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A comparison of oto-acoustic emissions and brain stem electric response audiometry in the normal newborn and babies admitted to a special care baby unit.

Brainstem auditory evoked potentials and oto-acoustic emissions have been recorded in 30 normal newborns and in 112 infants admitted to a special care baby unit as part of a study to determine whether these tests can be used to detect the hearing impaired infant. All the ears tested in the normal newborns, where the infant was quiet enough to complete the test, produced a brain stem electric response at a stimulus level less than or equal to 53 dB nHL (dB relative to normal hearing) and 96% produced an oto-acoustic emission at the highest level tested of 41 dB nHL. The mean threshold of the oto-acoustic emission in the normal newborns was 17.7 dB lower than the mean brain stem electric response threshold. The range of thresholds were similar. In the special care infants 84% of ears produced a brain stem electric response at a screening level of 43 dB nHL and 81% of ears produced an oto-acoustic emission at a screening level of 31 dB nHL.

Acoustic Stimulation↗

A Drosophila clathrin light-chain gene: sequence, mapping, and absence of neuronal specialization.

Because mammalian light chains have been implicated in the regulation of clathrin coat assembly and neuronal specialization of clathrin-mediated vesicle trafficking, a clathrin light-chain gene of Drosophila has been sought as a genetically tractable model for these developmental membrane-trafficking systems. A light-chain gene has been identified and its expression examined in various developmental stages and tissues by reverse transcriptase-polymerase chain reaction (RT-PCR). A cDNA clone, originally identified from a partial sequence in the Berkeley Drosophila Genome Project EST database, has been sequenced completely and shown to encode a polypeptide with extensive sequence similarity to vertebrate and invertebrate clathrin light chains. Secondary structure algorithms predict an extensive coiled-coil over a region extending from amino acid residues 100 to 170, in excellent agreement with previous analyses of mammalian light chains. By in situ hybridization to larval polytene chromosomes, the gene has been mapped to cytologic position 77A on the left arm of chromosome 3. An RT-PCR analysis, coupled with PCR analysis of genomic DNA, showed that there is no neural specialization of the Drosophila clathrin light chain corresponding to that observed in mammalian neuronal light chains. The neuron-specific alternative splicing of clathrin light chains thus appears to be restricted to vertebrates, where it may contribute to the more complex information-processing capacity of higher nervous systems.

Alternative Splicing↗

The special prenatal clinic: one approach to women and substance abuse.

We aimed to determine if the trend in substance use in this central core of a large inner-city area confirmed an increase in marijuana use among young women < 22 years of age as childbearing years were beginning or if marijuana use and harder drug use were greatest among women beyond the teens and the early second decade of life and to describe one prenatal care intervention. Statistical reports for the Special Prenatal Clinic, a Harlem clinic for women with a current or past history of substance use, were reviewed from 1985 (the clinic's inception) through March 1996 to determine the trends, patterns, and types of drug use. Findings chronicled the beginning and rise in crack cocaine use, especially after 1986, confirmed an increase in marijuana use by adolescents since 1992, and suggest that the risk for use of hard drugs increases with age, predominantly in the childbearing years. Intervention by the Special Prenatal Clinic aided case-finding, allowed for comprehensive care, offered women opportunities for behavior change, and increased their chances of keeping their babies after delivery.

Adolescent↗

Home telehealth special interest group: past, present, and future.

The American Telemedicine Association (ATA) established the Home Telehealth Special Interest Group (SIG) in 1999. Its mission is to support the expansion and use of telehealth, remote monitoring and disease management applications in the home. The SIG has many areas of interest and has focused on raising public and professional awareness about the benefits of home telehealth, developing and standardizing clinical guidelines for the delivery of services and advocating for reimbursement through state and federal funding. SIG membership has grown dramatically, to more than 425 members today. These numbers make it the fastest growing and largest of the ATA's Special Interest Groups.

Disease Management↗

The Rib43a protein is associated with forming the specialized protofilament ribbons of flagellar microtubules in Chlamydomonas.

