Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The case of a 40-year-old patient with congenital trisomy 8 and sex chromosome mosaicism is discussed. The main clinical features were: mental retardation, thick and darkly pigmented skin, prominent forehead, convergent strabismus, high arched palate, flexion contractures of the extremities, and numerous skeletal abnormalities. The patient developed severe aplastic anemia followed by an interim period of preleukemia which developed into acute leukemia. Electron microscope examination of the white blood cells at the stage of the aplastic anemia showed ultrastructural abnormalities similar to those observed in other genetic disorders with a predisposition to leukemia, as well as in leukemia.
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PMID:Aplastic anemia followed by leukemia in congenital trisomy 8 mosaicism. Ultrastructural studies of polymorphonuclear cells in peripheral blood. 124 72

Improved leukemia therapies in children have brought about prolonged remissions with extramedullary relapses being reported in sites other than the most common (bone marrow, testes, brain, and spinal cord). A 3-1/2 year-old boy with a history of acute lymphocytic leukemia presented with total retinal detachment in one eye. Painful glaucoma unresponsive to medical therapy necessitated enucleation. Histopathologic examination documented the presence of a dense leukemic cellular infiltrate replacing a totally detached, necrotic retina. Tumor cells also were present in the optic nerve. The child had remained free of leukemia for 3 years after systemic and intrathecal chemotherapy, supplemented by craniospinal radiation. This represents the first case of relapse of acute lymphocytic leukemia presenting solely as a retinal detachment. Our case also underscores the point that the treatment of leukemia after an isolated ocular relapse can be associated with a favorable outcome.
J Pediatr Ophthalmol Strabismus
PMID:Retinal detachment in a child as the first sign of leukemic relapse: histopathology, MRI findings, treatment, and tumor-free follow up. 749 64

The purpose of our study was to derive an alternate end-point to death or moribund appearance for the frequently used L1210 model of murine leukemia. In reviewing the published literature, we were unable to identify a suitable intermediate marker of substantive disease that predicted outcome in the BDF1 recipient of the L1210 leukemia. In an attempt to refine the use of animals in our laboratory, we developed a scoring sheet for behavioral and physical changes that followed intravenous injection of L1210 lymphocytic leukemia cells into BDF1 recipients. At 12-h intervals for the first 2 days after tumor-cell injection and at 6-h intervals thereafter, animals were observed and scored for each parameter. When death was imminent, animals were euthanized by inhalation of methoxyflurane followed by decapitation. Changes in physical and behavioral characteristics then were correlated with the end-point of death. Changes occurred in the mice approximately 7 days after tumor cell inoculation and 24 h before death. The earliest of these signs was hunched posture, followed by one or more other characteristics including decreased activity, increased facial swelling, ears in backward position, abdominal swelling, squinting eyes, and labored breathing. From these data, we were able to develop criteria for early euthanasia. Use of these intermediate end-points likely will substantially reduce the stress on the animals without compromising scientific outcomes in experiments using this or related preclinical models of cancer.
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PMID:Determination of a humane endpoint in the L1210 model of murine leukemia. 1195 99

Strabismus 1 (STB1/VANGL2) and Strabismus 2 (STB2/VANGL1), which have been cloned and characterized using bioinformatics and cDNA-PCR, are human homologues of Drosophila tissue polarity gene strabismus (stbm)/Van Gogh (Vang). STB1 and STB2 are tetra-membrane-spanning proteins with 73.1% total-amino-acid identity. Serine-rich domain and Strabismus-homology (STH1 and STH2) domains are conserved among human STB1, STB2, Xenopus Stbm, and Drosophila Stbm. STH2 domain with the C-terminal Ser/Thr-X-Val motif is implicated in binding with Dishevelled (DVL) proteins. STB1 gene is clustered with CASQ1 gene on human chromosome 1q21-q23, while STB2 gene is clustered with CASQ2 gene on human chromosome 1p13. STB1 and STB2 genes are located around cancer susceptibility loci or recombination hot spots in the human genome. STB1 is moderately expressed in K-562 (leukemia), G-361 (melanoma), and MKN7 (gastric cancer) cells. STB2 is highly expressed in MKN28, MKN74 (gastric cancer), BxPC-3, PSN-1, and Hs766T (pancreatic cancer) cells. On the other hand, STB1 and STB2 are significantly down-regulated in several cancer cell lines and primary tumors. Xenopus homologue of human STB1 and STB2 regulates negatively the WNT - beta-catenin signaling pathway. Loss-of-function mutations of genes encoding negative regulators of WNT - beta-catenin signaling pathway lead to carcinogenesis. Based on functional aspects and human chromosomal loci, STB1 gene and STB2 gene are predicted to be potent tumor suppressor gene candidates. STB1 and STB2 might be suitable targets for tissue engineering in the field of re-generative medicine and for chemoprevention and treatment in the field of clinical oncology.
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PMID:Strabismus (STB)/Vang-like (VANGL) gene family (Review). 1206 Aug 45

