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Biomedical subjects

M S Swanson

Publications and source records attributed to M S Swanson.

At least 19 recordsLinked to original sources
PubMed1992

Surgical treatment of obesity and its effect on diabetes: 10-y follow-up.

Since 1980 we have performed the identical Greenville gastric bypass (GGB) procedure on 479 morbidly obese patients with an acceptable morbidity and a mortality rate of 1.2%. The weight loss in the series was well maintained over the follow-up period of 10 y. The GGB can control non-insulin-dependent diabetes mellitus (NIDDM) in most patients. The group of 479 patients included 101 (21%) with NIDDM and another 62 (13%) who were glucose impaired. Of these 163 individuals, 141 reverted to normal and only 22 (5%) remained with inadequate control of their carbohydrate metabolism. Those patients who were older or whose diabetes was of longer duration were less likely to revert to normal values. The gastric bypass operation is an effective approach for the treatment of morbid obesity. Along with its control of weight, the operation also controls the hyperglycemia, hyperinsulinemia, and insulin resistance of the majority of patients with either glucose impairment or frank NIDDM.

Adult↗
PubMed1992

SPT4, SPT5 and SPT6 interactions: effects on transcription and viability in Saccharomyces cerevisiae.

The SPT4, SPT5 and SPT6 genes of Saccharomyces cerevisiae were identified originally by mutations that suppress delta insertion mutations at HIS4 and LYS2. Subsequent analysis has demonstrated that spt4, spt5 and spt6 mutations confer similar pleiotropic phenotypes. They suppress delta insertion mutations by altering transcription and are believed to be required for normal transcription of several other loci. We have now analyzed interactions between SPT4, SPT5 and SPT6. First, the combination of mutations in any two of these three genes causes lethality in haploids. Second, some recessive mutations in different members of this set fail to complement each other. Third, mutations in all three genes alter transcription in similar ways. Finally, the results of coimmunoprecipitation experiments demonstrate that at least the SPT5 and SPT6 proteins interact physically. Taken together, these genetic and biochemical results indicate that SPT4, SPT5 and SPT6 function together in a transcriptional process that is essential for viability in yeast.

Chromosomal Proteins, Non-Histone↗
PubMed1992

Is type II diabetes mellitus (NIDDM) a surgical disease?

Since February 1, 1980, 515 morbidly obese patients have undergone the Greenville gastric bypass (GGB) operation. Of these, 212 (41.2%) were euglycemic, 288 (55.9%) were either diabetic or had glucose intolerance, and 15 (2.9%) were unable to complete the evaluation. After the operation, only 30 (5.8%) patients remained diabetic (and 20 of these improved), 457 (88.7%) became and have remained euglycemic, and inadequate data prevented classification of the other 28 (5.4%). The patients who failed to return to normal glucose values were older and their diabetes was of longer duration than those who did. The effect of the GGB was not only limited to the correction of abnormal glucose levels. The GGB also corrected the abnormal levels of fasting insulin and glycosylated hemoglobin in a cohort of 52 consecutive severely obese patients with non-insulin-dependent diabetes. The GGB effectively controls weight. If morbid obesity is defined as 100 pounds over ideal body weight, 89% of the patients are no longer "morbidly" obese within 2 years. In most patients, the control of the weight has been well maintained during the 11 years of follow-up; most of the upward creep in weight of 20.8% between 24 and 132 months was from the 49 (9.5%) patients who had staple line breakdowns between the large and small gastric pouches. Non-insulin-dependent diabetes, previously considered a chronic unrelenting disease, can be controlled in the severely obese by the gastric bypass. Whether the correction of glucose metabolism affects the complications of diabetes is unknown. Whether the gastric bypass should be considered for patients with advanced non-insulin-dependent diabetes but who are not severely obese deserves consideration. The GGB has an unacceptably high rate of staple line failure. Accordingly, the authors have recently changed their procedure to one that divides the stomach rather than partitions it with staples.

Adolescent↗
PubMed1991

In vivo detection of snRNP-rich organelles in the nuclei of mammalian cells.

