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Biomedical subjects

J Keller

Publications and source records attributed to J Keller.

At least 145 records · Page 8Linked to original sources
PubMed1995

Brain injury and tumor necrosis factors induce calbindin D-28k in astrocytes: evidence for a cytoprotective response.

Calbindin is a 28 kDa calcium-binding protein expressed in restricted neuronal populations in the mammalian brain where it may play a role in protecting neurons against excitotoxic insults. Recent findings indicate that electrical activity and some neurotrophic factors can induce the expression of calbindin in neurons. We now report that brain injury, effected by systemic administration of the excitotoxin kainate or mechanical trauma, induces expression of calbindin in cells of the corpus callosum and subcortical white matter. Immunohistochemical analysis using antibodies to the astrocyte-specific proteins (glial fibrillary acidic protein and S-100 beta) established the identity of calbindin immunoreactive cells as astrocytes. Because brain injury is known to induce the expression of several neurotrophic factors and cytokines, we employed cultures of hippocampal and neocortical astrocytes to test the hypothesis that such factors can induce expression of calbindin in astrocytes. Tumor necrosis factors (TNF alpha and TNF beta), cytokines that are expressed in response to brain injury, induced the expression of calbindin in cultured rat hippocampal and neocortical astrocytes. Two neurotrophic factors, basic fibroblast growth factor and nerve growth factor, did not induce calbindin in astrocytes. TNF-treated, calbindin-expressing astrocytes were resistant to acidosis and calcium ionophore toxicity, suggesting that TNFs and calbindin may serve a cytoprotective role in astrocytes in the injured brain.

Animals↗
PubMed1995

Virtual reality in surgical education.

Virtual reality (VR) is an emerging technology that can teach surgeons new procedures and can determine their level of competence before they operate on patients. Also VR allows the trainee to return to the same procedure or task several times later as a refresher course. Laparoscopic surgery is a new operative technique which requires the surgeon to observe the operation on a video-monitor and requires the acquisition of new skills. VR simulation could duplicate the operative field and thereby enhance training and reduce the need for expensive animal training models. Our preliminary experience has shown that we have the technology to model tissues and laparoscopic instruments and to develop in real time a VR learning environment for surgeons. Another basic need is to measure competence. Surgical training is an apprenticeship requiring close supervision and 5-7 years of training. Technical competence is judged by the mentor and has always been subjective. If VR surgical simulators are to play an important role in the future, quantitative measurement of competence would have to be part of the system. Because surgical competence is "vague" and is characterized by such terms as "too long, too short" or "too close, too far," it is possible that the principles of fuzzy logic could be used to measure competence in a VR surgical simulator. Because a surgical procedure consists of a series of tasks and each task is a series of steps, we will plan to create two important tasks in a VR simulator and validate their use. These tasks consist of laparoscopic knot tying and laparoscopic suturing. Our hypothesis is that VR in combination with fuzzy logic can educate surgeons and determine when they are competent to perform these procedures on patients.

Clinical Competence↗
PubMed1995

Delivery and fate of oral mesalamine microgranules within the human small intestine.

BACKGROUND/AIMS: Oral use of mesalamine in inflammatory bowel disease requires slow-release preparations to prevent premature absorption and inactivation. Resulting luminal concentrations within the human small intestine are unknown. The aim of this study was to determine human intestinal delivery patterns of mesalamine from a microgranule preparation (Pentasa; Ferring Arzeimittel, Kiel, Germany) effective in Crohn's disease with small bowel involvement. METHODS: A multilumen tube for duodenal, jejunal, and ileal aspiration and marker perfusion was placed in 6 normal subjects. Levels of luminal, plasma, and urinary mesalamine and its main metabolite, acetyl mesalamine, were measured for 7 hours after ingestion of mesalamine (500 mg) with a labeled meal. RESULTS: Gastric emptying of mesalamine paralleled the meal, and its release occurred throughout the small intestine (cumulative, 20% of dose). For 4 hours, mean luminal mesalamine and acetyl mesalamine concentrations were 52 and 38 micrograms/mL (duodenum), 59 and 82 micrograms/mL (jejunum), and 64 and 104 micrograms/mL (ileum). Cumulative colonic delivery was 82% (7% dissolved, 75% in microgranules), and urinary excretion was 3.5%. CONCLUSIONS: Although the major part of continuous-release mesalamine is delivered to the colon, large proportions are liberated and available at high concentrations within the small intestinal lumen, thus explaining its therapeutic efficacy in small intestinal Crohn's disease.

