Biomedical subjects

Y Qu

Publications and source records attributed to Y Qu.

At least 37 records · Page 2Linked to original sources

PubMed2000

Tetrasomy 15q25-->qter: cytogenetic and molecular characterization of an analphoid supernumerary marker chromosome.

Tetrasomy for the distal long arm of chromosome 15 is a rare finding. It has been previously described in seven patients, all of whom had a supernumerary marker chromosome (SMC) derived from distal 15q. These SMC contained no apparent centromeres (C-band/alpha-satellite negative), and belong to a novel class of SMC with neocentromeres. We present the oldest surviving patient with tetrasomy for distal 15q. The proposita was a 10-year-old girl with moderate to severe mental retardation, absent speech, hypotonia, minor facial anomalies, unusual digits, and pigmentation anomalies. Mosaicism for a symmetrical SMC was identified in metaphases from lymphocytes and fibroblasts. Parental karyotypes were normal, indicating a de novo origin for the SMC. FISH with a whole chromosome paint for chromosome 15 showed that the SMC was derived entirely from chromosome 15. However, C-banding and FISH with chromosome 15 probes D15Z1, D15S11, SNRPN, and PML were all negative. FISH with the FES probe at 15q26 showed hybridization to both ends of the SMC. The marker was interpreted as an analphoid inverted duplication of 15q25-->qter containing a presumed neocentromere. Previous molecular studies suggested either a mitotic or paternal meiotic origin for these distal 15q SMC. However, molecular analysis with chromosome 15 polymorphic markers showed that the analphoid SMC(15) in the proposita originated from a maternal meiotic error. The origins and mechanisms involved in formation of these distal 15q SMC appear to be more diverse than for the proximal pseudodicentic SMC(15).

Abnormalities, Multiple↗

PubMed2000

Synthesis, characterization, and cytotoxicity of trifunctional dinuclear platinum complexes: comparison of effects of geometry and polyfunctionality on biological activity.

The synthesis of two new isomeric trifunctional dinuclear platinum complexes of formula [¿PtCl(NH(3))(2)¿micro-NH(2)(CH(2))(6)NH(2)-¿PtCl(2)(N H(3))¿](+) (1, 2/c,c and 1,2/t,c) is reported. Their biological activity in selected human tumor cell lines sensitive and resistant to CDDP (cisplatin, cis-[Pt(NH(3))(2)Cl(2)]) is described and compared with the profile for their bifunctional analogues, [¿cis/trans-PtCl(NH(3))(2)¿(2)micro-NH(2)(CH(2))(6)NH(2)](2+ ). The trifunctional dinuclear platinum complexes showed a unique profile of cytotoxicity against human cancer cell lines, with low resistance factors in A2780, CH1, and 41M cell lines. The resistance factor is dependent on the geometry of the Pt coordination spheres - suggesting that these may be associated with DNA-binding modes. Retention of activity against CDDP-resistant cell lines and a different spectrum of activity compared to CDDP and also within different classes of polynuclear platinum complexes suggest that not only are they mechanistically different from mononuclear platinum complexes but also each individual class of polynuclear platinum structure may have its own unique character.

Amines↗

PubMed2000

Sampling extracellular aspartate, glutamate and gamma-aminobutyric acid in striate cortex of awake cat by in vivo microdialysis: surgical and methodological aspects.

A method which permits repeated microdialysis in the cortical layers of area 17 of the awake cat is described. Under visual control through a surgical microscope and using a stereotactic instrument, four probe guides are permanently implanted in area 17 of one hemisphere of the anesthetized animal and two fixation bars are mounted on the skull to allow fixation of the cat in a stereotactic frame. The implantation of four probe guides in the same hemisphere allows simultaneous sampling from different cortical regions serving different parts of the visual field. A removable transparent cover protects the probe guides. After recovery from surgery the awake cats are trained to adapt to a fixation of 5 h in a stereotaxic apparatus. Once adapted to that situation, the cats are ready for microdialysis experiments without anesthesia. The day of the experiment, the awake animal was fixed in the stereotactic frame and the probes inserted into the guides. To test the validity of the method, the basal efflux and the depolarization efflux, triggered by the addition of 65 mM K(+) to the artificial cerebrospinal fluid, of the amino acids aspartate, glutamate and gamma-aminobutyric acid are measured by two HPLC-electrochemical detection methods. The exact localization of the probes and the reaction of the surrounding tissue is studied using immunocytochemistry for glutamate and glial fibrilary acidic protein. Our neurochemical and morphological results suggest the feasibility of multiple and repeated probe insertions for microdialysis experiments in the cerebral cortex of awake and behaving cat. This method provides a new tool to investigate the cortical plasticity.