The in vivo distribution of snRNPs has been analysed by microinjecting fluorochrome-labelled antisense probes into the nuclei of live HeLa and 3T3 cells. Probes for U2 and U5 snRNAs specifically label the same discrete nuclear foci while a probe for U1 snRNA shows widespread nucleoplasmic labelling, excluding nucleoli, in addition to labelling foci. A probe for U3 snRNA specifically labels nucleoli. These in vivo data confirm that mammalian cells have nuclear foci which contain spliceosomal snRNPs. Co-localization studies, both in vivo and in situ, demonstrate that the spliceosomal snRNAs are present in the same nuclear foci. These foci are also stained by antibodies which recognize snRNP proteins, m3G-cap structures and the splicing factor U2AF but are not stained by anti-SC-35 or anti-La antibodies. U1 snRNP and the splicing factor U2AF closely co-localize in the nucleus, both before and after actinomycin D treatment, suggesting that they may both be part of the same complex in vivo.

Animals↗
PubMed1991

Long-term studies of mental health after the Greenville gastric bypass operation for morbid obesity.

From February 1, 1980, to May 1, 1989, 462 patients underwent the Greenville gastric bypass at the East Carolina University School of Medicine. The operation effectively maintained satisfactory weight loss after 9 years (mean weight preoperatively, 293 lbs; at 24 months, 179 lbs; at 96 months, 194 lbs). The gastric bypass favorably affected non-insulin-dependent diabetes, hypertension, and physical and role functioning. In the most recent 157 patients, our studies were extended to study the effects of the gastric bypass on mental health. The significant improvements in mental health indices that were observed 6 and 12 months after surgery eroded by the end of 2 years. This return of the mental health indices to the preoperative status, plus the late occurrence of 3 suicides and 2 deaths from alcohol abuse among the total 462 patients, suggest that long-term follow-up and continued emotional support are essential ingredients for successful bariatric surgery.

Adult↗
PubMed1991

The SNF2, SNF5 and SNF6 genes are required for Ty transcription in Saccharomyces cerevisiae.

The Saccharomyces cerevisiae SNF2, SNF5 and SNF6 genes were initially identified as genes required for expression of SUC2 and other glucose repressible genes. The Suc- defect in all three of these classes of mutants is suppressed by mutations in the SPT6 gene. Since mutations in SPT6 had also been identified as suppressors of Ty and solo delta insertion mutations at the HIS4 and LYS2 loci, we have examined Ty transcription in snf2, snf5 and snf6 mutants and have found that Ty transcription is abolished or greatly reduced. The snf2, snf5 and snf6 defect for Ty transcription, like the defect for SUC2 transcription, is suppressed by spt6 mutations. In contrast to other mutations that abolish or greatly reduce Ty transcription (in the SPT3, SPT7 and SPT8 genes), mutations in these SNF genes do not cause suppression of insertion mutations. This result suggests that the SNF2, SNF5 and SNF6 gene products act by a distinct mechanism from the SPT3, SPT7 and SPT8 gene products to promote transcription of Ty elements. This result also suggests that a reduction of Ty transcription is not always sufficient for activation of adjacent gene expression.

Blotting, Northern↗
PubMed1991

Extended storage of platelets in an artificial medium with the platelet activation inhibitors prostaglandin E1 and theophylline.

The addition of platelet activation inhibitors to the anticoagulant and the replacement of plasma with a fortified electrolyte medium have been shown separately in previous work to improve the storage of platelets during a 2-week period. In the present study, we have combined these strategies to investigate whether a synergistic improvement could be obtained. A total of 85 concentrates was studied with 300 nM prostaglandin E1 (PGE1) and 1.9 mM theophylline added to the whole blood, platelet-rich plasma (PRP), and/or the storage medium during the preparation of platelet concentrates. In vitro markers of platelet aggregation, respiration, and cell integrity were measured over a 20-day storage period and evaluated in an analysis of variance. We found that a single-step addition of PGE1 and theophylline to the PRP prior to centrifugation was not sufficient in terms of preventing a rapid fall in pH, rise in pO2, fall in pCO2, loss of hypotonic shock response, and loss of aggregation response, compared to the addition of the inhibitors to the storage medium used to resuspend the platelet pellet. Factorial analysis showed that a reduction in the surface-to-volume ratio of the storage container further improved the maintenance of platelet respiration and, for three in vitro markers (hypotonic shock response, released lactic dehydrogenase, and surface glycoprotein Ib levels) displayed an interactive effect with the inhibitors. The addition of protease inhibitors to the formulation of PGE1 and theophylline showed further improvement in several markers. These findings demonstrate the possibility of preserving platelets for 15-20 days with the synergistic effects of activation inhibitors and an electrolyte storage medium fortified with citrate, buffers, and dextrose.(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗
PubMed1991

SPT5, an essential gene important for normal transcription in Saccharomyces cerevisiae, encodes an acidic nuclear protein with a carboxy-terminal repeat.

