Serious Failure Modes After EVAR Are Device Specific.

OBJECTIVES: Type I and III endoleaks following endovascular aneurysm repair (EVAR) can lead to catastrophic events that require major re-interventions. We reviewed our experience with aortic endograft re-interventions for type I and III endoleaks and other serious failures among different devices. METHODS: We retrospectively reviewed patients with a prior EVAR who underwent open conversion (OC) or major endovascular intervention (MEI) (re-lining, cuff/limb extension, parallel graft) for type I/III endoleaks at our institution from 2002 to 2019. Baseline characteristics, procedural details, re-interventions, and outcomes were collected. RESULTS: A total of 229 patients (194 men) underwent re-interventions for type I and III endoleaks after EVAR (90 OC, 139 MEI) for devices implanted between 1997 and 2019. Average age at re-intervention was 78±8.5 years. A total of 135 (59%) were implanted at our institution, whereas 93 (41%) were referred. Median time to re-intervention was 4 years with 25% to 75% interquartile range (IQR) of 2.2-6.6 years. There was no significant difference in baseline demographics or type of re-interventions (OC/MEI) between device types. 42/229 (18%) presented with ruptured aneurysms, 20/229 (9%) were symptomatic, whereas the rest presented with asymptomatic radiographic findings. Type 1A endoleak was present in 146/229 (63.8%-72 with proximal migration), type IB in 46/229 (20.1%), type IIIA in 37/229 (16.6%), type IIIB in 15/229 (6.5%), and persistent aneurysm sac growth with no radiographic evidence of an endoleak in 6/229 (2.6%). Devices included most commercial products: AFX, Excluder, AneuRx, Ancure, Endurant, and Zenith. A smaller number of investigational devices accounted for the rest. Type 1A endoleak was the most common indication for re-intervention among all devices except for AFX and ancure devices, proximal migration was a frequent presentation with AneuRx. AFX devices more frequently presented with a type III and ancure devices more frequently presented with a type IB endoleak. CONCLUSIONS: Serious failure modes after EVAR differ between endografts and occur throughout the follow-up period. This is important to guide targeted interrogation of surveillance studies and follow-up schedules, even for discontinued devices, as well as comparisons between various series and estimation of EVAR failure rates. CLINICAL IMPACT: Surveillance after EVAR is critical for long term success of the repair, understanding of the differential modes of failure of every graft available is important in the longitudinal evaluation of these endografts. Equally important is the understanding of the modes of failure of legacy endografts that are no longer on the market but still being followed, in order to be able to tailor a surveillance regiemn and the evntual repair if needed.

First Robinsoniella peoriensis aortic cross homograft mycotic pseudoaneurysm: A case report and review of the literature.

Mycotic aortic aneurysm is a rare and challenging complication of aortic homografts caused by an infection and is associated with high morbidity and mortality. We report the first case of an aortic cross homograft mycotic pseudoaneurysm caused by Robinsoniella peoriensis in a 70-year-old man. Our patient underwent surgery for a recurrence of aortic cross mycotic pseudoaneurysm at the level of the aortic homograft he had had 7 years before. A clot-removal of the pseudoaneurysm was surgically carried out and the homograft was completely removed. Anaerobic culture from tissue samples yielded pure growth of a spore-forming Gram-positive rod, identified later as Robinsoniella peoriensis by 16S rRNA gene sequencing. The patient was then discharged with oral clindamycin according to the in vitro susceptibility testing. Identification of R. peoriensis might be challenging in clinical laboratories with no access to molecular methods.

NOTES total mesorectal excision (TME) for patients with rectal neoplasia: a preliminary experience.

BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) and single-incision laparoscopy are emerging, minimally invasive techniques. Total mesorectal excision (TME), the gold standard treatment for patients with resectable distal rectal tumors, is usually performed in an "up-to-down" approach, either laparoscopically or via open techniques. A transanal, "down-to-up" TME has already been reported. Our NOTES variant of TME (NOTESTME) is based on a transperineal approach without any form of abdominal assistance. The aim was to reduce further the invasiveness of the procedure while optimizing the anatomical definition of the distal mesorectum. This approach may lead to reduced postoperative pain, decreased hernia formation and improved cosmesis when compared to standard laparoscopy. METHODS: NOTESTME was attempted in 16 patients with distal rectal neoplasia (i.e., distal edge of the tumor lower than the pouch of Douglas, between 0 and 12 cm from the dentate line). Additional inclusion criteria consisted of an ASA status ≤III and the absence of previous abdominal surgery. RESULTS: NOTESTME was completed in all patients. Additional abdominal, single-incision laparoscopic assistance was required in 6 (38 %) patients. Mean operative time was 265 min (range 155-440 min). The morbidity rate was 18.8 % (two small bowel obstructions and one pelvic abscess), requiring re-operation in each case. No leaks occurred, and the mortality rate at 30 and 90 days was 0 %. Resection margins were negative in all patients. A median of 17 nodes (range 12-81) was retrieved per specimen. Mean length of hospital stay was 10 days (range 4-29 days). Patients were followed for an average of 7 months (range 3-23 months). CONCLUSION: NOTESTME was feasible and safe in this series of patients with mid- or low rectal tumors. The short-term mortality and morbidity rates are acceptable, with no apparent compromise in the oncological quality of the resection. Larger, randomized controlled trials with long-term follow-up are warranted.

Peripatellar synovitis: comparison between non-contrast-enhanced and contrast-enhanced MRI and association with pain. The MOST study.

PURPOSE: To assess the diagnostic performance of signal changes in Hoffa's fat pad (HFP) assessed on non-contrast-enhanced (CE) magnetic resonance imaging (MRI) in detecting synovitis, and the association of pain with signal changes in HFP on non-CE MRI and peripatellar synovial thickness on CE MRI. METHODS: The Multicenter Osteoarthritis (MOST) Study is an observational study of individuals who have or are at high risk for knee OA. All subjects with available non-CE and CE MRIs were included. Signal changes in HFP were scored from 0 to 3 in two regions using non-CE MRI. Synovial thickness was scored from 0 to 2 on CE MRI in five peripatellar regions. Sensitivity, specificity and accuracy of HFP signal changes were calculated considering synovial thickness on CE MRI as the reference standard. We used logistic regression to assess the associations of HFP changes (non-CE MRI) and synovial thickness (CE MRI) with pain from walking up or down stairs, after adjusting for potential confounders. RESULTS: A total of 393 subjects were included. Sensitivity of infrapatellar and intercondylar signal changes in HFP was high (71% and 88%), but specificity was low (55% and 30%). No significant associations were found between HFP changes on non-CE MRI and pain. Grade 2 synovial thickness assessed on CE MRI was significantly associated with pain after adjustments for potential confounders. CONCLUSION: Signal changes in HFP detected on non-CE MRI are a sensitive but non-specific surrogate for the assessment of synovitis. CE MRI identifies associations with pain better than non-CE MRI.

Three-dimensional radiographic assessment of the mandibular interforaminal donor site in different vertical facial growth types.

PURPOSE: To assess volumetrically, the impact of vertical facial growth types (VFGT) on the mandibular interforaminal region as a potential bone donor site. MATERIAL AND METHODS: 60 cone beam computed tomography (CBCT) scans of adult individuals were classified in three groups according to their SN-GoGn angle: hypodivergent group (hG) (N=20), normodivergent group (NG) (N=19) and hyperdivergent group (HG) (N=21). Total harvestable bone volume (TBV), cortico-cancellous bone volume (CBV-cBV), and cortical bone surface (CBS) were evaluated. ANOVA test followed by Tukey post hoc tests were used to compare the mean continuous outcomes according to their VFGT. RESULTS: The whole sample showed a mean TBV of 1376.32±541.01mm3, CBV of 468.52±121.54mm3 and cBV of 908.73±474.71mm3. The mean CBS amounted to 782.58±146.80mm2. The comparison between the groups stated a significantly different mean TBV and cBV (-p-value<0.001). The mean CBS was significantly different (-p-value=0.015): the smallest for the NG, but not significantly different (-p-value<0.001): the highest for the HG, intermediate for the NG and the smallest for the hG. CONCLUSION: Hypodivergent individuals have the thickest cancellous bone suitable for an onlay bone graft, while hyperdivergent individuals have the thinnest bone ideal for a 3D grafting approach.

WALANT in hand surgery: Ischemic complications and their medicolegal implications in France: A systematic review of the literature and of French legal databases.

