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Biomedical subjects

J Sundberg

Publications and source records attributed to J Sundberg.

At least 19 recordsLinked to original sources

Assessment of nasal and sinus nitric oxide output using single-breath humming exhalations.

Nasal nitric oxide (NO) levels increase greatly during humming compared to silent exhalation. In this study, the physiological and anatomical factors that regulate NO release during humming have been characterised in 10 healthy subjects and in a model of the sinus and the nose. Single-breath humming caused a large initial peak in nasal NO output, followed by a progressive decline. The NO peak decreased in a step-wise manner during repeated consecutive humming manoeuvres but recovered completely after a silent period of 3 min. Topical nasal application of an NO synthase inhibitor reduced nasal NO by >50% but had no effect on the increase evoked by humming. Silently exhaled nasal NO measured immediately after repeated humming manoeuvres was between 5-50% lower than basal silent NO exhalation, suggesting variable continuous contribution from the sinuses to nasal NO. Among the factors known to influence normal sinus ventilation, ostium size was the most critical during humming, but humming frequency was also of importance. In conclusion, humming results in a large increase in nasal nitric oxide, which is caused by a rapid gas exchange in the paranasal sinuses. Combined nasal nitric oxide measurement with and without humming could be of use to estimate sinus ventilation and to better separate nasal mucosal nitric oxide output from sinus nitric oxide in health and disease.

Adult↗

The pathogenesis of advanced cervical cancer provides the basis for an empirical therapeutic vaccine.

The pathogenesis of carcinogenic human papillomavirus (HPV) infections of the cervix includes early induction of peripheral tolerance of tissue-infiltrating lymphocytes and an imbalanced Th2 response to HPV early virus proteins. As lesions become progressively dysplastic, major histocompatibility complex (MHC)-1 molecules are down-regulated on the surface of abnormal keratinocytes. When the target of MHC-1 class-restricted cytotoxic lymphocytes disappears, immune deviation to a Th2 response becomes more dominant. After severely dysplastic lesions become invasive, cervical cancer cells die and release HPV E6 and E7 oncoproteins that react with anti-E6 and anti-E7 antibodies to form insoluble immune complexes in antibody excess under the continuing influence of immune deviation. On the basis of this knowledge of the pathogenesis of advanced cervical cancer, we believe that successful immunotherapeutic treatments of these patients will use a vaccine formulation that will break peripheral tolerance in association with biological response modifiers that will enable the patient's immune system to switch classes from Th2 to Th1 while up-regulating MHC-1 molecules on cancer cells. Like prophylactic vaccines against HPV, successful therapeutic vaccine against cervical cancer may have to be universal rather than individualized to be efficacious.

Drug Design↗

Long-term-average spectrum characteristics of country singers during speaking and singing.

Five premier male country singers involved in our previous studies spoke and sang the words of both the national anthem and a country song of their choice. Long-term-average spectra were made of the spoken and sung material of each singer. The spectral characteristics of county singers' speech and singing were similar. A prominent peak in the upper part of the spectrum, previously described as the "speaker's formant," was found in the county singers' speech and singing. The singer's formant, a strong spectral peak near 2.8 kHz, an important part of the spectrum of classically trained singers, was not found in the spectra of the country singers. The results support the conclusion that the resonance characteristics in speech and singing are similar in country singing and that county singing is not characterized by a singer's formant.

Adult↗

Level and center frequency of the singer's formant.

The "singer's formant" is a prominent spectrum envelope peak near 3 kHz, typically found in voiced sounds produced by classical operatic singers. According to previous research, it is mainly a resonatory phenomenon produced by a clustering of formants 3, 4, and 5. Its level relative to the first formant peak varies depending on vowel, vocal loudness, and other factors. Its dependence on vowel formant frequencies is examined. Applying the acoustic theory of voice production, the level difference between the first and third formant is calulated for some standard vowels. The difference between observed and calculated levels is determined for various voices. It is found to vary considerably more between vowels sung by professional singers than by untrained voices. The center frequency of the singer's formant as determined from long-term spectrum analysis of commercial recordings is found to increase slightly with the pitch range of the voice classification.

Female↗

Consistency of inhalatory breathing patterns in professional operatic singers.

Respiratory behavior is generally considered important to voice function, the assumption being that it affects the voice source. Accurate and consistent control of the voice source is particularly important in professional operatic singing. An erratic behavior of a factor influencing voice production is incompatible with a well-controlled vocal behavior. We analyzed the consistency of inhalatory breathing patterns during singing in five professional operatic singers, using the same material as in a previous investigation of phonatory breathing patterns. Rib cage (RC) and abdominal wall (AW) movements were recorded by respiratory inductive plethysmography. Consistency was analyzed in terms of the mean correlation between three takes of ten musical phrases. Results revealed a high consistency in lung volume (LV) change and RC movements in all singers and in AW movements in three singers. Consistency across different phrases was slightly lower. The results are compatible with the idea that inhalatory behavior is important to voice source in singing. A high correlation between LV change and RC movement was found in all singers and between LV change and AW movement in three. The contribution to LV change from RC was greater than that from AW in all singers.

