Circadian oscillations in protein and mRNA levels of the period gene of Drosophila melanogaster.
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Biomedical subjects
Publications and source records attributed to J C Hall.
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With improvement in perinatal management and advances in neonatal intensive care, congenital anomalies have emerged as a major cause of neonatal mortality and morbidity. A 1 year review (1985) of all the admissions to our neonatal intensive care unit (NICU) showed that 78 of 790 (10%) had one or more congenital anomalies. Of these, 26% died in the NICU; another 10% died during the first year; therefore the total mortality of infants with congenital anomalies in the first year of life was 36%. Even though they accounted for only 10% of the total admissions, the infants with congenital anomalies were responsible for 13% of the total NICU patient-days, 26% of the total NICU mortality, 32% of all deaths within the first year, and 35% of all NICU infants with intrauterine growth retardation (IUGR). Of interest, 67% of the infants with anomalies were suspected or diagnosed prenatally. Of these, 54% were delivered by cesarean section, done for fetal reasons in the majority of cases. The highest mortality was associated with (1) multiple abnormal prenatal ultrasound findings; (2) extreme prematurity (less than 30 weeks gestation); and (3) the presence of IUGR. These findings raise concerns about the use of resources in the management of the pregnancy and the delivery of infants with congenital anomalies, particularly when diagnosed prenatally.
We present the case of an 85 year old woman who was found to have a type III choledochal cyst with cholangiocarcinoma. The case is unusual because of the advanced age of the patient, the presence of both stones and a carcinoma in a type III cyst, and the associated congenital abnormalities.
1. Physiological recordings were made from single auditory fibers in the frog eighth nerve to determine quantitatively how the different behaviorally relevant temporal parameters (the signal rise-fall time, duration, and rate of amplitude modulation) of complex sounds are encoded in the auditory periphery. Individual temporal parameters were varied. Response functions (RFs) were constructed with respect to each of these parameters using each unit's best excitatory frequency (BF) as the carrier. 2. In response to a change in signal rise-fall time, auditory nerve fibers showed little change in the mean spike count or firing rate, i.e., all fibers displayed ALL-PASS RFrfts. But the transient components, particularly the early phasic component, of responses varied with rise-fall times; these components were more pronounced in the responses to stimuli with shorter rise-fall times. 3. In response to an increase in signal duration, auditory nerve fibers showed a corresponding increase in firing duration and thus in the mean spike count, giving rise to HIGH-PASS RFdurs. The shape of response curves differed among fibers; the difference appeared to be related to the fiber's temporal adaptation characteristic. When the firing rate was measured, all fibers displayed higher mean firing rates in response to shorter duration stimuli than they did to longer duration stimuli, thus giving rise to LOW-PASS response functions. 4. To determine the response transfer functions to modulation rate, pulsed (PAM) and sinusoidally (SAM) amplitude-modulated signals were used. These signals differed substantially in terms of their envelopes and how they varied with AM rate. Data were analyzed by 1) plotting spike counts against the AM rate to derive modulation transfer functions (MTFspks) and 2) plotting synchronization coefficients (SCs) against the AM rate to generate MTFscs. 5. In response to PAM stimuli, all fibers showed an increase in mean spike count with modulation frequency over the range examined, giving rise to HIGH-PASS MTFspks. 6. For SAM stimuli, the average energy and duty cycle are independent of AM rate. Most (79%) auditory fibers showed little selectivity for AM rate over a range of 5-400 Hz, giving rise to ALL-PASS MTFspks. The remaining auditory fibers displayed LOW-PASS MTFspks, i.e., there was a distinct decline in the mean spike count with increasing AM rate. 7. In response to PAM stimuli, most fibers showed good response synchrony at low AM rates but the SC declined with an increase in the AM rate (i.e., LOW-PASS MTFscs). The cut-off frequency was typically very high, averaging 90 pulses/s.(ABSTRACT TRUNCATED AT 400 WORDS)
1. Single-unit responses to different temporal acoustic parameters were characterized in the dorsal medullary nucleus (DMN) of the Northern leopard frog, Rana pipiens pipiens. Our goal was to provide both a quantitative and a qualitative assessment of the neural representation of behaviorally relevant temporal acoustic patterns in the frog's DMN. 2. Acoustic stimuli included tone bursts having different durations, rise times, or rates of amplitude modulation (AM). Several metrics were used to compute temporal response functions for each of these, including mean spike count, average firing rate, and/or peak firing rate. Synchronization coefficients were also used to characterize responses to stimuli presented at different AM rates. 3. On the basis of mean spike count, the temporal response functions of DMN neurons with respect to signal rise time could be characterized as 1) all-pass, in which the mean spike count was largely independent of rise time, or 2) fast-pass, in which the mean spike count decreased with increasing rise time. Fast-pass response functions were of two types, those that decayed rapidly and those that decayed gradually from their peak values. 