Brain ; metabolism ; pathology ; Child, Preschool ; Chromatography, High Pressure Liquid ; Diagnosis, Differential ; Folate Receptor 1 ; genetics ; metabolism ; Folic Acid ; blood ; cerebrospinal fluid ; metabolism ; Folic Acid Deficiency ; diagnosis ; drug therapy ; etiology ; Humans ; Infant ; Leucovorin ; therapeutic use ; Malnutrition ; complications ; diagnosis ; Tetrahydrofolates ; cerebrospinal fluid ; metabolism

Livedoid vasculopathy is a hyalinizing vascular disease characterized by thrombosis and ulceration of the lower extremities. It can be caused by an alteration in control of coagulation with the formation of thrombi within dermal blood vessels. We report a case of livedoid vasculopathy with hyperhomocysteinemia due to MTHFR mutation, which is treated by folic acid and which also showed very unusual clinical manifestations. A 38-year-old male visited the department of dermatology with a 1 year history of purplish-brown purpura with punched-out ulcers on both lower legs. He had a history of homocysteinemia due to methylene tetrahydrofolate reductase (MTHFR) mutation. The histopathologic findings of the lesional skin revealed dense superficial and deep perivascular and perifollicular infiltrates of lymphocytes and fibrin deposition within the vessels in the dermis. On the basis of clinical and pathological findings, livedoid vasculopathy with hyperhomocysteinemia due to MTHFR mutation was diagnosed and improved by the treatment of 1 mg of folic acid daily.
Blood Vessels ; Dermatology ; Dermis ; Fibrin ; Folic Acid ; Humans ; Hyalin ; Hyperhomocysteinemia ; Leg ; Lower Extremity ; Lymphocytes ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) ; Purpura ; Skin ; Tetrahydrofolates ; Thrombosis ; Ulcer ; Vascular Diseases

PURPOSE: Generally, a mucinous carcinoma (Muc) of the colon show higher rates of microsatellite instability (MSI) than a non-mucinous carcinoma (non-Muc). Mutated methylenetetrahydrofolate reductase (MTHFR) brings about low enzyme activity, which may reduce genomic DNA methylation. These processes may be critical for the oncogenic transformation of human cells. We compared the relationship of MSI and MTHFR polymorphism in Muc to that in non-Muc. METHODS: From March 2003 to August 2007, genomic DNA was isolated from whole blood and tissue specimens of 285 colorectal cancer patients (Muc: 31 cases, non-Muc: 254 cases) and 448 normal control patients. These were subjected to MSI analysis and MTHFR genotyping by using PCR-based restriction fragment length polymorphism analyses. RESULTS: MSI was significantly more frequent in the Muc group (40.7%) than in the non- Muc group (14.8%). The frequencies of polymorphism of MTHFR 677C>T were CC (31.5%), CT (57%), and TT (11.5%) in the patient group and 32.4%, 53.1%, and 14.5% in the control group. In the Muc group, the frequencies of polymorphism of MTHFR 677C>T were CC (36%), CT (56%), TT (8%), and in the non-Muc group, they were 31.1%, 57%, and 11.9%. The frequencies of polymorphism of MTHFR 1298A>C were AA (73%), AC (21.3%), and CC (5.7%) in the patient group and 69.6%, 28.6%, and 1.8% in the control group. In the Muc group, the frequencies of polymorphism of MTHFR 1298A>C were AA (50%), AC (30%), and CC (20%), and in the non-Muc group, they were 76%, 20.3%, and 3.7%. The Muc group showed higher frequencies of the CC variant than the non-Muc group (P-value=0.018). No relation between MSI and MTHFR polymorphisms were seen in any comparison of the Muc and the non-Muc groups. CONCLUSIONS: The Muc group showed higher rates of MSI than the non-Muc group, but no definite difference between the Muc and the non-Muc groups was noted in the case of polymorphism of MTHFR 677C>T. However, the TT-type variant showed slightly lower frequencies in the Muc group than in the non-Muc group. On the contrary, the Muc group showed a higher rate of the CC variant in polymorphism of MTHFR 1298A>C. These inconsistent results seem to be due to the small size of the Muc group, so further study is needed.
Adenocarcinoma, Mucinous ; Colon ; Colorectal Neoplasms ; DNA ; DNA Methylation ; Humans ; Methylenetetrahydrofolate Reductase (NADPH2) ; Microsatellite Instability ; Microsatellite Repeats ; Mucins ; Oxidoreductases ; Polymorphism, Restriction Fragment Length ; Succinimides ; Tetrahydrofolates