WALANT (Wide Awake Local Anesthesia No Tourniquet) presents a theoretical risk of digital ischemia due to the presence of epinephrine, associated to the local anesthetic. For this reason, in France, the market authorization prohibits the use of epinephrine in digital extremities. The main objective of the present study was to assess the risk of ischemic complications reported in literature, and then to analyze the medicolegal implications in France. A systematic literature review was performed by three independent readers, using the PubMed and Embase databases. Also, declarations of claims and legal proceedings between 2007 and 2020 in France were examined in the official national Légifrance and Doctrine databases. Eight of the 424 articles retrieved were selected. Only 3 cases of digital necrosis following local anesthesia with adrenalized lidocaine were reported. Adrenalized xylocaine may be considered in case of peripheral microcirculation disorder. From a medicolegal point of view, no complaints or medicolegal implications were associated with WALANT in France. It seems that the market authorization for adrenalized local anesthesia could be extended to use in the digital extremities. However, the lack of medical and legal data calls for caution. We therefore recommend the use of an institutional protocol specifying the cases of overdose and the patient's pathway, and training for practitioners wishing to use this technique.

A comparison of dedicated 1.0 T extremity MRI vs large-bore 1.5 T MRI for semiquantitative whole organ assessment of osteoarthritis: the MOST study.

OBJECTIVE: To date semiquantitative whole-organ scoring of knee osteoarthritis (OA) relies on 1.5 Tesla (T) Magnetic resonance imaging (MRI) systems. Less costly 1.0 T extremity systems have been introduced that offer superior patient comfort, but may have limitations concerning field-of-view and image quality. The aim of this study was to compare semi-quantitative (SQ) scoring on a 1.0 T system using 1.5 T MRI as the standard of reference. METHODS: The Multicenter Osteoarthritis Study (MOST) is a longitudinal study of individuals who have or are at high risk for knee OA. A sample of 53 knees was selected in which MRI was performed on a 1.0 T extremity system as well as on a 1.5 T scanner applying a comparable sequence protocol. MRIs were read according to the Whole Organ Magnetic Resonance Imaging Score (WORMS) score. Agreement was determined using weighted kappa statistics. Sensitivity, specificity and accuracy were assessed using the 1.5 T readings as the reference standard. In addition the number of non-readable features was assessed. RESULTS: Agreement (w-kappa) for seven main WORMS features (cartilage, bone marrow lesions (BMLs), osteophytes, meniscal damage and extrusion, synovitis, effusion) ranged between 0.54 (synovitis) and 0.75 (cartilage). Sensitivity ranged between 68.1% (meniscal damage) and 88.1% (effusion). Specificity ranged between 63.6% (effusion) and 96.4% (BMLs). Although the overall rate of non-readable features was very low, it was higher for the 1.0 T system (1.9% vs 0.2%). CONCLUSIONS: Semiquantitative whole organ scoring can be performed using a 1.0 T peripheral scanner with a moderate to high degree of agreement and accuracy compared to SQ assessment using a 1.5 T whole body scanner. Our results are comparable to the published inter- and intra observer exercises obtained from 1.5 T systems. Sensitivity to change of longitudinal scoring was not evaluated in this cross-sectional design and should be investigated in future validation studies.

BK viral enhancer element and a human cellular homolog.

Comparison of two closely related primate papovaviruses, simian virus 40 (SV40) and human BK virus (BKV), reveals that the only region of extensive divergence, the tandem sequences adjacent to the origins of DNA replication, is responsible in SV40 for enhancing early gene expression. This study demonstrates a similar enhancer function for the analogous repeated region in BKV. The dissimilarity in sequence of the BKV and SV40 enhancer elements suggests that they may have been acquired since SV40 and BKV diverged. A locus cloned from the human genome homologous to the BKV tandem repeats has been shown to function as low level enhancer element in mammalian cells. These data support the hypothesis that viral enhancer sequences may be evolutionarily related to host cell sequences.

Reversal of oncogenesis by the expression of a major histocompatibility complex class I gene.

