Neuroanatomy: mushrooming mushroom bodies.
A revolution is spreading in the study of mushroom bodies, structures within the insect brain that mediate learning and memory processes and pheromonal discrimination of the opposite sex.
Animals↗
Biomedical subjects
R L Davis
Publications and source records attributed to R L Davis.
Risk factors for the infant prone sleep position.
OBJECTIVE: To identify parental characteristics associated with infants being placed to sleep in the prone position. STUDY DESIGN: Cross-sectional survey. PATIENTS: Randomly selected King County, Washington, infants born on the same days as King County infants who died of sudden infant death syndrome between November 1992 and October 1994. METHODS: Parents of study infants responded to a telephone interview about sleep position in their infants. Parents were asked how they usually put their infants to bed during the previous 2 weeks, and if they were aware of any recent advice on sleep position in young infants. Demographic data were also collected during the telephone interview. Logistic regression was used to identify infant and parental characteristics associated with the prone sleep position. RESULTS: Parents of 178 infants were interviewed; 28.1% responded that their infants usually slept prone, 66.9% slept nonprone, and 5% had no usual sleep position. Parents who were unaware of sleep position advice were more likely to place their infants prone than those who were aware of this advice (odds ratio, 3.5; 95% confidence interval, 1.5-7.8). Among parents who were aware of sleep position advice, mothers younger than 20 years were more than 10 times as likely to place their infants prone than were older mothers (odds ratio, 10.7; 95% confidence interval, 1.1-107.0). For those who were unaware of sleep position advice, single mothers were more likely to place their infants prone (odds ratio, 14.0; 95% confidence interval, 1.5-133.2). Single mothers and parents of low-birth-weight infants were more likely to be unaware of recent medical advice regarding optimal sleep position for infants. CONCLUSIONS: The results of this study may provide direction to future efforts to encourage nonprone sleeping. Knowledge of the risk is associated with decreased use of prone sleep position. Single mothers should be targeted for intensive educational efforts regarding the hazards of prone sleeping. Among teenage mothers, awareness of the association between prone sleeping and sudden infant death syndrome may not be adequate to change behavior; educational interventions that are more focused for this age group may be needed.
Adult↗
Follow-up of Papanicolaou smears diagnosed as atypical squamous cells of undetermined significance.
In the first year since the institution of the Bethesda system at UCDMC, 549/7,388 (7.43%) Papanicolaou (Pap) smears were diagnosed as having an epithelial abnormality. One hundred ninety-three of the 549 (35.1%) of the abnormal smears received an ASCUS diagnosis, representing 2.61% of the total volume. Follow-up was obtained on 124/193 (64.2%) and consisted of colposcopy with biopsy in 38.3%, one repeat Pap smear in 51.2%, and two or more repeat Pap smears in 10.5%. Follow-up revealed a squamous intraepithelial lesion (SIL) in 29.1%, ASCUS in 12.9%, and no evidence of an epithelial lesion in 58.0%. Review of the original ASCUS Pap smear from the group with no epithelial lesion on follow-up showed increased inflammation plus metaplasia and/or reactive changes in 69.5% and ASCUS in 19.5%. This study demonstrates that a significant percentage of ASCUS Pap smears represent SIL. However, many Pap smears with reactive, inflammatory changes are misclassified as ASCUS and would be best diagnosed under "Reactive/Reparative Changes" in the Bethesda system. Careful attention to criteria for ASCUS and inflammatory and reactive atypia is recommended to avoid misclassification and to make this category more meaningful to the clinician.
Carcinoma in Situ↗
Fine-needle aspiration cytology of sarcoma: retrospective review of diagnostic utility and specificity.
