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M Mittelman

Publications and source records attributed to M Mittelman.

At least 73 records · Page 4Linked to original sources
PubMed1992

[Unusual presentation of malignant melanoma of the small intestine].

2 patients with unusual presentations of malignant melanoma involving the small intestine, a 75-year-old woman and a 78-year-old man, are described. One underwent laparotomy for diagnosis and removal of a retroperitoneal mass, with no preoperative evidence of the primary disease. The other underwent emergency laparotomy for small bowel obstruction due to intussusception, which was found to result from a metastatic melanoma. A melanoma had been completely resected from the patient's thigh a month previously, but full investigation before the operation for intussusception failed to establish the diagnosis. Malignant melanoma tends to spread to the small intestine, but tumors of this organ are very rare. Preoperative diagnosis is important since it may improve the outcome of surgical intervention, as well as the prognosis in general.

Aged↗
PubMed1992

DNA sequence variation in a negative control region 5' to the beta-globin gene correlates with the phenotypic expression of the beta s mutation.

The clinical diversity of sickle cell anemia is strongly related to the degree of intracellular hemoglobin S (Hb S) polymerization, which in turn is dependent on the intracellular concentration of Hb S. We have recently defined a region of DNA approximately 500 bp 5' to the human beta-globin gene that acts as a silencer for the transcription of this gene and have shown that a polymorphism in this sequence is associated with a thalassemic phenotype of the beta-globin gene. In this work we have examined the correlation of DNA sequence polymorphisms in this silencer with binding of a previously identified putative repressor protein, BP1, and with the expression of Hb S in individuals heterozygous for the beta s allele. It was found that specific configurations of the motif, (AT)x(T)y, are homogeneous for the major haplotypes of the beta-globin gene cluster described on beta s chromosomes. Binding of BP1 was measured to DNA of three haplotypes: Indian, Benin, and Bantu. BP1 binds most tightly to DNA of the Indian haplotype, and these patients produce less beta s protein than Benin patients, whose DNA exhibits weaker affinity for BP1. Binding of BP1 is the weakest to DNA of the Bantu haplotype, which is associated with clinically more severe sickle cell symptoms. These data are consistent with the hypothesis that these polymorphisms may not be neutral and that the DNA sequence at this site may affect the expression of the beta s gene. Such an effect may be synergistic with other genetic variables, such as fetal hemoglobin levels, F-cell numbers, and the number of alpha-globin genes, in determining intracellular polymerization and, thus, the severity of the sickle cell syndromes.

Africa↗
PubMed1992

Binding of erythroid and non-erythroid nuclear proteins to the silencer of the human epsilon-globin-encoding gene.

To clarify the molecular mechanisms involved in the developmental control of hemoglobin-encoding genes we have been studying the expression of these genes in human cells in continuous culture. We have previously reported the presence of a transcriptional control element with the properties of a silencer extending from -392 to -177 bp relative to the cap site of the human epsilon-globin-encoding gene [Cao et al., Proc. Natl. Acad. Sci. USA 86 (1989) 5306-5309]. We also showed that this silencer has stronger inhibitory activity in HeLa cells, as compared to K562 human erythroleukemia cells. Using deletion mutants and cis-cloned synthetic oligodeoxyribonucleotides in transient expression assays, nucleotide sequences responsible for this effect have now been further delimited to 44 bp located from -294 to -251 bp. Gel electrophoresis mobility shift assays and DNaseI footprinting assays demonstrate that these negative regulatory sequences are recognized differently by proteins present in nuclear extracts obtained from HeLa and K562 cells. Two binding proteins are detected in K562 nuclear extracts, while only one is found in extracts from HeLa cells. Possible mechanisms by which these proteins may regulate transcription of the epsilon-globin-encoding gene in erythroid and non-erythroid cells are discussed.

Base Sequence↗
PubMed1992

Thromboembolic complications in beta thalassemia major.

Thromboembolic complications in beta-thalassemia major have seldom been reported and their association with risk factors such as left ventricular failure and postsplenectomy thrombocytosis has remained speculative. In this report we describe 4 patients with unusual thromboembolic manifestations: recurrent arterial occlusion, recurrent pulmonary thromboembolism, venous thrombosis and a fatal cerebrovascular event. Although in all patients both risk factors were present, the precise causes for their thromboembolic complications were not identified. In 1 patient, however, a marked increase in hematocrit following blood transfusion resulted, in all likelihood, in a fatal cerebrovascular infarction. We suspect that these patients (constituting 4% of our beta-thalassemic group) represent a subset of those with high susceptibility to both arterial and venous thromboembolic complications.

Adolescent↗
PubMed1992

Myelokathexis and monocytosis in a patient with gastric cancer.

A 66-year-old patient developed leukocytosis, neutrophilia and monocytosis following surgery for gastric carcinoma. The polymorphonuclear cells showed a marked shift to the right and abnormally hypersegmented or pyknotic nuclei, whereas the monocytes were vacuolized. The bone marrow was hypercellular with an increased number of multilobed polymorphonuclear cells. This myeloid cell defect is compatible with the nuclear abnormalities described as myelokathexis. The combination of the nuclear abnormalities of the polymorphonuclear cells with persistent monocytosis suggests the possibility of a paraneoplastic variant of myelodysplasia.

