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1.
Clin Genet ; 93(2): 387-391, 2018 02.
Article in English | MEDLINE | ID: mdl-28787085

ABSTRACT

We report a consanguineous Arab family with 3 affected siblings who display a disorder of global developmental delay, learning difficulties, facial dysmorphism, hearing impairments, and cataract. The clinical phenotype was associated with characteristic brain magnetic resonance imaging (MRI) features of axonal guidance defects involving anterior commissure agenesis as well as scattered areas of polymicrogyria-cobblestone complex. Whole genome sequencing revealed a novel nonsense mutation (159609921C>T) that segregated in the family consistent in an autosomal recessive pattern. This mutation located in the C-terminal region shared by the Schwanomin-Interacting Protein1 (SCHIP1) isoforms including the IQCJ-SCHIP1. The in vitro expression of SCHIP1 and IQCJ-SCHIP1 truncated mutant isoforms (NM_001197109.1; p.R209* and NM_001197114.1; p.R501*, respectively) were markedly reduced as compared to their full-length versions suggesting protein stability/folding impairment. The pathogenic nature of this mutation is supported by a previously reported mouse knockout of Schip1 isoforms, which phenocopied the human axon guidance abnormality. This is the first report of a SCHIP1/IQCJ-SCHIP1 point mutation in humans associated with a neurological-developmental phenotype.


Subject(s)
Brain/physiopathology , Carrier Proteins/genetics , Developmental Disabilities/genetics , Neurodevelopmental Disorders/genetics , Animals , Axons/pathology , Brain/abnormalities , Brain/diagnostic imaging , Child , Child, Preschool , Developmental Disabilities/diagnostic imaging , Developmental Disabilities/physiopathology , Female , Homozygote , Humans , Infant , Magnetic Resonance Imaging , Male , Neurodevelopmental Disorders/diagnostic imaging , Neurodevelopmental Disorders/physiopathology , Pedigree , Phenotype , Point Mutation/genetics , Whole Genome Sequencing
2.
Clin Genet ; 89(2): 210-6, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26285796

ABSTRACT

We present a Qatari family with two children who displayed a characteristic phenotype of congenital marked pain insensitivity with hypohidrosis and progressive aseptic destruction of joints and vertebrae resembling that of hereditary sensory and autonomic neuropathies (HSANs). The patients, aged 10 and 14, remained of uncertain genetic diagnosis until whole genome sequencing was pursued. Genome sequencing identified a novel homozygous C65S mutation in the LIFR gene that is predicted to markedly destabilize and alter the structure of a particular domain and consequently to affect the functionality of the whole multi-domain LIFR protein. The C65S mutant LIFR showed altered glycosylation and an elevated expression level that might be attributed to a slow turnover of the mutant form. LIFR mutations have been reported in Stüve-Wiedemann syndrome (SWS), a severe autosomal recessive skeletal dysplasia often resulting in early death. Our patients share some clinical features of rare cases of SWS long-term survivors; however, they also phenocopy HSAN due to the marked pain insensitivity phenotype and progressive bone destruction. Screening for LIFR mutations might be warranted in genetically unresolved HSAN phenotypes.


Subject(s)
Leukemia Inhibitory Factor Receptor alpha Subunit/genetics , Mutation/genetics , Pain Insensitivity, Congenital/genetics , Pain Insensitivity, Congenital/pathology , Spine/pathology , Adolescent , Amino Acid Sequence , Base Sequence , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Leukemia Inhibitory Factor Receptor alpha Subunit/chemistry , Magnetic Resonance Imaging , Male , Models, Molecular , Molecular Sequence Data , Pain Insensitivity, Congenital/diagnostic imaging , Phenotype , Radiography , Spine/diagnostic imaging
3.
Reprod Fertil Dev ; 28(7): 936-947, 2016 Jun.
Article in English | MEDLINE | ID: mdl-25562384

ABSTRACT

We investigated the local modulation of some histochemical properties of oviducts of the dromedary (Camelus dromedarius), focusing on the immnolocalisation of hyaluronic acid (HA) synthases (HAS2 and HAS3), hyaluronidases (HYAL2 and HYAL1) and the HA receptor CD44 in the ampulla and isthmus. Abundant acidic mucopolysaccharides (glycosaminoglycans) were detected by Alcian blue staining along the luminal surface of both ciliated and non-ciliated epithelial cells (LE). Staining for HAS2 was higher in the primary epithelial folds of the ampulla compared with the isthmus, especially in secretory cells, adluminal epithelial surface and supranuclear cell domain. HAS3 staining was stronger in the LE of the isthmus than ampulla. HYAL2 was detected in the LE in the ampulla and isthmus and was more intense in the adluminal projections of secretory cells. HYAL1 was weakly detected in the LE with no difference between the ampulla and isthmus. Strong CD44 immunostaining was present in the LE of the ampulla and isthmus. CD44 staining was higher in secretory cells than in ciliated epithelial cells and was higher in the supranuclear region than the basal region of the cytoplasm. In conclusion, we provide evidence that HA synthesis and turnover occur in the camel oviduct. Differences in HAS2 and HAS3 expression suggest regional differences in the molecular size of HA secreted in oviductal fluid that may influence oviduct-gamete interaction in the camel.