Fine-needle aspiration cytology (FNA) is useful because of its low cost, quick turn around time, and low incidence of complications. This study investigates the role FNA plays in the evaluation of sarcoma. We reviewed all the pathologic material from patients with sarcoma or a FNA diagnosis suggestive of sarcoma at the University of California-Davis Medical Center (1985-1994). Fifty-two of 196 patients identified (26.5%) were evaluated with FNA exhibiting 46 soft tissue and 6 bone lesions located in the extremities (19), trunk (19), head and neck (8), retroperitoneum (3), and abdominal cavity (3). Among 196 patients identified, those evaluated by FNA had soft tissue rather than bone lesions (P < .001) and primary sites other than in the extremities (P < .001). The primary neoplasms for the 52 FNA patients included 47 sarcomas (10 malignant fibrous histiocytomas and 16 other types), 1 intramuscular myxoma, 2 lymphomas, and 2 spindle cell (sarcomatoid) carcinomas. In 43 patients (22% of total), FNA was used first, before a primary diagnosis. The FNA report showed the correct specific neoplasm in only 20.9%. However, the FNA reports reflected an effective positive diagnosis leading to appropriate diagnostic biopsy in 88.4%, while only 7.0% were misleading (benign or inflammatory) and 4.6% inadequate. Review of FNA slides for 32 of 43 patients in which FNA was used first, in a blinded fashion, exhibited 21.9% specificity for the specific neoplasm, and 88.4% effective positive diagnoses. In 9 patients, FNA was utilized to investigate recurrence. Five out of 5 instances of recurrent sarcoma were identified by FNA. However, FNA misidentified recurrence in 3/4 instances, exhibiting suspicious cells from regenerating skeletal muscle (2) and a traumatic neuroma (1). The specific diagnosis for sarcomas is challenging even with surgical material. FNA usually does not provide a specific diagnosis (only in 20.9% of cases) and review of routinely prepared slides showed the same specificity as reflected by the original FNA report, at times formulated with the benefit of immunohistochemistry or electron microscopy. FNA effectively evaluated lesions in 45 of 52 patients (86.5%), confirming the useful screening role for this technique in sarcomas.
Adult↗
The Drosophila brain revisited by enhancer detection.
The patterns of gene expression in the Drosophila brain were studied by using the lacZ reporter gene carried on an enhancer detector element. From the analysis of serial sections of the heads of 6000 enhancer detector lines, reporter gene expression in some lines was found to generally follow boundaries established by cell type or anatomy, revealing distinct patterns of lacZ expression restricted to the lamina, the medulla, mushroom bodies, antennal lobes, or other anatomical subdivisions. About 15% of the lines showed ubiquitous expression in most or all head tissues and 25% of the lines showed expression throughout the CNS. Another quarter of the lines showed widespread expression in the CNS, with large regions of the brain showing expression. This suggests that the majority of detected genes are expressed with little spatial specificity. The expression patterns produced by 12 different insertions at the rutabaga locus were found to be extremely similar in the brain and offer strong evidence that the enhancer detector elements generally report the activity of an adjacent gene. Only 15% of the lines were judged to have relatively specific expression in one brain region, including those with preferential or specific expression in the mushroom bodies, antennal lobes, lamina, medulla, etc. The cytological insertion sites for elements showing preferential mushroom body expression were found to be dispersed in the genome at approximately 50 different chromosomal regions. In addition to providing a broad picture of the transcriptional activity in the Drosophila brain, these enhancer detector lines offer access to interesting new genes and form a novel collection of lines in which identifiable brain cells are marked in a reproducible way.
Animals↗
Comparison of bromodeoxyuridine uptake and MIB 1 immunoreactivity in medulloblastomas determined with single and double immunohistochemical staining methods.