Animals↗

PubMed2000

Embryonic stem cells differentiate into oligodendrocytes and myelinate in culture and after spinal cord transplantation.

Demyelination contributes to the loss of function consequent to central nervous system (CNS) injury. Enhanced remyelination through transplantation of myelin-producing cells may offer a pragmatic approach to restoring meaningful neurological function. An unlimited source of cells suitable for such transplantation therapy can be derived from embryonic stem (ES) cells, which are both pluripotent and genetically flexible. In this paper we show that oligodendrocyte cultures can be reliably produced from retinoic acid-induced ES cells and that these oligodendrocytes can myelinate axons in vitro. Methods were further developed for generating highly enriched cultures of oligodendrocytes through an additional culturing step, producing an intermediate "oligosphere" stage. To test whether ES cells can survive, migrate, and differentiate into mature myelin-producing cells in areas of demyelination in the adult CNS, ES cells were transplanted into the dorsal columns of adult rat spinal cord 3 days after chemical demyelination. In the demyelination site, large numbers of ES cells survived and differentiated primarily into mature oligodendrocytes that were capable of myelinating axons. Furthermore, when oligosphere cells were transplanted into the spinal cords of myelin-deficient shiverer (shi/shi) mutant mice, the ES cell-derived oligodendrocytes migrated into the host tissue, produced myelin and myelinated host axons. These studies demonstrate the ability of ES cell-derived oligodendrocytes to myelinate axons in culture and to replace lost myelin in the injured adult CNS. Transplantation of ES cells may be a practical approach to treatment of primary and secondary demyelinating diseases in the adult CNS.

Animals↗

PubMed2000

Potent blockade of sodium channels and protection of brain tissue from ischemia by BIII 890 CL.

We have synthesized a new benzomorphan derivative, 2R-[2alpha,3(S*), 6alpha]-1,2,3,4,5,6-hexahydro-6,11, 11-trimethyl-3-[2-(phenylmethoxy)propyl]-2, 6-methano-3-benzazocin-10-ol hydrochloride (BIII 890 CL), which displaced [(3)H]batrachotoxinin A-20alpha-benzoate from neurotoxin receptor site 2 of the Na(+) channel in rat brain synaptosomes (IC(50) = 49 nM), but exhibited only low affinity for 65 other receptors and ion channels. BIII 890 CL inhibited Na(+) channels in cells transfected with type IIA Na(+) channel alpha subunits and shifted steady-state inactivation curves to more negative potentials. The IC(50) value for the inactivated Na(+) channel was much lower (77 nM) than for Na(+) channels in the resting state (18 microM). Point mutations F1764A and Y1771A in transmembrane segment S6 in domain IV of the alpha subunit reduced the voltage- and frequency-dependent block, findings which suggest that BIII 890 CL binds to the local anesthetic receptor site in the pore. BIII 890 CL inhibited veratridine-induced glutamate release in brain slices, as well as glutamate release and neurotoxicity in cultured cortical neurons. BIII 890 CL (3-30 mg/kg s.c.) reduced lesion size in mice and rats when administered 5 min after permanent focal cerebral ischemia at doses that did not impair motor coordination. In contrast to many other agents, BIII 890 CL was neuroprotective in both cortical and subcortical regions of the rat brain. Our results demonstrate that BIII 890 CL is a potent, selective, and highly use-dependent Na(+) channel blocker that protects brain tissue from the deleterious effects of focal cerebral ischemia in rodents.

Animals↗

PubMed2000

Gene expression of Na+/Ca2+ exchanger during development in human heart.

