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Uriel Katz

Publications and source records attributed to Uriel Katz.

10 recordsLinked to original sources
PubMed2026

Further Support for Association of DAND5 with Autosomal Recessive Laterality Disorders.

BACKGROUND: Laterality defects are rare congenital malformations that encompass congenital heart defects (CHDs) together with abnormalities of visceral organ arrangement (situs inversus or situs ambiguous). These defects may be isolated or part of a syndromic presentation with multisystem involvement. While over 50 genes have been implicated in laterality disorders, across multiple modes of inheritance, many cases remain molecularly undiagnosed. We sought to elucidate the molecular basis of dextrocardia, CHDs and visceral heterotaxy in two unrelated individuals of Arab-Muslim descent. METHODS: Detailed clinical phenotyping and exome sequencing (ES) were performed for each of the probands, followed by familial segregation analysis. RESULTS: ES revealed a shared homozygous variant in the Dan Domain Family Member 5 (DAND5) gene (NM_152654.3): c.396_397dup, p.(Tyr133SerfsTer11). DAND5 encodes a member of the Cerberus-related DAN protein family, which is involved in the establishment of left body asymmetry. This frameshift variant introduces a premature stop codon within the final exon, which is predicted to escape nonsense-mediated decay (NMD), resulting in a truncated protein lacking the functional DAN domain. CONCLUSIONS: DAND5 has recently been suggested as a candidate gene in heterotaxy and CHDs. Our findings further support biallelic loss of function variants in DAND5 autosomal recessive laterality defects.

Female↗
PubMed2006

Long term safety of IVIg therapy in multiple sclerosis: 10 years experience.

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system. The majority of MS patients have a relapsing-remitting course with progressive neurological disability that accumulates over the years. Intravenous Immunoglobulin (IVIg) has demonstrated benefit in the treatment of some patients with relapsing-remitting MS. Concerns about adverse events of IVIg, mainly acute renal failure and thromboembolic events have been raised in the medical literature. We examined the adverse events profile of IVIg treatment in a large cohort of 293 relapsing-remitting MS patients treated with an initial loading dose of IVIg (0.4 g/Kg body weight/day, for 5 consecutive days) and additional booster dose infusions (0.4 g/Kg body weight/booster dose, every 6 weeks) as a maintenance treatment. A total of 9281 IVIg infusions were administered within a mean treatment period of 3.8 +/- 3.5 years (3 months-10 years). The main adverse event during the loading dose period was headache, occurring in 12.6% of the patients. The annual rate of any adverse event during the IVIg maintenance period was 4.4% during the first year and had a trend to decrease with every passing year of treatment. Adverse events during the loading dose did not predict adverse events during the maintenance phase. No severe adverse events were recorded. We conclude that IVIg is a safe therapy in MS either for short or for long-term periods.

Adult↗
PubMed2005

IVIg therapy in autoimmunity and related disorders: our experience with a large cohort of patients.

Intravenous immunoglobulin (IVIg) is used to treat a number of immune-deficiencies and autoimmune diseases. It has been shown that IVIg contains anti-idiotypic antibodies, which explains its immunomodulatory action. In murine models, recent investigations have demonstrated that IVIg can prevent and reduce the affliction by systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS) and scleroderma. Relevant disease-specific fractions of IVIg were able to reproduce and even enhance the therapeutic effect in a murine model.IVIg treatment before tumor resection in rodents inoculated with melanoma and sarcoma cells dramatically improved the cure rate (50%) in comparison to the control group (0%). In patients affected by SLE, several clinical manifestations responded to IVIg treatment including serositis, hematological manifestations, treatment-resistant nephritis and central nervous system involvement. Similarly, in women with recurrent fetal loss due to APS, IVIg was able to diminish the abortion rate. Vasculitides such as Churg-Strauss' and Wegener's and skin fibrosis in patients affected by scleroderma improved after IVIg treatment. In agreement with in vitro investigations, prolonged survival has been noted in cancer patients treated with IVIg. We suggest that in the presence of a steroid and immunosuppressive-resistant autoimmune disease, IVIg is a rational and safe choice.

Adolescent↗
PubMed2005

Intravenous immunoglobulin: adverse effects and safe administration.