Hyperhomocysteinemia is known to be associated with an increased risk of myocardial infarction, stroke, peripheral arterial disease, and venous thrombosis. Gene polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) may account for reduced enzyme activity and hyperhomocysteinemia. A recent study has documented evidence of polygenic regulation of plasma homocyteine. We report here on a case of occlusive stroke at young age and hyperhomocysteinemia with homozygous VN (677C to T) variant in the MTHFR gene as well as homozygous D/D (2756G to A) variant in the MS gene.
5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase/*genetics ; Adult ; Cerebrovascular Accident/*genetics ; DNA/metabolism ; DNA Restriction Enzymes/metabolism ; Family Health ; Female ; Genotype ; Homocysteine/blood/genetics ; *Homozygote ; Human ; Hyperhomocysteinemia/*genetics ; Male ; Polymorphism (Genetics) ; Tetrahydrofolates/*genetics ; Variation (Genetics)

BACKGROUND: Recurrent aphthous stomatitis (RAS) is usually the earliest sign of Behcet's disease. Hyperhomocysteinemia can damage endothelial cells and progress to obstructive vascular disease. It has been reported that hyperhomocysteinemia is a marker of activation in Behcet's disease. Enzyme 5,10-methylenetetrahydrofolate reductase may be one of the main factors that regulates plasma homocysteine levels. Homozygosity for the C677T (MTHFR C677T) mutation is associated with reduced activity of this enzyme and considered the most common genetic cause of elevated serum homocyteine levels. However its relationship to vascular injury in Behcet's disease remains controversial, and its relationship to RAS is unknown. Apolipoprotein E (Apo E) has both immunoregulatory and anti-infective features. Search for Apo E polymorphism and lipid composition in RAS patients might be a clue to pathogenesis of RAS. OBJECTIVE: To analyze the relationship of MTHFR gene C677T polymorphism, several epidemiologic factors such as age and sex, smoking, lipid composition and Apo E polymorphism to vasculitis in RAS, we assessed the MTHFR gene C677T polymorphism, Apo E polymorphism and lipid composition in RAS and normal population. METHODS: We analyzed data from the General Health survey conducted on 1,243 participants (M:F=281:962) over a 20 year-old in Incheon city. Medical interview and laboratory test for methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, apolipoprotein E polymorphism were completed. Statistical significance was analyzed by chi-square test and multistep logistic regression analysis. RESULTS: Among normal population over the age of twenty, a total of 34.2% (426/1,243) had RAS. Female predominance (4.5:1, p=0.003) was noted. The incidence of RAS in age group 20 to 39 year old is higher than the over 40 age group. The incidence is higher in smoking group compared to the nonsmoking group in multistepwise logistic regression analysis. Frequency of the MTHFR C677T genotypes was highest at CT compared to CC and TT homozygous genotype in normal and RAS patients group. There was no significant statistical differences in MTHFR genotypes in RAS patients compared to the control group. Similarly, Apo E genotype analysis revealed no significant statistical differences either. Apo E genotype and total cholesterol, HDL-cholesterol, triglyceride level didn't show any associations. CONCLUSION: This study revealed insignificant association between the MTHFR C677T mutation and RAS. Apo E genotype didn't show a significant statistical difference in RAS patients compared to normal controls.
Apolipoproteins ; Apolipoproteins E ; Cholesterol ; Endothelial Cells ; Epidemiologic Factors ; Female ; Genotype ; Health Surveys ; Homocysteine ; Humans ; Hyperhomocysteinemia ; Incidence ; Logistic Models ; Methylenetetrahydrofolate Reductase (NADPH2) ; Oxidoreductases ; Plasma ; Smoke ; Smoking ; Stomatitis, Aphthous ; Tetrahydrofolates ; Vascular Diseases ; Vascular System Injuries ; Vasculitis

PURPOSE: Hyperhomocysteinemia is known as a risk factor for atherosclerosis. Preclinical arteriosclerosis is noted and premature atherosclerosis is known to be accelerated in Kawasaki disease (KD) patients. Genetic polymorphisms in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene result in elevated plasma homocysteine concentrations and are known to be associated with the development of coronary artery disease. Our hypothesis is that single nucleotide polymorphisms (SNPs) of the MTHFR gene are related to the development of KD and coronary artery lesions (CALs). METHODS: For this study, we selected 3 candidate single nucleotide polymorphisms (SNPs) (rs2274976, rs1801131, and rs1801133) of MTHFR. These SNPs are located on chromosome 1p36.3. We included 101 KD patients and 306 healthy adults as controls in this study. CALs were seen in 38 patients. Genotypes of the selected SNPs were determined by direct sequencing and analyzed with SNPAlyze. RESULTS: The genetic distribution and allelic frequency of the 3 MTHFR SNPs (rs2274976, rs1801131, and rs1801133) were not significantly different in patients with KD compared to the control group (P=0.71, 0.17, and 0.96, respectively). There was no difference in the genetic distribution of the MTHFR SNPs between the normal control group and the CAL group (P=0.43, 0.39, 0.52 respectively). CONCLUSION: The genetic distribution of the MTHFR SNPs (rs2274976, rs1801131, and rs1801133) was not different in the KD group compared to the control group. In addition, the genetic distribution of these SNPs was not different in the CAL group compared to the control group in the Korean population.
Adult ; Arteriosclerosis ; Atherosclerosis ; Coronary Artery Disease ; Coronary Vessels ; Genotype ; Homocysteine ; Humans ; Hyperhomocysteinemia ; Methylenetetrahydrofolate Reductase (NADPH2) ; Mucocutaneous Lymph Node Syndrome ; Oxidoreductases ; Plasma ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Risk Factors ; Tetrahydrofolates

