Mouse globin system: a functional and evolutionary analysis.

Structural and functional analysis of the mouse alpha-globin and beta-globin genes reveals that the globin genes are encoded in discontinous bits of coding information and that each gene locus is much more complex than was originally supposed. Each seems to consist of an array of several authentic genes as well as several apparently inactive pseudogenes. Comparison of the sequences of some of these genes to one another indicates that chromosomal DNA is a dynamic structure. Flanking and intervening sequences change in two ways: quickly, by duplication and extensive insertions and deletions, and slowly, by point mutation. Active coding sequences are usually limited to the slower mode of evolution. In addition to identifying fast and slow modes of evolution, it has also been possible to test the function of several signals that surround these genes and to identify those that appear to play a role in gene expression.

Dorsal sympathectomy for hyperhidrosis--the posterior paravertebral approach.

Definitive therapy for hyperhidrosis is sympathectomy. The authors have used a posterior approach to perform 36 dorsal sympathectomies for upper extremity hyperhidrosis in 18 patients (12 female, 6 male). All 18 patients suffered from excessive sweating of the upper extremity (17 palmar, 1 axillary) that caused significant psychological and occupational problems. Eleven patients (61.1%) had lower extremity involvement as well. For all 18 patients conservative medical treatment had failed. Bilateral operations were performed, via a posterior extrapleural approach, through the bed of the third rib. All 36 limbs were relieved of excess sweating. There were no deaths and only two minor wound complications. In no patient did Horner's syndrome develop. Long-term follow-up did not reveal any recurrence of hyperhidrosis. Two patients did complain of compensatory hyperhidrosis of the lower extremities. Dorsal sympathectomy was effective in all of the patients with upper extremity hyperhidrosis in this series. The posterior approach is technically simple, allows simultaneous bilateral operations, and is associated with only infrequent minor complications.

Interruption of the vena cava by means of the Greenfield filter: expanding the indications.

Between 1978 and 1985, 88 patients underwent insertion of the Greenfield vena cava filter. In 21 of the 88 patients (23.9%) the filter was inserted prophylactically. Sixteen of the 21 prophylactic insertions were performed before total joint replacement in patients with a history of venous thromboembolism. Operative morbidity (4.6%) was minor and occurred only early in the series. The operative mortality rate was 4.6%. None of the deaths were related to filter insertion or pulmonary embolism. Follow-up in 65 patients (73.9%) ranged from 1 to 60 months (mean, 16.4 months). Leg edema developed in 9.2% (6/65), stasis ulceration in 3.1% (2/65), caval occlusion in 7.5% (3/40), and recurrent nonfatal embolism in 3.1% (2/65) of the patients. In the patients who received prophylactic filters before total joint replacement, there were no filter-related complications or episodes of pulmonary embolism. This series confirms the safety and effectiveness of the Greenfield filter and suggests that the indications for its use might be liberalized to include prophylactic insertion of the device in certain high-risk patients.

Arterial embolectomy: a 34-year experience with 400 cases.

A series of 400 peripheral arterial embolectomies performed in 326 patients over a 34-year period is presented. Operative mortality was 11.0 per cent overall and 10.0 per cent in patients after the introduction and use of Fogarty catheters. The plateau in mortality is related to the association with serious underlying cardiac disease. The amputation rate was 9.5 per cent, with a corresponding 90.5 per cent limb salvage rate. Cardiac disease was the most common cause of emboli and was responsible for the majority of deaths. Mortality was considerably higher in patients with aortic and iliac emboli and in patients with recent myocardial infarcts. Amputation rates were higher with femoral and popliteal emboli and correlated directly with the time delay from onset of symptoms to performance of embolectomy. Higher amputation rates in the second half of the series are related to liberalization of the indications for embolectomy. Prompt operative management of patients with peripheral arterial emboli remains the treatment of choice. Low mortality and amputation rates can be achieved with early embolectomy and routine use of heparin.

Bovine pericardial patch angioplasty in carotid endarterectomy.