Intravenous immunoglobulin (IVIg) is administered for various indications and generally considered a safe therapy. Most of the adverse effects (AEs) associated with IVIg administration are mild and transient. The immediate AEs include headache, flushing, malaise, chest tightness, fever, chills, myalgia, fatigue, dyspnea, back pain, nausea, vomiting, diarrhea, blood pressure changes, tachycardia, and anaphylactic reactions, especially in IgA-deficient patients. Late AEs are rare and include acute renal failure, thromboembolic events, aseptic meningitis, neutropenia, and autoimmune hemolytic anemia, skin reactions, and rare events of arthritis. Pseudohyponatremia following IVIg is important to be recognized. Renal failure, usually oliguric and transient, occurs mostly on using sucrose-containing products owing to osmotic injury. Among high-risk patients who have a previous renal disease, dehydration, diabetes mellitus, advanced age, hypertension, hyperviscosity, or are treated by other nephrotoxic medications, administration of a non-sucrose-containing IVIg product after accomplishing hydration, in a low concentration and a slow infusion rate while supervising urine output and kidney function, is recommended. Thromboembolic complications occur because of hyperviscosity especially in patients having risk factors including advanced age, previous thromboembolic diseases, being bedridden, diabetes mellitus, hypertension, dyslipidemia, or those receiving high-dose IVIg in a rapid infusion rate. Immediate AEs can be treated by the slowing or temporary discontinuation of the infusion and symptomatic therapy with analgesics, nonsteroidal anti-inflammatory drugs, antihistamines, and glucocorticoids in more severe reactions. Slow infusion rate of low concentration of IVIg products and hydration, especially in high-risk patients, may prevent renal failure, thromboembolic events, and aseptic meningitis.

Acute Kidney Injury↗
PubMed2003

Helicobacter pylori reinfection is common in Peruvian adults after antibiotic eradication therapy.

To characterize posttreatment recurrence of Helicobacter pylori in Peru, 192 adults with H. pylori-positive gastric biopsy specimens were monitored by (14)C-Urea breath test, after eradication of H. pylori by use of amoxicillin, clarithromycin, and omeprazole. The cumulative risk of recurrence at 18 months was 30.3% (95% confidence interval, 21.4%-39.3%). Randomly amplified polymorphic DNA patterns and DNA sequence data established that, among 28 pairs of H. pylori isolates from pretreatment and recurrent infections, 6 (21%) were genetically similar, suggesting recrudescence of the previous infection, and 22 (79%) were different, suggesting reinfection with a new strain that differed from that involved in the initial infection. Eating mainly outside of the home was a risk factor for infection with a new strain (adjusted relative risk [RR], 5.07), whereas older age was a protective factor (adjusted RR, 0.20). Although an increase in the anti-H. pylori IgG antibody titer corresponded to recurrence, pretreatment and recurrent infections were similar with respect to quantitative culture colony counts and histologic characteristics, suggesting that neither prior eradication nor the memory immune response measurably alters the risk or burden of recurrent infection. Although eradication with antibiotics was successful, the high rate of reinfection suggests that treatment is unlikely to have a lasting public health effect in this setting.

Adolescent↗
PubMed2003

A virulence attenuated amoebapore-less mutant of Entamoeba histolytica and its interaction with host cells.

Entamoeba histolytica, the protozoan parasite which causes amoebiasis, is an exclusively human pathogen so developing a vaccine could effectively impact the spread of the disease. Recently we developed a genetically modified avirulent strain, termed G3, from the virulent E. histolytica strain HM-1:IMSS. The new strain lacks the important virulence factor, the amoebapore-A. The objective of our current study was to investigate the avirulence of the attenuated strain as well as to examine the antigenic and immunogenic responses of these trophozoites as potential candidates for a live vaccine. Functional assays were conducted to characterise the virulent behaviour of the G3 strain. This behaviour was compared to the virulent strain HM-1:IMSS and the non-virulent strain Rahman. Western blots were conducted to confirm the lack of amoebapore-A in the E. histolytica G3 strain and to demonstrate that it had no influence on the presence of other virulence factors. Results of these two sets of tests proved the G3 strain to be phenotypically similar to the avirulent Rahman strain while antigenically identical to the virulent HM-1:IMSS, apart from the lack of the amoebapore-A protein. Intraperitoneal immunisation of hamsters with G3 trophozoites compared to sham immunised hamsters resulted in IgG anti-HM-1:IMSS antibodies. The level of humoral response was variable and further testing has to take place before introducing this new strain as a vaccine.

Animals↗
PubMed2002

Entamoeba histolytica expressing a dominant negative N-truncated light subunit of its gal-lectin are less virulent.

The 260-kDa heterodimeric Gal/GalNAc-specific Lectin (Gal-lectin) of Entamoeba histolytica dissociates under reducing conditions into a heavy (hgl, 170 kDa) and a light subunit (lgl, 35 kDa). We have previously shown that inhibition of expression of the 35-kDa subunit by antisense RNA causes a decrease in virulence. To further understand the role of the light subunit of the Gal-lectin in pathogenesis, amoebae were transfected with plasmids encoding intact, mutated, and truncated forms of the light subunit lgl1 gene. A transfectant in which the 55 N-terminal amino acids of the lgl were removed, overproduced an N-truncated lgl protein (32 kDa), which replaced most of the native 35-kDa lgl in the formation of the Gal-lectin heterodimeric complex and exerted a dominant negative effect. Amoebae transfected with this construct showed a significant decrease in their ability to adhere to and kill mammalian cells as well as in their capacity to form rosettes with and to phagocytose erythrocytes. In addition, immunofluorescence confocal microscopy of this transfectant with anti-Gal-lectin antibodies showed an impaired ability to cap. These results indicate that the light subunit has a role in enabling the clustering of Gal-lectin complexes and that its N-truncation affects this function, which is required for virulence.

Animals↗