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Biomedical subjects

J Kim

Publications and source records attributed to J Kim.

At least 721 records · Page 40Linked to original sources

Evolution of B2 repeats: the muroid explosion.

B2 repeats are a group of short interspersed elements (SINEs) specific for rodent genomes. Copy numbers were determined for different rodent genera. All the Muroid (rat, mouse, deer mouse, hamster, gerbil) rodent genomes analyzed exhibited 80,000-100,000 copies per haploid genome, whereas the squirrel genome contains only 2,500 copies, and fewer than 100 (if any) copies were observed for the Hystricognath rodents (guinea pig and nutria). These findings demonstrate that there was an 'explosion' of amplification of B2 elements within muroid rodents. The similar copy number of B2 elements within the different muroid species could be explained by formation of a high proportion of the B2 elements prior to the divergence of the different muroid species. However, the 3'-end of the B2 sequence is unique between murid and cricetid rodents suggesting that the majority of elements amplified after the divergence of these species. Also consistent with recent amplification of these elements in parallel within the muroid genomes is the finding that within mouse and rat there are distinct subfamilies of B2 repeats. The pattern of consistent parallel amplification of B2 elements in muroid species contrasts with the sporadic nature of ID repeat amplification in the same genomes. The consensus of the young mouse subfamily of elements corresponds to the B2 RNA that is preferentially transcribed in embryonic, tumor, and normal liver cells. The subfamily is young based on both its low divergence from the subfamily consensus sequence and the finding that the most recent B2 element insertions in the mouse genome are members of this subfamily.

Animals↗

Studies on the effects of selenium on rumen microbial fermentation in vitro.

The effects of selenium (Se) on ruminant microbial fermentation were investigated in vitro using rumen microflora collected from a rumen-fistulated dairy cow. First, the effects of L-selenomethionine (SeMet; at 0.2 or 2 ppm Se) in the presence or absence of wheat bran (WB, 500 mg per incubation flask) were evaluated. Second, the effects of several forms of Se (elemental Se: 50 ppm Se; sodium selenite: 2 ppm Se; SeMet: 2 ppm Se) were compared. Results showed that the amounts of short-chain fatty acids (SCFAs) tended to be increased by SeMet treatment, whereas SeMet in the presence of WB transiently suppressed fermentation. The addition of SeMet tended to increase the production of acetate while reducing the production of butyrate with the without WB supplementation. Among the different Se compounds tested, the amounts of SCFAs were greater with SeMet treatment, which yielded a higher proportion of acetate compared to other treatments. Selenite did not influence the total SCFAs concentrations; however, it increased the relative proportion of butyrate at the expense of acetate. Elemental Se did not significantly affect fermentation. Higher bacterial Se concentrations were observed for selenite than for SeMet. It was concluded that Se supplementation can influence rumen microbial fermentation and that Se compounds differ in this regard.

Acetic Acid↗

Effects of selenium on colonic fermentation in the rat.

Studies were conducted to determine the effects of dietary selenium (Se) on the hindgut microbial activity in rats. Selenium was fed as L-selenomethionine (SeMet) at either 0 or 2 ppm Se in the presence or absence of wheat bran (WB, 10%), a known substrate for the enteric microflora. Wheat bran feeding caused the greatest fermentation, measured by the production of short-chain fatty acids (SCFAs) along the entire intestinal tract and feces; however, its effects were suppressed by SeMet in the proximal large bowel, cecum, and colon. Selenium significantly enhanced fermentation in the colon and rectum, but not in the cecum or feces. Selenium was found in association with the bacterial cell fractions of gut contents and feces: 40-46% of the total Se was associated with colonic microbes and 58% in fecal microbes. Increased acetate and reduced butyrate production were driven by the addition of Se regardless of whether WB was fed.

Animals↗

Ca2+-channel-dependent and -independent inhibition of exocytosis by extracellular ATP in voltage-clamped rat adrenal chromaffin cells.