Administration, Oral↗
PubMed1995

Effects of prehospital care on outcome in patients with cardiac illness.

STUDY OBJECTIVE: To compare outcomes of patients with acute cardiac illness transported by ambulance for whom prehospital care was provided by emergency medical technician-paramedics (EMT-Ps) or EMTs trained in defibrillation (EMT-Ds). DESIGN: A prospective chart review carried out over 3.5 years. SETTING: The Hamilton-Wentworth region of Ontario, Canada, which covers 1,136 km2 and includes five receiving hospitals. PARTICIPANTS: We prospectively identified 8,720 potentially eligible patients from approximately 30,000 who presented to the ambulance service. We reviewed hospital charts to confirm eligibility. The group of 8,720 patients yielded 3,066 patients with acute cardiac illness who met all other eligibility requirements. We excluded patients in cardiac arrest. RESULTS: Incidence of myocardial infarction (MI), length of hospital stay, and mortality were evaluated. Analysis was performed with chi 2 tests for association, linear regression, and logistic regression. Of the eligible patients who received prehospital EMS care, 783 sustained MIs. The proportions of people discharged alive with the diagnosis of MI did not differ between crew types (P = .16). Average hospital stay was 13 days in both groups for patients with the discharge diagnosis of MI; hospital stay ranged from 9 (EMT-D) to 11 days (EMT-P) for any patient with a discharge diagnosis other than MI. These values were statistically similar. The odds ratio of having had an MI after treatment by an EMT-D crew was 1.02 (95% confidence interval, .86 to 1.21) compared with that for treatment by an EMT-P crew. CONCLUSIONS: In an urban setting with short (less than 10 minutes) average transport times, the availability of prehospital paramedic care does not affect occurrence of MI, length of hospital stay, or mortality of patients presenting to the EMS system with cardiac illness.

Aged↗
PubMed1995

Influence of indomethacin on bone turnover related to orthodontic tooth movement in miniature pigs.

The purpose was to evaluate the influence of a prostaglandin inhibitor, indomethacin, on the tissue reaction related to orthodontic tooth movement. Sixteen miniature pigs were chosen for the study, eight of which received indomethacin perorally every day of the 39-day observation period. Sentalloy expansion springs (GAC, Central Islip, N.Y.) delivering 100 cN were inserted on a segmented arch between the central lower incisors. Intravital labeling with tetracycline was used for the evaluation of the rate of bone formation. After the pigs were killed, the bone turnover was evaluated on undecalcified methacrylate embedded sections and on microradiographs. The histomorphometric analysis of bone turnover revealed that the relative extent of resorption surfaces was decreased significantly in the indomethacin treated animals. Formation surfaces were also decreased although not significantly. The bone turnover, but not the mineralization rate, was influenced. The results corroborate the recommendation that prostaglandin inhibitors should be avoided during orthodontic treatments.

Administration, Oral↗
PubMed1995

Imaging of chondrosarcoma with histopathological and prognostic correlation. An analysis of 49 cases mainly based on plain film radiography.

PURPOSE: To investigate the course of chondrosarcoma in relation to radiographic and histopathologic findings. MATERIAL AND METHODS: 49 consecutive patients seen during an 11-year-period were analysed, including re-evaluation of their radiographic and histopathologic material. RESULTS: Forty-two patients had radiographic changes typical for cartilaginous tumours, in 37 with malignant stigmata. Seven patients had malignant changes not typical for chondrosarcoma. By histopathologic grading 16 patients had grade I, 17 grade II and 16 grade III tumours. Six of the grade II-III tumours were histopathologic variants (mesenchymal, dedifferentiated or myxoid chondrosarcomas). Surgical removal of the tumour was performed in 42 patients, 41 of whom were followed up for 0.4-11.4 years (median 3.8 years). Local recurrence occurred in 7 patients, and 11 patients developed metastases. Ten patients, 4 with local recurrence and metastases, and 6 with metastases only were dead at the end of the follow-up. The actuarial 5-year overall survival rate was 64%. The occurrence of local recurrence, metastases and death was found to be related to the histopathologic grades II and III. Atypical radiographic features only occurred in grade II-III tumours and were related to metastases and death, but not to local recurrence. CONCLUSION: Atypical radiographic findings were related to high-grade malignancy and poor prognosis.

Adolescent↗
PubMed1995

Directed tagging of the Arabidopsis FATTY ACID ELONGATION1 (FAE1) gene with the maize transposon activator.

