Biomedical subjects

R L Davis

Publications and source records attributed to R L Davis.

At least 181 records · Page 10Linked to original sources

PubMed1993

Immunohistochemical double staining with immunogold-silver and alkaline phosphatase to identify nuclear markers of cellular proliferation.

To facilitate cell kinetics studies of brain tumors labeled with thymidine analogs, we developed a new method to identify nuclei labeled sequentially with bromodeoxyuridine (BUdR) and iododeoxyuridine (IUdR) by double staining with immunogold-silver and alkaline phosphatase. Patients received an intraoperative infusion of BUdR; excised tumor specimens were immediately labeled with IUdR in vitro, fixed with 70% alcohol, embedded in paraffin, and cut into 6 microns sections. The sections were incubated first with BR-3, a monoclonal antibody that recognizes only BUdR, and then with IU-4, a monoclonal antibody that recognizes both BUdR and IUdR; sections were counterstained with hematoxylin to identify unlabeled nuclei. Nuclei labeled only with IUdR stained red, whereas those labeled with BUdR or with both BUdR and IUdR stained black against a red background; unlabeled nuclei stained blue. This method was the most efficient differential staining technique to identify nuclei labeled only with IUdR and those labeled with BUdR among unlabeled nuclei.

Alkaline Phosphatase↗

PubMed1993

Idiopathic hypertrophic cranial pachymeningitis. Report of three cases.

Hypertrophic cranial pachymeningitis is a rare, idiopathic form of granulomatous pachymeningitis. This report describes three cases of hypertrophic cranial pachymeningitis and discusses the clinical, radiographic, and pathological findings in these and other reported cases. These lesions typically cause progressive cranial nerve palsies, headaches, and cerebellar dysfunction. They occur in patients of all age groups; the peak incidence is in the sixth decade. Hypertrophic cranial pachymeningitis is best identified by magnetic resonance imaging. The diagnosis is established by excluding all other granulomatous and infectious diseases. A dural biopsy is essential to confirm the diagnosis. Hypertrophic cranial pachymeningitis is initially responsive to steroid therapy, but in most cases it recurs or progresses despite treatment. Surgical excision of granulomas is occasionally necessary to alleviate a mass effect. The long-term outcome remains uncertain for most patients, but progressive disease is usually fatal owing to cranial neuropathies.

Aged↗

PubMed1993

Microtubule aggregates in a clival chordoma.

We report a case of a clival chordoma in a 21-year-old man that ultrastructurally demonstrated large numbers of microtubule aggregates within the rough endoplasmic reticulum. Histologically, the tumor demonstrated classic chordoma architecture characterized by numerous physaliphorous cells and an abundant extracellular matrix. The tumor cells stained strongly for cytokeratin, S100 protein, and epithelial membrane antigen, indicative of the epithelial origin of this tumor. Ultrastructurally, the most conspicuous feature of this tumor consisted of parallel bundles of criss-crossing microtubules within the rough endoplasmic reticulum. These microtubules had a diameter of approximately 27 nm and did not demonstrate an internal structure. To our knowledge, this is the first report of microtubule aggregates in a spheno-occipital chordoma. We note that microtubule aggregates have been described in a number of different entities, and though proposed as a specific feature of "chondroid chordoma," they are a nonspecific finding.

Adult↗

PubMed1993

Congenital brain tumors.

The most common brain tumor that was present or produced symptoms at birth was teratoma. In this series of congenital tumors, teratomas occurred over 5 times more frequently than the second most common type, astrocytoma. They were often immature because of primitive neural elements and, rarely, a component of mixed malignant germ cell tumors. Incidence between sexes was nearly identical among histologic types that were reported at least 10 times, except for choroid plexus papilloma, which exhibited a male predominance. Four of five meningiomas occurred in males and 4 of 5 sarcomas in females. The predilection of neonatal brain tumors for supratentorial locations was also observed in this series of tumors present at birth. Teratomas occurred above the tentorium almost exclusively and all craniopharyngiomas and 14 of 16 choroid plexus tumors occurred supratentorially. At birth, large head or tense fontanel was a presenting sign in at least 55% of patients. Neurologic symptoms as initial symptoms were comparatively rare. Teratomas and craniopharyngiomas are tumors believed to arise because of developmental defects and these were the tumors that most often occurred with other anomalies. Anomalies were usually located in the head, with cleft lip or palate being most frequent. Prognosis for patients with brain tumors at birth was very poor, usually because of the massive size of the tumor. However, if small and favorably located, tumors were resected successfully. The most favorable outcomes were with choroid plexus tumors where aggressive treatment led to disease-free survival.