Subject(s)
Camelus , Hyaluronan Synthases/physiology , Hyaluronoglucosaminidase/physiology , Oviducts/enzymology , Animals , Epithelial Cells , Female
4.
Korean J Parasitol ; 51(3): 297-304, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23864740

ABSTRACT

Trichinosis is a parasitic zoonosis caused by the nematode Trichinella spiralis. Anthelmintics are used to eliminate intestinal adults as well as tissue-migrating and encysted larvae. This study aimed to investigate the effects of ivermectin and myrrh obtained from the aloe-gum resin of Commiphora molmol on experimental trichinosis. Ninety albino mice were orally infected with 300 T. spiralis larvae. Drugs were tested against adult worms at day 0 and day 5 and against encysted larvae on day 15 and day 35 post-infection (PI). Mature worms and encysted larvae were counted in addition to histopathological examination of muscle specimens. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein, albumin, globulin, urea, and creatinine values were estimated. Significant reductions in mean worm numbers were detected in ivermectin treated mice at day 0 and day 5 PI achieving efficacies of 98.5% and 80.0%, while efficacies of myrrh in treated mice were 80.7% and 51.5%, respectively. At days 15 and 35 post-infection, ivermectin induced significant reduction in encysted larval counts achieving efficacies of 76.5% and 54.0%, respectively, while myrrh efficacies were 76.6% and 35.0%, respectively. AST, ALT, urea, and creatinine levels were reduced, while total proteins were increased in response to both treatments compared to their values in the infected non-treated mice. Ivermectin use for controlling T. spiralis could be continued. Myrrh was effective and could be a promising drug against the Egyptian strains of T. spiralis with results nearly comparable to ivermectin.


Subject(s)
Antiparasitic Agents/pharmacology , Ivermectin/pharmacology , Terpenes/pharmacology , Trichinella spiralis , Trichinellosis/drug therapy , Animals , Antiparasitic Agents/administration & dosage , Drug Therapy, Combination , Ivermectin/administration & dosage , Mice , Terpenes/administration & dosage
5.
Article in English | WPRIM (Western Pacific) | ID: wpr-79743

ABSTRACT

Trichinosis is a parasitic zoonosis caused by the nematode Trichinella spiralis. Anthelmintics are used to eliminate intestinal adults as well as tissue-migrating and encysted larvae. This study aimed to investigate the effects of ivermectin and myrrh obtained from the aloe-gum resin of Commiphora molmol on experimental trichinosis. Ninety albino mice were orally infected with 300 T. spiralis larvae. Drugs were tested against adult worms at day 0 and day 5 and against encysted larvae on day 15 and day 35 post-infection (PI). Mature worms and encysted larvae were counted in addition to histopathological examination of muscle specimens. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein, albumin, globulin, urea, and creatinine values were estimated. Significant reductions in mean worm numbers were detected in ivermectin treated mice at day 0 and day 5 PI achieving efficacies of 98.5% and 80.0%, while efficacies of myrrh in treated mice were 80.7% and 51.5%, respectively. At days 15 and 35 post-infection, ivermectin induced significant reduction in encysted larval counts achieving efficacies of 76.5% and 54.0%, respectively, while myrrh efficacies were 76.6% and 35.0%, respectively. AST, ALT, urea, and creatinine levels were reduced, while total proteins were increased in response to both treatments compared to their values in the infected non-treated mice. Ivermectin use for controlling T. spiralis could be continued. Myrrh was effective and could be a promising drug against the Egyptian strains of T. spiralis with results nearly comparable to ivermectin.