Mutations in the SPT5 gene of Saccharomyces cerevisiae were isolated previously as suppressors of delta insertion mutations at HIS4 and LYS2. In this study we have shown that spt5 mutations suppress the his4-912 delta and lys2-128 delta alleles by altering transcription. We cloned the SPT5 gene and found that either an increase or a decrease in the copy number of the wild-type SPT5 gene caused an Spt- phenotype. Construction and analysis of an spt5 null mutation demonstrated that SPT5 is essential for growth, suggesting that SPT5 may be required for normal transcription of a large number of genes. The SPT5 DNA sequence was determined; it predicted a 116-kDa protein with an extremely acidic amino terminus and a novel six-amino-acid repeat at the carboxy terminus (consensus = S-T/A-W-G-G-A/Q). By indirect immunofluorescence microscopy we showed that a bifunctional SPT5-beta-galactosidase protein was located in the yeast nucleus. This molecular analysis of the SPT5 gene revealed a number of interesting similarities to the previously characterized SPT6 gene of S. cerevisiae. These results suggest that SPT5 and SPT6 act in a related fashion to influence essential transcriptional processes in S. cerevisiae.

Alleles↗
PubMed1990

The asymptomatic patient with suspected myocardial contusion.

Diagnostic criteria and guidelines for hospital admission for suspected myocardial contusion (MCC) remain unclear. This study defines and examines the clinical sequelae of patients admitted with a suspicion of MCC. Criteria for observation following isolated, minor blunt chest trauma are suggested. Hospital and trauma registry records of patients admitted over a 33-month period with suspected MCC were reviewed. Conventional evaluation criteria, cardiac-related complications, and associated injuries were analyzed for 524 patients. Twenty-eight cardiac-related complications occurred in 27 of 524 patients (5%). These complications included 23 dysrhythmias, 3 infarctions, and 2 pericardial effusions. There were 23 patients with abnormal admission electrocardiograms and 4 with normal ones. Of the latter, one patient developed dysrhythmia 4 hours after admission, and three had other major multi-system injuries requiring admission to the intensive care unit. The overall incidence of cardiac-related complications in minimally injured patients was 0.1%. There were no complications in patients with isolated chest wall contusions, a normal admission electrocardiogram, and a normal rhythm at 4 hours. There was no significant association between creatine phosphokinase isoenzymes or echocardiogram and cardiac-related complications. The complete absence of significant cardiac sequelae in patients with isolated chest wall contusion, normal admission and 4-hour electrocardiograms, and no other associated major injuries suggests that these patients need not be admitted.

Adult↗
PubMed1990

SPT6, an essential gene that affects transcription in Saccharomyces cerevisiae, encodes a nuclear protein with an extremely acidic amino terminus.

SPT6 is an essential gene of Saccharomyces cerevisiae that appears to play a role in transcription. Mutations in the SPT6 (SSN20, CRE2) gene suppress delta insertion mutations in the 5' regions of HIS4 and LYS2 and mutations in cis- and/or trans-acting elements that are required for expression of SUC2 and ADH2. We report here that SPT6 encodes a 170-kilodalton highly charged protein with an extremely acidic amino terminus. By use of an epitope-tagged SPT6 protein, we have determined by indirect immunofluorescence that the SPT6 protein is located in the nucleus.

Amino Acid Sequence↗
PubMed1989

Absence of luminal intrinsic factor after gastric bypass surgery for morbid obesity.

Abnormally low serum cobalamin levels (less than 180 pg/ml) have been observed in 154 of 429 patients (36%) at an average of 22 months (range 3-64 months) after gastric bypass surgery for morbid obesity. Twenty-four patients underwent a Schilling test and retrograde endoscopy of the bypassed gastric segment to determine the presence of intrinsic factor (IF) in gastric aspirates and in mucosal biopsies at 22 +/- 4 months after surgery. Five patients had a normal cobalamin level (405 +/- 44 pg/ml), and gastric juice intrinsic factor was present in three of them (11 +/- 7 ng/ml). Nineteen patients had a low cobalamin level (113 +/- 8 pg/ml), and gastric juice IF was found in only two subjects of this group (10 ng/ml each). Basal gastric juice IF concentration of healthy control subjects was 24 +/- 5 ng/ml. Schilling test results were normal in all five patients of the first group and in only nine patients of the group with cobalamin deficiency after surgery. To assess whether IF was present within the parietal cells of subjects with absent luminal IF, we studied gastric biopsy material of 14 patients using a well-characterized indirect immunoperoxidase method. IF was identified in fundic mucosal biopsy specimens of all 14 patients with absent gastric juice IF. We conclude that cobalamin deficiency occurs in a significant number of patients after gastric bypass and is associated with absence of gastric juice IF. We propose that this abnormality might be caused by inadequate secretion of IF from the bypassed stomach.