Scopolamine hydrobromide trihydrate is used in ophthalmic preparations and as a preanesthetic sedative. Its major use is in transdermal patches for the treatment of motion sickness. Scopolamine hydrobromide trihydrate was selected for study because of considerable human exposure resulting from its use in prescription and over-the-counter preparations. Scopolamine was a suspect carcinogen because it contains an aliphatic epoxide moiety which may act as a biological alkylating agent. Male and female F344/N rats and B6C3F1 mice received scopolamine hydrobromide trihydrate (89% pure) in distilled water by gavage for 16 days, 14 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and mouse peripheral blood erythrocytes. 16-DAY STUDY IN RATS: Groups of five male and five female rats were administered 0, 75, 150, 300, 600, or 1,200 mg scopolamine hydrobromide trihydrate/kg body weight in distilled water by gavage for 16 days. All rats survived to the end of the study. The final mean body weights and body weight gains of males receiving 600 and 1,200 mg/kg and the mean body weight gain of males receiving 300 mg/kg were significantly lower than those of the control group. Clinical findings included bilateral pupillary dilation in all dosed animals and red eyelids in males and females receiving 1,200 mg/kg. There were no significant treatment-related gross or microscopic lesions. 16-DAY STUDY IN MICE: Groups of five male and five female mice were administered 0, 150, 250, 450, 900, or 1,800 mg scopolamine hydrobromide trihydrate/kg body weight in distilled water by gavage for 16 days. One male and two females receiving 1,800 mg/kg and one female receiving 150 mg/kg died during the study. The final mean body weights and body weight gains of dosed mice were similar to those of the control groups. Clinical findings related to scopolamine hydrobromide trihydrate administration included bilateral pupillary dilation and squinting in all dosed males and females. The relative liver weights of males receiving 1,800 mg/kg and of females in all dosed groups were significantly greater than those of the control groups. There were no significant treatment-related gross or microscopic lesions. 14-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats were administered 0, 15, 45, 135, 400, or 1,200 mg scopolamine hydrobromide trihydrate/kg body weight in distilled water by gavage for 14 weeks. One female receiving 45 mg/kg, one male and one female receiving 135 mg/kg, six males and one female receiving 400 mg/kg, and eight males and seven females receiving 1,200 mg/kg died during the study. The final mean body weights and mean body weight gains of all dosed males and females were significantly lower than those of the control groups. Clinical findings included bilateral pupillary dilation in all dosed males and females and reddening of the eyes in 15 mg/kg males and 135, 400, and 1,200 mg/kg males and females. Hematocrit, hemoglobin concentration, and/or erythrocyte count in male and female rats receiving 45 mg/kg or greater were slightly higher than those of the control groups. In general, these changes were most prominent in rats in the 400 and 1,200 mg/kg groups. Higher hematocrit, hemoglobin concentration, and erythrocyte count were likely due to hemoconcentration from dehydration (relative erythrocytosis). A minimal to mild mature neutrophilia, evidenced by higher segmented neutrophil numbers than in the control group, occurred in all dosed male rats. Sperm morphology and vaginal cytology parameters in dosed rats were similar to those in the control groups. Nine male and five female dosed rats died from esophageal obstructions consisting of feed and bedding material in the posterior pharynx. Tracheal obstruction occurred concurrently with esophageal obstruction as a result of food build-up in the oropharyngeal region. This condition is considered to be secondary to the inhibitory effects of scopolamine hydrobromide trihydrate on salivary gland secretions and on esopon esophageal smooth muscle involved in swallowing. There were no other significant treatment-related gross or microscopic findings. 14-WEEK STUDY IN MICE: Groups of 10 male and 10 female mice were administered 0, 15, 45, 135, 400, or 1,200 mg scopolamine hydrobromide trihydrate/kg body weight in distilled water by gavage for 14 weeks. One male receiving 135 mg/kg and two males and one female receiving 1,200 mg/kg died during the study. The final mean body weights and mean body weight gains of all dosed male groups and females receiving 45 mg/kg and above were significantly lower than those of the control groups. Clinical observations included bilateral pupillary dilation, hyperactivity, and hypoactivity. A minimal to mild mature neutrophilia, similar to that which occurred in the 14-week rat study, occurred in male mice receiving 45 mg/kg or greater. As in the rat study, there was no microscopic evidence of inflammation that could account for the neutrophilia. The estrous cycle length of 1,200 mg/kg females was significantly greater than that in the control group. There were no significant treatment-related gross or microscopic lesions. 