Adult↗

Describing different styles of singing: a comparison of a female singer's voice source in "Classical", "Pop", "Jazz" and "Blues".

The voice is apparently used in quite different manners in different styles of singing. Some of these differences concern the voice source, which varies considerably with loudness, pitch, and mode of phonation. We attempt to describe voice source differences between Classical, Pop, Jazz and Blues styles of singing as produced in a triad melody pattern by a professional female singer in soft, middle and loud phonation. An expert panel was asked to identify these triads as examples of either Classical, Pop, Jazz or Blues. The voice source was analysed by inverse filtering. Subglottal pressure Ps, closed quotient QClosed, glottal compliance (ratio between the air volume contained in a voice pulse and Ps), and the level difference between the two lowest source spectrum partials were analysed in the styles and in four modes of phonation: breathy, flow, neutral, and pressed. The same expert panel rated the degree of pressedness in the entire material. Averages across pitch were calculated for each mode and style and related to their total range of variation in the subject. The glottogram data showed a high correlation with the ratings of pressedness. Based on these correlations a pressedness factor was computed from the glottogram data. A phonation map was constructed with the axes representing mean adduction factor and mean Ps, respectively. In this map Classical was similar to flow phonation, Pop and Jazz to neutral and flow phonation, and Blues to pressed phonation.

Female↗

Voice source differences between falsetto and modal registers in counter tenors, tenors and baritones.

Vocal registers are generally assumed to be associated with the voice source, i.e. the pulsating transglottal airflow. The waveform of this airflow was analysed by inverse filtering in professional singers, four counter tenors, five tenors, and four baritones singing the syllable [pae:] in soft, middle, and loud voice in modal and falsetto/counter tenor register. Subglottal pressure, estimated from the intra-oral pressure during the occlusion for the consonant [p], closed quotient, relative glottal leakage, and the relative level of the fundamental were analysed. The counter tenors used comparatively low subglottal pressures and mostly showed a closed phase in their flow glottogram waveform. For a given value of the closed quotient, the fundamental tended to be stronger in falsetto than in modal register. The observed voice source differences between the registers seem related to a greater vocal fold thickness in modal than in falsetto register.

Adult↗

Perceptual and acoustic analysis of vocal registers in 10-year-old children.

Register transitions were identified by a group of five experts on child voices in recordings of 15 10-year-old children who sustained the vowel [a:] at different pitches throughout their vocal range. Two had mutational voices, seven had deviant voices and six were controls with normal voices. The control group had one register transition at a mean fundamental frequency of 511 Hz, or about 25% higher than in adult voices. This difference between adult and child voices may be because of the difference in trachea length, as proposed by Titze (J. Voice 1988; 3: 183-194). Children with either functional or physiological voice deviations exhibited a transition at a mean frequency of 417 Hz. A second transition was found in four voices at a mean frequency of 902 Hz. No correlation was found between the occurrence of register transitions and discontinuities in the upper and lower voice range profile contours.

Child↗

The C3H/HeJBir mouse model: a high susceptibility phenotype for colitis.

C3H/HeJBir is a substrain of C3H/HeJ mice that was generated by selective breeding for the phenotype of spontaneous colitis. These mice show increased B cell and T cell reactivity to antigens of the enteric bacterial flora. CD4+ T cells from this strain cause colitis, when activated by enteric bacterial antigens and transferred to histocompatible severe combined immunodeficient recipients. The expression of the disease phenotype of spontaneous colitis is greatly influenced by housing conditions and probably requires an immunostimulatory enteric flora. This strain seems to carry multiple susceptibility genes for colitis as does the parental C3H/HeJ strain; the genes involved are being mapped. This strain represents a high susceptibility phenotype for colitis that is providing insight into the interactions among immune, environmental and genetic factors that can result in IBD.

Animals↗

Protein binding of mercury in milk and plasma from mice and man--a comparison between methylmercury and inorganic mercury.

