Pressure generated by syringes: implications for hydrodissection and injection of dense connective tissue lesions.

OBJECTIVE: Hydrodissection and high-pressure injection are important for the treatment of dense connective tissue lesions including rheumatoid nodules, Dupuytren's contracture, and trigger finger. The present study determined the optimal syringes for high-pressure injection of dense connective tissue lesions. METHODS: Different sizes (1, 3, 5, 10, 20, and 60 mL) of a mechanical syringe (reciprocating procedure device) with a luer-lock fitting were studied. Twenty operators generated maximum pressure with each mechanical syringe size, and pressure was measured in pounds per square inch (psi). Subsequently, 223 dense connective tissue lesions were injected with different sizes of syringes (1, 3, or 10 mL). Outcomes included (i) successful intralesional injection and (ii) clinical response at 2 weeks. RESULTS: Smaller syringes generated significantly more injection pressure than did larger syringes: 1 mL (363 ± 197 psi), 3 mL (177 ± 96 psi), 5 mL (73 ± 40 psi), 10 mL (53 ± 29 psi), 20 mL (32 ± 18 psi), and 60 mL (19 ± 12 psi). Similarly, smaller syringes were superior to larger syringes for intralesional injection success: 10 mL: 34% (15/44) vs. 1 mL: 100% (70/70) (p < 0.001) and 3 mL: 91% (99/109) (p < 0.001). CONCLUSION: Smaller syringes (≤ 3 mL) are superior to larger syringes (≥ 5 mL) for successful hydrodissection and high-pressure intralesional injection of dense connective tissue lesions.

Human middle cerebral artery blood velocity during sexual intercourse.

Although the augmentation of central hemodynamics during human sexual intercourse is well established, dynamic changes in human regional cerebral blood flow have not been reported. Noninvasive transcranial Doppler ultrasonography has been well validated and allows direct, continuous measurement of phasic blood velocity in the human middle cerebral artery (a linear index of regional cerebral blood flow). The middle cerebral artery supplies the premotor and primary sensorimotor cortical regions for the arms, upper and lower trunk, and head. Blood velocities in this vessel have been shown to increase significantly with sensory stimuli and physical stresses. Accordingly, we tested the hypothesis that human sexual intercourse increases middle cerebral artery blood velocity. We used noninvasive, transcranial Doppler ultrasonography (95% confidence limits for precision +/- 7%) to measure blood velocity in the left middle cerebral artery of 10 male and 10 female, sexually acquainted, healthy adults (age range, 23 to 47 years; mean, 30 years). To eliminate signal artifacts and allow complete freedom of motion, a modified low profile, temporal fossa transducer was secured by minimal unobtrusive forehead strapping. Continuous measurements of phasic blood velocity and heart rate were made in a private bedroom setting during rest (control), preexcitement, excitation, prepenetration, penetration, preorgasm, orgasm, and resolution with the untethered instrumented subject in the supine missionary position. Heart rate and blood velocity responses were similar in both sexes. During orgasm, the maximal heart rate increased significantly (P < 0.05): 49 +/- 44% in women, 65 +/- 32% in men, and 58 +/- 38% combined from a combined resting value of 77 +/- 11 standard deviations SD beats per minute. Importantly, blood velocity in the middle cerebral artery of the 20 subjects remained unchanged (P > 0.10) from a resting value of 56 +/- 15 cm/s. In conclusion, in both sexes, human middle cerebral artery blood velocity, a linear index of human regional cerebral blood flow, does not increase significantly (P > 0.10) during human sexual intercourse.

Viewpoint dependence and object discriminability.

In an attempt to reconcile results of previous studies, several theorists have suggested that object recognition performance should range from viewpoint invariant to highly viewpoint dependent depending on how easy it is to differentiate the objects in a given recognition situation. The present study assessed recognition across depth rotations of a single general class of novel objects in three contexts that varied in difficulty. In an initial experiment, recognition in the context involving the most discriminable object differences was viewpoint invariant, but recognition in the least discriminable context and recognition in the intermediate context were equally viewpoint dependent. In a second experiment, utilizing gray-scale versions of the same stimuli, almost identical viewpoint-cost functions were obtained in all three contexts. These results suggest that differences in the geometry of stimulus objects, rather than task difficulty, lie at the heart of previously discrepant findings.

Recognizing silhouettes and shaded images across depth rotation.