Subject(s)
Animals , Mice , Antiparasitic Agents/administration & dosage , Drug Therapy, Combination , Ivermectin/administration & dosage , Terpenes/administration & dosage , Trichinella spiralis , Trichinellosis/drug therapy
6.
Neuropediatrics ; 41(1): 18-23, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20571986

ABSTRACT

Aicardi-Goutières syndrome (AGS) is a genetically heterogeneous disorder showing variability in age of onset and clinical features. Chilblain lesions have been described in AGS patients and recent papers have discussed the clinical, molecular and cutaneous histopathological overlap with chilblain lupus. Here we report on 2 unrelated children with AGS and chilblain lesions, whose clinical histories and examination findings well illustrate the wide phenotypic variability that can be seen in this pleiotropic disorder. Although both patients show remarkable similarity in the histopathology of their associated skin lesions, with thrombi formation, fat necrosis and hyalinization of the subcutaneous tissue, we note that the histopathology reported in other AGS cases with chilblains does not necessarily demonstrate this same uniformity. Our findings highlight the significant role of the characteristic chilblain skin lesions in the diagnosis of AGS, and variability in the associated histopathology which may relate to the stage and severity of the disease.


Subject(s)
Basal Ganglia Diseases/complications , Basal Ganglia Diseases/diagnosis , Chilblains/etiology , Eye Diseases/complications , Lupus Erythematosus, Systemic/complications , Basal Ganglia Diseases/genetics , Calcinosis/genetics , Calcinosis/pathology , Chilblains/genetics , Child , Consanguinity , DNA Mutational Analysis , Eye Diseases/etiology , Eye Diseases/genetics , Female , Humans , Infant , Lupus Erythematosus, Systemic/genetics , Male , Monomeric GTP-Binding Proteins/genetics , SAM Domain and HD Domain-Containing Protein 1 , Seizures/complications , Seizures/genetics , Skin/pathology , Tomography, X-Ray Computed/methods
7.
Am J Med Genet A ; 149A(10): 2173-80, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19764032

ABSTRACT

Ciliopathies are an expanding group of rare conditions characterized by multiorgan involvement, that are caused by mutations in genes encoding for proteins of the primary cilium or its apparatus. Among these genes, CEP290 bears an intriguing allelic spectrum, being commonly mutated in Joubert syndrome and related disorders (JSRD), Meckel syndrome (MKS), Senior-Loken syndrome and isolated Leber congenital amaurosis (LCA). Although these conditions are recessively inherited, in a subset of patients only one CEP290 mutation could be detected. To assess whether genomic rearrangements involving the CEP290 gene could represent a possible mutational mechanism in these cases, exon dosage analysis on genomic DNA was performed in two groups of CEP290 heterozygous patients, including five JSRD/MKS cases and four LCA, respectively. In one JSRD patient, we identified a large heterozygous deletion encompassing CEP290 C-terminus that resulted in marked reduction of mRNA expression. No copy number alterations were identified in the remaining probands. The present work expands the CEP290 genotypic spectrum to include multiexon deletions. Although this mechanism does not appear to be frequent, screening for genomic rearrangements should be considered in patients in whom a single CEP290 mutated allele was identified.


Subject(s)
Abnormalities, Multiple/genetics , Antigens, Neoplasm/genetics , Cilia , Neoplasm Proteins/genetics , Antigens, Neoplasm/metabolism , Base Sequence , Cell Cycle Proteins , Cilia/genetics , Cilia/pathology , Cytoskeletal Proteins , DNA Mutational Analysis , Female , Fetus/metabolism , Fetus/pathology , Gene Deletion , Genetic Testing , Humans , Neoplasm Proteins/metabolism , RNA, Messenger/analysis , Syndrome
8.
Neurology ; 70(7): 556-65, 2008 Feb 12.
Article in English | MEDLINE | ID: mdl-18268248

ABSTRACT

Joubert syndrome and related cerebellar disorders (JSRD) are a group of recessive congenital ataxia conditions usually showing neonatal hypotonia, dysregulated breathing rhythms, oculomotor apraxia, and mental retardation. The pathognomonic finding in JSRD is the unique molar tooth sign (MTS) on brain imaging. There is a tremendously broad spectrum of signs and symptoms mainly including kidney, retina, and liver disease, along with polydactyly and facial dysmorphisms. Here we propose a new diagnostic classification within JSRD that includes four major subtypes. To test this classification, we performed a systematic recruitment and genetic evaluation from a single referral center in Egypt. Thirteen families were identified, four showed evidence of linkage to one of the four known genetic loci, three showed novel AHI1 mutations, and nine were excluded from known loci. Each family could be classified into one of the four subtypes. This classification may thus be useful in the evaluation of patients with JSRD.


