Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined causes and hematological consequences of low serum cobalamin (vitamin B12) concentration in two representative population samples of 70-year-old (N = 293) and 75-year-old subjects (N = 486). Subjects with values below 130 pmol/liter (4.8% and 5.6%, respectively) were investigated with Schilling test, upper gastrointestinal endoscopy, determination of serum gastrin and group I pepsinogens, and bone marrow examination. Gastrointestinal abnormalities of etiologic significance were found in 26 of the 32 examined subjects: atrophy of the gastric body mucosa (N = 16, with pernicious anemia in six), partial gastrectomy (N = 6), and intestinal malabsorption (N = 4). Megaloblastic hematopoiesis was found in 10 individuals, four of whom had macrocytic anemia. Our results indicate that low serum cobalamin concentration in the elderly is usually a consequence of disease rather than of high age per se and that gastric mucosal atrophy is a major etiologic factor.
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PMID:Low serum cobalamin levels in a population study of 70- and 75-year-old subjects. Gastrointestinal causes and hematological effects. 271 46

Cobalamin (vitamin B12) is an essential nutrient derived exclusively from bacterial sources. It is an essential cofactor for three known enzymatic reactions. Untreated deficiency, caused by either the autoimmune disease pernicious anemia or nutritional lack, results in a macrocytic anemia and/or subacute combined degeneration of the spinal cord and is eventually fatal. Cobalamin in serum is bound to two proteins, transcobalamin and haptocorrin. The former is responsible for the essential delivery of cobalamin to most tissues. Inadequate tissue availability of cobalamin results in increased concentration of methylmalonic acid and homocyst(e)ine due to inhibition of methylmalonyl-CoA mutase and methionine synthase, respectively. Strict vegetarians have long been known to be at risk of cobalamin deficiency, which develops insidiously over many years. It is now clear that a significant number of the elderly and HIV-positive individuals are also at increased risk of deficiency. Any individual with reduced ability to split cobalamin from food-protein may also become deficient even though intrinsic factor is present. Diagnosis of cobalamin deficiency has frequently relied on total serum cobalamin and the Schilling test. Newer approaches such as analysis of methylmalonic acid, homocyst(e)ine, holotranscobalamin, anti-intrinsic factor antibodies, and serum gastrin may provide more cost-effective testing, as well as identify those with a covert deficiency.
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PMID:Cobalamin. 887 26

Iron deficiency is a known complication of achlorhydria and may precede the development of pernicious anemia. Among 160 patients with autoimmune gastritis identified by hypergastrinemia and strongly positive antiparietal antibodies, we explored the overlap between 83 subjects presenting with iron deficiency anemia (IDA), 48 with normocytic indices, and 29 with macrocytic anemia. Compared with macrocytic patients, patients with IDA were 21 years younger (41 +/- 15 years versus 62 +/- 15 years) and mostly women. All groups had a high prevalence of thyroid disease (20%) and diabetes (8%) suggestive of the autoimmune polyendocrine syndrome. Stratification by age cohorts from younger than 20 years to older than 60 years showed a regular and progressive increase in mean corpuscular volume (MCV) from 68 +/- 9 to 95 +/- 16 fl, serum ferritin levels from 4 +/- 2 to 37 +/- 41 microg/L, gastrin level from 166 +/- 118 to 382 +/- 299 pM/L (349 +/- 247 to 800 +/- 627 pg/mL), and a decrease in cobalamin level from 392 +/- 179 to 108 +/- 65 pg/mL. The prevalence of Helicobacter pylori infection was 87.5% at age younger than 20 years, 47% at age 20 to 40 years, 37.5% at 41 to 60 years, and 12.5% at age older than 60 years. These findings challenge the common notion that pernicious anemia is a disease of the elderly and imply a disease starting many years before the establishment of clinical cobalamin deficiency, by an autoimmune process likely triggered by H pylori.
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PMID:Variable hematologic presentation of autoimmune gastritis: age-related progression from iron deficiency to cobalamin depletion. 1700 59

Pernicious anemia is a megaloblastic anemia caused by vitamin B12 deficiency, and is the end-stage of autoimmune gastritis that typically affects persons older than 60 years. It is the most common cause of vitamin B12 deficiency. Pernicious anemia can also be diagnosed concurrently with other autoimmune diseases. We report the occurrence of megaloblastic anemia in a 22-year-old woman with chronic autoimmune thyroiditis for 10.5 years. Recently, she presented with microcytic anemia, and iron deficiency anemia was diagnosed initially. After administration of ferrous sulfate, macrocytic anemia was revealed and vitamin B12 deficiency was detected. Pernicious anemia was highly suspected because of the endoscopic finding of atrophic gastritis, and high titer of antigastric parietal cell antibody, as well as elevated serum gastrin level. After intramuscular injections of hydroxycobalamine 100 microg daily for 10 days, and monthly later, her blood counts returned to normal.
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PMID:Coexistence of megaloblastic anemia and iron deficiency anemia in a young woman with chronic lymphocytic thyroiditis. 1705 Jan 98