Outline-shape information may be particularly important in the recognition of depth-rotated objects because it provides a coarse shape description which gives first-pass information about the structure of an object. In four experiments, we compared recognition of silhouettes (showing only outline shape) with recognition of fully shaded images of objects, by means of a sequential-matching task. In experiments 1 and 2, the first stimulus was always a shaded image, and the second stimulus was either a shaded image or a silhouette. Recognition costs associated with a change in viewpoint were no greater for silhouettes than they were for shaded images. Experiments 3 and 4 replicated the design of the earlier experiments, but showed a silhouette as the initial stimulus, rather than a shaded image. In these cases, recognition costs associated with a change in viewpoint were greater for silhouettes than for shaded images. Combined, these results indicate that, while visual representations clearly include additional information, outline shape plays an important role in object recognition across depth rotation.

Testing conditions for viewpoint invariance in object recognition.

Based on the geon structural description approach, I. Biederman and P.C. Gerhardstein (1993) proposed 3 conditions under which object recognition is predicted to be viewpoint invariant. Two experiments are reported that satisfied all 3 criteria yet revealed performance that was clearly viewpoint dependent. Experiment 1 demonstrated that for both sequential matching and naming tasks, recognition of qualitatively distinct objects became progressively longer and less accurate as the viewpoint difference between study and test viewpoints increased. Experiment 2 demonstrated that for single-part objects, larger effects of viewpoint occurred when there was a change in the visible structure, indicating sensitivity to qualitative features in the image, not geon structural descriptions. These results suggest that the conditions proposed by I. Biederman and P.C. Gerhardstein are not generally applicable, the recognition of qualitatively distinct objects often relies on viewpoint-dependent mechanisms, and the molar features of view-based mechanisms appear to be image features rather than geons.

Minimal truncation of the c-myb gene product in rapid-onset B-cell lymphoma.

Oncogenic activation of c-myb by insertional mutagenesis has been implicated in rapid-onset B-cell lymphomas induced by the nonacute avian leukosis virus EU-8. In these tumors, proviruses are integrated either upstream of the c-myb coding region or within the first intron of c-myb. Tumors with either type of integration contained identical chimeric mRNAs in which the viral 5' splice site was juxtaposed to the 3' splice site of c-myb exon 2 and myb exon 1 was eliminated. Both classes of integrations generated truncated Myb proteins that were indistinguishable by Western analysis. In contrast to most other examples of c-myb activation, the truncation consisted of only 20 N-terminal amino acids and did not disrupt either the DNA binding domain near the N terminus or the negative regulatory domain near the C terminus of Myb. The significance of the 20-amino-acid Myb truncation to tumorigenesis was tested by infection of chicken embryos with retroviral vectors expressing different myb gene products. While virus expressing either wild-type c-myb or c-myb mutated at the N-terminal casein kinase II sites was only weakly oncogenic at 10 weeks, the minimally truncated myb virus induced a high incidence of rapid-onset tumors, including B-cell lymphomas, sarcomas, and adenocarcinomas.

Genetic determinant of rapid-onset B-cell lymphoma by avian leukosis virus.

Infection of 10 day-old chicken embryos with the recombinant avian leukosis virus (ALV) EU-8 induces a high incidence of rapid-onset B-cell lymphoma by insertional activation of the c-myb gene. LR-9, a related ALV with differences from EU-8 in the gag and pol genes, induces rapid-onset lymphoma at only a low incidence. To localize the viral determinant(s) responsible for this biologic difference, we constructed and tested a series of reciprocal chimeras between EU-8 and LR-9 ALVs. The ability to induce rapid-onset lymphoma efficiently was localized to a 925-nucleotide (nt) region of the EU-8 gag gene. Sequence analysis of the region revealed a 42-nt deletion in EU-8 relative to LR-9, as well as some single-nucleotide changes. A mutant virus, delta LR-9, constructed by deleting these 42 nt from LR-9, also induced rapid-onset lymphoma at a high frequency, confirming the biologic significance of this deletion. This deletion removed nt 735 to 776, which lies within a cis-acting RNA element that negatively regulates splicing (NRS). The deletion was shown to cause an increase in splicing efficiency, which may lead to increased production of a truncated myb gene product from an ALV-myb readthrough RNA.

Rapid induction of B-cell lymphomas by avian leukosis virus.

Avian leukosis viruses (ALVs) that induce rapid B-cell lymphomas integrate into the c-myb gene and produce an ALV-myb read-through RNA, which is spliced to produce a truncated Myb protein. The genetic determinants of such recombinant ALVs have been mapped to a 42-nt deletion within the gag gene. This deletion increases splicing efficiency since it is located within a negative regulator of splicing. We propose that the deletion leads to increased production of Myb protein by increasing splicing of an ALV-myb pre-mRNA.

bic, a novel gene activated by proviral insertions in avian leukosis virus-induced lymphomas, is likely to function through its noncoding RNA.