OBJECTIVE: In immature animal hearts, lower activity of sarcoplasmic reticulum and lower densities of Ca2+ channels highlight the potentially vital role of the Na+/Ca2+ exchanger (NCX) to excitation-contraction coupling. To date, studies on NCX expression have been restricted to late developmental stages. The distribution and gene expression of NCX during early ontogeny is not known, especially in humans. In the present report, we systematically characterized changes in NCX gene expression in human heart during development, with particular emphasis in early ontogeny. METHODS: Human hearts during early gestation (9- to 20-week gestation), neonatal (1 to 2 days after birth) and adulthood (18-40 years old) were used. NCX mRNA levels were studied using RNase Protection Assay (RPA) and NCX protein levels were assessed by Western blot. Wet weight was also used as the tissue base. Immunolocalization studies using confocal microscopy were performed in isolated fetal cardiac myocytes. RESULTS: Normalization of NCX mRNA derived from ventricles against an early gestational age (10-week gestation) shows that NCX mRNA levels nominally increased from 1 to 1.13 at 19-week gestation then decreased to 0.74 (P < 0.05) at neonate and further decreased to 0.23 (P < 0.05) at adult stages. NCX protein levels increased from 1 at 9-week gestation to 3 (P < 0.05) at 20-week gestation and then decreased to 1.8 (P < 0.05) at neonate and to 1.87 (P < 0.05) at adult stages. Confocal imaging of fetal cardiac myocytes revealed intense homogeneous membrane staining and abundance of NCX protein at this stage. CONCLUSIONS: The data demonstrate changes in NCX transcript and NCX protein levels as well as total RNA and proteins during human heart development. Per wet weight, NCX mRNA was 4.5 times greater at early fetal than adult stages and NCX protein was 2 times greater at adult than the early fetal stage indicating considerable post-transcriptional regulation. These findings provide new insights into the understanding of temporal changes in NCX in the developing heart at the gene level. The functional significance remains to be determined.

Blotting, Western↗

PubMed2000

Effect of partial sensory deprivation on monoaminergic neuromodulators in striate cortex of adult cat.

The role of monoaminergic neuromodulators in the reorganization of cortical topography following limited sensory deprivation in the adult cat was investigated. The total concentrations of dopamine, noradrenaline, serotonin and their major metabolites were measured in the visual cortex of both normal control and experimental animals using microbore high-performance liquid chromatography coupled with electrochemical detection. The experimental animals were subjected to a binocular retinal lesion corresponding to the central 10 degrees of vision and killed two weeks post-lesion. The sensory deprivation was confirmed in area 17 by measuring immediate-early gene zif-268 messenger RNA expression. Following the retinal lesion, the total concentrations of noradrenaline and dopamine were significantly higher in the non-deprived cortex of retinal lesion cats than in the deprived cortex of retinal lesion cats and the cortex of normal animals. This pattern follows the release of the excitatory neurotransmitter glutamate under the same conditions. Serotonin levels were significantly lower in the deprived cortex, and its metabolite 5-hydroxyindole-3-acetic acid was significantly higher in the non-deprived cortex than in deprived cortex and normal cortex. From these results, we suggest that the modulation of noradrenaline, dopamine and serotonin is regulated by visual afferent activity.

Animals↗

PubMed2000

A sodium channel signaling complex: modulation by associated receptor protein tyrosine phosphatase beta.

Voltage-gated sodium channels in brain neurons were found to associate with receptor protein tyrosine phosphatase beta (RPTPbeta) and its catalytically inactive, secreted isoform phosphacan, and this interaction was regulated during development. Both the extracellular domain and the intracellular catalytic domain of RPTPbeta interacted with sodium channels. Sodium channels were tyrosine phosphorylated and were modulated by the associated catalytic domains of RPTPbeta. Dephosphorylation slowed sodium channel inactivation, positively shifted its voltage dependence, and increased whole-cell sodium current. Our results define a sodium channel signaling complex containing RPTPbeta, which acts to regulate sodium channel modulation by tyrosine phosphorylation.

Animals↗

PubMed2000

Cooperative changes in GABA, glutamate and activity levels: the missing link in cortical plasticity.