Brain Neoplasms↗

PubMed1992

Acquisition of myogenic specificity by replacement of three amino acid residues from MyoD into E12.

The basic helix-loop-helix (bHLH) protein MyoD is a transcription factor that is important for the induction of the myogenic phenotype. The DNA binding basic region (13 amino acids) is necessary for recognition of the consensus MyoD binding site, for transcriptional activation, and for conversion of fibroblasts to muscle. In contrast, the non-tissue-specific bHLH protein E12 can bind to the MyoD binding site but does not induce myogenesis. Here, it is shown that only two amino acids in the MyoD basic region and a single amino acid from the junction, which separates the basic region and helix 1, are sufficient for myogenic specificity when substituted into the corresponding region of E12. These findings suggest that the recognition of particular determinants in the basic region is required for conversion of fibroblasts to muscle.

Amino Acid Sequence↗

PubMed1992

Specificity of VIIIth nerve regeneration in lower vertebrates.

From the initial studies of Sperry (Am. J. Physiol, 144:735-741, 1945) to more recent investigations, the regenerative capacity of the VIIIth cranial nerve in nonmammalian vertebrates has been noted for its robust and accurate recovery of functional connections after transection. The VIIIth cranial nerve contains nerve fibers that link functionally distinct sensory epithelial to various areas within the central nervous system (CNS), yet after transection these multiple components of the nerve navigate back to their original central target areas, without innervating inappropriate nuclei. A number of factors may be required to establish and direct VIIIth nerve regeneration. Cellular interactions appear to be necessary for the initiation of outgrowth and the maintenance of neural connections. The release of chemotropic substances from target cells has been postulated as the most likely mechanism guiding the reinnervation of central targets. Furthermore, the growth characteristics of these neurons in tissue culture, without target cells present, indicates that intrinsically regulated growth features may also contribute to the process of VIIIth nerve regeneration.

Animals↗

PubMed1992

The Drosophila learning and memory gene rutabaga encodes a Ca2+/Calmodulin-responsive adenylyl cyclase.

Four putative adenylyl cyclase genes from Drosophila melanogaster were identified by virtue of their extensive sequence homology with mammalian cyclases. One corresponds to the learning and memory gene rutabaga and is most similar to the mammalian brain Ca2+/calmodulin (CaM)-responsive cyclase. In a mammalian expression system, rutabaga cyclase activity was stimulated approximately 5-fold by the presence of Ca2+/CaM. A point mutation, identified at this locus in rut1 mutant flies, resulted in loss of detectable adenylyl cyclase activity. New P element insertion-induced rutabaga mutations mapped to within 200 nucleotides of the 5' end of the rutabaga cDNA. These data confirm the identity of the rutabaga locus as the structural gene for the Ca2+/CaM-responsive adenylyl cyclase and show that the inactivation of this cyclase leads to a learning and memory defect.

Adenylyl Cyclases↗

PubMed1992

Cell kinetic analysis of human brain tumors by in situ double labelling with bromodeoxyuridine and iododeoxyuridine.