The bic locus is a common retroviral integration site in avian leukosis virus (ALV)-induced B-cell lymphomas originally identified by infection of chickens with ALVs of two different subgroups (Clurman and Hayward, Mol. Cell. Biol. 9:2657-2664, 1989). Based on its frequent association with c-myc activation and its preferential activation in metastatic tumors, the bic locus is thought to harbor a gene that can collaborate with c-myc in lymphomagenesis and presumably plays a role in late stages of tumor progression. In the present study, we have cloned and characterized two novel genes, bdw and bic, at the bic locus. bdw encoded a putative novel protein of 345 amino acids. However, its expression did not appear to be altered in tumor tissues, suggesting that it is not involved in oncogenesis. The bic gene consisted of two exons and was expressed as two spliced and alternatively polyadenylated transcripts at low levels in lymphoid/hematopoietic tissues. In tumors harboring bic integrations, proviruses drove bic gene expression by promoter insertion, resulting in high levels of expression of a chimeric RNA containing bic exon 2. Interestingly, bic lacked an extensive open reading frame, implying that it may function through its RNA. Computer analysis of RNA from small exon 2 of bic predicted extensive double-stranded structures, including a highly ordered RNA duplex between nucleotides 316 and 461. The possible role of bic in cell growth and differentiation is discussed in view of the emerging evidence that untranslated RNAs play a role in growth control.

Spatial language and spatial representation.

This study explores the commonalities between linguistic and visual representations of space. In particular, because common types of spatial relations, specifically closed-class spatial forms in language and qualitative spatial relations in perception, have been proposed in both representational systems, we investigate whether they share underlying structural similarities. Moreover, while visual spatial relations are a basic element of several theories of object representation, they have been characterized mainly in terms of their linguistic counterparts and without direct evidence about their organization. In order to illuminate the nature of these structures, as well as demonstrate possible correspondences between the two systems, we compare how the spatial relationship between pairs of objects in a scene is encoded linguistically and visually. Spatial language was investigated by having subjects either generate (Experiment 1) or rate the applicability of (Experiment 2) spatial terms for describing the spatial relationship between object pairs. Both the frequency of use and the applicability of spatial terms were highest when the two objects were in vertical or in horizontal alignment. Spatial representation was investigated by paradigms in which subjects either recalled the position of one object relative to the other (Experiment 3) or judged whether one object presented sequentially was in the same or a different position relative to the other (Experiment 4). The accuracy of position estimates and the sensitivity to shifts in position were both highest when the rated object was in a spatial location where spatial terms had been judged to have high applicability in Experiments 1 and 2. These results indicate that the structure of space as encoded by language may be determined by the structure of spatial relations in visual representation.

Total blood flow to arteriovenous malformations.

Normal perfusion pressure breakthrough is considered to be a great hazard during or after resection of large arteriovenous malformations (AVMs). This article presents the total blood flow to the AVMs, particularly those of greater than 3 cm in diameter (greater than 14.1 cm3 in volume), which have multiple compartments. The total blood flow into the AVMs in the sensory-motor area in 6 patients averaged 830 +/- 285 cc/min and those in the visual area in 4 patients averaged 358 +/- 33 cc/min. These flow values were compared to total flow through the intracranial arteries (756 cc/min). Large volume of blood flow into the AVMs carries a significant post-operative risk of normal profusion pressure breakthrough. Redistribution of blood flow from large AVMs into the cerebrovascular bed is an important factor for circulatory regulation to occur after their resection. The risk of normal profusion pressure breakthrough must be minimized by surgical technique discussed in the text.

Can somatosensory evoked potential monitoring predict energy dynamics during controlled hypotension?

Somatosensory evoked potentials and redox (reduction/oxidation ratio) of cytochrome a,a3 were studied simultaneously before, during, and after controlled hypotension used for arteriovenous malformation resection. These studies were also conducted before and after ED-IC (external-internal carotid) bypass procedures for treatment of patients with transient ischaemic attacks. The former served as an acute model and the latter as a chronic model of low blood flow (ischaemia). The use of non-invasive reflection spectrophotometry (for redox studies) in conjunction with somatosensory evoked potentials (SSEP) has demonstrated that metabolic and electrophysiological changes parallel each other during "controlled" hypotension. The authors conclude that an analysis of SSEP changes are valuable in the study of metabolic and functional states of the brain during controlled hypotension.

The block to transcription elongation is promoter dependent in normal and Burkitt's lymphoma c-myc alleles.