Different intracortical mechanisms have been reported to contribute to the substantial topographic reorganization of the mammalian primary visual cortex in response to matching lesions in the two retinas: an immediate expansion of receptive fields followed by a gradual shift of excitability into the deprived area and finally axonal sprouting of laterally projecting neurons months after the lesion. To gain insight into the molecular mechanisms of this adult plasticity, we used immunocytochemical and bioanalytical methods to measure the glutamate and GABA neurotransmitter levels in the visual cortex of adult cats with binocular central retinal lesions. Two to four weeks after the lesions, glutamate immunoreactivity was decreased in sensory-deprived cortex as confirmed by HPLC analysis of the glutamate concentration. Within three months normal glutamate immunoreactivity was restored. In addition, the edge of the unresponsive cortex was characterized by markedly increased glutamate immunoreactivity 2-12 weeks postlesion. This glutamate immunoreactivity peak moved into the deprived area over time. These glutamate changes corresponded to decreased spontaneous and visually driven activity in unresponsive cortex and to strikingly increased neuronal activity at the border of this cortical zone. Furthermore, the previously reported decrease in glutamic acid decarboxylase immunoreactivity was found to reflect decreased GABA levels in sensory-deprived cortex. Increased glutamate concentrations and neuronal activity, and decreased GABA concentrations, may be related to changes in synaptic efficiency and could represent a mechanism underlying the retinotopic reorganization that occurs well after the immediate receptive field expansion but long before the late axonal sprouting.

Animals↗

PubMed2000

A Bayesian approach to finite mixture models in bioassay via data augmentation and Gibbs sampling and its application to-insecticide resistance.

After continued treatment with an insecticide, within the population of the susceptible insects, resistant strains will occur. It is important to know whether there are any resistant strains, what the proportions are, and what the median lethal doses are for the insecticide. Lwin and Martin (1989, Biometrics 45, 721-732) propose a probit mixture model and use the EM algorithm to obtain the maximum likelihood estimates for the parameters. This approach has difficulties in estimating the confidence intervals and in testing the number of components. We propose a Bayesian approach to obtaining the credible intervals for the location and scale of the tolerances in each component and for the mixture proportions by using data augmentation and Gibbs sampler. We use Bayes factor for model selection and determining the number of components. We illustrate the method with data published in Lwin and Martin (1989).

Algorithms↗

PubMed2000

[Value of fractional curettage of prehysterectomy in endometrial neoplasms].

OBJECTIVE: To evaluate the value of fractional curettage in the histologic type, histologic grade and cervical involvement of the endometrial carcinoma. METHODS: A total of 691 cases of endometrial carcinoma in fractional curettage specimen were analyzed retrospectively, patients with no carcinoma postoperatively in the removed uterus were excluded from the study. Those endocervical curettages with adenocarcinoma according the histologic relationship between tumor tissue and endocervical tissue were divided into 4 main groups. RESULTS: (1) The inaccurate rate of histologic type in prehysterectomy curettage was 8.83% (61/691). About a half poorly differentiated adenocarcinomas were undergraded in the prehysterectomy curettage. (2) In 691 cases of endometrial carcinomas, 159 (23.01%) cases were determinated cervical involvement by tumor in the hysterectomy specimen, of which 88 cases had tumor tissue in the prehysterectomic curettage. In a variety of histologic appearances of endocervical curettage, the ratio of cervical involvement by tumor in hysterectomy was respectively group I 30.30% (10/33), group II 9 cases (9/9), group III 100.00% (40/40), group IV 46.88% (29/63), those without tumor tissue in the endocervical curettage 12.68% (71/560). CONCLUSIONS: (1) The reliability of histologic type of endometrial carcinoma based on the findings of the fractional curettage specimen in related to the tumor type. The diagnosis of poorly differentiated adenocarcinomas in the prehysterectomy specimen is limited. (2) Determinating the presence or absence of cervical involvement can't only depend upon the endocervical curettage with or without tumor tissue. It is suggested that those endocervical curettage with tumor tissue be divided into 4 main groups according the histologic relationship between tumor tissue and endocervical tissue, group II and group III are good predictors of cervical involvement by tumor.

Cervix Uteri↗

PubMed2000

[A clinical analysis of 31 cases with pulmonary damage caused by scrub typhus].

OBJECTIVE: To deepen the understanding of pulmonary damage caused by scrub typhus. METHODS: 31 cases of pulmonary damage caused by scrub typhus from 1993 to 1998 were reviewed with chest radiographs, chest B-ultrasound, etc. RESULTS: 44% cases with scrub typhus showed a pulmonary damage (31/70), in which 66% (20/31) had cough, 53% (16-31) had sputum, 53% (16/31) had rales and the most symptoms were mild. Chest X-rays: 45% (14/31) showed pulmonary interstitial lesion, 53%(16/31) pulmonary effusion lesion and 8 cases pleural lesion. 26% (8/31) of pleural effusion was confirmed by chest B-ultrasound. Respiratory failure was found in 5 cases. All cases were treated with chloramphenicol and(or) doxycyclinum and made a good recovery. CONCLUSION: The pulmonary damage caused by scrub typhus should be paid more attention to for avoiding misdiagnosis.

