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Biomedical subjects

D L Johnson

Publications and source records attributed to D L Johnson.

At least 145 records · Page 8Linked to original sources

Embryological basis of some aspects of cerebral vascular fistulas and malformations.

The literature on the formation of cerebral veins is reviewed to obtain a better understanding of some cerebrovascular anomalies. Clinical observations such as the entry of the superior ophthalmic vein into the cavernous sinus through the inferior rather than the superior orbital fissure, the relative infrequency of middle cerebral vein backflow in the presence of an extensive cavernous fistula, and the relative infrequency of hemorrhage in relation to the inferior petrosal fistula all relate to the persistence of an older venous pathway. The frequent occurrence of hemorrhage in association with the superior petrosal sinus fistula and the frequent failure of the superior petrosal sinus to connect to the cavernous sinus similarly have an embryological explanation. The frequent association of the vein of Galen aneurysm and an absent or deformed straight sinus probably relates to the time at which the paired internal cerebral veins fuse into one channel. It is speculated that the origins of cerebral venous malformations (CVMs) and arteriovenous malformations (AVMs) probably relate to sequential formation and absorption of surface veins, which occur in human embryonic development mainly in the 40- to 80-mm length interval, although persistent AVM growth is possible even after birth. The frequent absence or anomaly of the middle cerebral vein and its failure to communicate with the cavernous sinus in the presence of both CVMs and AVMs are linked to the late development of that vein and to its even later connection to the cavernous sinus.

Fistula↗

Cerebral venous malformation-arteriovenous malformation transition forms.

Three cases of cerebral venous malformation (CVM) are presented to demonstrate the triad that characterizes CVM: abnormal surface venous drainage, a "star-cluster" system of deep collecting veins, and a deep draining vein. Four other cases are introduced that illustrate this triad and show an additional feature, namely arterial fistulization; these cases represent arteriovenous malformations (AVMs). A final case demonstrates a CVM within an AVM. Both of these structures have a common draining vein and an identical venous core. On the basis of the cases described and of others less suitable for illustration, it is postulated that an AVM is a fistulized CVM and that both relate to a failure in the development of the cortical venous mantle. This proposition is based on the authors' observations and their assessment of the "best possible fit."

Cerebral Angiography↗

Ultrastructure of selected struvite-containing urinary calculi from cats.

OBJECTIVE: To elucidate the ultrastructural details of struvite-containing urinary calculi from cats. DESIGN: Specimens studied were inclusive of the range of textures visible during preliminary analysis by use of a stereoscopic dissecting microscope. Textural types, which were used to infer crystal growth conditions, were differentiated with regard to crystal habit, crystal size, growth orientation, and primary porosity. SAMPLE POPULATION: Thirty specimens were selected from a collection of approximately 1,600 feline urinary calculi: 20 of these were composed entirely of struvite, and 10 consisted of struvite and calcium phosphate (apatite). PROCEDURE: Qualitative and quantitative analyses of specimens included use of plain and polarized light microscopy, x-ray diffractometry, scanning electron microscopy with backscattered electron imagery, x-ray fluorescence scans, and electron probe microanalysis. RESULTS: Four textural types were recognized among struvite calculi, whereas 2 textural types of struvite-apatite calculi were described. CONCLUSIONS: The presence of minute, well interconnected primary pores in struvite-containing urinary calculi from cats is an important feature, which may promote possible interaction of calculi with changes in urine composition. CLINICAL RELEVANCE: Primary porosity, which can facilitate interaction between the calculus and changing urine composition, may explain the efficacy of dietary or medicinal manipulations to promote the dissolution of struvite-containing uroliths from this species.

Animals↗

Human syngeneic intestinal transplantation: evaluation of enterocyte viability with serum levels of intestinal fatty acid binding protein.

In a case of human syngeneic intestinal transplantation, the post-operative course was complicated by the Systemic Inflammatory Response System (SIRS). This syndrome was characterized by negative cultures and elevated levels of the pro-inflammatory cytokines, IL-1 beta, IL-6 and TNF. In keeping with current concepts of translocation across the enterocyte barrier as the etiology of SIRS, levels of intestinal fatty acid binding protein (I-FABP), an enterocyte-specific protein, also increased. These observations suggest that (i) a clinical syndrome consistent with translocation may occur in the absence of rejection in intestinal transplantation, and (ii) I-FABP may serve as a clinically relevant marker for enterocyte injury.

Adult↗

Ultrastructure of selected struvite-containing urinary calculi from dogs.