Aberrant c-myc expression patterns occur in human Burkitt's lymphoma cells, which consistently exhibit c-myc chromosomal translocations, mutations within and flanking the translocated allele, a loss of the block to transcription elongation in exon 1, and a promoter shift to use of the upstream P1 promoter. To define the mechanism responsible for the loss of transcription elongation blockage and resulting c-myc deregulation in Burkitt's lymphoma, we analyzed transcription patterns after transfer of normal and Burkitt's lymphoma c-myc alleles into murine cells and Xenopus oocyte germinal vesicles. We have determined that although the mutations within and surrounding several Burkitt's lymphoma c-myc alleles are not sufficient, in themselves, to abrogate the transcription elongation block, transcription initiation from the P2 promoter may be necessary to obtain the block to transcription elongation. To test directly the role of c-myc promoters in programming transcription elongation blockage, we analyzed transcription patterns from in vitro mutagenized c-myc genes containing deletions of either the P1 or P2 promoter. These data confirm that P1-initiated c-myc transcripts do not terminate at discrete sites near the 3' end of exon 1, whereas P2-initiated transcripts either terminate or read through the transcription block signals. Therefore, overexpression and/or constitutive expression from the c-myc P1 promoter may contribute to increased readthrough transcription in Burkitt's lymphoma cells and, hence, to aberrant expression patterns or levels of c-myc steady-state transcripts. In addition, the ability of normal cells to modulate c-myc P2-initiated transcription to either read through or to block elongation provides a fine control mechanism over c-myc steady-state RNA levels.

Preparation of a detailed restriction map of the avian leukosis virus MAV-2(O).

Unintegrated MAV-2(O) DNA was isolated from infected chicken embryo fibroblasts and inserted into the lambda bacteriophage vector lambda gtWES lambda B. Three x 10(6) bacteriophage plaques were screened, yielding a total of seven clones, six of which contained DNA representing the complete MAV-2(O) genome. Viral DNA was isolated from four of the clones and was used to transfect chicken embryo fibroblasts. All four clones produced virus as monitored by reverse transcriptase assay. When the four cloned viruses were inoculated into 10-day-old embryos, all hatched chickens developed osteopetrosis. One clone, lambda 9, induced osteopetrosis at a rate of onset and severity identical to that induced by the MAV-2(O) parental stock. This clone was selected for further study. To facilitate restriction mapping, the viral DNA from lambda 9 was subcloned into plasmid vector pUC 12 to construct a plasmid called p9. Cleavage of p9 DNA with single and multiple restriction endonucleases and hybridization with gene-specific probes identified the restriction fragments obtained. A comprehensive restriction map of cloned MAV-2(O) was generated and is compared with published maps and sequences of other avian retroviruses.

Multiple proto-oncogene activations in avian leukosis virus-induced lymphomas: evidence for stage-specific events.

We have examined avian leukosis virus-induced B-cell lymphomas for multiple, stage-specific oncogene activations. Three targets for viral integration were identified: c-myb, c-myc, and a newly identified locus termed c-bic. The c-myb and c-myc genes were associated with different lymphoma phenotypes. The c-bic locus was a target for integration in one class of lymphomas, usually in conjunction with c-myc activation. The data indicate that c-myc and c-bic may act synergistically during lymphomagenesis and that c-bic is involved in late stages of tumor progression.

Structural organization of upstream exons and distribution of transcription start sites in the chicken c-myb gene.

We mapped and sequenced three upstream exons of the chicken c-myb gene and the regions flanking the first coding exon. We found multiple potential binding sites for transcription factors in the 5'-noncoding region, a T-rich stretch of 78 base pairs (bp) (68% T) in the first intron, and four fairly long open reading frames in the antisense direction of the first coding exon and its flanking regions. Three major transcription start sites, contained within a single 11-bp region, were identified by S1 nuclease analysis and primer extension. A sequence comparison of the avian and murine c-myb genes revealed a highly conserved sequence of 124 bp in the 5'-noncoding region. Its location between the putative transcription factor binding sites and the major transcription start sites suggests that it may play an important regulatory role in c-myb expression.

Absence of missense mutations in activated c-myc genes in avian leukosis virus-induced B-cell lymphomas.

We have determined the nucleotide sequences of two independent DNA clones which contained the activated c-myc genes from avian leukosis virus-induced B-cell lymphomas. Neither of these c-myc genes contained missense mutations. This strongly supports the notion that the c-myc proto-oncogene in avian leukosis virus-induced B-cell lymphomas can be oncogenically activated by altered expression of the gene without a change in the primary structure of the gene product.