Fifty-seven patients with brain tumors (29 gliomas, 23 meningiomas, 5 miscellaneous) received infusions of intravenous iododeoxyuridine (IUdR) and bromodeoxyuridine (BUdR) 1-5 hr apart shortly before tumor removal. Excised tumor specimens were stained sequentially for BUdR and IUdR. The percentage of BUdR-labelled cells was determined to establish the labelling index (LI), or S-phase fraction, and the ratio of cells labelled only with IUdR to cells labelled with BUdR or with BUdR and IUdR was determined to calculate the duration of S-phase (Ts) and the potential doubling time (Tp) of each tumor. The BUdR LIs varied from less than 1% to 20%, reflecting the malignancy of each tumor. Despite the difference in LIs, however, Ts was fairly uniform (mean +/- SD, 8.7 +/- 2.0 hr). Tp varied from 2 days to more than 1 month and correlated closely with the BUdR LIs (Tp = 23/LI0.93; r2 = 0.91). Double-labelling studies with IUdR and BUdR allow the S-phase fraction, Ts and Tp to be determined from a single biopsy specimen and thus provide more useful information on the growth characteristics of individual tumors than can be obtained by single-labelling studies with BUdR.

Brain Neoplasms↗

PubMed1992

Proliferative potential and outcome in pediatric astrocytic tumors.

In 43 pediatric patients (29 male, 14 female) with primary astrocytic tumors of the central nervous system (CNS), the correlation was evaluated between outcome and proliferative potential, measured by the bromodeoxyuridine (BrdU) labeling index (LI). Twenty-five patients had low-grade gliomas, 13 had anaplastic gliomas, and 5 had glioblastomas multiforme (GBM). All patients underwent surgery; 37 also had chemotherapy, radiation therapy, or both. The median BrdU LIs were less than 1% (range 0-9.3%) in low-grade gliomas, 2.3% (range 0-21.2%) in anaplastic gliomas, and 7.7% (range 0-21.3%) in GBM. Seven of eight patients with BrdU LI greater than 5% have died (median survival 29 weeks). Median survival has not been reached in patients with BrdU LI less than 1% (19/22 alive) or between 1% and 5% (12/13 alive) after median follow-up periods of 165 and 120 weeks, respectively. A high BrdU LI correlated with short survival (p = 0.0001); the association between malignant histology and short survival was weaker (p = 0.019). BrdU LI is therefore a significant predictor of outcome in patients with primary CNS astrocytomas and appears to be a stronger predictor than histology in patients with low-grade and anaplastic gliomas. More patients need to be studied to confirm these preliminary observations.

Adolescent↗

PubMed1992

Predicting the recurrence of ependymomas from the bromodeoxyuridine labeling index.

The usefulness of histopathological grading in predicting the prognosis of patients with ependymomas is controversial. To clarify the discrepancy between the histological malignancy and the prognosis of these tumors, we estimated the proliferative potential of 32 intracranial and intraspinal ependymomas and correlated the findings with the clinical behavior. Each patient received an intraoperative infusion of bromodeoxyuridine (BUdR, 200 mg/m2 i.v.) before tumor removal; the BUdR labeling index (LI), or percentage of BUdR-labeled cells, was determined immunohistochemically in excised specimens. The mean BUdR LI (+/- SD) of intracranial malignant ependymomas was 4.1 +/- 2.8%. Nonmalignant intracranial and intraspinal ependymomas and subependymomas had mean LIs of 1.5 +/- 0.9%, 1.1 +/- 0.3%, and less than 1%, respectively. Overall, 44% of the tumors recurred. There were no statistically significant differences in the recurrence rates of intracranial and intraspinal ependymomas, including subependymomas (43% and 44%, respectively), or of intracranial ependymomas with LIs greater than 1.0% and less than 1.0% (67% and 44%, respectively). However, the early recurrence rate (within 24 months after treatment) of tumors with LIs greater than 1.0% was higher than that of tumors with LIs of less than 1.0% (100% vs. 25%, P less than 0.05). The BUdR LI also showed a statistically significant inverse correlation with the time to recurrence. These findings indicate that BUdR LI reflects the proliferative potential of individual ependymomas and can be used to help predict the recurrence and estimate the prognosis of these tumors.

Adolescent↗

PubMed1992

Histochemical study of pituitary adenomas with Ki-67 and anti-DNA polymerase alpha monoclonal antibodies, bromodeoxyuridine labeling, and nucleolar organizer region counts.