The FATTY ACID ELONGATION1 (FAE1) gene of Arabidopsis is required for the synthesis of very long chain fatty acids in the seed. The product of the FAE1 gene is presumed to be a condensing enzyme that extends the chain length of fatty acids from C18 to C20 and C22. We report here the cloning of FAE1 by directed transposon tagging with the maize element Activator (Ac). An unstable fae1 mutant was isolated in a line carrying Ac linked to the FAE1 locus on chromosome 4. Cosegregation and reversion analyses established that the new mutant was tagged by Ac. A DNA fragment flanking Ac was cloned by inverse polymerase chain reaction and used to isolate FAE1 genomic clones and a cDNA clone from a library made from immature siliques. The predicted amino acid sequence of the FAE1 protein shares homology with those of other condensing enzymes (chalcone synthase, stilbene synthases, and beta-ketoacyl-acyl carrier protein synthase III), supporting the notion that FAE1 is the structural gene for a synthase or condensing enzyme. FAE1 is expressed in developing seed, but not in leaves, as expected from the effect of the fae1 mutation on the fatty acid compositions of those tissues.

Acetyltransferases↗
PubMed1995

Bacterial community structures of phosphate-removing and non-phosphate-removing activated sludges from sequencing batch reactors.

The bacterial community structures of phosphate- and non-phosphate-removing activated sludges were compared. Sludge samples were obtained from two sequencing batch reactors (SBRs), and 16S rDNA clone libraries of the bacterial sludge populations were established. Community structures were determined by phylogenetic analyses of 97 and 92 partial clone sequences from SBR1 (phosphate-removing sludge) and SBR2 (non-phosphate-removing sludge), respectively. For both sludges, the predominant bacterial group with which clones were affiliated was the beta subclass of the proteobacteria. Other major groups represented were the alpha proteobacterial subclass, planctomycete group, and Flexibacter-Cytophaga-Bacteroides group. In addition, several clone groups unaffiliated with known bacterial assemblages were identified in the clone libraries. Acinetobacter spp., thought to be important in phosphate removal in activated sludge, were poorly represented by clone sequences in both libraries. Differences in community structure were observed between the phosphate- and non-phosphate-removing sludges; in particular, the Rhodocyclus group within the beta subclass was represented to a greater extent in the phosphate-removing community. Such differences may account for the differing phosphate-removing capabilities of the two activated sludge communities.

Acinetobacter↗
PubMed1995

Automated chromosome classification limitations due to image processing.

Automated chromosome classification from metaphase spreads has been a difficult research problem over the past 30 years. Numerous techniques have been implemented to address the research problem. Image processing techniques support many methods utilized for automated and/or semiautomated karyotyping. Some current systems correctly classify individual chromosomes at high rates but lack the capability to properly classify chromosomes for entire cells consistently. Most systems attain high classification rates ignoring overlapping metaphase chromosomes for testing purposes. Chromosome classification depends on identifying features common to each chromosome class or number. Some of the common features incorporated into various chromosome classification systems include length, centromere location, banding pattern, and width. To complicate classification, chromosome features tend to vary not only between people but from cell to cell for the same person. Additionally, chromosomes found in metaphase spreads may have any orientation and virtually any degree of overlap with other chromosomes present. Besides the inherent barriers impeding chromosome classification, many systems perform image processing operations to the chromosomes for feature determination. Image processing operations, such as image rotation, that manipulate the chromosome grey-level information may distort the feature calculations utilized in karyotyping. Consequently, feature stability becomes an important issue for improving karyotyping capability.

Chromosomes, Human↗
PubMed1994

Ganciclovir treatment of herpes simplex thymidine kinase-transduced primary T lymphocytes: an approach for specific in vivo donor T-cell depletion after bone marrow transplantation?