Subject(s)
Cerebellar Diseases/diagnosis , Cerebellar Diseases/genetics , Cerebellum/pathology , Cerebellum/physiopathology , Genetic Predisposition to Disease/genetics , Mutation/genetics , Abnormalities, Multiple/genetics , Atrophy/genetics , Atrophy/pathology , Atrophy/physiopathology , Cerebellar Diseases/classification , Chromosome Disorders/classification , Chromosome Disorders/diagnosis , Chromosome Disorders/genetics , Chromosome Mapping , DNA Mutational Analysis , Egypt , Female , Genetic Testing , Genotype , Humans , Kidney Diseases/diagnostic imaging , Kidney Diseases/genetics , Kidney Diseases/physiopathology , Liver Diseases/diagnostic imaging , Liver Diseases/genetics , Liver Diseases/physiopathology , Magnetic Resonance Imaging , Male , Neural Pathways/pathology , Neural Pathways/physiopathology , Phenotype , Predictive Value of Tests , Retinal Degeneration/genetics , Retinal Degeneration/pathology , Retinal Degeneration/physiopathology , Syndrome , Ultrasonography
9.
Pharmazie ; 58(11): 788-92, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14664332

ABSTRACT

Thiosemicarbazides undergo different cyclization reactions to give five membered heterocycles. The product of cyclization depends on the reagent used. This cyclization leads to the formation of 1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole derivatives. The reaction of thioglycolyl hydrazide derivatives of the 1,2,4-triazole compounds was discussed. The activity against hepatitis B virus (HBV) has been tested.


Subject(s)
Antiviral Agents/chemical synthesis , Antiviral Agents/pharmacology , Oxazoles/chemical synthesis , Oxazoles/pharmacology , Thiazoles/chemical synthesis , Thiazoles/pharmacology , Triazoles/chemical synthesis , Triazoles/pharmacology , Cell Line , Cell Survival/drug effects , Drug Screening Assays, Antitumor , Enzyme-Linked Immunosorbent Assay , Hepatitis B virus/drug effects , Humans , Indicators and Reagents , Magnetic Resonance Spectroscopy , Methylation , Reverse Transcriptase Polymerase Chain Reaction
11.
Acta Chem Scand (Cph) ; 49(8): 609-14, 1995 Aug.
Article in English | MEDLINE | ID: mdl-7662442

ABSTRACT

Methyl 2-deoxy-3-O-[2-(formylamino)ethyl]-5-O-trityl-D-erythro- pentofuranoside (4) was obtained in a 3-O alkylation reaction by treatment with 2-chloroethylamine in DMF. Compound 4 afforded alpha nucleosides as the main products when condensed with uracils under the Vorbrüggen conditions. The nucleosides were deblocked by treatment with 80% acetic acid and subsequently with sodium methoxide in methanol.


Subject(s)
Antiviral Agents/chemical synthesis , Deoxyuridine/analogs & derivatives , Deoxyuridine/chemical synthesis , Animals , Antiviral Agents/pharmacology , Cell Survival/drug effects , Cells, Cultured , Chlorocebus aethiops , Deoxyuridine/pharmacology , HIV-1/drug effects , Haplorhini , Vero Cells/drug effects
12.
J Biosoc Sci ; 22(1): 19-32, 1990 Jan.
Article in English | MEDLINE | ID: mdl-2298758

ABSTRACT

A longitudinal study of twenty-six breast-feeding and twelve non-breast-feeding postpartum women was conducted in Assiut, Egypt in order to determine the time that ovulation resumed after childbirth, and the effect of breast-feeding frequency on the period of lactational anovulation. Breast-feeding women experienced the onset of follicular development, vaginal bleeding, ovulation and pregnancy significantly later than women who did not breast-feed. Ovulatory and non-ovulatory breast-feeders reported similar frequencies of breast-feeding episodes. The introduction of dietary supplements commonly preceded ovulation. An algorithm using three simple variables observable to the breast-feeding mother was found to predict up to 100% of the first ovulations. All breast-feeding women who did not give supplements and did not have a vaginal bleeding episode by 6 months postpartum were anovular by strict criteria for ovulation. Ovulation did not precede bleeding or supplementation in the women who experienced these events before 6 months, yielding a highly effective formula for preventing unplanned pregnancy by the informed use of breast-feeding.