We examined the growth potential of 17 medulloblastomas by single and double immunohistochemical staining with bromodeoxyuridine (BUdR) and MIB 1, a monoclonal antibody for Ki-67 protein, in serial sections of ethanol-fixed, paraffin-embedded tissues; we also assessed the heterogeneity of the immunoreactivity in the tumors. In the most active areas, the BUdR labeling index (LI) was 6.8 to 26.9% (HCl hydrolysis) and 7.5 to 28.8% (microwave heating), and the MIB 1 proliferating cell index (PCl) was 14.9 to 56.5%. Linear regression analysis showed that the BUdR LI correlated with the MIB 1 PCI (p < 0.001). The ratio of MIB 1-positive to BUdR-positive cells was 2.2 +/- 0.4 by both single and double staining. BUdR-positive nuclei were heterogeneously distributed in all cases, especially in areas with scattered foci of necrosis. Three tumors had areas with many MIB 1-positive but few BUdR-positive nuclei; these areas were associated with recent tumor necrosis. However, in most of the tumors, the densities of BUdR-positive and MIB 1-positive cells changed concomitantly from area to area. These changes were clearly shown by double immunostaining. Thus, transcapillary passage of BUdR does not appear to be impeded in most medulloblastomas. This study suggests that MIB 1 immunostaining provides essentially the same data as BUdR labeling for assessing the proliferative potential of medulloblastomas.
Adolescent↗
Biochemistry of insect learning: lessons from bees and flies.
Recent advances in the study of learning in insects are examined with an emphasis on two of the most powerful model systems, the honeybee (Apis mellifera) and the fruit fly (Drosophila melanogaster). The honeybee exhibits easily manipulated feeding behavior coupled with extremely high mnemonic fidelity. The size of the honeybee brain has allowed for electrophysiological analysis of the neural correlates of behavior, sometimes with single cell resolution, as well as identification of critical brain regions. Drosophila has proved to be invaluable in the genetic dissection of learning. Through analysis of learning and memory mutants the biochemistry of critical steps has been elucidated and the temporal phases of memory in the fly have been described. Two regions of brain neurophil are essential for olfactory learning in these species: the antennal lobes and the mushroom bodies. In spite of similarities, temporal, and possibly biochemical aspects of learning differ markedly between these organisms.
Animals↗
Prone sleep position and the sudden infant death syndrome in King County, Washington: a case-control study.
OBJECTIVE: To determine whether the prone sleep position was associated with an increased risk of the sudden infant death syndrome (SIDS). STUDY DESIGN: Population-based case-control study. PARTICIPANTS: Case subjects were infants who died of SIDS in King County, Washington. Control subjects were randomly selected infants born in King County. Up to four control subjects were matched on date of birth to each case subject. METHODS: During the study period, November 1992 through October 1994, sleep-position data were collected on infants who died of SIDS by the King Count Medical Examiner's Office during their investigation of the deaths. Parents of infants chosen as control subjects were contacted by telephone, and sleep position information was obtained. Infants who usually slept on their abdomen were classified as sleeping prone; those who usually slept on the side or back were categorized as sleeping nonprone. The adjusted odds ratio for prone sleep position as a risk factor for SIDS was calculated with conditional logistic regression after control for race, birth weight, maternal age, maternal marital status, household income, and maternal cigarette smoking during pregnancy. RESULTS: Sleep position data were collected on 47 infants with SIDS (77% of eligible infants) and 142 matched control subjects; 57.4% of infants who died of SIDS usually slept prone versus 24.6% of control subjects (p < 0.00001). The unadjusted odds ratio for prone sleep position as a risk factor for SIDS was 4.69 (95% confidence interval: 2.17, 10.17). After control for potentially confounding variables, the adjusted odds ratio for prone sleep position was 3.12 (95% confidence interval: 1.08, 9.03). CONCLUSION: Prone sleep position was significantly associated with an increased risk of SIDS among a group of American infants.
Adult↗
DAMB, a novel dopamine receptor expressed specifically in Drosophila mushroom bodies.