Inorganic mercury has previously been shown to be excreted to milk from plasma to a higher extent than methylmercury. Protein binding of mercury as methylmercury and inorganic mercury in whey and plasma from mouse and man was studied in order to get a better understanding of the transport of mercury into milk. Mice were administered a single i.v. dose of 0.25 mg Hg/kg body weight labelled with (CH3)203HgCl or 203HgCl2, resulting in 11 ng Hg/g milk and 38 ng Hg/g milk after 1 h, respectively. Milk and plasma from mice and man were also incubated with the respective radiolabelled compound (150 ng Hg/g milk or plasma). Casein, fat and whey fractions in milk from methylmercury treated mice were found to contain 11, 39 and 34%, respectively, and from inorganic mercury treated mice 31, 15 and 41%, respectively, of the total amount of mercury in milk. Serum albumin was a major mercury binding protein in whey and plasma from mice for both methylmercury and inorganic mercury, as demonstrated by FPLC gel filtration and anion-exchange chromatography and further characterised by SDS-PAGE for whey. In addition, anion-exchange chromatography indicated that inorganic mercury, but not methylmercury, in whey from mouse milk formed a dimer of serum albumin. The unbound fraction of mercury in whey and plasma from mice was very small (<0.7%), and somewhat higher in plasma and whey from man. It is concluded, that the unbound fraction in plasma cannot be a determining factor for the observed differences in milk excretion between the two mercury compounds. Instead, it is suggested that methylmercury and to some extent inorganic mercury are transferred from plasma into milk using albumin as a passive carrier.

Adult↗

Lactational exposure and neonatal kinetics of methylmercury and inorganic mercury in mice.

The concentration of mercury in milk and the distribution pattern in the sucking pup was followed over time after administration of a single iv injection of 0.5 mg/kg body wt of 203Hg-labeled methylmercuric chloride or mercuric chloride to lactating mice on Day 10 of lactation. Mercury concentrations in milk of the dams and in whole body, blood, plasma, GI-tract, liver, kidneys, and brain of the offspring were followed up to 11 days after dosing (until lactational Day 21). Following the inorganic mercury dose to the dams, most of the mercury in milk was delivered to the pups during the first 24 h, but the maximum mercury concentration in plasma and tissues of pups was not reached until 7 days after dosing, indicating a prolonged absorption of inorganic mercury in the sucking pup. Pups of dams given methylmercury were exposed to a much lower and constant mercury concentration in milk. The estimated accumulated mercury dose via milk per pup of dams given methylmercury was less than half of that estimated after the inorganic mercury dose. When the accumulated dose via milk from methylmercury-exposed dams was compared to the amount of mercury in pup's carcass (whole body minus GI-tract including content), it was revealed that almost all mercury delivered via milk was absorbed, and that the suckling pups had a very low elimination of mercury until lactational Day 17. Lactational exposure following a maternal methylmercury or inorganic mercury dose resulted in almost similar mercury concentrations in liver, kidneys, and plasma of the suckling, but higher concentrations in brain (as most 14 times) and also twice as high mercury body burden in the methylmercury group. Thus, differences in kinetics indicate that lactational exposure of methylmercury is a greater hazard for the breast-fed infant than inorganic mercury.

Animals↗

Consistency of phonatory breathing patterns in professional operatic singers.

Breathing strategy is generally regarded as an important factor in operatic singing, because it is assumed to affect phonation. If so, professional singers should exhibit well-controlled, replicable breathing movements when repeating the same phrase. The purpose of the present study was to investigate to what extent professional opera singers show a consistent, exhalatory breathing behavior in a quasi-realistic concert situation. Respiratory movements were documented in 5 professional operatic singers, two women and three men, by means of respiratory inductive plethysmography. Comparison of respiratory data gathered from 3 renderings of the same phrases revealed high consistency with regard to lung volume (LV) behavior. The same applied to rib cage (RC) movements, suggesting a great relevance of RC control in singing. Consistency in abdominal wall (AW) movement was observed in 2 singers. These observations are in accordance with the idea that the breathing strategy plays an important role in voice production during singing. In addition, the correlation between LV changes, on the one hand, and RC and AW movements on the other, was examined. The contribution to LV changes from the RC and the AW varied across singers, thus suggesting that professional operatic singing does not request a uniform breathing strategy.

Abdominal Muscles↗

Formant frequencies in country singers' speech and singing.

In previous investigations breathing kinematics, subglottal pressures, and voice source characteristics of a group of premier country singers have been analyzed. The present study complements the description of these singers' voice properties by examining the formant frequencies in five of these country singers' spoken and sung versions of the national anthem and of a song of their own choosing. The formant frequencies were measured for identical phonemes under both conditions. Comparisons revealed that the singers used the same or slightly higher formant frequencies when they were singing than when they were speaking. The differences may be related to the higher fundamental frequency in singing. These findings are in good agreement with previous observations regarding breathing, subglottal pressures, and voice source, but are in marked contrast to what has been found for classically trained singers.

Adult↗

Voice source characteristics in six premier country singers.

Voice source characteristics as derived from inverse filtering were analyzed in 6 country singers' speech and singing. Results showed that the closed quotient varied systematically with vocal loudness, and that glottal compliance (the ratio between transglottal AC volume displacement and subglottal pressure) decreased with increases in fundamental frequency but remained unaffected by vocal loudness. No striking differences were found in source characteristics between speech and singing within subjects. The degree of phonatory press, as judged by a panel of 19 expert listeners, appeared related to the range in which the singer was singing and to the sound pressure level gain from a doubling of subglottal pressure.