2-YEAR STUDY IN RATS: Groups of 60 male and 60 female rats were administered 0, 1, 5, or 25 mg scopolamine hydrobromide trihydrate/kg body weight in distilled water by gavage for 104 weeks. Ten males and ten females from each dose group, excluding the 1 mg/kg female group, were evaluated at 15 months. Survival, Body Weights, Clinical Findings, and Ophthalmic Examination Findings: The survival rates of female rats receiving 1 and 25 mg/kg were significantly lower than that of the control group. Mean body weights of 1 and 5 mg/kg males and females were similar to those of the controls throughout the study. However, mean body weights of 25 mg/kg males and females were generally lower than those of the control groups after about week 25. Clinical findings included bilateral pupillary dilation in all dosed males and females. Ophthalmic examination revealed no significant findings. Hematology: Compared to controls, hematocrit was slightly higher in the 25 mg/kg male rats, similar to the effects observed in the 14-week study; this is consistent with dehydration resulting in hemoconcentration. Reticulocyte numbers in the 25 mg/kg female rats were slightly lower than those in the controls. This result is consistent with the lower body weights, and thus a decreased nutritional status, exhibited by these animals. Plasma Scopolamine Determinations: The serum scopolamine concentrations were 6 ng scopolamine/mL serum for the 5 mg/kg female sample and 12 and 28 ng/mL for the 25 mg/kg male and female samples, respectively. The amounts of scopolamine in the other serum samples were below the minimum detection limit (4 ng/mL) of the analysis method. Neurobehavioral Findings: Horizontal motor activity of 25 mg/kg females was significantly greater than that of the control group on days 90, 180, and 360. Startle response of 5 and 25 mg/kg females was significantly lower than that of the control group on day 90. On day 180, passive avoidance of 25 mg/kg males was significantly lower than that of the control group. Pathology Findings: The incidences of adenoma of the pituitary gland pars distalis decreased with increasing dose in both male and female rats; however, this trend was only significant in males (males: vehicle control, 19/49; 1 mg/kg, 17/49; 5 mg/kg, 13/50; 25 mg/kg, 10/50; females: 20/50, 13/60, 14/50, 10/50). The incidences of adenoma of the pituitary gland pars distalis in 25 mg/kg males and all groups of dosed females were below the NTP historical control range. The incidences of hyperplasia were not significantly different from those in the control groups. The incidences of mononuclear cell leukemia in 25 mg/kg males and females were significantly lower than those of the control groups (males: 33/50, 21/50, 26/50, 24/50; females: 20/50, 6/60, 13/50, 4/50). The incidence of mononuclear cell leukemia in females receiving 25 mg/kg was well below the NTP historical range. 2-YEAR STUDY IN MICE: Groups of 70 male and 70 female mice were administered 0, 1, 5, or 25 mg scopolamine hydrobromide trihydrate/kg body weight in distilled water by gavage for 104 to 105 weeks. Ten control animals and ten animals from each dose level were evaluated at 15 months. Survival, Body Weights, Clinical Findings, and Ophthalmic Examination Findings Survival of dosed males and females was similar to that of the controls. The mean body weights of males and females receiving 1 mg/kg were similar to those of the control groups throughout the majority of the study. The mean body weights of 5 mg/kg males and females were slightly lower than those of the controls. The mean body weights of males and females receiving 25 mg/kg were lower than those of the control groups after week 13. Clinical findings included bilateral pupillary dilation in all dosed male and female groups. Ophthalmic examination revealed no significant findings. Hematology: Hematocrit, hemoglobin concentration, and erythrocyte count in 25 mg/kg female mice were slightly lower than those in the control group. These results are consistent with development of a minimal normocytic, normochromic nonresponsive anemia. The anemia may be related to the lower body weights exhibited by these animals and are presumed to be due to a decreased nutritional status. Pathology Findings: The combined incidences of hepatocellular neoplasms (adenoma or carcinoma) occurred with a significant negative trend in males and females (males: vehicle control, 30/50; 1 mg/kg, 33/50; 5 mg/kg, 14/50; 25 mg/kg, 15/50; females: 22/51, 21/50, 16/50, 9/51). The combined incidences of hepatocellular neoplasms in 5 and 25 mg/kg males were within the NTP historical control range. The incidences of clear cell foci and eosinophilic foci in dosed male groups, and eosinophilic foci in 25 mg/kg females, were significantly lower than those of the control groups. The incidences of many spontaneously occurring nonneoplastic lesions were significantly lower in dosed mice than in the control groups and usually decreased with increasing dose. These included kidney nephropathy, alveolar epithelial hyperplasia, hyperplasia of the pancreatic islets, bone marrow myelofibrosis, hyperplasia of the pituitary gland pars distalis, cystic hyperplasia of the uterus, and hematopoietic cell proliferation of the spleen. The decreased incidences of these spontaneous lesions were most likely a result of lower body weights in dosed animals. GENETIC TOXICOLOGY: Scopolamine hydrobromide trihydrate did not induce mutations in any of five strains of Salmonella typhi murium, with or without S9 metabolic activation enzymes, nor did it induce sister chromatid exchanges in cultured Chinese hamster ovary cells, with or without S9. A weakly positive response was obtained, however, in a chromosomal aberrations test conducted in cultured Chinese hamster ovary cells with very high doses of scopolamine hydrobromide trihydrate in the presence of S9; without S9, no increase in aberrations was noted. Despite the evidence for chromosomal damage observed in vitro, no increase in the frequencies of micronucleated normochromatic erythrocytes was observed in peripheral blood samples of male or female mice exposed to scopolamine hydrobromide trihydrate for 14 weeks by gavage. CONCLUSIONS: Under the conditions of these 2-year gavage studies, there was no evidence of carcinogenic activity of scopolamine hydrobromide trihydrate in male or female F344/N rats or B6C3F1 mice administered 1, 5, or 25 mg/kg. Synonyms: Scopolamine hydrobromide, 6,7-epoxytropan-3-yl, euscopol, hydroscine hydrobromide, hyoscine bromide, (-)-hyoscine hydrobromide, hysco, isoscopil, scopolammonium bromide, (s)-tropate hydrobromide trihydrate, lα-tropyl-a-scopine
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PMID:NTP Toxicology and Carcinogenesis Studies of Scopolamine Hydrobromide Trihydrate (CAS No. 6533-68-2) in F344 Rats and B6C3F1 Mice (Gavage Studies). 1259 30