4. The minimum threshold varied with signal rise time for cells showing fast-pass but not all-pass response functions. Minimum response thresholds for fast-pass neurons were typically higher with slower signal rise time. 5. The filtering characteristics of cells displaying fast-pass rise time response functions were dependent on signal level, becoming all-pass when signal levels exceeded 30-40 dB above the minimum threshold. 6. Approximately 44% of DMN neurons exhibiting fast-pass response functions for signal rise time showed all-pass filtering characteristics when broadband noise rather than best frequency tones were used, thereby signifying an influence of signal spectrum on the pass-band characteristics of these cells. 7. All DMN neurons, regardless of discharge pattern, showed maximal instantaneous firing rates to signals having short (less than 25 ms) rise times. Response functions based on instantaneous firing rate were, therefore, fast-pass in nature. These responses were independent of signal level and spectrum. 8. There was an ordinal relationship between signal duration and the duration of tonic but not phasic unit discharges. This relationship was not intensity dependent. 9. On the basis of mean spike count, the temporal response functions of DMN neurons with respect to signal duration were characterized as 1) all-pass, in which the mean spike count was largely independent of signal duration, or 2) long-pass, in which the mean spike count increased with increasing signal duration.(ABSTRACT TRUNCATED AT 400 WORDS)
Stress has been considered a physiological regulator of GH and PRL secretion in humans. The stressors used in studies have often been extreme. The influence of commonplace stressors on the endocrine system has not been clarified. Therefore, to better define the role of commonplace stressors on GH and PRL secretion, we evaluated the effect of examination stress on GH and PRL secretion in 37 male medical students. We performed hourly sampling for 24 h for GH and PRL 4 weeks before, during exam week, and 2 weeks after major examinations in the fall and spring of their first year. Stress, as evaluated by the Perceived Stress Scale (PSS), increased as expected during examination weeks, but there was no correlation between the PSS scores and mean day or night GH and PRL secretion. Twenty-four-hour GH and PRL secretion was not significantly altered during examinations in either fall or spring. A significant seasonal influence, however, was noted on GH secretion, with both daytime and nocturnal GH secretion being consistently higher in the Fall than in the Spring. We conclude that examination stress does not significantly influence mean daytime or nocturnal GH and PRL concentrations. We suggest that serum GH and PRL levels may not be significantly altered in man by commonplace stressors. Also, seasonal effects may be operative in the control of human GH secretion.
A genetically defined element of the fruitless (fru) locus in Drosophila melanogaster regulates the development of a male-specific muscle spanning the fifth abdominal segment in adult males, the 'muscle of Lawrence' (MOL). The region is defined by two cytological deletions, each with a breakpoint that co-maps with previously described mutant courtship phenotypes at cytogenetic interval 91B on the third chromosome. Flies that carry both of these deletions are viable, and males express abnormalities of courtship similar to those caused by the fru inversion breakpoint at 91B. In addition, these double-deletion males show the complete absence of the MOL, suggesting that they have little or no gene expression of a postulated MOL determinant; the musculature in the fifth abdominal segment of these mutants to indistinguishable from that of a normal female. Other mutant combinations that produce fruitless courtship phenotypes--including deletion and inversion breakpoints, and a marked transposon inserted at 91B--produce intermediate forms of the MOL. A new genetic variant, induced by imprecise excision of the marked transposon, is homozygous lethal and disrupts fru functions related to courtship and the MOL. The MOL is shown to be dispensable for fertility and is therefore not the causative factor of fru-induced behavioral sterility. These genetic variants and their phenotypic results are discussed with regard to a model for the organization of the fru locus.
We evaluated the relationship between PPC and various putative risk factors in a prospective longitudinal study of 1,000 patients undergoing abdominal surgery. Transient subclinical events were excluded by defining PPC as positive clinical findings in combination with either positive sputum microbiology, unexplained pyrexia, or positive chest roentgenographic findings. The overall incidence of PPC was 23.2 percent (232/1,000). Multivariate analysis identified seven factors which were associated with PPC: ASA classification greater than 2, upper abdominal surgery, residual intraperitoneal sepsis, age greater than 59 years, BMI greater than 25, preoperative hospital stay greater than 4 days, and colorectal or gastroduodenal surgery (overall F score = 33.5, p less than 0.0001). The ASA classification was the most powerful indicator of risk in both the univariate and the multivariate analyses. The combination of ASA classification greater than 1 and age greater than 59 years identified 88 percent (205 of 232) of the patients who developed PPC. These findings provide clinicians and clinical investigators with a simple means of identifying patients who are at high risk of PPC after abdominal surgery.
The authors present a case in which the diagnosis of prostate cancer metastatic to the skin was made by skin biopsy with immunoperoxidase stains for prostatic specific antigen and prostatic acid phosphatase. These are tests that should be performed when the location of the primary malignancy is not otherwise evident.