Methionine synthase (MS, EC2.1.1.13), a key enzyme in the folate metabolism area catalyzing methyl transfer from N5-methyltetrahydrofolate to homocysteine to give tetrahydrofolate and methionine, takes a core position in folate cycle, one-carbon-unit transfer and sculpture amino acid pathways. Cobalamin-dependent methionine synthase was purified from rat liver. The enzyme was purified 609-fold to near homogeneity by batch chromatography on DE-52, anion-exchange chromatography on Q Sepharose Fast Flow and CHT-I hydroxyapatite column and was identified by SDS-PAGE and Western blotting. The enzyme activity was determined by spectrophotometric assay. In addition, the influencing factor and optimal reaction condition were performed. The steady state kinetic of rat liver methionine synthase was similar to that of other mammalian cobalamin-dependent methionine synthase which employed a Ping-Pong mechanism. The result indicated that cobalamin-dependent methionine synthase purified from rat liver is suitable for screening and studying methionine synthase specific inhibitors.
5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase ; isolation & purification ; metabolism ; Animals ; Electrophoresis, Polyacrylamide Gel ; Folic Acid Antagonists ; pharmacology ; Liver ; chemistry ; Male ; Methotrexate ; pharmacology ; Quinazolines ; pharmacology ; Rats ; Rats, Wistar ; Tetrahydrofolates ; metabolism ; Thiophenes ; pharmacology

Adolescent ; Antimetabolites, Antineoplastic ; adverse effects ; therapeutic use ; Child ; Child, Preschool ; Drug Interactions ; Drug Therapy, Combination ; Female ; Humans ; Male ; Methotrexate ; adverse effects ; therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; Sex Factors ; Tetrahydrofolates ; administration & dosage ; therapeutic use ; Treatment Outcome

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cisplatin ; administration & dosage ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Fluorouracil ; administration & dosage ; Humans ; Intestinal Neoplasms ; drug therapy ; Lung Neoplasms ; drug therapy ; Male ; Phytotherapy ; Tetrahydrofolates ; administration & dosage

OBJECTIVETo evaluate the efficacy and safety of the combination of oxaliplatin and ELF (VP16/CF/5-Fu) regimen in the treatment of patients with advanced gastric cancer.

METHODSOxaliplatin was given at a dose of 100 mg/m(2) i.v. 2 hours D1, calcium folinate (CF) 200 mg/m(2) i.v. 1/2 hour D1 approximately D3, 5-fluorouracil (5-Fu) 500 mg/m(2) i.v. 2 hours D1 approximately D3 and etoposide 100 mg/m(2) i.v. 3 hours D1 approximately D3. Cycles were repeated every 21 days. Efficacy and safety were evaluated every 2 cycles.

RESULTSSixty-nine patients were enrolled into the study. All cases were pathologically confirmed as gastric cancer (adenocarcinoma in 57 cases and signet ring cell carcinoma in 12 cases). 42 patients had newly diagnosed disease, and 27 patients had received previous chemotherapy. 62 patients were analyzed for response (7 complete responses and 25 partial responses) with total response rate 51.61%. The median time to progression was 5.7 months and the median overall survival was 9.2 months. The most common hematologic toxicities were anemia (29.0%), leucopenia (51.2%) and thrombocytopenia (21.2%). No grade 4 and grade 5 hematologic toxicities were observed. The most common non-hematologic toxicities were nausea (46.5%), vomiting (41.1%), peripheral sensory neuropathy (47.1%), and grade 2 alopecia (27.3%).

CONCLUSIONThis oxaliplatin combined with ELF regimen shows good efficacy and acceptable safety in advanced gastric cancer patients. It is worthy to be proved as a suitable alternative regimen in this indication.

Adenocarcinoma ; drug therapy ; pathology ; Adult ; Aged ; Anemia ; chemically induced ; Antineoplastic Agents ; administration & dosage ; adverse effects ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carcinoma, Signet Ring Cell ; drug therapy ; pathology ; Etoposide ; adverse effects ; therapeutic use ; Female ; Fluorouracil ; adverse effects ; therapeutic use ; Humans ; Leucovorin ; adverse effects ; therapeutic use ; Leukopenia ; chemically induced ; Levoleucovorin ; Male ; Middle Aged ; Nausea ; chemically induced ; Neoplasm Staging ; Organoplatinum Compounds ; administration & dosage ; adverse effects ; Remission Induction ; Stomach Neoplasms ; drug therapy ; pathology ; Survival Rate ; Thrombocytopenia ; chemically induced ; Vomiting ; chemically induced