OBJECTIVE: To elucidate the ultrastructural details of struvite-containing urinary calculi from dogs. SAMPLE POPULATION: 38 specimens were selected from a collection of approximately 13,000 canine urinary calculi: 18 of these were composed entirely of struvite, and 20 consisted of struvite and calcium phosphate (apatite). PROCEDURE: Qualitative and quantitative analyses of specimens included use of plain and polarized light microscopy, x-ray diffractometry, scanning electron microscopy with backscattered electron imagery, x-ray fluorescence scans, and electron microprobe analysis. RESULTS: 4 textural types were recognized among struvite calculi, and 4 textural types of struvite-apatite calculi were described. Evidences of calculus dissolution were described from 4 calculi studied. CONCLUSIONS: The presence of small, well interconnected primary pores in struvite-containing urinary calculi from dogs appears to be a significant factor in determining the possible interaction of calculi with changes in the urine composition. The progress of dissolution from the calculus surface to the calculus interior appears to be largely affected by the primary porosity originally present between crystals forming the calculus framework. Apatite was observed to be more resistant to dissolution than struvite. CLINICAL RELEVANCE: The prevalence of fine concentric laminations having low porosity, and the common occurrence of apatite among struvite-containing urinary calculi from dogs may be 2 reasons why the efficacy of dietary and medicinal manipulations in dissolving urinary calculi is greater among cats than it is among dogs.

Animals↗

Characterizing the outlines of degraded fine-particles by fractal dimension.

Fractal dimension has been used extensively as a descriptor of the rugged outlines of fine-particles. Potentially, it may be a useful parameter for characterizing the outlines of fine-particles which have been subjected to some form of chemical degradation. Here, fractal dimension values have been computed for the outlines of microscopic lead fine-particles both before and after weak hydrochloric acid dissolution experiments. Values obtained for the post-dissolution rugged profiles were greater than those of the pristine fracture grains which had a Euclidean form. The profiles of the degraded fine-particles could be characterized by a single fractal dimension value, or they exhibited multifractal behavior. Data from profiles of fine-particles lead from the natural environment of the soil suggest that fractal dimension calculations may provide a useful descriptor for particles which have undergone chemical dissolution and transformation in such an environment.

Environmental Pollutants↗

Enlarging skull fractures in children.

Large skull fractures are conventionally followed radiographically until healing occurs. Fractures which enlarge or remain unhealed are commonly termed "leptomeningeal cysts" or "growing skull fractures". This study of ten children with this injury and a review of the literature shows that a true leptomeningeal cyst is seldom present and that skull fractures do not "grow". Moreover, careful history-taking and physical examination will correctly identify all enlarging or unhealed skull fractures of childhood without the need for plain radiographs or computed tomography of the skull.

Arachnoid Cysts↗

Long-term results of curative resection of "minimally invasive" colorectal cancer.

PURPOSE: The aim of this study was to determine the long-term outcome after curative resection of colorectal cancers that extend only into the submucosa ("minimally invasive") and to evaluate potential histologic predictors of lymph node metastases. METHODS: Seventy-nine patients who underwent curative resection of minimally invasive colorectal cancer and were followed for at least five years were studied retrospectively. RESULTS: The series was comprised of 53 men and 26 women, with a mean age of 61 years. The lesion was in the colon in 47 patients and the rectosigmoid or rectum in 32 patients. Open surgery followed attempted endoscopic tumor removal in 25 patients. Lymph node metastasis, found in 11/79 patients (13.9 percent), was associated with worse outcome: 36.4 percent of node(+) patients developed recurrence, vs. only 5.9 percent of node(-) patients (P < 0.005). The cumulative survival rate was also worse in node(+) vs. node(-) patients: 72.7 percent vs. 91.1 percent at five years (P < 0.05) and 45.5 percent vs. 65.3 percent at ten years (P < 0.05). Five histopathologic characteristics were identified as risk factors for lymph node metastasis: 1) small clusters of undifferentiated cancer cells ahead of the invasive front of the lesion ("tumor budding"); 2) a poorly demarcated invasive front; 3) moderately or poorly differentiated cancer cells in the invasive front; 4) extension of the tumor to the middle or deep submucosal layer; 5) cancer cells in lymphatics. Whereas patients with three or fewer risk factors had no nodal spread, the rate of lymph node involvement with four or more risk factors was 33.3 percent and 66.7 percent, respectively. CONCLUSIONS: Metastasis is not infrequent in "minimally invasive" colorectal cancer. Appropriate bowel resection with lymph node dissection is indicated if such a lesion exhibits more than three histologic risk factors for metastasis.