Ciliary and flagellar microtubules contain a specialized set of three protofilaments, termed ribbons, that are composed of tubulin and several associated proteins. Previous studies of sea urchin sperm flagella identified three of the ribbon proteins as tektins, which form coiled-coil filaments in doublet microtubules and which are associated with basal bodies and centrioles. To study the function of tektins and other ribbon proteins in the assembly of flagella and basal bodies, we have begun an analysis of ribbons from the unicellular biflagellate, Chlamydomonas reinhardtii, and report here the molecular characterization of the ribbon protein rib43a. Using antibodies against rib43a to screen an expression library, we recovered a full-length cDNA clone that encodes a 42,657-Da polypeptide. On Northern blots, the rib43a cDNA hybridized to a 1. 7-kb transcript, which was up-regulated upon deflagellation, consistent with a role for rib43a in flagellar assembly. The cDNA was used to isolate RIB43a, an approximately 4.6-kb genomic clone containing the complete rib43a coding region, and restriction fragment length polymorphism analysis placed the RIB43a gene on linkage group III. Sequence analysis of the RIB43a gene indicates that the substantially coiled-coil rib43a protein shares a high degree of sequence identity with clones from Trypanosoma cruzi and Homo sapiens (genomic, normal fetal kidney, and endometrial and germ cell tumors) but little sequence similarity to other proteins including tektins. Affinity-purified antibodies against native and bacterially expressed rib43a stained both flagella and basal bodies by immunofluorescence microscopy and stained isolated flagellar ribbons by immuno-electron microscopy. The structure of rib43a and its association with the specialized protofilament ribbons and with basal bodies is relevant to the proposed role of ribbons in forming and stabilizing doublet and triplet microtubules and in organizing their three-dimensional structure.

Algal Proteins↗

Insulin-regulated release from the endosomal recycling compartment is regulated by budding of specialized vesicles.

In several cell types, specific membrane proteins are retained intracellularly and rapidly redistributed to the surface in response to stimulation. In fat and muscle, the GLUT4 glucose transporter is dynamically retained because it is rapidly internalized and slowly recycled to the plasma membrane. Insulin increases the recycling of GLUT4, resulting in a net translocation to the surface. We have shown that fibroblasts also have an insulin-regulated recycling mechanism. Here we show that GLUT4 is retained within the transferrin receptor-containing general endosomal recycling compartment in Chinese hamster ovary (CHO) cells rather than being segregated to a specialized, GLUT4-recycling compartment. With the use of total internal reflection microscopy, we demonstrate that the TR and GLUT4 are transported from the pericentriolar recycling compartment in separate vesicles. These data provide the first functional evidence for the formation of distinct classes of vesicles from the recycling compartment. We propose that GLUT4 is dynamically retained within the endosomal recycling compartment in CHO cells because it is concentrated in vesicles that form more slowly than those that transport TR. In 3T3-L1 adipocytes, cells that naturally express GLUT4, we find that GLUT4 is partially segregated to a separate compartment that is inaccessible to the TR. We present a model for the formation of this specialized compartment in fat cells, based on the general mechanism described in CHO cells, which may explain the increased retention of GLUT4 and its insulin-induced translocation in fat cells.

3T3 Cells↗

Mammalian ykt6 is a neuronal SNARE targeted to a specialized compartment by its profilin-like amino terminal domain.

SNAREs are required for specific membrane fusion throughout the endomembrane system. Here we report the characterization of rat ykt6, a prenylated SNARE selectively expressed in brain neurons. Immunofluorescence microscopy in neuronal and neuroendocrine cell lines revealed that membrane-associated ykt6 did not colocalize significantly with any conventional markers of endosomes, lysosomes, or the secretory pathway. However, ykt6-containing membranes displayed very minor overlaps with lysosomes and dense-core secretory granules and were similar to lysosomes in buoyant density. Thus, ykt6 appears to be specialized for the trafficking of a unique membrane compartment, perhaps related to lysosomes, involved in aspects of neuronal function. Targeting of this SNARE to the ykt6 compartment was mediated by its profilin-like amino-terminal domain, even in the absence of protein prenylation. Although several other R-SNAREs contain related amino-terminal domains, only the ykt6 version was able to confer the specialized localization. Rat ykt6, which contains an arginine in its SNARE motif zero-layer, was found to behave like other R-SNAREs in its SNARE assembly properties. Interestingly, cytosolic ykt6, constituting more than half of the total cellular pool, appeared to be conformationally inactive for SNARE complex assembly, perhaps indicative of a regulatory mechanism that prevents promiscuous and potentially deleterious SNARE interactions.

Amino Acid Motifs↗

Specially designed sweeteners and food for diabetics--a real need?