The histopathologic data for lung carcinoma were reviewed in 4928 patients between 1964 and 1985. The analysis of this data indicates that lung cancer is increasing in our region. Squamous carcinoma remains the most frequent type in men, followed by adenocarcinoma. Small cell carcinoma is the second most frequent type in women, after adenocarcinoma. Small cell carcinoma has increased over the past years and may become the most common type of lung cancer in women, a development that might result in increased numbers of deaths. Lung cancer data must be carefully analyzed in view of the impact on selection of therapy, patient management, and education.
Mutations in the period (per) gene of Drosophila melanogaster affect both circadian and ultradian rhythms. Levels of per gene product undergo circadian oscillation, and it is now shown that there is an underlying oscillation in the level of per RNA. The observations indicate that the cycling of per-encoded protein could result from per RNA cycling, and that there is a feedback loop through which the activity of per-encoded protein causes cycling of its own RNA.
Courtship songs of normal males and those expressing short-period, long-period, and arrhythmic mutations at the period (per) locus of Drosophila melanogaster have been reanalyzed for rhythmic components, using spectral treatments of the fluctuating rates of tone pulse production that occur during courtship. It was concluded, as in previous studies, that such songs are strongly rhythmic, except for courtships performed by per01 males. Songs produced by males expressing this and other per alleles were compared to computer-generated "random" ones. Interpulse interval variations influenced by per01 and songs stimulated to be arrhythmic both were found to be associated with cryptic rhythmicities; several such period values, extracted by the spectral analyses, defined very short cycle durations. We discuss the implications of these findings and of some recently reported results that have challenged the existence of rhythmicity in Drosophila songs.
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Clock is a semidominant X-linked mutation that results in shortening the period of Drosophila melanogaster's free-running locomotor activity rhythm from ca. 24.0 to ca. 22.5 hr. This mutation similarly shortened the phase response curve, determined by resetting activity rhythms with light pulses. Eclosion peaks for Clk cultures were separated by only 22.5 hr instead of the normal 24 hr. Clk was mapped close to, but separable from, another rhythm mutation--period01--by recombination. The estimated distance between these two mutations was short enough to suggest that Clk could be a per allele. If this is the case, the new mutant is unique in that it, unlike other per variants, is associated with essentially normal 1-min courtship song rhythms when Clk is expressed in males. Also, the new rhythm variant could not, in contrast to a short-period per mutation, have its effects on free-running activity rhythms uncovered by deletions. This result, and the lack of coverage of Clk's effects by duplications, suggest that it is not a simple hypomorphic or amorphic mutation.
The efficacy of three gastric restriction operations were compared in a prospective randomized study of 310 morbidly obese subjects. The median patient age was 34 years (range, 18 to 62 years). They were predominantly female (13:1) and had a median pre-operative weight that was 198% of their ideal weight (range, 160% to 318%). There was an equitable dispersion of perceived risk factors between the groups under study and there were no deaths during the perioperative period. Compliance with follow-up at 3 years was 91%. When success was defined as a loss of more than 50% of excess weight or a current pregnancy, the success rates at 3 years were 17% for gastrogastrostomy, 48% for vertical gastroplasty, and 67% for Roux-en-Y gastric bypass (p less than 0.001). Although the gastric bypass operation took longer to perform, there were similar outcome patterns for the three groups during the postoperative period. We conclude that the Roux-en-Y gastric bypass is the preferred procedure for the surgical treatment of morbid obesity.
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1. The dorsal medullary nucleus (DMN) of frogs is the presumed homolog of the mammalian cochlear nucleus (CN). Like the CN, the DMN is the sole target of centrally projecting primary auditory-nerve fibers and the first central auditory-processing center. To study the transformation of acoustic information in the DMN, we have utilized relatively simple stimuli--tone bursts--to detail the temporal discharge patterns of DMN neurons that can be compared with those shown by auditory-nerve fibers. 2. Based on the shape of poststimulus time (PSTH) and interspike interval (ISIH) histograms, we observed six distinctive discharge patterns to tone bursts presented at the best excitatory frequency (BEF), 10 dB above threshold. Four of these (primary-like type 1-4) resembled discharge patterns seen at the level of the auditory nerve, whereas two (phasic and phasic burst) were only observed in the DMN. 3. At stimulus levels of 20-30 dB above BEF threshold several phasic neurons became tonic responders, whereas several primary-like type-2 cells gave "pauser" discharges. The response patterns of the remaining cells were intensity independent. 4. We further showed that many of the single-unit discharge patterns were related to other neuronal response properties; specifically, spontaneous firing rate, intensity-rate functions, threshold, latency, BEF, and sharpness of tuning (Q10). 5. The implications of our findings are discussed with respect to 1) the transformation of acoustic information as it is passed from the auditory nerve to the DMN, and 2) the functional organization of the DMN.
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