Adult↗

Human acute tubular necrosis: a lectin and immunohistochemical study.

To determine the nephron segment distribution of tubular epithelial damage and regeneration and the proliferative activity of various nephron segments in human acute tubular necrosis (ATN) with an antibody to proliferating cell nuclear antigen (PCNA) and to compare the findings in native kidneys with ATN with those in transplant kidneys with ATN, archival tissues from 12 native and 21 transplant kidney biopsy specimens and nine transplant nephrectomy specimens were collected that all showed obvious morphological signs of ATN. Nineteen patients with transplant kidneys with ATN were immunosuppressed with cyclosporine and 11 were immunosuppressed with prednisone and azathioprine. There was a predominance of "regenerating" tubules (tubules with thin epithelium) in the distal nephron in native kidneys with ATN; in the transplant kidneys this was less conspicuous. The number of Tamm-Horsfall protein (THP)-positive tubules was decreased in all kidneys with ATN compared with normal human kidneys. In contrast, the number of THP-positive casts was much higher in all kidneys with ATN than in the normal kidneys. In transplant kidneys with ATN the number of THP-positive casts was substantially lower than in native kidneys with ATN. The macula densa appears to maintain its morphological integrity in kidneys with ATN. Both regenerating and normal appearing tubules expressed vimentin and HLA-DR. The proliferation index (PI; ie, percentage of PCNA-positive nuclei) of the renal tubular epithelium in normal control kidneys varied between 0.22 and 0.33, depending on the tubule segment. The highest PI was noted in the transplant kidneys with ATN not treated with cyclosporine (8.0), followed by the native kidneys with ATN (4.4) and the transplant kidneys with ATN treated with cyclosporine (4.3). We did not find any significant difference in the PI between the regenerating (5.0) and normal appearing (5.6) tubules. Proximal tubules (8.7) showed significantly higher PI values than distal tubules (3.5) in transplant kidneys with ATN. Our results show substantial differences between native kidneys and transplant kidneys with ATN. Tubular epithelial cell proliferation in human ATN is prominent and appears to correlate with the severity of ATN. Light microscopically normal appearing tubules and regenerating tubules participate equally in the regeneration of injured tubules. Cyclosporine may have an inhibitory effect on cell regeneration (proliferation) in human transplant kidneys with ATN.

Cell Division↗

Insertion-site anatomy of the human menisci: gross, arthroscopic, and topographical anatomy as a basis for meniscal transplantation.

A cadaveric study was performed to determine the insertion-site anatomy of the human menisci, their topographical relationships to adjacent intra-articular structures, and which arthroscopic portal provides for optimal visualization of each insertion site. Fifteen fresh-frozen cadaver knees were studied (ages 48 to 63 years). Ten knees underwent arthroscopy using four standard arthroscopic portals. Visualization and placement of an arthroscopic guide over each meniscal horn insertion site was attempted through the four arthroscopic portals. Guide wires were drilled to mark horn insertions followed by a gross dissection to evaluate accuracy of the guide wire gross dissection to evaluate accuracy of the guide wire placement and to isolate meniscal horn insertion sites. Insertion sites were outlined and evaluated for size and topographical relationships to other intra-articular structures. Five additional knees were dissected free of all soft tissues except the tibial insertions of the meniscal roots and anterior cruciate ligament/posterior cruciate ligament. Each tibia was mounted in a jig and a digitizing system was used to record coordinates of points along the outline of each bony meniscal horn insertion site, the ACL tibial insertion, and the articular surface of each tibial plateau. The x, y, z coordinates for each point were calculated and loaded into a computer program allowing for surface area determination and computer-generated topographical maps to assess relative position of each specific insertion site. Placement of the arthroscope in the anterolateral portal allows optimal visualization and guide wire placement for both lateral meniscal horn insertion sites. Medial meniscal anterior and posterior horn insertion sites are best visualized with the arthroscope in the anteromedial and posteromedial portals respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Arthroscopy↗

Comparison of three measures of injury severity in children with traumatic brain injury.

