Beta-globin gene cluster haplotypes in sickle cell patients from southwest Iran.

Sickle cell anemia in Iran is accompanied by a high level of HbF and mild clinical presentation. Here we report haplotypes of the beta gene cluster found in 81 randomly selected sickle cell patients, including 47 sickle cell anemia (SS), 17 sickle cell trait (AS), and 17 sickle/thalassemia (S/thal) from southwest Iran. We found all five common typical haplotypes as well as five atypical haplotypes in our patients. Except for four patients with homozygous Benin haplotype, none of the other African typical haplotypes were found in a homozygous state. Arab-Indian was found to be the most prevalent haplotype in the study population. This haplotype accounted for 51.1% as the homozygous form in SS patients, where 69.1% of chromosomes in these patients had the Arab-Indian haplotype. Bantu A2 was the second most prevalent haplotype among all patients. The mean %HbF in SS patients was 27.83 and in the homozygous Arab-Indian haplotype it was still higher (30.40%), while in AS patients the %HbF was only 1.20. The high %Ggamma chain (71.81) in the Arab-Indian homozygous haplotype was concomitant with the presence of an Xmn I site in both chromosomes. The presence of the Arab-Indian haplotype as the predominant haplotype might be suggestive of a gene flow to/from Saudi Arabia or India. More haplotype investigations of a normal population can clarify the high incidence of Bantu A2 haplotype in our population.

Immunoperoxidase study in alpha-chain disease.

Peroxidase-antiperoxidase technique was applied to search for the presence of alpha-chain protein in cells of the infiltrate from six cases of alpha-chain disease (one immunoblastic sarcoma and five plasmacytosis cases). Cases of poorly differentiated lymphocytic and Burkitt's type lymphomas, IgA myeloma, and tuberculous enteritis served as controls. Infiltrate cells from alpha-chain disease showed heavy and diffuse staining with anti-alpha-chain and not light-chain antisera. The myeloma reacted with both anti-alpha and anti-kappa antisera. Plasma cells from tuberculous enteritis showed variable staining with anti-heavy- and anti-light-chain antisera, while control lymphomas did not stain at all. We suggest that immunoenzyme histochemistry is a useful tool in demonstrating intracellular alpha-chain protein.

Acute leukemia in adults.

Prospective data on 40 new cases of adult onset (greater than 15 years of age) acute leukemia is presented. Acute lymphoblastic leukemia (ALL) accounted for more than half of all the acute leukemias and represented 75% of the acute leukemias in the 15--25 years. The reasons for this finding remain to be explained. age group. The mean leukocyte count was significantly higher in the ALL group as compared to acute myelogenous leukemia (AML) patients (111.7 x 103 + 26.3 x 103 versus 19.3 x 103 +/- 6.1 x 103, respectively). Thrombocytopenia, anemia and hemorrhagic signs including petechiae, ecchymoses and gum bleeding were more common in the AML group. This study verifies our clinical impression that ALL is more frequent than AML among our adult patients below the age of 25 years. The reasons for this finding remain to be explained.

Primary upper small-intestinal lymphoma and alpha-chain disease. Report of 10 cases emphasizing pathological aspects.

Ten cases of primary upper small-intestinal lymphoma associated with alpha-chain protein in serum were discovered in a prospective study of the sera of patients with immunoproliferative small-intestinal disease (IPSID). Patients were mostly young males presenting with abdominal pain, weight loss, and diarrhea and showing laboratory evidence of carbohydrate, fat, and vitamin B12 malabsorption and hypoalbuminemia. The more frequently encountered pathologic abnormality was a diffusely nodular jejunal mucosa produced by a plasmacytic infiltrate of variable cell maturity involving a varible depth of small bowel wall with or without involvement of the mesenteric or para-aortic-lymph node complex and, in one instance, the liver. A less frequent picture included circumferential ulcerative and constrictive transmural tumors of the upper small intestine produced by a malignant lymphoma with involvement of abdominal lymph nodes. Small-intestinal surface epithelial abnormalities, a dense mantle of mature plasma cells overlying the lymphoma, a pronounced follicular lymphoid hyperplasia adjacent to and at distances from the lymphoma were other features of note in our IPSID cases associated with alpha-chain protein.

Alpha heavy-chain disease in southern Iran.

A prospective study of 32 patients with primary upper small intestinal lymphoma in our region revealed 10 cases of alpha heavy-chain disease. Patients were mostly in the second and third decades of life and males predominated. Weight loss, diarrhea, and abdominal pain were the most common complaints and clubbing the most frequent physical findings. Laboratory tests revealed a malabsorption pattern on intestinal x-rays, and malabsorption of xylose, fat, and vitamin B12 was frequently noted. Dense plasmacytic infiltrate of the lamina propria of small bowel was the most frequent pathologic finding while true neoplasm of the lymphoid system (ie, immunoblastic sarcoma) was encountered in 20% of the cases.

Mild sickle-cell anaemia in Iran associated with high levels of fetal haemoglobin.

Sixteen subjects, with sickle-cell anaemia, all Iranians (ages 3 to 56 years), with very mild symptomatology are reported. Some of the subjects had been totally asymptomatic. Splenomegaly was noted in 9 cases. There was an increase in the mean level of fetal haemoglobin (18%); this is the probable explanation for the mild phenotype. In 29 subjects with sickle-cell trait, the level of HbF was also significantly raised as compared with normal (1-6% vs. 0-6%). The mechanism of increased synthesis of HbF is unknown. The findings are similar to those reported in the Shiite Moslems of Saudi Arabia suggesting that in these populations there is a genetically-determined ability to produce high levels of Hb F in the presence of the sickle-cell gene.

Combined zinc and iron compared with iron supplementation of diets of 6- to 12-year old village schoolchildren in southern Iran.

The effects of supplementation of the diets of 6- to 12-year-old children in a village near Shiraz in Iran with zinc plus iron or iron alone, together with the indispensable amino acids in the form of egg white protein, vitamins, minerals, and corn oil have been evaluated. Initially 48 of 59 children had zinc concentrations below the minimum found in well-nourished persons. Eight months of supplementation with zinc plus iron (20 mg daily of elemental zinc as carbonate and 20 mg ferrous iron as fumarate) failed to stimulate growth or bone development or to bring about an increase in plasma zinc concentrations. However, supplementation with iron in the above amount was associated with an acceleration of growth in height and weight. The persistence of low concentrations of zinc in plasma and the failure of supplemental zinc to stimulate growth are attributed to the poor availability of both dietary and supplemental zinc resulting from sequestering action of fiber and phytate present in large amounts in the unleavened whole meal bread consumed by villagers. In addition, the results suggest that simultaneous administration of iron and zinc supplements may impair utilization of the metals.

The dependence of the hemoglobin (beta plus gamma)/alpha chain synthetic ratio on the degree of anemia in beta-thalassemia (38561).

The peripheral blood hemoglobin (beta plus gamma)/alpha chain synthetic ratio in three homozygous beta-thalassemic subjects was shown to increase towards unity as their hematocrits were raised by stepwise transfusion. The observation that the chain synthetic ratio can vary in a given individual is discussed in relation to current understanding about the regulation of hemoglobin synthesis.