Adult↗
PubMed1989

Primary structures of the heterogeneous nuclear ribonucleoprotein A2, B1, and C2 proteins: a diversity of RNA binding proteins is generated by small peptide inserts.

We have isolated cDNAs for the major heterogeneous nuclear ribonucleoprotein (hnRNP) A2, B1, and C2 proteins and determined their nucleotide and deduced amino acid sequences. The A2 and B1 cDNAs are identical except for a 36-nucleotide in-frame insert in B1. Similarly, the sequence of the C2 protein cDNA is related to that of C1 in that C2 contains an extra 39 in-frame nucleotides. Therefore, the B1 amino acid sequence is identical to A2 except for the insertion of 12 amino acids near its amino terminus, and C1 and C2 are also identical to each other except for an extra 13 amino acids near the middle of C2. All three proteins are members of a large family of RNA binding proteins that contain the consensus sequence-type RNA binding domain (CS-RBD). The A2 and B1 proteins have a modular structure similar to that of the hnRNP protein A1: they contain two CS-RBDs and a glycine-rich auxiliary domain at the carboxyl terminus. The CS-RBDs of A2 and B1 have approximately 80% amino acid identity with those of A1, whereas the glycine-rich auxiliary domain is considerably more divergent with less than 30% of the amino acids being identical. These findings indicate that the addition of small peptides, probably by alternative pre-mRNA splicing, generates some of the diversity apparent among hnRNP proteins.

Amino Acid Sequence↗
PubMed1989

A novel heterogeneous nuclear RNP protein with a unique distribution on nascent transcripts.

Immediately after the initiation of transcription in eukaryotes, nascent RNA polymerase II transcripts are bound by nuclear proteins resulting in the formation of heterogeneous nuclear ribonucleoprotein (hnRNP) complexes. hnRNP complexes from HeLa cell nuclei contain greater than 20 major proteins in the molecular mass range of 34,000-120,000 D. Among these are the previously described A, B, and C groups of proteins (34,000-43,000 D) and several larger, and as yet uncharacterized, proteins. Here we describe the isolation and characterization of a novel hnRNP protein termed the L protein (64-68 kD by mobility in SDS-polyacrylamide gels). Although L is a bona fide component of hnRNP complexes, it also appears to be a different type of hnRNP protein from those previously characterized. A considerable amount of L is found outside hnRNP complexes, and monoclonal antibodies to the L protein also strongly stain unidentified discrete nonnucleolar structures, in addition to nucleoplasm, in HeLa cell nuclei. Interestingly, the same antibodies stain the majority of nonnucleolar nascent transcripts from the loops of lampbrush chromosomes in the newt, but the most intense staining is localized to the landmark giant loops. The L protein is the first protein of giant loops identified so far, and antibodies to it thus provide a useful tool with which to study these unique RNAs. In addition, isolation and sequencing of cDNA clones for the L protein from human cells predicts a glycine- and proline-rich protein of 60,187 D, which contains two 80 amino acid segments only distantly related to the RNP consensus sequence-type RNA-binding domain. The L protein, therefore, is a new type of hnRNP protein.

Amino Acid Sequence↗
PubMed1988

Translocation and rearrangement of myeloperoxidase gene in acute promyelocytic leukemia.

Acute promyelocytic leukemia (subtype M3) is characterized by malignant promyelocytes exhibiting an abundance of abnormally large or aberrant primary granules. Myeloperoxidase (MPO) activity of these azurophilic granules, as assessed by cytochemical staining, is unusually intense. In addition, M3 is universally associated with a chromosomal translocation, t(15;17)(q22;q11.2). In this report, the MPO gene was localized to human chromosome 17 (q12-q21), the region of the breakpoint on chromosome 17 in the t(15;17), by somatic cell hybrid analysis and in situ chromosomal hybridization. By means of MPO complementary DNA clones for in situ hybridization and Southern blot analysis, the effect of this specific translocation on the MPO gene was examined. In all cases of M3 examined, MPO is translocated to chromosome 15. Genomic blot analyses indicate rearrangement of MPO in leukemia cells of two of four cases examined. These findings suggest that MPO may be pivotal in the pathogenesis of acute promyelocytic leukemia.

Bone Marrow↗