Five case histories are presented. Waldenstrom's macroglobulinaemia caused bilateral central retinal vein occlusion, proptosis was the presenting feature of retro-orbital plasmacytoma in relapsed multiple myeloma, a red painful eye was due to neovascular glaucoma in primary polycythaemia, bilateral VIth nerve palsy caused convergent squint and diplopia in meningeal relapse of acute lymphoblastic leukaemia and lymphoma of the eyelid caused complete ptosis. Interdisciplinary management is described. Ophthalmological lesions in haematological disease should be promptly recognized and managed. Collaboration between ophthalmology and haematology departments may be effective for palliative management.
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PMID:Ophthalmic manifestations of haematological disorders. 2417 39

Vincristine is used in the treatment of leukemias, solid tumors, and lymphomas. A case of a 2-year-old boy undergoing treatment for leukemia who developed sudden onset bilateral ptosis and ophthalmoplegia along with generalized neuropathy due to vincristine's neurotoxic effects is presented. He was successfully treated with pyridoxine and pyridostigmine. The possible mechanisms of action and the treatment for vincristine-induced neuropathy are discussed. Prompt treatment and close follow-up is needed, especially in children because prolonged ptosis and motility restriction may have a profound effect on a child's visual function.
J Pediatr Ophthalmol Strabismus 2015 Jul 07
PMID:Vincristine-Induced Neuropathy Presenting as Ptosis and Ophthalmoplegia in a 2-Year-Old Boy. 2617 28