The classical transplantation antigens (the major histocompatibility complex class I antigens) play a key role in host defense against cells expressing foreign antigens. Several naturally occurring tumors and virally transformed cells show an overall suppression of these surface antigens. Since the class I molecules are required in the presentation of neoantigens on tumor cells to the cytotoxic T lymphocytes, their absence from the cell surface may lead to the escape of these tumors from immunosurveillance. To test this possibility, a functional class I gene was transfected into human adenovirus 12-transformed mouse cells that do not express detectable levels of class I antigens; the transformants were tested for expression of the transfected gene and for changes in oncogenicity. The expression of a single class I gene, introduced by DNA-mediated gene transfer into highly tumorigenic adenovirus 12-transformed cells, was sufficient to abrogate the oncogenicity of these cells. This finding has important implications for the regulation of the malignant phenotype in certain tumors and for the potential modulation of oncogenicity through derepression of the endogenous class I genes.

Primary rat embryo cells transformed by one or two oncogenes show different metastatic potentials.

Second-passage rat embryo cells were transfected with a neomycin resistance gene and the activated form of the c-Ha-ras I gene, or with these two genes plus the adenovirus type 2 E1a gene. Foci of morphologically transformed cells were observed in both cases; however, the frequency of transformation was at least ten times higher with two oncogenes than with the ras gene alone. All the transformed cell lines gave rise to rapidly growing tumors when injected subcutaneously into nude mice. All but one of the cell lines transformed by the ras oncogene alone formed metastatic nodules in the lungs of animals that had been injected subcutaneously with transformed cells. When transformed cells were injected intravenously, all the ras single-gene transformants gave rise to many metastatic lung nodules. In contrast, cell lines transformed with ras and E1a did not generate metastases after subcutaneous injection and gave rise to very few metastatic lung nodules after intravenous injection. These data demonstrate that a fully malignant cell with metastatic potential, as measured in an immunodeficient animal, can be obtained from early passage embryo cells by the transfection of the ras oncogene alone.

The tat gene of human T-lymphotropic virus type 1 induces mesenchymal tumors in transgenic mice.

Human T-lymphotropic virus type 1 (HTLV-1) is a suspected causative agent of adult T-cell leukemia. One of the viral genes encodes a protein (tat) that not only results in transactivation of viral gene expression but may also regulate the expression of certain cellular genes that are important for cell growth. Transgenic mice that expressed the authentic tat protein under the control of the HTLV-1 long terminal repeat were generated, and cell types that are permissive for the viral promoter and the effects of the tat gene on these cells were studied. Three of eight founder mice with high levels of expression of the transgene in muscle were bred and then analyzed. All developed soft tissue tumors at multiple sites between 13 to 17 weeks of age. This phenotype was transmitted to nine of nine offspring that inherited the tat gene and were available for analysis. The remaining five founders expressed the transgene in the thymus, as well as in muscle. This second group of mice all exhibited extensive thymic depletion and growth retardation; in all of these mice, death occurred between 3 to 6 weeks of age before tumors became macroscopically visible. The tat gene under the control of the HTLV-1 regulatory region showed tissue-specific expression and the tat protein efficiently induced mesenchymal tumors. The data establish tat as an oncogenic protein and HTLV-1 as a transforming virus.

A transgenic mouse model for human neurofibromatosis.

Human T-lymphotropic virus type 1 (HTLV-1) has been associated with the neurologic disorder tropical spastic paraparesis and possibly with multiple sclerosis. The tat gene of HTLV-1 under control of its own long terminal repeat is capable of inducing tumors in transgenic mice. The morphologic and biologic properties of these tumors indicate their close resemblance to human neurofibromatosis (von Recklinghausen's disease), the most common single gene disorder to affect the nervous system. The high spontaneous incidence of this disease, together with the diverse clinical and pathologic features associated with it, suggests that environmental factors may account for some of the observed cases. Multiple tumors developed simultaneously in the transgenic tat mice at approximately 3 months of age, and the phenotype was successfully passed through three generations. The tumors arise from the nerve sheaths of peripheral nerves and are composed of perineural cells and fibroblasts. Tumor cells from these mice adapt easily to propagation in culture and continue to express the tat protein in significant amounts. When transplanted into nude mice, these cultured cells efficiently induce tumors. Evidence of HTLV-1 infection in patients with neural and other soft tissue tumors is needed in order to establish a link between infection by this human retrovirus and von Recklinghausen's disease and other nonlymphoid tumors.

The human c-ras1H oncogene: a mutation in normal and neoplastic tissue from the same patient.