In the first part of this study, the effect of four isocaloric mixed breakfast meals on the blood glucose and urinary glucose losses was tested in nine adult diabetics and in three healthy subjects, ages 60 to 75. Three of the test meals consisted of a base diet supplemented with applesauce sweetened with sucrose, fructose, or sorbitol. In the fourth test meal, the starch was increased together with saccharine. In the second part of the study, analyses for free glucose and sucrose in several timed food preparations, ordinary as well as food preparations specially designed for diabetics, were performed. The amount of sucrose equivalents (S(eg)) in one ordinary serving of the various products was estimated. No significant differences among sucrose, fructose, and sorbitol-containing meals with respect to the effect on the blood glucose level or on glucosuria were found. The saccharine-containing meal gave a significantly greater blood glucose increase at 60 min only. The amount of sucrose in ordinary marinated foods, such as herring, cucumber, and common beet was negligible. Water-packed fruits supplied one half of the amount of S(eq) or less, compared with fruits packed in sorbitol-sweetened syrup. The amount of S(eq) in the latter products as well as in fruits packed in unsweetened juice equalled that of the fleshy substance of ordinary sucrose-sweetened products. It was concluded that fructose or sorbitol has no advantages over sucrose, as regards the effect on blood glucose in well-regulated adult diabetics, and that it seems unnecessary to have specially sweetened foods designed for diabetics.

Aged↗

Food group and macronutrient intakes, trial years 1-6, in the special intervention and usual care groups in the Multiple Risk Factor Intervention Trial.

This chapter presents changes in dietary intake reported by men in the special intervention (SI) and usual care (UC) groups from baseline through 6 y of follow-up in the Multiple Risk Factor Intervention Trial. Changes in nutrients by SI men after 1 y of following the intensive intervention program were as follows: reduced intake of total fat (from 38.4% to 34.3% of energy), saturated fatty acids (14.2% to 10.4% of energy), and cholesterol (448 to 263 mg/d), and increased intake of polyunsaturated fatty acids (from 6.4% to 8.6% of energy). These changes were maintained and did not increase through the remaining 5 y. UC men reported small changes in similar directions. Most of the change in saturated fatty acid intake by SI participants was from high-fat meat and high- and medium-fat dairy products. Reduction in dietary cholesterol was achieved primarily by substantial decreases in intake of eggs and high-fat meats. Several baseline factors were associated with amount of dietary change in SI men. Greater changes were seen in men with higher baseline serum cholesterol concentrations, in those not consuming a special diet, in nonsmokers followed by lighter smokers, in hypertensive than in non-hypertensive men, in older participants, in white than in black men, in moderate drinkers than in nondrinkers or those consuming > or = 22 drinks/wk, and in those with no "stressful life events" than in those reporting one or more life events.

Cholesterol, Dietary↗

Nutritional adequacy of diets reported at baseline and during trial years 1-6 by the special intervention and usual care groups in the Multiple Risk Factor Intervention Trial.

This chapter addresses whether a fat-modified diet as implemented by special intervention participants in the Multiple Risk Factor Intervention Trial affected intake of vitamins and minerals, and whether nutritional adequacy was altered by this dietary intervention. Despite likely underreporting of intake, for men in the special intervention group, most mean intakes of 15 micronutrients estimated from 24-h recalls were above established recommended dietary allowances. A few means were slightly below; lowest was zinc at 77% (from 98% at baseline) followed by calcium at 79% (from 102% at baseline). Calculated as nutrient densities (per 1000 kcal), nutrients that were below indexes of nutritional quality (the corresponding standard based on nutrient density) during follow-up, although not reduced below baseline by this measure, were vitamin D, calcium, iron (marginally), and zinc. Analyses by food groups indicated that intake of these nutrients might have been improved by greater replacement of high- and medium-fat dairy products with low-fat dairy products (for vitamin D and calcium) and of high-fat meats with low-fat meats, fish, or poultry (for iron and zinc), or (because iron was adequate) by increasing consumption of vegetables and whole-grain products. The safety of the eating pattern was further confirmed by more favorable micronutrient profiles in men who adhered best to the intervention program, as measured by degree of serum cholesterol reduction and weight loss.

Body Weight↗

Relation of body mass and alcohol, nutrient, fiber, and caffeine intakes to blood pressure in the special intervention and usual care groups in the Multiple Risk Factor Intervention Trial.