The growth potential of 65 pituitary adenomas was determined by histochemical analysis with Ki-67 and anti-DNA polymerase alpha monoclonal antibodies, bromodeoxyuridine (BrdUdR) labeling, and counts of argyrophilic nucleolar organizer regions (Ag-NORs). The mean proliferating cell indices (PCIs) determined by Ki-67 and anti-DNA polymerase alpha and the BrdUdR labeling index (LI) were generally very low [1.0 +/- 0.2%, 1.1 +/- 0.2%, and 0.5 +/- 0.1% (+/- SE), respectively]. Apart from adrenocorticotropic hormone-positive adenomas, which had significantly higher indices, there were no statistically significant differences in the indices among the other subtypes of pituitary adenomas. Recurrent tumors had higher Ki-67 and DNA polymerase alpha PCIs and BrdUdR LIs (3.6%, 4.2%, 1.4%) than primary tumors (0.8%, 0.8%, 0.3%; P less than 0.005). The number of Ag-NORs did not correlate significantly with any of the three indices. The mean number of Ag-NORs was higher in nonfunctioning adenomas than in functioning adenomas (2.04 vs 1.66, P less than 0.005); among prolactin-positive adenomas, those treated preoperatively with bromocriptine had more Ag-NORs than untreated tumors (1.75 vs 1.57, P less than 0.005). These results suggest that the Ki-67 and DNA polymerase alpha PCIs and the BrdUdR LI predict the growth potential of individual pituitary adenomas, whereas the number of Ag-NORs appears to correlate with hormone production rather than with the proliferative potential.

Adenoma↗

PubMed1992

Highly anaplastic astrocytoma: a review of 357 patients treated between 1977 and 1989.

Between May 1977 and August 1989, 357 patients (199 male, 158 female; median age 40 years) with highly anaplastic astrocytomas other than glioblastoma multiforme were treated according to any of several protocols used in studies by the University of California, San Francisco, and the Northern California Oncology Group. The data evaluated were age, Karnofsky Performance Score, survival, time to tumor progression, therapy, and the effect of treatment at the time of progression. The records of 219 patients were taken from the University of California database, and those of the other 138 were taken from the Northern California Oncology Group computer files. Their median Karnofsky Performance Score was 90% (range 40-100%), the overall median survival was projected as 170.9 weeks, and the median time to first tumor progression was 127.3 weeks. The median survival time measured after the first progression was 41.3 weeks. Age and Karnofsky Performance Score had a significant influence on survival and on time to the first tumor progression, whereas extent of surgery and the use of interstitial brachytherapy in the initial therapy did not. We conclude that these patients can expect a median survival of over 3 years, that young age and high Karnofsky Performance Score have a positive influence on survival, and that salvage therapies can extend survival after the onset of tumor progression for nearly a year. Although it did not lengthen survival when used in initial therapy, interstitial brachytherapy used at the time of tumor progression was associated with increased survival.

Adolescent↗

PubMed1992

Neurite regeneration from single primary-auditory neurons in vitro.

Neurons of the VIIIth cranial nerve in lower vertebrates precisely reconnect with their targets after sustaining injury. It is not known, however, whether the regenerating neurites are guided entirely by external cues or may also be directed by intrinsic mechanisms. To address this issue, single adult primary-auditory neurons were dissected from goldfish and placed in an in vitro environment, devoid of the normal complement of satellite cells, neighboring neurons, and synaptic targets, to observe their patterns of growth. Because acutely isolated neurons showed little neurite outgrowth, neurite regeneration was enhanced by focally crushing the VIIIth cranial nerve 2 to 24 h prior to removal for tissue culture. Neurons that regenerated under identical culture conditions showed growth patterns that could be categorized into three separate groups based on both their morphology and growth patterns. They either 1) remained unbranched (54%), 2) bifurcated or trifurcated into major branches directly from the myelinated stump (V-shaped) (19%), or 3) bifurcated from a regenerated process (Y-shaped), sometimes with a third, smaller branch (27%). Unbranched and V-shaped neurites grew at a constant elongation rate, while Y-shaped neurites grew variably, with alternating retractions and elongations. Neurite elongation was completed in a uniform time period of approximately 15 days despite the differences in elongation rate, maximum length, and latency to growth onset. The neurite branching morphology and manner of growth revealed in this study indicated that adult regenerating neurons can reproduce some elements of the final branching patterns in the absence of extrinsic cues, a capability which may ultimately contribute to the fidelity of reconnection seen in vivo.

