differentiating (days 7–11). However, when BN formation by the cells had already reached a plateau (day 28), the activity was increased by treatment with T3 at 10^-7-10^-6 M. OCN production was increased dose dependently by this treatment with T3 (2.1-fold and 1.3-fold of control at 10^-8 M on days 11 and 28, respectively). Similar increases were observed in the levels of OCN mRNA. In addition, increases in phosphorylated OPN in the medium (day 11) and mineralized matrix (day 28) were observed (1.5-fold at 10^-8-10^-6 M), while OPN synthesis and the level of its mRNA were depressed by T3 (60-70% of control at 10^-8 M). These results suggest that T3 regulates osteoblastic differentiation and activity depending on the state of cell differentiation: T3 suppresses the differentiation of osteoprogenitor cells to osteoblasts, but enhances the functional activity of mature osteoblasts. © 1994 Wiley-Liss, Inc.     

Fertilizing ability in vivo and in vitro of spermatozoa of rats and mice treated with alpha-chlorohydrin.

The fertilizing ability of epididymal spermatozoa from rats and mice treated for 3 or 4 or 9 or 10 days with various doses of alpha-chlorohydrin was tested in vitro, and in vivo by intrauterine insemination. The minimum doses (per kg/day) needed to affect fertilization significantly were: rat, in vitro, 8-8 mg for 3 or 4 days, 4-4 mg for 4 days and 2-7 mg for 9 or 10 days; in vivo, 4-4 mg for 3 or 4 days and 2-7 mg for 9 or 10 days: mouse, in vitro, 4-4 mg for 3 days and 13-3 mg for 9 days; in vivo, 44-2 mg for 3 days and 26-5 for 9 days. Rats were infertile for at least 18 days after receiving 44-2 mg alpha-chlorohydrin/kg/day for 3 days, but fertilizing ability, tested in vivo and in vitro, was restored 10-11 days and 15-18 days, respectively, after daily treatment with 11-1 mg alpha-chlorohydrin/kg for 3 days.     

广饶新石器时代人类头骨的小变异

通过对山东广饶新石器时代大汶口文化墓地90年代发掘的61具成年头骨进行小变异特征出现率的观察与统计并在此基础上进行聚类分析和主成分分析研究认为,广饶人群的蒙古人种地区类型属于东亚类型。同时本文结果提示,在明确蒙古人种地区类型的主成分分析研究中,贡献率较大的三个小变异特征为下颌舌骨肌线桥、舌下神经管二分、眶上孔,这将为以后人们用小变异方法从事这方面的研究中如何选择观察项目方面提供了基础。     

Numerical variation of the presacral vertebral column in three population groups in North America

A total of 1,239 skeletons from among Mongoloid, Caucasoid and Negroid population groups in North America was examined for variations in the number of presacral vertebrae. The overall incidence of variation was 11%; 6% with 23 and 5% with 25 presacral vertebrae. Differences in total variation among the three groups were not significant, but differences in the incidence of 23 and 25 presacral vertebrae among the groups were highly significant. Numerical vertebral variation occurred in 11% of both sexes, but with males having a higher frequency of 25 presacral vertebrae and females having a higher frequency of 23 presacral vertebrae. The incidence of the specific variation of 23 or 25 presacral vertebrae was not significantly different among the males of the three groups studied, whereas 23 presacral vertebrae were found significantly more often in the Negroid females. Numerical variation of vertebrae was not associated with age. The data strongly support the conclusion that the total frequency of variation in the number of presacral vertebrae is a specific characteristic of any particular population group and that there is a tendency in all population groups toward an increase in number in males and a decrease in number in females.     

Anomalous caudal vena cava passing through the vertebral canal in a calf

A 15-day-old female Holstein-Friesian calf with an anomalous caudal vena cava was examined macroscopically, roentgenologically, and histologically. The calf, weighing 43 kg, had severe scoliosis. A common renal vein merged into a single venous trunk formed by the union of the left and right common iliac veins. The trunk entered the vertebral canal through the left intervertebral foramen formed by the last (13th) thoracic and the first lumbar vertebrae. The trunk continued along the ventral side of the narrowing spinal cord inside the canal, and then ran out the left intervertebral foramen formed by the 8th and 9th thoracic vertebrae and emptied via the right azygos vein into the cranial vena cava. In contrast, the hepatic vein passed through the foramen vena cava independently of the trunk and entered the right atrium directly. The pathogenesis of the present anomaly may be explained as follows: The right subcardinal vein, failing to make connection with the liver, shunted directly into the right azygos vein derived from the right supracardinal vein. The body axis began to curve before ossification of the vertebrae occurred. Consequently, the developing right supracardinal vein, located close to the spinal cord, is thought to have become enclosed in the vertebrae with the spinal cord during the early fetal stages.