This chapter presents analyses of relations of dietary variables to blood pressure, systolic (SBP) and diastolic (DBP), for men in the special intervention (SI) and usual care (UC) groups in the Multiple Risk Factor Intervention Trial. For each dietary factor, analyses were done at baseline, for trial years 1-6, and for change from baseline to years 1-6. Analyses were done for all participants and for men receiving or not receiving antihypertensive drug treatment and were controlled for age, race, education, serum cholesterol, smoking, special diet status, and (for specific nutrients) body mass index and alcohol intake. Nutrient data for trial years 1-6, which are based on four or five dietary recalls per man, are more reliable than the baseline or change data, which are based on only one recall. Therefore, this summary focuses on data for trial years 1-6, for SI and UC men pooled. Regression analyses confirmed direct independent relations of body mass index, alcohol intake, sodium, and ratio of sodium to potassium to SBP and DBP, and an inverse relation of potassium to SBP and DBP. Dietary starch was directly related to SBP and DBP; dietary saturated fatty acid and cholesterol and Keys score were directly related to DBP; dietary magnesium, fiber, and caffeine were inversely related to SBP and DBP; and dietary protein, polyunsaturated fatty acids, the ratio of polyunsaturated to saturated fatty acid, and other simple carbohydrates were inversely related to DBP. Method problems, all tending to produce underestimations, are also reviewed.

Alcohol Drinking↗

Special histologic stains are rarely beneficial for the evaluation of HIV-related gastrointestinal infections.

During a 28-month period, endoscopic mucosal biopsy specimens from all HIV-infected patients were submitted for routine histologic evaluation. Immunoperoxidase staining for cytomegalovirus and herpesvirus antigens (esophagus), mycobacterial and fungal staining, and Gram staining of mucosal biopsy specimens were done. Special fungal and acid-fast stains were selectively performed in patients with absolute CD4 cell counts of less than 200 cells per microliter (200 x 10(6)/L) and/or with diarrhea and or wasting syndrome. Treatment was based on the endoscopic and histologic findings, and long-term follow-up was performed. The 121 symptomatic HIV-infected patients underwent 221 upper and/or lower endoscopies with 285 biopsy sites. The sensitivity and specificity of H&E staining for the diagnosis of gastrointestinal cytomegalovirus were 97% and 100%, respectively. The results of fungal and mycobacterial stains neither altered therapy nor identified previously undiagnosed infections in any patient. Long-term follow-up revealed no patient in whom an infection was missed on routine H&E, which affected outcome. Routine H&E staining is accurate for the diagnosis of gastrointestinal opportunistic infections in HIV-infected patients. Special histologic stains for fungal, mycobacterial, and viral infections did not increase the diagnostic yield or alter medical therapy but doubled the costs.

AIDS-Related Opportunistic Infections↗

Chemotherapy of advanced NSCLC in special patient population.

The elderly and patients with Performance Status (PS) of 2, constitute the so-called special patient population. The tolerability of chemotherapy in this population is globally worse, and treatment approaches should be different. Platinum-based combination chemotherapy is currently recommended as the standard treatment for patients with advanced non-small-cell lung cancer (NSCLC), but its role in special patient population is controversial. The best treatment for elderly patients with advanced NSCLC is still debated. In the first randomized study dedicated to elderly NSCLC patients, single-agent vinorelbine showed superiority over supportive care alone, both in terms of survival and quality of life. In a large randomized trial, gemcitabine plus vinorelbine failed to show any advantage over either agent alone. Subset analyses suggest that the efficacy of platinum-based combination chemotherapy is similar in fit older and younger patients, with an acceptable increase in toxicity for elderly patients. However, the role of platin-based chemotherapy needs to be defined in prospective randomised trials. With the current evidence, single-agent chemotherapy with a third-generation drug (vinorelbine, gemcitabine, taxanes) should be the recommended option for non-selected elderly patients with advanced NSCLC. Also for PS2 patients there is no consensus on standard treatment. On the basis of current evidence, chemotherapy treatment appears justified for patients with advanced NSCLC and PS2. Single-agent chemotherapy (gemcitabine, vinorelbine, taxanes) could be the preferred option, although carboplatin-based or low-dose cisplatin-based doublets may represent alternative options. Stronger evidence is expected from new clinical research specifically focused on PS2 patients. High priority should be given to the evaluation of tolerability and efficacy of platinum-based combinations and role of new targeted therapies.

Aged↗

SEQGEL: a versatile and comfortable DNA editor which supports a special keyboard and a speech synthesizer.

A DNA editor for an Apple II is described which contains many additional functions apart from just editing sequences. The data files are normal ASCII text or binary files and can thus be used easily by other programs. The program supports a special keyboard which greatly facilitates typing of DNA sequences. Furthermore a speech synthesizer is supported by the editor. The speech feedback, together with the special keyboard, reduces typing errors to a minimum.