The c-ras1H oncogene can be distinguished from its normal cellular counterpart by the loss of a restriction endonuclease site. This sequence alteration is the basis of a rapid screening method for the presence of this oncogene. DNA's from 34 individuals were screened by this method, and all were homozygous for the normal allele. In contrast, DNA from a patient's bladder tumor, as well as DNA from his normal bladder and leukocytes, were heterozygous at that restriction endonuclease site. Further restriction enzyme mapping pinpointed the change in the mutant allele as being one of two nucleotides, either of which would change the 12th amino acid (glycine) in the normal c-ras1H gene product. Point mutations in the codon for this amino acid have previously been described in a bladder tumor cell line and in the viral oncogene v-rasH. These results indicate that the patient carried a c-ras1H oncogene in his germ line, raising the possibility that the c-ras1H oncogene confers a predisposition to neoplasia.

Functional insertion of an Alu type 2 (B2 SINE) repetitive sequence in murine class I genes.

The regulation of expression of the family of MHC (major histocompatibility complex) class I genes is complex. Sequence analysis has revealed that class I genes from the H-2D subregion of the MHC (which includes the D and L genes) differ from the class I gene from the H-2K subregion (the K gene) by the insertion of a type 2 Alu-like repetitive element (the murine B2 sequence) within the 3' noncoding region of the D and L genes. The consequence of this insertion in the D and L genes is the introduction of a novel polyadenylation signal, which is preferentially used over the more distal signal, the analog of that found in the K gene. The insertion of the type 2 Alu-like sequence results in a change in the preferred site for endonucleolytic cleavage which is necessary for generating a correct 3' terminus for polyadenylation. The data demonstrate that the type 2 Alu-like sequence has a function; the data also suggest a possible regulatory role of this sequence in the expression of class I genes.

JC virus enhancer-promoter active in human brain cells.

A human papovavirus, JCV, is the etiologic agent of the fatal demyelinating disease, progressive multifocal leukoencephalopathy. The JCV 98-base-pair tandem repeats, located to the late side of the viral replication origin, were shown to be a transcriptional regulatory element with enhancer-like activity in human fetal glial cells. These tandem repeats share significant homology with the 82-nucleotide rat brain-specific identifier RNA sequence.

Endovascular treatment of acute aortic isthmic rupture: concerning midterm results.

BACKGROUND: We evaluated midterm results of endovascular management of traumatic aortic isthmic ruptures. METHODS: Between 2001 and 2008, 10 patients (seven males, mean age 38 years) underwent endovascular treatment of an acute aortic rupture. Eight procedures were emergent, with four cases of hemodynamic instability with Glasgow scores of 3, 5, and 7. Associated traumas were severe brain, liver, and pelvic bone injuries. All procedures were performed with transoesophageal echocardiography monitoring. We used two AneuRx and nine Medtronic Talent or Valiant stent grafts. RESULTS: All patients survived their traumatic isthmic rupture. In nine patients, stent-graft deployment was successful. One patient experienced a distal migration needing a laparotomy and deployment of an additional new thoracic stent graft. The mean intensive care unit stay was 48 hr (range 24-168). The mean hospital stay was 11 days (range 8-43). All patients were controlled clinically and by contrast computed tomography (CT) according to the EUROSTAR protocol. There were no endoleaks, stent graft-related complications, or late deaths during a mean follow-up of 49 months. The control CT showed a lack of apposition of the proximal part of the stent graft at the inner curve of the aortic arch in three patients. CONCLUSION: The midterm results of endovascular treatment of acute traumatic aortic isthmic rupture are encouraging and compare favorably to the surgical approach. Late follow-up is required to exclude possible stent-graft complications, especially in young patients with angulated aortic arches.

trans Activation of the simian virus 40 late transcription unit by T-antigen.