PIP: A longitudinal study of 26 breastfeeding and 12 non-breastfeeding postpartum women was conducted in Assiut, Egypt in order to determine the time that ovulation resumed after childbirth, and the effect of breastfeeding frequency on the period of lactational anovulation. The breastfeeding group consisted of women ages 18-40 who had successfully breastfed at least 1 child. Breastfeeding women experienced the onset of follicular development, vaginal bleeding, ovulation and pregnancy significantly later than women who did not breastfeed. Ovulatory and non-ovulatory breastfeeders report similar frequencies of breastfeeding episodes (9-10 times in 24 hours). The introduction of dietary supplements commonly preceded ovulation. An algorithm using 3 simple variables observable to the breastfeeding mother was found to predict up to 100% of the 1st ovulations. All breastfeeding women who did not give supplements and did not have a vaginal bleeding episode by 6 months postpartum were anovular by strict criteria for ovulation. Ovulation did not precede bleeding or supplementation in the women who experienced these events before 6 months, yielding a highly effective formula for preventing unplanned pregnancy by the informed use of breastfeeding.


Subject(s)
Breast Feeding , Fertility/physiology , Adolescent , Adult , Egypt , Female , Humans , Longitudinal Studies , Ovulation
13.
Z Kinderchir ; 40(5): 303-7, 1985 Oct.
Article in English | MEDLINE | ID: mdl-4072431

ABSTRACT

We present 5 uncommon cases: One case of perineal canal in a female; two cases of perineal groove in females, one with normal anus and another with ectopic perineal anus. Two cases of perineal canal in males. The canal is deep in the perineum, runs forward above the root of scrotum, close to the floor of the urethra (which is normal), and opens on the undersurface of the penis. One of them is associated with covered anus incomplete with anocutaneous fistula as well opening on the scrotal raphe. In all 5 cases the perineal canal or gutter opens posteriorly in the ectodermal anal canal, immediately below the line of anal valves. A third look to the origin of these conditions will be discussed versus the 1st and 2nd looks of Stephens and Chatterjee. Embryological and histopathological studies will support our point of view.


Subject(s)
Anal Canal/abnormalities , Perineum/abnormalities , Rectal Fistula/congenital , Anal Canal/surgery , Female , Humans , Infant , Infant, Newborn , Male , Perineum/surgery , Rectal Fistula/surgery
14.
Contraception ; 30(5): 391-405, 1984 Nov.
Article in English | MEDLINE | ID: mdl-6440735

ABSTRACT

Sixty-three women had NORPLANT implants inserted during the first eight days of the menstrual cycle. Blood specimens were withdrawn at the time of insertion and every three days during one of the following months of observation; the first, third, sixth, ninth and twelfth month after insertion. Ten subjects were sampled at multiple times during implant use. A total of 83 months of observation was available. The serum concentrations of levonorgestrel (LNG), FSH, LH, prolactin (PRL), estradiol (E2) and progesterone (prog) were measured in each specimen. LNG concentration rapidly declined during the first 15 days of use, the decline became more gradual during the subsequent two weeks, and an almost steady level was reached during the remainder of the year. There were no significant trends of change in the levels of FSH, LH, E2 and prog during the year. Frequent peaks in E2 concentration were observed and were generally associated with or followed by LH surges. PRL concentration showed a slight but significant rise during the second half of the year. Rises in prog concentration suggestive of ovulation occurred in 36 percent of the months of observation. However, in all these instances, there were evidences suggestive of deficient luteal phase. The bleeding episodes were usually, but not always, related to decline in E2 and prog concentrations.


Subject(s)
Gonadal Steroid Hormones/blood , Norgestrel/administration & dosage , Adult , Contraceptives, Oral, Combined/administration & dosage , Contraceptives, Oral, Combined/blood , Drug Implants , Estradiol/blood , Female , Follicle Stimulating Hormone/blood , Humans , Levonorgestrel , Luteinizing Hormone/blood , Menstrual Cycle/drug effects , Norgestrel/blood , Progesterone/blood , Prolactin/blood
16.
Pharmazie ; 35(7): 394-8, 1980.
Article in English | MEDLINE | ID: mdl-7413710

ABSTRACT

Some new amides of substituted oxamic acid which embody different moieties of the anti-inflammatory drugs were prepared through two routes of synthesis. The physico-chemical properties as well as the anti-inflammatory activity of these compounds were determined. Preliminary pharmacological testing revealed the superiority of most of the screened compounds as anti-inflammatory agents with relatively low toxicity as compared with acetylsalicylic acid. Correlation between structure and biological activity was suggested.


Subject(s)
Amino Acids/chemical synthesis , Anti-Inflammatory Agents/chemical synthesis , Oxamic Acid/chemical synthesis , Animals , Anti-Inflammatory Agents/toxicity , Aspirin/pharmacology , Female , Histamine , Inflammation/chemically induced , Lethal Dose 50 , Male , Oxamic Acid/analogs & derivatives , Oxamic Acid/pharmacology , Oxamic Acid/toxicity , Rats , Xylenes
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