Base Sequence↗

Time is of the essence: a conjecture that hemispheric specialization arises from interhemispheric conduction delay.

Tomasch (1954) and Aboitiz et al. (1992) found the majority of the fibers of the human corpus callosum are under 1 micron in diameter. Electron microscopic studies of Swadlow et al. (1980) and the detailed study of LaMantia and Rakic (1990a) on macaques show the average size of the myelinated callosal axons also to be less than 1 micron. In man, the average-sized myelinated fiber interconnecting the temporal lobes would have a one-way, interhemispheric delay of over 25 msec. Thus, finely detailed, time-critical neuronal computations (i.e., tasks that strain the capacity of the callosum and hence could not be handled by just the larger fibers) would be performed more quickly via shorter and faster intrahemispheric circuits. While one transit across the commissural system might yield tolerable delays, multiple passes as in a system involving "setting" would seem prohibitively slow. We suggest that these temporal limits will be avoided if the neural apparatus necessary to perform each high-resolution, time-critical task is gathered in one hemisphere. If the, presumably overlapping, neural assemblies needed to handle overlapping tasks are clustered together, this would lead to hemispheric specialization. The prediction follows that the large brains of mammals such as elephants and cetaceans will also manifest a high degree of hemispheric specialization.

Animals↗

Cortical specialization for processing first- and second-order motion.

Distinct mechanisms underlying the visual perception of luminance- (first-order) and contrast-defined (second-order) motion have been proposed from electrophysiological, human psychophysical and neurological studies; however a cortical specialization for these mechanisms has proven elusive. Here human brain imaging combined with psychophysical methods was used to assess cortical specializations for processing these two kinds of motion. A common stimulus construction was employed, controlling for differences in spatial and temporal properties, psychophysical performance and attention. Distinct cortical regions have been found preferentially processing either first- or second-order motion, both in occipital and parietal lobes, producing the first physiological evidence in humans to support evidence from psychophysical studies, brain lesion sites and computational models. These results provide evidence for the idea that first-order motion is computed in V1 and second-order motion in later occipital visual areas, and additionally suggest a functional dissociation between these two kinds of motion beyond the occipital lobe.

Adult↗

Hemispheric specialization for processing auditory nonspeech stimuli.

The left hemisphere specialization for speech perception might arise from asymmetries at more basic levels of auditory processing. In particular, it has been suggested that differences in "temporal" and "spectral" processing exist between the hemispheres. Here we used functional magnetic resonance imaging to test this hypothesis further. Fourteen healthy volunteers listened to sequences of alternating pure tones that varied in the temporal and spectral domains. Increased temporal variation was associated with activation in Heschl's gyrus (HG) bilaterally, whereas increased spectral variation activated the superior temporal gyrus (STG) bilaterally and right posterior superior temporal sulcus (STS). Responses to increased temporal variation were lateralized to the left hemisphere; this left lateralization was greater in posteromedial HG, which is presumed to correspond to the primary auditory cortex. Responses to increased spectral variation were lateralized to the right hemisphere specifically in the anterior STG and posterior STS. These findings are consistent with the notion that the hemispheres are differentially specialized for processing auditory stimuli even in the absence of linguistic information.

Acoustic Stimulation↗

Hemispheric specialization in human prefrontal cortex for resolving certain and uncertain inferences.

Uncertainty is a fact of life that must be accommodated in real-world decision making. Although it has been suggested that the right prefrontal cortex (PFC) has a special role to play in decision making under uncertainty, there is very little hard data to support this hypothesis. To better understand the roles of left and right PFCs in reasoning and decision making in situations with complete and incomplete information, we administered simple inference problems to 18 patients with lateralized focal lesions to PFC (9 right hemisphere, 9 left hemisphere) and 22 age- and education-matched normal controls. The stimuli were systematically manipulated for completeness of information regarding the status of the conclusion. Our results demonstrated a 2-way interaction such that patients with left PFC lesions were selectively impaired in trials with complete information, whereas patients with right PFC lesions were selectively impaired in trials with incomplete information. These results provide compelling evidence for hemispheric specialization for reasoning in PFC and suggest that the right PFC has a critical role to play in reasoning about incompletely specified situations. We postulate this role involves the maintenance of ambiguous mental representations that temper premature overinterpretation by the left hemisphere.

Adult↗