Eighty-six traumatically brain-injured children aged 6 to 15 years who were consecutively admitted to a pediatric Level I trauma center were recruited for participation in the study. A comprehensive battery of behavioral, cognitive, communicative, social, motoric, and neurological tests was administered to the children from 12 to 36 months postinjury. The performance of three severity indices, the Glasgow Coma Scale (GCS), the ASCOT probability of survival, and the head injury component of the Anatomic Profile, was compared with respect to their association with long-term outcomes in five neurological domains, as assessed by linear regression models. The ASCOT probability of survival was correlated to test scores in all five domains. The GCS and the head injury component of the Anatomic Profile were each correlated to outcome in only one domain. The ASCOT probability of survival, which includes coded variables for the GCS, systolic blood pressure, and respiratory rates on admission, as well as a measure of multisystem anatomic injury, was the most sensitive indicator of head injury severity and was associated with outcomes beyond survival and death in this population. Probability of survival is a promising brain injury severity index that may be useful in efforts to assess new medical and rehabilitative therapies for children with traumatic brain injury.

Adolescent↗

Erythropoietin receptor: application in drug development.

Erythropoietin (EPO) is the primary hormone responsible for the growth and maturation of red blood cells in mammals. In contrast to many other growth factors, the specificity of EPO for mature erythroid cells has lead to its development as a safe and efficacious therapeutic, EPREX. The medical benefits of EPREX have been well established in the treatment of anaemic chronic renal failure patients, anaemic HIV patients treated with AZT, cancer chemotherapy patients, and patients wishing to donate their own blood prior to elective surgery (autologous predonation). Due to the chronic nature of EPO therapy, it would be desirable to have an orally administered 'second generation' molecule. An understanding of the structural basis of the interaction of EPO with its receptor will aid in the design of an oral anaemia drug. In this study, a series of mutations have been generated in a truncated form of the receptor comprising the extracellular region, termed EPO binding protein (EBP). One mutant, in which alanine replaces phenylalanine at position 93 (F93A) has a 500-fold reduction in binding compared to wild-type EBP. A neutralizing anti-EBP antibody binds poorly to the F93A mutant, while a non-neutralizing anti-EBP antibody binds wild-type and F93A equally well. Information from this mutational analysis can be applied to a receptor 3-D model and ultimately used in drug development.

Amino Acid Sequence↗

The hepatitis B virus X protein increases the cellular level of TATA-binding protein, which mediates transactivation of RNA polymerase III genes.

The hepatitis B virus X gene product transactivates a variety of cellular and viral genes. The mechanism for X induction of RNA polymerase (pol) III genes was investigated. By using Drosophila S-2 cells stably transformed with the X gene, the transient expression of a tRNA gene is enhanced. Comparing the transcriptional activities of extracts derived from these cells, all three types of RNA pol III promoters are stimulated by X. Interestingly, both S-2 and rat 1A cells stably transformed with the X gene produce increased cellular levels of the TATA-binding protein (TBP). By using various kinase inhibitors, it was found that the X-mediated increases in both transcription and TBP are dependent upon protein kinase C activation. Since TBP is a subunit of TFIIIB, the activity of this component fractionated from extracts derived from control and X-transformed cells was analyzed. These studies reveal that TFIIIB activity is substantially more limiting in control cells and that TFIIIB isolated from X-transformed cells has increased activity in reconstitution assays compared with TFIIIB isolated from control cells. Conversely, comparison of TFIIIC from control and X-transformed cell extracts revealed that there is relatively little change in its ability either to reconstitute transcription or to bind to DNA and that there is no change in the catalytic activity of RNA pol III. Studies were performed to determine whether directly increasing cellular TBP alone could enhance RNA pol III gene transcription. Transient expression of a TBP cDNA in rat 1A cells was capable of stimulating transcription activity from the resultant extracts in vitro. Together, these results demonstrate that one mechanism by which X mediates transactivation of RNA poll III genes is by increasing limiting TBP via the activation of cellular signaling pathways. The discovery that X increases cellular TBP, the universal transcription factor, provides a novel mechanism for the function of a viral transactivator protein and may explain the ability of X to produce such large and diverse effects on cellular gene expression.

Animals↗

Predicting outcome in the tethered cord syndrome: a study of cord motion.

Thirty-two children with spinal dysraphism have been studied with phase MRI to assess longitudinal cord motion. Seventeen children who were asymptomatic and who had normal or slightly decreased motion were not operated. Fifteen had signs and symptoms of spinal cord tethering as well as decreased cord motion and underwent surgery. None of the nonsurgical patients have become symptomatic. The children with markedly decreased cord motion did not improve after surgery. A trend was seen toward a better outcome in younger patients with slight or moderate decrease in cord motion. All children with worse outcome were previously operated meningomyeloceles who had markedly decreased cord motion and who were greater than 10 years old.

Adolescent↗