Adult↗

Identification of a novel SCD gene and expression of the SCD gene family in mouse skin.

We have refined the position of asebia locus by genotyping DNA from more than 600 backcross mice derived from asebia mouse and a genetically unrelated strain. One of the candidate genes in the locus is stearoyl-CoA desaturase (SCD). Previously two members of this gene family, namely SCD1 and SCD2, have been described. We have found, for the first time, that these SCD genes are expressed in skin. Moreover, we have identified a third species of SCD in the mouse skin. The most prominent SCD species is SCD1 in the mouse skin. The implications of this gene family to skin are discussed.

Animals↗

Effects of subglottal pressure variation on professional baritone singers' voice sources.

Five professional operatic baritone singers' voice-source characteristics were analyzed by means of inverse filtering of the flow signal as captured by a flow mask. The subjects sang a long sustained diminuendo, from loudest to softest, three times on the vowels [a:] and [ae:] at fundamental frequencies representing 25%, 50%, and 75% of their total pitch range as measured in semitones. During the diminuendos, they repeatedly inserted the consonant [p] so that associated subglottal pressures could be estimated from the oral pressure during the p-occlusions. Pooling the three takes of each condition, ten subglottal pressures, equidistantly spaced between highest and lowest, were selected for analysis. Sound-pressure levels (SPL), peak-to-peak glottal airflow, maximum flow declination rate, closed quotient, glottal dc flow, and the level difference between the two lowest partials of the source spectrum (H1-H2) were determined. All parameters except the glottal dc flow showed a systematic variation with subglottal pressure or the fractional excess pressure over threshold. The results are given in terms of equations representing the average across subjects for the relation between subglottal pressure and each of the mentioned voice-source parameters.

Adult↗

Kinetics of methylmercury and inorganic mercury in lactating and nonlactating mice.

The elimination of mercury was followed for 9 days (Days 10-19 of lactation) in milk and/or 21 days in blood and plasma of lactating and nonlactating mice administered a single iv injection of either 203Hg-labeled methylmercuric chloride or 203Hg-labeled mercuric chloride (0.5 mg Hg/kg body wt). Demethylation of methylmercury to inorganic mercury was taken into consideration by analyzing the data with a combined pharmacokinetic model based on the assumption of constant blood plasma ratios for methylmercury and inorganic mercury. A three-compartment model fitted the blood and plasma concentrations vs time profiles for both compounds. Plasma clearance and volume of distribution at steady state for methylmercury were 95. 3 ml/h/kg and 18,500 ml/kg, respectively, in lactating mice, and significantly higher than in nonlactating mice with values of 47.1 ml/h/kg and 9400 ml/kg, respectively. The terminal half-lives of methylmercury in plasma were similar, 170 h in lactating and 158 h in nonlactating mice. No differences were observed between the pharmacokinetic parameters in lactating and nonlactating mice administered inorganic mercury. The lactational transfer of mercury was more efficient following administration of inorganic mercury than after administration of methylmercury, with a five times higher peak concentration in milk, higher milk:plasma concentration ratios, and 8% of the administered dose excreted in milk compared with 4% for methylmercury. Mercury concentrations in milk following an iv dose of inorganic mercury decreased with a terminal half-life of 107 h, whereas after administration of methylmercury, the concentration of total mercury in milk remained at an almost constant level during the whole period of investigation. There was a nonlinear relationship between mercury in milk and plasma following inorganic mercury administration. It is suggested that inorganic mercury enters the mammary gland by a carrier-mediated transport system, which is saturated at high plasma levels of inorganic mercury. The present study shows that physiological changes during lactation alter the pharmacokinetics for methylmercury in mice but not for inorganic mercury.

Animals↗

Effects of lung volume on vertical larynx position during phonation.

The vertical position of the larynx seems to be relevant to voice function. As a high vertical larynx position is often seen in hyperfunctional and strained voices, a lowering of a habitually elevated larynx is sometimes a specific goal in clinical voice therapy and different larynx-lowering exercises are used to achieve this goal. Earlier investigations have shown that pitch and to some extent also vocal loudness are relevant to vertical larynx position. In the present investigation, we examine if lung volume affects vertical larynx position. Using a multi-channel electroglottograph, the larynx position was measured in 29 healthy, vocally untrained subjects, who phonated at different lung volumes, pitches, and degrees of vocal loudness. The main results were that high lung volume was clearly associated with a lower larynx position as compared to low lung volume. In addition, vertical larynx position was strongly correlated with pitch. Both of these dependencies were shown to be stronger in males than in females. Our results suggest that lung volume is a factor that is highly relevant to larynx height in untrained subjects.

Adult↗