Allogeneic bone marrow transplantation (BMT) is associated with a severe complication--graft-versus-host disease (GVHD). Although effectively preventing GVHD, ex vivo T-lymphocyte marrow depletion unfortunately increases graft rejection and reduces the graft-versus-leukemia (GVL) effect. The ex vivo transfer of the herpes simplex thymidine kinase (HS-tk) suicide gene into T cells before their infusion with hematopoietic stem cells could allow for selective in vivo depletion of these T cells with ganciclovir (GCV) if subsequent GVHD was to occur. Thus, one could preserve the beneficial effects of the T cells on engraftment and tumor control in patients not experiencing severe GVHD. To obtain T cells specifically depleted by GCV, we transduced primary T cells with a retroviral vector containing the HS-tk and neomycin resistance (NeoR) genes. Gene transfer was performed by coculturing PHA +/- CD3- or alloantigen-stimulated purified T cells on an irradiated retroviral vector producer cell line or by incubating the T cells in supernatant from the producer. Subsequent culture in G418 for 1 week allowed for the selection of transduced cells. GCV treatment of interleukin-2-responding transduced and selected cells resulted in greater than 80% growth inhibition, whereas GCV treatment of control cells had no effect. Similarly, the allogeneic reactivity of HS-tk-transduced cells was specifically inhibited by GCV. Combining transduced and nontransduced T cells did not show a bystander effect, thus implying that all of the cells inhibited by GCV were indeed transduced. Lastly, studies involving the transduction of the HUT-78 (T-lymphoma) cell line suggest that stable expression of HS-tk can be maintained over 3 months in vitro in the absence of G418. In summary, we have established the feasibility of generating HS-tk-transduced T cells for subsequent in vivo transfer with hematopoietic stem cells and, if GVHD occurs, specific in vivo GCV-induced T-cell depletion in allogeneic BMT recipients.

Bone Marrow↗
PubMed1994

Vascularized bone flaps in oromandibular reconstruction. A comparative anatomic study of bone stock from various donor sites to assess suitability for enosseous dental implants.

OBJECTIVE: To identify donor sites from which vascularized bone may be harvested capable of accepting osseointegrated implants of the minimum dimensions required to ensure long-term implant stability. DESIGN: An anatomic study of the most commonly employed donor sites for vascularized bone in oromandibular reconstruction was conducted on 28 cadavers. SETTING: Academic tertiary referral center. PARTICIPANTS: Twenty-eight freshly embalmed, adult white cadavers (16 male, 12 female) were dissected. INTERVENTION: The ipsilateral fibula, iliac crest, radius, and lateral border of the scapula were harvested and multiply sectioned at predetermined sites. OUTCOME MEASURE: Implantability was determined for each section based on measurements of height, width, and cross-sectional area utilizing computer planimetry. RESULTS: The iliac crest was the most consistently implantable donor site, followed by the scapula, fibula, and radius (83%, 78%, 67%, and 21% of sections from each donor site satisfying the criteria for implantability). Consistent regional differences in implantability were encountered at each donor site except the scapula. CONCLUSIONS: Following ablation of oromandibular malignant neoplasms, restoration of stable retentive dentition is a prerequisite to a successful functional oral rehabilitation. This is best achieved with enosseous implants, capable of supporting a stable dental prosthesis, placed directly into vascularized bone flaps at the time of mandibular reconstruction. The implications of the results obtained in this study for gender, donor site selection, and orientation of the vascularized bone flap are discussed.

Aged↗
PubMed1994

10A1 MuLV induces a murine leukemia that expresses hematopoietic stem cell markers by a mechanism that includes fli-1 integration.

The 10A1 murine leukemia virus induces tumors that lack lineage-specific markers found on myeloid, T-cell, and B-cell lineages. Either erythroid or multipotent stem cells can have this phenotype; therefore we have used fluorescence-activated cell sorter analysis with either multipotent stem cell markers or markers found on lineage-restricted precursors to differentiate between these two possibilities. The results showed that tumors induced by 10A1 expressed multipotent stem cell markers as well as some lineage-restricted precursor markers. To further study the tumor phenotype, we analyzed total RNAs from 10A1-induced tumors by Northern blotting for c-kit, erythropoietin receptor, and T-cell gamma receptor mRNAs. Most of the tumors contained these mRNAs, which are characteristic of early hematopoietic cells. These results are consistent with the hypothesis that 10A1-induced tumor cells are early multipotent hematopoietic stem cells. Southern blot analysis revealed that 14 of 14 10A1-induced tumor cell DNAs examined contained MuLV integrations into the fli-1 gene. The results strongly suggested that promoter insertion into fli-1 is required for tumor formation.

Animals↗
PubMed1994

Intrauterine growth retardation: fluctuation of fetal pH measured between beginning and at the completion of labor.

UNLABELLED: The aim of this study was to evaluate the fluctuation of fetal pH in blood samples taken at the beginning of labor and at the moment of birth as related to intrauterine growth retardation syndrome. This is a prospective follow-up of term gestations, of which 41 were diagnosed as intrauterine growth retardation (IUGR) and 61 as normal ones. pH was measured in scalp blood sample at the beginning of the labor and in umbilical artery right after birth in both groups respectively. The rate of decrease of pH value in relation to duration of labor was determined for each case. Our results are: 1) Lower baseline pH were found in the IUGR group (pH 7.32 vs 7.34, p < 0.01), lower arterial blood pH at birth/.23 +/- 0.08 vs 7.27 +/- 0.08, p < 0.05). 2) Faster decrease of the pH during the labor (0.019 unit/hour vs 0.012, p < 0.05) as related to IUGR. CONCLUSION: IUGR fetuses are more acidotic at the beginning of the labor, and the rate of decrease of the fetal pH per unit of time during the labor is faster at least in a theoretical situation nevertheless it will require more studies if any practical applications are thought of.