Patch angioplasty during carotid endarterectomy (CEA) has been shown to reduce the incidence of both early and late complications. Controversy continues, however, over the ideal patch material. Bovine pericardium (Vascu-Guard Biovascular Inc., Saint Paul, MN) offers an attractive alternative to other patch materials because of its handling and suturing characteristics that are similar to that of autogenous material. This study examines the perioperative and midterm results of bovine pericardial patch angioplasty during CEA. We studied 112 patients who underwent 129 CEAs with bovine pericardial patch angioplasty during an 18-month period. Data were collected regarding demographics, operative indications, perioperative complications, and the occurrence of late adverse outcomes based primarily on follow-up arterial duplex studies. Among this group there were 63 male (56%) and 49 female (44%) patients whose mean age was 71.8 +/- 9.1 years. In these patients there was the typical distribution of atherosclerotic risk factors. Seventy-four patients (66%) had symptomatic disease preoperatively and the remaining 38 patients (34%) were asymptomatic. Temporary cranial nerve palsy occurred in three patients (2%). There were no perioperative strokes, acute occlusions, bleeding episodes requiring reoperation, or deaths. The patients were followed up to 54 months postoperatively with a mean follow-up time of 41.7 +/- 4.4 months. During this period two patients (2%) developed three significant restenoses (70-99%). All required reoperation. There were no asymptomatic occlusions, infections, aneurysms, or rupture. These data demonstrate that bovine pericardial patch angioplasty during CEA is associated with a low incidence of both perioperative and midterm adverse outcomes.

Distinctive nucleotide sequences of promoters recognized by RNA polymerase containing a phage-coded "sigma-like" protein.

We report the nucleotide sequences of two promoters for bacteriophage SP01 "middle" genes. These promoters are recognized by a modified form of Bacillus subtilis RNA polymerase that contains a phage-coded "sigma-like" regulatory protein (gp28) in place of the bacterial sigma factor. Both promoters shared the identical hexanucleotide 5'A-G-G-A-G-A at about 35 base pairs preceding the start point of transcription and the identical heptanucleotide 5'-T-T-T-A-T-T-T (T is the thymine analog 5-hydroxymethyluracil in SP01 DNA) located about 10 base pairs preceding the transcriptional start point. The significance of these sequences in comparison with nucleotide sequences of promoters recognized by sigma-containing RNA polymerases is discussed.

Promoter recognition by phage SP01-modified RNA polymerase.

A modified form of Bacillus subtilis RNA polymerase containing a phage SP01-coded regulatory protein (the gene 28 product) selectively transcribes "middle" genes of the phage genome in vitro. In this paper, we identify a subset of restriction endonuclease fragments of SP01 DNA that promote specific transcription by the phage-modified polymerase. In the absence of nucleoside triphosphates, RNA polymerase containing the gene 28 protein selectively binds to these DNA fragments thereby forming stable binary complexes that can be isolated on nitrocellulose filters. In contrast, unmodified RNA polymerase containing sigma factor selectively binds to and transcribes a subset of phage DNA fragments that contain "early" sequences and that are in large part distinct from the fragments recognized by the phage-modified transcriptase. Our results strongly suggest that phage "early" and "middle" genes are transcribed from distinct promoters and that the RNA polymerase containing the gene 28 protein binds to sites that are located at or near promoters for SP01 "middle" genes.

Nucleotide sequence of a promoter recognized by Bacillus subtilis RNA polymerase.

We report the nucleotide sequence of a promoter recognized by RNA polymerase from the gram-positive bacterium Bacillus subtilis. This promoter, which was isolated from B. subtilis phage SP01 DNA, is homologous to promoters for Escherichia coli RNA polymerase; the sequences of the "-35 region" and the "Pribnow box" were 5'TTGACT and 5'CATAAT, respectively (T is the thymine analog 5-hydroxymethyluracil in SP01 DNA). These sequences each differed by only a single base pair from the preferred sequences for E. coli promoters. Not surprisingly, the SP01 promoter was actively transcribed in vitro by E. coli RNA Polymerase as well as by B. subtilis RNA polymerase.

In vitro transcription of normal, mutant, and truncated mouse alpha-globin genes.

We have transcribed various alpha-globin gene-containing templates by using a simplified in vitro system and have shown that the 5' end of each of the RNA polymerase II-specific transcripts corresponds to that of authentic alpha-globin mRNA. Using a truncated alpha-globin gene fragment, we then localized the promotor region of the adult alpha-globin gene to a 138-base-pair fragment of alpha-globin DNA, 141 nucleotides of which precede the initiation site. In contrast, when two naturally occurring alpha-globin gene mutants were tested as templates, no RNA polymerase II-dependent initiation was detected. Comparison of the nucleotide sequences of the normal and mutant alpha-globin genes has allowed us to focus upon nucleotide positions that might be essential for promoter activity.

The effect of 5-bromodeoxyuridine on the synthesis of nuclear and cytoplasmic DNA-binding proteins isolated from sea urchin embryos.