Membrane currents and capacitance were measured to examine the effects of extracellular ATP on exocytosis in voltage-clamped rat adrenal chromaffin cells. ATP reversibly inhibited Ca2+ current (ICa) and exocytosis. The dependency of exocytosis on ICa evoked by 1-s depolarizations was determined. However, inhibition of exocytosis was 2.6 times larger than that estimated from the reduction of ICa, implying the existence of a Ca2+-channel-independent pathway. This inhibition did not rely on a further reduction of the intracellular Ca2+ concentration spike. ATP reduced the rate of exocytosis induced by clamping the intracellular Ca2+ concentration. Pertussis toxin blocked the inhibitory effects of ATP on ICa and exocytosis. Although RB-2, a P2Y antagonist, blocked the inhibitory effect of ATP on ICa, RB-2 itself produced large increase or decrease in membrane capacitance. Adenosine inhibited ICa via a pertussis-toxin-sensitive pathway but did not significantly inhibit exocytosis. Our data show that extracellular ATP inhibits exocytosis via inhibition of ICa by activation of a pertussis-toxin-sensitive G-protein linked to P2Y receptors. Furthermore, our data strongly suggest that ATP activates another pathway, which is also G-protein dependent and accounts for the majority of the inhibitory effect of ATP on exocytosis.

Adenosine Triphosphate↗

Ischemic intervals during warm blood cardioplegia in the canine heart evaluated by phosphorus 31-magnetic resonance spectroscopy.

OBJECTIVE: Warm blood cardioplegia requires interruption by ischemic intervals to aid visualization. We evaluated the safety of repeated interruption of warm blood cardioplegia by normothermic ischemic periods of varying durations. METHODS: In three groups of isolated cross-perfused canine hearts, left ventricular function was measured before and for 2 hours of recovery after arrest, which comprised four 15-minute periods of cardioplegia alternating with three ischemic intervals of 15, 20, or 30 minutes (I15, I20, and I30). Metabolism was continuously measured by phosphorus 31-magnetic resonance spectroscopy. RESULTS: Adenosine triphosphate level fell progressively as ischemia was prolonged; after recovery, adenosine triphosphate was 99% +/- 6%, 90% +/- 1% (p = 0.0004 vs control), and 68% +/- 3% (p = 0.0002) of control levels in I15, I20, and I30, respectively. Intracellular acidosis with ischemia was most marked in I30. After recovery, left ventricular maximal systolic elastance at constant heart rate and coronary perfusion pressure was maintained in I15 but fell to 85% +/- 3% in I20, (p = 0.003) and to 65% +/- 6% (p = 0.003) of control values in I30, while relaxation (tau) was prolonged only in I30 (p = 0.007). CONCLUSIONS: Hearts recover fully after three 15-minutes periods of ischemia during warm blood cardioplegia, but deterioration, significant with 20-minute periods, is profound when the ischemic periods are lengthened to 30 minutes. This suggests that in the clinical setting warm cardioplegia can be safely interrupted for short intervals, but longer interruptions require caution.

Adenosine Triphosphate↗

Electrospray mass spectrometry of testosterone esters: potential for use in doping control.

The study described involves an attempt to identify 17 beta-fatty acid esters of testosterone in blood plasma following administration of such agents. These drugs are therapeutic but are increasingly misused by athletes in an attempt to improve sports performance. The mass spectral properties of testosterone esters under electrospray ionization are described. These esters (testosterone acetate, propionate, isocaproate, benzoate, enanthate, cypionate, phenylpropionate, decanoate, and undecanoate) essentially give only a protonated molecular ion (MH+) under "optimum sensitivity" mass spectrometric conditions but could be induced to fragment in the source or collision cell of a triple quadrupole mass spectrometer. The underivatized steroid esters were analyzed by direct infusion because development of solvent systems compatible with high-performance liquid chromatography (HPLC) was not achieved for these nonpolar compounds. HPLC/MS (mass spectrometry) was possible when the steroids were converted to polar, water soluble, Girard hydrazones, and almost all were separated by microbore C4 HPLC using a water, acetonitrile, TFA gradient. The mass spectra under optimal ionization conditions essentially comprised only a molecular ion (M+), but source fragmentation gave major ions at M - 59 and M - 87 for all compounds. The molecular ion and these fragment ions were monitored in a selected-ion-recording (SIR) method developed for detecting the steroids in plasma. Using this methodology, testosterone enanthate and undecanoate could be detected after intramuscular injection or oral administration of the drugs. Further development of the technique could form the basis of a protocol for confirming the misuse of testosterone in sport, especially if sensitivity could be improved.