The modulatory neurotransmitters that trigger biochemical cascades underlying olfactory learning in Drosophila mushroom bodies have remained unknown. To identify molecules that may perform this role, putative biogenic amine receptors were cloned using the polymerase chain reaction (PCR) and single-strand conformation polymorphism analysis. One new receptor, DAMB, was identified as a dopamine D1 receptor by sequence analysis and pharmacological characterization. In situ hybridization and immunohistochemical analyses revealed highly enriched expression of DAMB in mushroom bodies, in a pattern coincident with the rutabaga-encoded adenylyl cyclase. The spatial coexpression of DAMB and the cyclase, along with DAMB's capacity to mediate dopamine-induced increases in cAMP make this receptor an attractive candidate for initiating biochemical cascades underlying learning.
Amino Acid Sequence↗
Olfactory learning deficits in mutants for leonardo, a Drosophila gene encoding a 14-3-3 protein.
Studies of Drosophila and other insects have indicated an essential role for the mushroom bodies in learning and memory. The leonardo gene encodes a Drosophila protein highly homologous to the vertebrate 14-3-3zeta isoform, a protein well studied for biochemical roles but without a well established biological function. The gene is expressed abundantly and preferentially in mushroom body neurons. Mutant alleles that reduce LEONARDO protein levels in the mushroom bodies significantly decrease the capacity for olfactory learning, but do not affect sensory modalities or brain neuroanatomy that are requisite for conditioning. These results establish a biological role for 14-3-3 proteins in mushroom body-mediated learning and memory processes, and suggest that proteins known to interact with them, such as RAF-1 or other protein kinases, may also have this biological function.
14-3-3 Proteins↗
Middle cerebral artery velocity correlates with nitroglycerin-induced headache onset.
Headache often accompanies treatment with nitroglycerin, but the cerebral hemodynamic effects and the exact mechanism of the headache are incompletely understood. Transcranial Doppler monitoring allows evaluation and monitoring of changes in blood flow velocity in the large intracranial arteries. The objective of this study was to assess middle cerebral artery (MCA) blood flow velocities with transcranial Doppler monitoring in subjects receiving continuous low-dose nitroglycerin intravenously or by patch, and correlate these with clinical headache. Twenty-eight normal adult men received nitroglycerin (0.12 micrograms/kg/min intravenously [n = 14] or 0.6 mg/min by transdermal patch [n = 14]), for up to 120 minutes, with monitoring of clinical headache status (standard 4-point scale), blood pressure, heart rate, end-expiratory PCO2 (CO2), and right MCA velocity. All subjects developed headache (mean time to onset, 34 min), reaching moderate or severe levels in 20. There were no differences in age, weight, mean blood pressure, mean heart rate, or resting end-tidal CO2 between those whose headache reached a moderate to severe level and those whose headache remained mild. MCA velocity decreased from baseline values at all levels of clinical headache (onset, -17%; moderate, -18%; severe, -16%; nitroglycerin stopped, -19%) (p, 0.0001 by t test for each stage of headache). MCA velocity remained decreased at the time of headache resolution (-14%; p < 0.001). Blood pressure, heart rate, and CO2 did not change significantly. There were no differences related to route of nitroglycerin dosing. These data show that continuous low doses of nitroglycerin by patch or intravenously produce headache in normal male subjects. MCA velocities were significantly decreased at headache onset and at all levels of headache severity. Changes in MCA velocity persisted beyond the clinical headache. These results suggest a direct MCA vasodilatory effect of nitroglycerin. This method may also be used to evaluate the intracranial hemodynamic effects of other vasoactive drugs, even in clinical settings.
Administration, Cutaneous↗
Differential distribution of potassium channels in acutely demyelinated, primary-auditory neurons in vitro.