We report a case of multiple duodenal, pancreatic, and gastric carcinoids. A 67-year old woman was admitted to our hospital for treatment of a duodenal carcinoid. Laboratory tests revealed that the patient was associated with macrocytic anemia and hypergastrinemia, and type A gastritis was shown by gastrofiberscopy. During surgery, another tumor was incidentally found in the head of the pancreas. The tumors in the duodenum and pancreas were completely excised by pancreatoduodenectomy and immunohistologically diagnosed as gastrin-and serotonin-producing carcinoids, respectively. Pathological examination revealed that in addition to the grossly found carcinoids, there were subclinical carcinoids, one of which was an endocrine cell micronest, located in the stomach and duodenum. The tumors in the duodenum, pancreas, and stomach showed different characteristics from one another morphologically and immunochemically. Although no definitive evidence has been obtained, some sort of genetic anomaly may have been involved in this case, and hypergastrinemia due to duodenal gastrinoma may induce multiple gastric carcinoids.
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PMID:Multiple carcinoids in the duodenum, pancreas and stomach accompanied with type A gastritis: a case report. 1746 12

A 55-year-old female with a history of psychosis and rheumatoid arthritis was admitted to the hospital for fatigue and dizziness. At admission, macrocytic anemia, high serum lactic acid dehydrogenase (LDH) and gastrin concentrations, decreased serum vitamin B12 concentration, with macroovalocytes and poikilocytes in peripheral blood smear suggested the diagnosis of pernicious anemia. Indirect antiglobulin test (IAT) was negative. Surprisingly, treatment by vitamin B12 and folic acid administered for two weeks was ineffective and followed by transitory worsening of hemoglobin concentration on day 8. Repeat direct antiglobulin test (DAT) and IAT were positive. This immunotransfusion conversion, suggesting the presence of autoimmune hemolytic anemia, could be explained by change in the macroblastic erythrocyte population, i.e. emerging red cells with completely exposed membrane antigens due to vitamin B12 treatment and/or higher degree of dysregulation of the lymphocyte clone secreting erythrocyte autoantibodies. We proposed the coexistence of pernicious and autoimmune hemolytic anemia; therefore, methylprednisolone was added to vitamin B12 treatment. This therapy successfully improved hemoglobin and erythrocyte concentration. Although megaloblastic-pernicious anemia is a common disease, association of pernicious and autoimmune hemolytic anemia with two mechanisms of hemolysis (ineffective erythropoiesis and immune mechanism) is a rare condition, with only several dozens of cases described so far.
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PMID:Combined megaloblastic and immunohemolytic anemia associated--a case report. 1938 72

Pernicious anemia (PA) is a macrocytic anemia that is caused by vitamin B(12) deficiency, as a result of intrinsic factor deficiency. PA is associated with atrophic body gastritis (ABG), whose diagnosis is based on histological confirmation of gastric body atrophy. Serological markers that suggest oxyntic mucosa damage are increased fasting gastrin and decreased pepsinogen I. Without performing Schilling's test, intrinsic factor deficiency may not be proven, and intrinsic factor and parietal cell antibodies are useful surrogate markers of PA, with 73% sensitivity and 100% specificity. PA is mainly considered a disease of the elderly, but younger patients represent about 15% of patients. PA patients may seek medical advice due to symptoms related to anemia, such as weakness and asthenia. Less commonly, the disease is suspected to be caused by dyspepsia. PA is frequently associated with autoimmune thyroid disease (40%) and other autoimmune disorders, such as diabetes mellitus (10%), as part of the autoimmune polyendocrine syndrome. PA is the end-stage of ABG. Long-standing Helicobacter pylori infection probably plays a role in many patients with PA, in whom the active infectious process has been gradually replaced by an autoimmune disease that terminates in a burned-out infection and the irreversible destruction of the gastric body mucosa. Human leucocyte antigen-DR genotypes suggest a role for genetic susceptibility in PA. PA patients should be managed by cobalamin replacement treatment and monitoring for onset of iron deficiency. Moreover, they should be advised about possible gastrointestinal long-term consequences, such as gastric cancer and carcinoids.
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PMID:Pernicious anemia: new insights from a gastroenterological point of view. 2127 87

Pernicious anemia is a macrocytic anemia due to cobalamin deficiency, which is the result of intrinsic factor deficiency. Pernicious anemia is associated with atrophic body gastritis, whose diagnostic criteria are based on the histologic evidence of gastric body atrophy associated with hypochlorhydria. Serological markers suggesting the presence of oxyntic mucosa damage are increased levels of fasting gastrin and decreased levels of Pepsinogen I. Without the now obsolete Schilling's test, intrinsic factor deficiency may not be proven, and gastric intrinsic factor output after pentagastric stimulation has been proposed. Intrinsic factor autoantibodies are useful surrogate markers of pernicious anemia. The management of patients with pernicious anemia should focus on the life-long replacement treatment with cobalamin and the monitoring to early diagnose an eventual onset of iron deficiency. Moreover, these patients should be advised about possible gastrointestinal long-term consequences, such as gastric cancer and carcinoids.
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PMID:Diagnosis and management of pernicious anemia. 2194 76