The authors describe a case of presumed endogenous fungal endophthalmitis in an immunocompetent pediatric patient with acute lymphoblastic leukemia. A 15-year-old boy with a history of high-risk B-cell acute lymphoblastic leukemia status post-chemotherapy presented with acute changes in vision in his left eye. Fundus examination revealed a white bi-lobed chorioretinal lesion with overlying vitritis and associated subretinal fluid. Magnetic resonance imaging of the brain revealed small ring-enhancing lesions in the right parietal and left occipital lobes. Blood, cerebrospinal fluid, aqueous, and vitreous cultures were all negative. Bone marrow and vitreous cytology were negative for malignant cells. The patient was treated for presumed fungal endophthalmitis with systemic and intravitreal voriconazole, followed by pars plana vitrectomy with intravitreal voriconazole and amphotericin B injections. The chorioretinal lesion resolved and visual acuity recovered to 20/20. Chorioretinal infiltrates in a patient with leukemia may require treatment even in the absence of a definitive diagnostic test result. Intervention should be guided by risk analysis and clinical judgment. [J Pediatr Ophthalmol Strabismus. 2017;54:e42-e46.].
J Pediatr Ophthalmol Strabismus 2017 Jun 29
PMID:Management of Presumed Endogenous Fungal Endophthalmitis in a Child With Acute Lymphoblastic Leukemia. 2866 43

This review highlights 4 case reports in the field of pediatric ophthalmology and strabismus published in the year 2015. The first article describes ocular presentations of acute childhood leukemia relapse. The second demonstrates the association of sector iris hemangioma with diffuse choroidal hemangioma. The third article provides a secondary procedure for persistent hypertropia in thyroid-related orbitopathy, and the fourth article describes a treatment for cyclic esotropia with temporary use of prismatic correction.
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PMID:The best of the best: a review of select pediatric ophthalmology and strabismus case reports published in 2015. 2892 7

Intellectual disability syndrome (IDS) associated with a hereditary persistence of fetal haemoglobin (HbF), also known as Dias-Logan syndrome, is commonly characterised by psychomotor developmental delay, intelectual disability, language delay, strabismus, thin upper lip, abnormalities of external ears, microcephaly, downslanting palpebral fissures. Sporadically, autism spectrum disorders and blue sclerae in infancy have been reported in IDS. Rarely, IDS-affected patients present with epilepsy and/or epileptic syndromes. It has been shown that a haploinsufficiency of the B cell leukaemia/lymphoma 11A gene (BCL11A) is responsible for IDS. Herein, we identified a novel de novo frameshift deletion (c.271delG; p.E91Afs*2) in the BCL11A gene in a boy affected with IDS. Interestingly, this heterozygous loss-of-function BCL11A mutation was also associated with a generalised idiopathic epilepsy and severe language delay observed in the patient. Moreover, our study showed that the combination of molecular genetic analyses with the monitoring of HbF was essential to make the final diagnosis of Dias-Logan syndrome. Because our patient suffered from well-controlled epilepsy, we propose to include the BCL11A gene in routinely used molecular genetic epilepsy-related gene panels. Additionally, many of the clinical features of IDS overlap with symptoms observed in patients with suspected alcohol spectrum disorders. Therefore, we also suggest monitoring HbF levels in patients with these syndromes to further facilitate clinical diagnosis.
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PMID:A Novel de novo Frameshift Mutation in the BCL11A Gene in a Patient with Intellectual Disability Syndrome and Epilepsy. 3290 78


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