1. Single-channel recordings of potassium channel activity were made from two populations of primary-auditory neurons maintained in tissue culture. The saccular nerve, which is the auditory component of the eighth cranial nerve in goldfish, was separated into two branches according to its peripheral innervation pattern. Neurons which innervated the rostral saccular macula corresponded to a class of cells that showed spike frequency adaptation; whereas, neurons which innervated the caudal macula were consistent with another type of cell that demonstrated bursting spontaneous firing patterns in vivo. Both somatic and internodal axonal membranes from each of these neuronal classes were studied after acute removal of the myelin sheath by microdissection. 2. Dye injections were used to discriminate neuronal from myelin membrane. After successful removal of the myelin, patch electrodes containing Lucifer yellow were used to fill a neuron and reveal its morphology within the myelin sheath. Patches on myelin led to filling of Schwann cells that surrounded the neuron. 3. Four kinds of potassium channels were observed and characterized according to unitary conductance, inactivation, and sensitivity to internal calcium. Three voltage-dependent K+ channel types were found on the somatic and axonal membrane of the two neuronal populations. Two channel types showed voltage-dependent inactivation and had average conductances of 32 and 19 pS, each with distinctive subconductance states. The third type of channel activity had an estimated conductance of 12 pS and was noninactivating. 4. The fourth type of channel was the Ca2(+)-activated K+ channel (k(Ca)), which was classified by the dependence of its activity on the calcium concentration at its cytoplasmic surface. Unlike the other three potassium channel types, this kind of channel was found exclusively on neurons that innervated the caudal sensory epithelium. As with the other kinds of potassium channels, it was found on both somatic and axonal internodal membranes.
Acute Disease↗
Physiology and biochemistry of Drosophila learning mutants.
Single gene mutants of Drosophila that are defective in learning/memory processes have increased substantially our understanding of the physiology, biochemistry, and anatomy underlying conditioned behaviors. Drosophila learning mutants can be separated into two general classes, those with structural defects in the brain and those without (conditioning mutants) any obvious brain alterations. From studies of brain structural mutants, two neuroanatomic areas have merged as important for normal conditioned behavior: the mushroom bodies and the central complex. Biochemical and molecular genetic studies of the conditioning mutants have implicated numerous types of molecules in learning, but the adenosine 3',5'-cyclic monophosphate (cAMP) second messenger pathway has emerged as especially important. Five different genes in this pathway, amnesiac (a product similar to adenylate cyclase activating peptides), dunce (cAMP phosophodiesterase), rutabaga (adenylyl cyclase), DCO (protein kinase A), and dCREB2 (cAMP-response element binding protein), have proven important for normal learning. The products of many of these learning mutants are enriched in mushroom bodies, which highlight the importance of mushroom bodies for normal learning and the cAMP second messenger cascade for the physiology of mushroom body cells in their role(s) underlying learning. Physiological studies of the mutants have demonstrated that plastic properties of synaptic transmission, including facilitation and posttetanic potentiation, are abnormal in the mutants. An appendix describing the currently used paradigms to test Drosophila behavior is included.
Animals↗
Patterns of epidermal growth factor receptor amplification in malignant gliomas.
Amplification of the gene for epidermal growth factor receptor (EGFR) is a common finding in malignant gliomas. We found that 18 of 29 grade 3 and grade 4 gliomas had EGFR amplification when assayed using fluorescence in situ hybridization. The amplification pattern suggests that the amplicon is contained within double minute chromosomes in most cases. EGFR copy number can differ by 20-fold in amplified cells within a single case. Polysomy 7 occurs frequently in both EGFR-amplified and -unamplified cells. More than one-third of the cases had < or = 10 percent of cells with amplified EGFR, and it is likely that these cases would not have been identified by methods that do not examine DNA on a cell by cell basis.
Brain Neoplasms↗
Maternal consumption of cured meats and vitamins in relation to pediatric brain tumors.