Acidosis↗
PubMed1994

Tennis elbow: a review.

Tennis elbow is a common yet sometimes complex musculoskeletal condition affecting many patients treated by physical therapists. The purpose of this article is to review the anatomy, clinical examination, differential diagnosis, conservative care, and surgical treatment for tennis elbow or lateral epicondylitis. Particular attention is given to determining the precise pathological cause of lateral epicondylitis, with consideration of intrinsic and extrinsic factors associated with this condition. This information should assist health care practitioners who treat patients with this disorder.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1994

Distraction effects on muscle. Leg lengthening studied in rabbits.

We investigated changes in the anterior tibial muscle during lengthening of the lower leg in rabbits. In 37 rabbits, an osteotomy of the right middle tibia was performed and was fixed by a unilateral external fixator. The rabbits were randomized into 6 groups. In groups 1, 2, and 3 the tibiae were distracted 0.5 mm/day. In groups 1 and 2, the rabbits were killed after 14 and 28 days of distraction, respectively, and in group 3 after 28 days of distraction, followed by 14 days of rest. Groups 1a, 2a, and 3a served as controls. They were treated similarly as groups 1, 2, and 3, but no distraction was performed. Proliferating cell nuclei were labeled with 5-bromo-2-deoxyuridine and were identified by immunohistochemical staining. The weight of the muscle was measured. During bone lengthening the muscle showed signs of growth, as indicated by increasing weight and number of proliferating cell nuclei. This was observed only during lengthening and it ceased when the lengthening was stopped.

Animals↗
PubMed1994

Evaluation of lipomatous soft tissue tumors by MR imaging.

Large soft tissue tumors--5 cm or greater--or deep-seated tumors have a greater risk of being malignant than smaller and superficially located tumors (9). In a period of 2 years 43 consecutive patients with lipomatous tumors 5 cm in diameter or greater were examined with MR imaging. The MR findings were correlated to histologic features and diagnosis. Twenty-six tumors were classic lipomas both on MR and at microscopy; 8 lipomas showed other features--some of them raising suspicion of malignancy at MR; all, however, were histologically benign. Nine tumors were considered malignant at MR imaging; all 9 proved to be malignant by microscopy.

Adipose Tissue↗
PubMed1993

Recurrent stage I endometrial adenocarcinoma in the nonirradiated patient: preliminary results of surgical "staging".

Recurrent endometrial carcinoma, even when clinically confined to the vagina or pelvis, is associated with poor survival. Pelvic radiotherapy for patients with localized recurrences who have not been previously irradiated has not been highly effective. Our hypothesis was that local salvage therapy fails because a significant number of patients have occult, subclinical distant metastases at the time of relapse. In order to accurately assess disease status at the time of the recurrence, we prospectively evaluated eight patients with recurrent disease limited to the vagina/pelvis by physical examination, routine laboratory tests, and radiologic imaging. All patients underwent a "staging" procedure which included laparotomy, selective pelvic/periaortic lymphadenectomy, peritoneal biopsies, and washings. Three (37.5%) of eight patients had upper abdominal disease found at laparotomy (95% confidence interval 0.11 to 0.71). Presence of subclinical metastases was associated with larger tumor size (> or = 2 cm) and elevated serum CA 125 antigen levels. Treatment was modified in three patients according to the results of surgical staging. One patient was treated with chemotherapy while two patients received whole-abdominal radiation in addition to pelvic fields. Seven of eight patients are alive 21 to 61 months following salvage therapy. Three (43%) of seven patients treated with radiotherapy suffered nonneoplastic bowel obstruction requiring laparotomy at 3, 6, and 15 weeks following completion of radiation therapy. Since 37.5% of patients with recurrent endometrial carcinoma clinically confined to the pelvis had occult upper abdominal disease, surgical reassessment may be warranted, especially in those with elevated serum CA 125 levels or large tumors. Our limited sample size precludes any definitive conclusions regarding our data. Further research will determine the frequency of subclinical metastases and the value of serum CA 125 levels in assessing disease status.

Adenocarcinoma↗