Adolescent↗

PubMed2000

[Changes of leukocyte rheologic characteristics and cell adhesion molecules in patients with multiple organ failure after severe trauma].

OBJECTIVE: To explore the changes of leukocyte rheologic characteristics and of cell adhesion molecule in patients with multiple organ failure (MOF) after severe trauma. METHODS: By using the erythrocyte deformability apparatus, platelet and thrombus adhesion dual-purpose apparatus and enzyme-linked immunosorbent assay (ELISA), We measured the leukocyte deformability (LD), leukocyte adhesion function (LAF), leukocyte CD18 expression, soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule (sVCAM-1) concentration in 36 MOF patients, 31 trauma patients, and 35 to be controls. RESULTS: The leukocyte filtration index (LFI), leukocyte adhesion rate (LAR), leukocyte CD18 expression, and sICAM-1 and sVCAM-1 concentration were significantly higher in MOF patients than in controls and trauma patients (F = 68.45 - 116.20, q = 12.161 - 21.374, P < 0.00), and the changes of these indicators in MOF deaths were more obvious than those in MOF survivors (t = 6.920 - 11. 665, P < 0.00). The LFI and LAR in MOF patients were positively related to leukocyte CD18 expression, sICAM-1, and sVCAM-1 concentration (r = 0.691 - 0.844, P < 0.001); LFI was positively related to LAR (r = 0.711, P < 0.001). CONCLUSION: The abnormalities of leukocyte rheologic characteristics and CAMs might be closely related to the occurrence of MOF and the severity of pathologic changes.

Adult↗

PubMed2000

[Expression of type I collagen and its receptor system in osteoblasts].

OBJECTIVE: To study the expression of type I collagen and its receptor system-integrin alpha 2 beta 1 in different passages of osteoblasts. METHODS: The expression of type I collagen and integrin alpha 2 beta 1 in the primary, sixth and fifteenth passage of osteoblasts were detected by S-P immunohistological staining technique, and their mRNA expression by quantity RT-PCR technique. RESULTS: Type I collagen and integrin alpha 2 beta 1 were expressed in different passages of osteoblasts and there was no significant difference among three passages by immunohistological technique. Their mRNA expression was gradually decreased with subculture. CONCLUSION: Type I collagen promotes the adhesion and phenotype expression of osteoblasts through its receptor-integrin alpha 2 beta 1. The reductive expression of type I collagen-receptor system will decline the phenotype of osteoblasts.

Cells, Cultured↗

PubMed2000

[SV40 and cell immortalization].

OBJECTIVE: To explore the SV40-mediated immortalization, the related factors and their roles in cell immortalization. METHODS: The original articles about cell immortalization and replicative senescence in recent decade were reviewed. RESULTS: Cell immortalization was a multifaceted phenomenon, it was involved in viral DNA integration, activation of telomerase, inactivation of growth suppressors, and so on, and their roles were closely related. CONCLUSION: The research on cell immortalization may be expected to provide important insights into a broad range of cellular biological phenomenon, and the immortalized cells can play important roles in the research of cell engineering and tissue engineering as standard cells.

Animals↗

PubMed1999

Functional roles of the extracellular segments of the sodium channel alpha subunit in voltage-dependent gating and modulation by beta1 subunits.