Brain tumors are the leading cause of death from childhood cancer, yet the causes of most of these tumors remain obscure. Few chemicals are effective in causing brain tumors experimentally after systemic administration of low doses; a notable exception is one group of N-nitroso compounds, the nitrosamides (in particular the nitrosoureas). Feeding pregnant animals nitrosamide precursors (e.g., sodium nitrite and an alkylamide such as ethylurea) causes a high incidence of nervous system tumors in offspring. This population-based epidemiological study was designed to test the hypothesis that maternal consumption during pregnancy of meats cured with sodium nitrite increases the risk of brain tumors among offspring. The intake of vitamins C and E blocks endogenous formation of nitroso compounds and was expected to be protective. Mothers of 540 children under age 20 with a primary brain tumor diagnosed during 1984-1991 and 801 control children in the same 19 counties on the U.S. West Coast were interviewed. Risk increased with increasing frequency of eating processed meats [odds ratio (OR) = 2.1 for eating at least twice a day compared to not eating; 95% confidence interval (CI) = 1.3-3.2; P = 0.003). Risk also increased with increasing average daily grams of cured meats or mg of nitrite from cured meats (P for each <0.005) but not with nitrate from vegetables. Daily use of prenatal vitamins throughout the pregnancy decreased risk (OR = 0.54; CI = 0.39-0.75). Risk among mothers who consumed above the median level of nitrite from cured meat was greater if vitamins were not taken (OR = 2.4; CI = 1.4-3.6) than if they were (OR = 1.3). These effects were evident for each of three major histological types and across social classes, age groups, and geographic areas. This largest study to date of maternal diet and childhood brain tumors suggests that exposure during gestation to endogenously formed nitroso compounds may be associated with tumor occurrence. Laboratory exploration is needed to: (a) define dietary sources of exposure to alkylamides; (b) investigate the reactivity of nitrite in high concentration such as around bits of cured meats in the stomach after ingestion compared to nitrite in dilute solution; and (c) confirm that simultaneous ingestion of alkylamides and cured meats leads to the endogenous formation of nitrosamides.
Adolescent↗
MR of intracranial extension of nasopharyngeal teratoma.
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Brain Neoplasms↗
Radiation therapy and bromodeoxyuridine chemotherapy followed by procarbazine, lomustine, and vincristine for the treatment of anaplastic gliomas.
PURPOSE: To conduct a Phase II study to evaluate the long-term efficacy and safety of radiotherapy combined with intravenous bromodeoxyuridine for patients with anaplastic glioma tumors. METHODS AND MATERIALS: Between 1983 and 1987, study patients received 1.7-1.8 Gy radiation once a day, Monday through Friday, to a total dose of 60 Gy. On the Thursday prior to beginning radiotherapy and for the next 5 weeks (6 weeks total), patients received a continuous 96 h intravenous infusion of bromodeoxyuridine at 0.8 g/m2/24 h; following radiotherapy, patients received procarbazine, lomustine (CCNU), and vincristine (PCV) for 1 year or until tumor progressed. RESULTS: One-hundred thirty eight patients (median age, 43 years) were evaluable for analysis. Estimated 4-year survival for the anaplastic astrocytoma (AA) stratum (n = 116) is 46%. For the astrocytoma (ASTRO) stratum (n = 22), the 6-year survival is estimated at 79%. Estimated 4-year progression-free survival for AAs is 42%, and for ASTROs, 68%. Whole brain irradiation was used in 23% and limited-field irradiation in 77%; patients receiving limited-field irradiation had a better survival rate (p = 0.07). Total tumor resection was performed in 15%, partial resection in 53%, and biopsy only in 32%. For the 81 patients with tumor recurrence, 34 (42%) are known to have received additional treatment(s). For AA, fits of the Cox proportional hazards regression model showed that covariates individually predictive of survival were younger age (p < 0.001), Karnofsky performance score (p = 0.10). Major toxicities were rash during Weeks 1 through 6 requiring dose modification in 14%, Grade > or = III leukopenia in 18%, and Grade > or = III thrombocytopeni in 9%. CONCLUSION: The study suggests that the bromodeoxyuridine-radiotherapy-PCV, compared with other published therapies, can improve progression-free survival, and aggressive treatment of ASTRO patients can lead to substantial increases in survival compared to published survival data.
Adolescent↗
Expression of osteopontin in the inner ear.
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Animals↗