Animals↗

PubMed1992

Preferential expression of the Drosophila rutabaga gene in mushroom bodies, neural centers for learning in insects.

Seven lines were isolated with P element insertions in the cytogenetic vicinity of the learning and memory gene, rutabaga, from an enhancer detector screen designed to mark genes preferentially expressed in mushroom bodies. Six of these lines performed poorly in learning and memory tests, and several failed to complement an existing rutabaga allele. Molecular cloning revealed that the P elements were inserted in the putative promoter of the rutabaga gene. RNA in situ hybridization and immunohistochemistry demonstrated that the expression of the rutabaga gene, which encodes a Ca2+/calmodulin-responsive adenylyl cyclase, is markedly elevated in the mushroom bodies of normal flies and that the insertion elements compromised its expression in the new rutabaga mutants. The reisolation of a known learning and memory gene, but with a heretofore unknown expression pattern, strongly supports the postulate that mushroom bodies are principal sites mediating olfactory learning and memory.

Alleles↗

PubMed1992

Effect of the addition of ciprofloxacin on theophylline pharmacokinetics in subjects inhibited by cimetidine.

OBJECTIVE: Although the effect of individual enzyme inhibitors on hepatic microsomal enzyme activity has been studied extensively, little data exist on the effects of combinations of inhibiting agents. The purpose of this study was to investigate the effect of the addition of a second hepatic oxidative enzyme inhibitor on the inhibition of metabolism in subjects already maximally inhibited by cimetidine. Ciprofloxacin was used as the second inhibitor. DESIGN: In a randomized crossover sequence, subjects received theophylline 5 mg/kg on day 6 of therapy with cimetidine 2400 mg/d, ciprofloxacin 1 g/d, both drugs, or while drug-free. SETTING: National Institutes of Health-funded General Clinical Research Center. PARTICIPANTS: Eight normal volunteers (6 men, 2 women; mean age 25.2 y). OUTCOME MEASURES: Theophylline pharmacokinetic parameters after each treatment were determined by model independent pharmacokinetic analysis. Statistical analysis of the data for differences between treatments was assessed by ANOVA for repeated measures. RESEARCH: When administered alone, ciprofloxacin and cimetidine caused a significant increase in theophylline elimination half-life and a decrease in clearance. Theophylline elimination half-life was significantly longer during combined therapy compared with either drug alone. Theophylline clearance was lower during combined treatment, although this relationship did not reach statistical significance. CONCLUSIONS: The addition of a second enzyme inhibitor in subjects receiving maximally inhibiting doses of cimetidine can produce a further decrease in the hepatic metabolism of drugs that are metabolized by the cytochrome P-450 microsomal enzyme system. As cimetidine and ciprofloxacin are frequently used together for a variety of common clinical indications, clinicians should be aware of this drug interaction and should consider that a similar effect may occur when other enzyme inhibitors are used concomitantly.

Adult↗

PubMed1992

Meningiomas: clinical implications of a high proliferative potential determined by bromodeoxyuridine labeling.