Aged↗
PubMed1991

Increased protein binding to a -530 mutation of the human beta-globin gene associated with decreased beta-globin synthesis.

Although some cases of the syndrome of hereditary persistence of fetal hemoglobin (HPFH) have been correlated with mutations causing a change in the binding of trans-acting factors to DNA sequences flanking the gamma-globin gene, this mechanism has not been described in beta-thalassemias upstream of the canonical promoter of the beta-globin gene. In this report we describe such a change in binding of a protein that may explain a silent carrier phenotype of beta-thalassemia. We have previously demonstrated the binding of a protein (BP1) derived from a nuclear extract of human K562 cells to DNA 5' to the human beta-globin gene in a region having a negative regulatory function. The binding of BP1 in this region can be detected by DNAse I footprinting and by gel mobility shift analysis. We have now compared binding of BP1 to the normal sequence and a mutated sequence (+ATA/-T at -530 bp from the cap site) from the silent carrier of beta-thalassemia. Using mobility shift assays we show that BP1 binds about nine times more strongly to the mutated sequence than the normal sequence. These results suggest the possibility that the decreased expression of the beta-globin gene exhibited by the carrier may be due, at least in part, to tighter binding of a protein which functions as a negative control element or repressor.

Base Sequence↗
PubMed1991

Primary flight training performance of student naval aviators with vision waivers.

Performance was studied for student naval aviators with waivers for defective uncorrected distance visual acuity who underwent primary flight training at NAS Whiting Field, FL, for fiscal year 1987 (cases = 45). Outcome variables were completion rate, primary flight training grades and flight hours. Controls for completion rate were all other students during that period (N = 1443). For training grades and hours, controls were selected who completed the same training squadron within 1 month of the case. Two controls were selected who progressed to the jet pipeline, with two additional controls selected who progressed to the same pipeline as the cases, either maritime/patrol or helicopter (controls = 180). Results demonstrated the cases were significantly more likely to complete training (p = 0.029), but not significantly different in primary flight grades or hours. These results suggest student naval aviators on vision waivers were competitive with their contemporaries.

Aviation↗
PubMed1989

A common protein binds to two silencers 5' to the human beta-globin gene.

The temporal sequence of expression of human globin genes during development suggests precise regulation of these genes. Recent studies have characterized a number of DNA sequences within or flanking the human beta-globin gene which are important in its regulation and several proteins which bind to these sequences have been identified. We have found two proteins which bind 5' to the human beta-globin gene. One of these proteins, which we designate BP1, binds to two sequences, one between -550 and -527 bp relative to the cap site, the other between -302 and -294 bp. A second protein, BP2, binds to sequences between -275 and -263 bp. The binding sites for both BP1 and BP2 are in two regions which function as silencers in a transient expression assay using the human erythroleukemia cell line K562. These results and others presented here suggest that BP1 may act as a repressor protein. Negative regulation seems to be an important component of tissue and developmental specific globin gene regulation.

Animals↗
PubMed1989

Trans-activation of human globin genes by HTLV-I tax1.

We studied the effects of a known retroviral trans-activating factor, HTLV-I tax1, on transcription of human globin genes. Transfection of HeLa cells by the cloned tax1 gene stimulated activity of both the beta- and epsilon-globin promoters approximately 20-fold, as measured by chloramphenicol acetyl transferase (CAT) assays. Studies of promoter 5'-deletion mutants revealed that the trans-activation response required only 185 base pairs (bp) of beta-globin 5'-flanking sequence or 177 bp of epsilon-globin 5' flanking sequence. These promoter regions contain either two (for beta) or three (for epsilon) copies of the pentanucleotide sequence CTGAC, which is characteristic of previously described tax1-responsive promoters. We also stably transfected tax1 into the erythroid cell line K562. Transfectants expressing tax1 showed increased transcription of epsilon-, gamma-, zeta-, and alpha-globins. This indicates that tax1 can stimulate transcription of globin genes in their native chromosomal location. This was confirmed by measurements of increases in intracellular hemoglobin as determined by an increased percentage of cells staining with benzidine and by spectrophotometric measurements of hemoglobin. The observed trans-activation of globin genes by tax1 may provide insight into normal regulation of globin genes by clarifying cis regulatory sequences. Furthermore, it suggests that the trans-acting effects of tax1 on heterologous genes are more widespread than was previously appreciated.

Base Sequence↗
PubMed1988

Sunbed lentigines.

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Biotechnology↗
PubMed1988

Multiple paraphilic diagnoses among sex offenders.

The psychiatric literature suggests that paraphiliacs can be expected to participate in only one type of deviant sexual behavior. Using self-reports gathered with assured confidentiality from 561 nonincarcerated paraphiliacs, we discovered that most paraphiliacs have had significant experience with as many as ten different types of deviant sexual behavior without regard, in many cases, to gender, age, and familial relationship of the victim. The relevance of these findings to our understanding of paraphiliacs and their treatment is discussed.

Adolescent↗