We have investigated the role of simian virus 40 (SV40) T-antigen in the induction of late gene expression independent of its function in amplifying templates through DNA replication. Northern blot and S1 nuclease analyses showed that stimulation occurred at the transcriptional level. At least two template elements, the T-antigen-binding sites and the 72-base-pair repeats, appeared to be important for this induction. Using template mutants, we demonstrated that deletions within T-antigen-binding site II decreased T-antigen-mediated late gene expression approximately 10- to 20-fold. In addition, multiple point mutations within a single retained copy of the SV40 72-base-pair repeat decreased T-antigen-mediated late gene expression. Using in vivo competition studies, we demonstrated that competitor DNA fragments containing the SV40 control region (nucleotides 5171 through 272) quantitatively decreased SV40 late gene expression in COS-1 cells. In contrast, competition with a plasmid containing SV40 nucleotides 1 through 294 (which removes all of T-antigen-binding site I and half of site II) was much less efficient. Finally, we demonstrated that in vivo competition experiments employing competitor fragments distal to the T-antigen-binding sites within the late template region (SV40 nucleotides 180 through 2533) resulted in superinduction of late gene expression in COS-1 cells. This finding suggests that negative factors such as repressors or attenuators may modulate late SV40 gene expression before induction. Our results are consistent with a model in which induction of late gene expression involves an interaction of the SV40 origin region with DNA-binding proteins, one of which may be T-antigen. Activation of the SV40 late transcription unit may involve induction of the SV40 enhancer or removal of a repressor-like protein or both.

Regulation of insulin mRNA abundance and adenylation: dependence on hormones and matrix substrata.

The insulin mRNA levels of rat insulinoma cell lines increased six- to eightfold, and the cells entered a transient state of growth arrest when they were cultured in serum-free, hormonally defined medium and on an extract of extracellular matrix derived from a basement membrane-secreting tumor line, EHS. Insulinoma cultures in growth arrest responded to glucose with a two- to threefold increase in insulin secretion associated with an insulin mRNA that contained a poly(A) tail that was 120 to 140 bases longer than normal.

Stimulation of the adenovirus E2 promoter by simian virus 40 T antigen or E1A occurs by different mechanisms.

We have examined the ability of simian virus 40 T antigen to stimulate transcription from the adenovirus E2 promoter. T antigen, produced from a cotransfected plasmid, stimulated chloramphenicol acetyltransferase enzyme and mRNA production from an E2 promoter-chloramphenicol acetyltransferase fusion plasmid (pEC113) in monkey kidney CV-1 cells. The level of stimulation of E2 transcription by simian virus 40 T antigen was equal to that observed in cotransfections of pEC113 and the adenovirus E1A gene product. Deletion mutations from the 5' end of the E2 promoter were examined for their ability to express basal, T-antigen, or E1A trans-activated promoter activity. In each case, deletion of upstream promoter sequences to -70 base pairs reduced chloramphenicol acetyltransferase expression to approximately 30% of the level observed with the intact E2 promoter. Deletion to -59 base pairs resulted in chloramphenicol acetyltransferase expression that was 3 to 5% of that observed with the intact E2 promoter. At saturating levels of the stimulatory proteins, the chloramphenicol acetyltransferase levels obtained in response to T antigen and adenovirus E1A were additive. COS-1 cells, which are derived from CV-1 cells and constitutively express simian virus 40 T antigen, do not support E2 promoter trans activation by T antigen. E1A trans activation of the E2 promoter is efficient in COS-1 cells. These results suggest that although promoter sequence requirements are similar, T antigen and E1A trans activate the E2 promoter by different mechanisms.

A transcriptional enhancer and an interferon-responsive sequence in major histocompatibility complex class I genes.

The major histocompatibility complex class I antigens play an indispensable role in cell-cell interactions. Perturbation of their expression has been shown to have deleterious physiological consequences, including the escape of transformed cells from immune detection. In an attempt to understand how class I genes are regulated, we dissected the Ld gene to identify potential control regions. By using a test vector containing the simian virus 40 early promoter placed upstream of the bacterial chloramphenicol acetyltransferase (cat) gene, we demonstrated the presence of a transcriptional enhancer within the 5'-flanking region. The sequence is functional in both orientations and has been mapped within 350 base pairs upstream of the Ld transcriptional start site. Although human adenovirus 12 can suppress endogenous class I genes, it cannot down-regulate the activity of the transiently transfected cat gene which has been placed under the control of the Ld enhancer and promoter. Our results suggested that if the human adenovirus 12-induced function regulates the expression of class I genes by a trans mechanism, then its target site must not be within 1.9 kilobases of the 5'-flanking region. Treatment of cells with interferon increases the accumulation of class I transcripts. Expression of the cat gene under the control of the Ld enhancer and promoter also can be up-regulated by interferon. Our study shows that the target sequence required for this enhancement resides, at least in part, within the same 350-base pair segment which contains the transcriptional enhancer.