The clinical behavior of meningiomas with a high proliferative potential was analyzed to determine if the bromodeoxyuridine (BUdR) labeling index (LI) could be used to predict recurrence and the time to reoperation. Each patient received an intraoperative infusion of BUdR to label cells in DNA synthesis; the percentage of S-phase cells, or BUdR LI, of each tumor was determined immunohistochemically. Of 178 meningiomas studied, 53 had BUdR LIs greater than or equal to 1%. Of these 53 tumors, 21 were diagnosed histopathologically as malignant meningioma. Twenty-two percent of nonmalignant tumors and 81% of malignant tumors were recurrent or recurred after the BUdR study; repeat studies were performed in four patients. The mean BUdR LI of recurrent tumors was significantly higher than that of the nonrecurrent tumors [3.9 +/- 2.6 versus 1.9 +/- 1.0% (SD), P less than 0.005]. The recurrence rate was 100% for tumors with LIs greater than or equal to 5%, 55.6% for those with LIs of 3 to 5%, and 30.6% for those with LIs of 1 to 3%; the percentages of malignant meningiomas in these groups were 88%, 78%, and 19%, respectively. Logarithmic regression analysis showed that the time to reoperation (in months) can be predicted from the BUdR LI as: 70.0 x LI (%)-1.2 (R = 0.76). This formula can be used to estimate the doubling time of individual tumors and to predict the period of greatest risk of recurrence of meningiomas with a high proliferative potential.

Adolescent↗

PubMed1992

Proliferative characteristics of juvenile pilocytic astrocytomas determined by bromodeoxyuridine labeling.

Bromodeoxyuridine (BUdR) labeling studies were performed to characterize the biological and clinical behavior of 50 juvenile pilocytic astrocytomas (JPAs) from 47 patients. Each patient received an i.v. infusion of BUdR before tumor resection; the excised tumor specimens were stained by the immunoperoxidase method with anti-BUdR monoclonal antibody to determine the BUdR labeling index (LI), or percentage of S-phase cells. The BUdR LI ranged from 0.22 to 4.3% (less than 1% in 34 and greater than or equal to 1% in 16; mean +/- SE, 1.05 +/- 0.13%). Tumors from younger patients often had higher LIs, but as the age of the patients increased, the frequency of tumors with LIs greater than or equal to 1% decreased. Tumors from male patients had higher LIs than those from female patients (1.36 +/- 0.20% [SE] vs. 0.75 +/- 0.13%; P less than 0.01), and tumors in the cerebellum had higher LIs than those in the hypothalamus (1.39 +/- 0.24% vs. 0.87 +/- 0.15%; P less than 0.05). The LI did not correlate with the gross appearance of the tumor (solid or cystic) or with outcome after the initial diagnosis. Overall, there was no difference in the LIs of primary and recurrent tumors. Four tumors (3 primary and 1 recurrent) that recurred after subtotal resection had a higher mean LI than 32 tumors that did not recur after subtotal resection (2.6 +/- 0.7% vs. 0.74 +/- 0.09%; P less than 0.005). None of 14 totally resected tumors (mean LI, 1.3 +/- 0.2%) has recurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1992

Histopathological follow-up study of 66 cerebral arteriovenous malformations after therapeutic embolization with polyvinyl alcohol.

Embolization with polyvinyl alcohol (PVA) is an accepted method of rendering complex arteriovenous malformations (AVM's) more amenable to surgery, but its effects on human vascular tissues have not been adequately documented. The authors reviewed the histopathology of 66 intracranial AVM's resected 1 to 76 days after embolization with PVA. The mean age of the patients was 36 years, and their AVM's were located in the cerebral hemispheres (92%), the cerebellum (6%), or the corpus callosum (2%). In 79% of cases, at least one vessel contained PVA particles; in most cases, the vessel was filled with sharp, angular PVA particles in a serpiginous pattern. Polyvinyl alcohol particles indented the endothelium in 69% of cases but were rarely found subendothelially. Clotted blood and fibroblasts were present among the particles, and abundant intraluminal mononuclear and polymorphonuclear inflammatory cells were found in all vessels containing PVA particles. Foreign-body giant cells appeared 2 to 14 days after embolization in the majority of cases. Patchy mural angionecrosis and necrotizing vasculitis were found in 39% of the cases. Recanalized lumina were seen in 18% of PVA-embolized vessels. Foreign materials resembling cotton fibers and other particulate substances, which were probably contaminants of the contrast solution or the embolic material, were found in 65% of the cases. These findings suggest a specific chain of events in the interaction between PVA and vessel wall components and may explain some important sequelae of embolization therapy.

Adolescent↗