Newly synthesized DNA-binding proteins were isolated from the nuclei and, separately from, the cytoplasm of sea urchin mofula stage embryos. The presence of 5-bromodeoxyuridine during embryogenesis did not appear to alter the synthesis of either class of DNA-binding proteins. This result tends to argue that cell differentiation in early embryos is not regulated by differential synthesis of DNA-binding proteins. Sea urchin mofulae synthesize a broad range, by molecular weight, or cytoplasmic DNA-binding proteins which dissociate from sea urchin DNA-cellulose at relatively high salt concentrations (0.6-2.0 M NaCl). The most prominant of these apparently high-binding-affinity proteins has an approximate molecular weight of 33,000.

Restriction cleavage map of SP01 DNA: general location of early, middle, and late genes.

A detailed restriction endonuclease map for the genome of Bacillus subtilis phage SP01 is presented. Sites of cleavage for the restriction enzymes BglII, EcoRI, HaeIII, and SalI were determined. This physical map showed that SP01 DNA was 140 kilobases in length and contained a repeated sequence of 12.4 kilobases at its termini. Combined with previously published information, we were also able to identify the general locations of genes expressed at early, middle, or late times in the phage lytic cycle. In particular, early genes were largely clustered in the terminal repeats, whereas a major cluster of late genes was located in the left-central portion of the genome.

Asymptomatic carotid bruit: long term outcome of patients having endarterectomy compared with unoperated controls.

During 20 years (1957-1977), 1286 carotid endarterectomies were performed on 1022 private patients with cerebrovascular insufficiency. Included were 132 patients undergoing 167 endarterectomies for asymptomatic cervical carotid bruits. Ages ranged from 42 to 82 years (mean: 64.7). Operative mortality was zero. There were two transient and two permanent operation-related neurologic deficits. Complete follow-up was achieved, extending to 184 months. During postoperative follow-up, six patients (4.5%) developed TIA's appropriate to the unoperated artery, three patients had strokes (2.3%), and three patients died of strokes (2.3%). To characterize the natural history of asymptomatic bruit and determine proper indications for prophylactic endarterectomy, a control series of 138 additional patients with asymptomatic bruit not operated upon when the bruit was discovered was studied. Ages ranged from 39 to 86 years (mean: 65.7). During follow-up extending to 180 months, 77 patients (55.8%) remained neurologically asymptomatic, 37 patients (26.8%) developed TIA's one month to 99 months after detection of bruit, and 24 patients (17.4%) sustained mild to profound frank strokes one week to 124 months postdetection. Three of these 24 (2.2%) died of stroke. Asymptomatic carotid bruits may be potential stroke hazards, the risk of which can be significantly reduced by appropriately applied endarterectomy. A protocol for managment is presented.

Intraoperative transvascular balloon catheter management for arterioureteral fistula.

An arterioureteral fistula is a rare but intriguing anomaly. Fewer than two dozen cases have been recorded, and all have relayed the extreme diagnostic and therapeutic challenges that this entity presents to the clinician. Factors contributing to the development of such a fistula include prolonged ureteral catheterization, prior pelvic vascular or urologic surgery, cancer or radiation. These patients are severely debilitated, and repair has a mortality rate in excess of 15%. Experience with such a patient is reported, as well as use of a minimally invasive approach to repair the abnormality. By using transvascular balloon occlusion of the involved iliac vessel and extra-anatomic vascular reconstruction, the significant morbidity and mortality associated with this disorder were avoided. Suspicion of an arterioureteral fistula should be increased in those at risk and treatment can be effected with this minimally invasive method.

Persistent sciatic artery and vein: an unusual case.

Persistent sciatic artery is a rare anomaly that has been reported in 48 patients in the North American literature. No report has contained more than two cases. This article discusses the first reported case of bilateral persistent sciatic arteries in a patient who also has normally developed superficial femoral arteries. This unique situation allowed removal of the superficial femoral artery for a malignant femoral nerve schwannoma without a concomitant reconstructive arterial procedure. A similar anomaly of the venous system permitted the operation to be done without compromising venous outflow.

Enhanced surgical exposure for the high extracranial internal carotid artery.

The need for enhanced surgical exposure for the high extracranial (Zone III) internal carotid artery is not uncommon. In certain circumstances, the posterior border and angle of the mandible may interfere with access to the distal internal carotid artery (ICA). The use of modified mandibular osteotomies has provided vascular surgeons in our institution with improved exposure of the ICA in selected cases. The intraoral sagittal split and extraoral vertical ramus osteotomies of the mandible allow manipulation of the posterior border and angle of the mandible with low morbidity and minimal postoperative complications. These procedures can be performed for both dentate and edentulous patients without the need for intermaxillary fixation. This paper introduces these modifications and discusses the benefits over previously described methods of mandibular manipulation.