Voltage-gated sodium channels consist of a pore-forming alpha subunit associated with beta1 subunits and, for brain sodium channels, beta2 subunits. Although much is known about the structure and function of the alpha subunit, there is little information on the functional role of the 16 extracellular loops. To search for potential functional activities of these extracellular segments, chimeras were studied in which an individual extracellular loop of the rat heart (rH1) alpha subunit was substituted for the corresponding segment of the rat brain type IIA (rIIA) alpha subunit. In comparison with rH1, wild-type rIIA alpha subunits are characterized by more positive voltage-dependent activation and inactivation, a more prominent slow gating mode, and a more substantial shift to the fast gating mode upon coexpression of beta1 subunits in Xenopus oocytes. When alpha subunits were expressed alone, chimeras with substitutions from rH1 in five extracellular loops (IIS5-SS1, IISS2-S6, IIIS1-S2, IIISS2-S6, and IVS3-S4) had negatively shifted activation, and chimeras with substitutions in three of these (IISS2-S6, IIIS1-S2, and IVS3-S4) also had negatively shifted steady-state inactivation. rIIA alpha subunit chimeras with substitutions from rH1 in five extracellular loops (IS5-SS1, ISS2-S6, IISS2-S6, IIIS1-S2, and IVS3-S4) favored the fast gating mode. Like wild-type rIIA alpha subunits, all of the chimeric rIIA alpha subunits except chimera IVSS2-S6 were shifted almost entirely to the fast gating mode when coexpressed with beta1 subunits. In contrast, substitution of extracellular loop IVSS2-S6 substantially reduced the effectiveness of beta1 subunits in shifting rIIA alpha subunits to the fast gating mode. Our results show that multiple extracellular loops influence voltage-dependent activation and inactivation and gating mode of sodium channels, whereas segment IVSS2-S6 plays a dominant role in modulation of gating by beta1 subunits. Evidently, several extracellular loops are important determinants of sodium channel gating and modulation.

Amino Acid Sequence↗

PubMed1999

A Bayesian hierarchical model for multi-level repeated ordinal data: analysis of oral practice examinations in a large anaesthesiology training programme.

Oral practice examinations (OPEs) are used in many anaesthesiology programmes to familiarize anaesthesiology residents with the format of the oral examination administered by the American Board of Anesthesiology. The OPE outcome (final grade) consists of 'Definite Not Pass', 'Probable Not Pass', 'Probable Pass' and 'Definite Pass'. In our study to assess the validity of the OPE, residents took an average of two (ranging from one to six) OPEs, each of which was evaluated by two board certified anaesthesiologists randomly selected from a pool of 12. A key question of interest was to identify factors, for example, the length of training, didactic experience and other characteristics, that most influence OPE outcome. In addition, we were interested in assessing the reliability of the final grade, that is, the covariance parameters are of interest as well. However, estimating variance components in multi-level data with an unequal number of repeated ordinal outcomes presents several statistical challenges, such as how to estimate high dimensional random effects parameters, especially for ordinal outcomes. We propose a Bayesian hierarchical proportional odds model for data with such complexity. The flexibility of such a model allows us to make inference on the association of OPE outcomes with other factors and to estimate the variance components as well.

Anesthesiology↗

PubMed1999

X-linked mental retardation syndrome with characteristic "coarse" facial appearance, brachydactyly, and short stature maps to proximal Xq.

We describe a three-generation family in which X-linked mental retardation (XLMR) is associated with minor facial anomalies and brachydactyly. Two brothers and four nephews have "coarse" facial appearance, brachydactyly with widening of the distal phalanges, short stature, and moderate mental retardation. The three obligate carrier women have normal intelligence and normal physical findings. The results of linkage analysis carried out in 1988 using restriction fragment length polymorphisms (RFLPs) were suggestive of linkage to DXYS1 and DXS101 in proximal Xq (Zmax = 1.63 at straight thetamax = 0.0) [Carpenter et al., 1988: Am J Med Genet 43:A139]. The family was restudied with 16 microsatellite loci from Xp11.4 through Xq24. Linkage analysis demonstrated significant linkage to DXS1003, ALAS2, AR, DXS986, DXS990, DXS454, DXS1106, DXS1105, and DXS1220 from Xp11.3 to Xq23 (Zmax = 2.53 at straight thetamax = 0.0). Recombinations detected between MAOB and DXS1055 and between DXS1220 and DXS1001 place the disease locus between Xp11.3 and Xq23. Among the genes known to map to this region is the XNP gene for the alpha-thalassemia/mental retardation syndrome (ATR-X). This fact, along with the phenotypic similarity between our patients and ATR-X males, led us to consider XNP as a candidate gene for this family. X-inactivation studies provided further evidence for the involvement of XNP by showing completely skewed X-inactivation patterns in the three obligate carrier females, a pattern characteristic of carriers of XNP mutations.

Abnormalities, Multiple↗