Chromatography, High Pressure Liquid↗

Motion integration over space: interaction of the center and surround motion.

Motion integration occurs over a restricted range of visual space. However, there have been studies suggesting interactions among motion detectors operating on widely separated spatial regions. To understand these lateral spatial interactions beyond motion pooling regions, we examined the effect of surrounding motion on the direction of the center stimulus under several stimulus conditions. We have found that there is a motion direction shift of the center stimulus caused by surrounding motion depending on its motion direction, spatial proximity to the center stimulus, contrast, speed, and the extent of motion area. This effect was observed both for monocular and dichoptic presentations of the pattern. However, the perceived direction shift decreased when the spatial frequency ratio of the center and surround stimuli varied, or a non-Fourier motion pattern was used for both center and surround stimuli. We present a model consisting of lateral inhibitory interactions between pattern motion unit networks to explain the direction shift observed in the experiments.

Contrast Sensitivity↗

Fluorescent dots in fluorescein angiography and fluorescein leukocyte angiography using a scanning laser ophthalmoscope in humans.

PURPOSE: The purpose of the study is to disclose the nature of fluorescent dots and segments traditionally observed with fluorescein angiography (FA) using a scanning laser ophthalmoscope (SLO 101; Rodenstock, München, Germany). The authors developed a new method, called fluorescein leukocyte angiography (FLA), to display directly the movement of leukocytes in human retinal vessels. METHODS: Fluorescein angiography was performed on two normal volunteers using a scanning laser ophthalmoscope and fluorescent dots and segments were observed. Fluorescein leukocyte angiography, using an injection of fluorescent buffy coat layer from which the fluorescent plasma and nonfluorescent erythrocytes have been removed externally, was performed on seven normal volunteers. Injection fluid smears were examined through a fluorescent microscope. Peripheral blood smears taken during midphase of FA and FLA also were examined. In addition, 15 early-phase FAs of central serous chorioretinitis (CSC) were studied retrospectively. RESULTS: In the FAs of normal volunteers, fluorescent dots were detected only in perimacular capillaries at early phase. Eight of the 15 CSC FAs examined showed both fluorescent dots and segments. In the FLAs, fluorescent dots were detected in whole retinal vessels for more than 30 minutes. Fluorescent segments were observed in FA but not in FLA. Injected fluid smears from one FLA showed fluorescent leukocytes and small platelets. However, in peripheral blood smears of the FLA, leukocytes and platelets were more visible and exhibited higher contrast than those of an FA due to background plasma fluorescence. The mean velocity of 21 flowing leukocytes in perifoveal capillaries was 1.37 +/- 0.35 mm/second in 2 FAs and that of 89 flowing leukocytes was 1.41 +/- 0.29 mm/second in 7 FLAs. CONCLUSIONS: The authors' observations suggest that fluorescent dots in scanning laser ophthalmoscope imaging are fluorescein-stained leukocytes, whereas fluorescent segments are the hyperfluorescent plasma that is located between rouleaux formations of erythrocytes. The velocity of the fluorescent dots could be measured in the perimacular capillaries by either FA or FLA; however, only FLA can display the flow of fluorescent leukocytes in large vessels.

Adult↗

Neonatal hearing screening with otoscopy, auditory brain stem response, and otoacoustic emissions.

A study was performed to investigate the relationship between external and middle ear factors and hearing screening results by auditory brain stem response (ABR) and transient evoked otoacoustic emissions (EOAEs). The ears of 200 well newborns aged 5 hours to 48 hours underwent screening by ABR and EOAEs, followed by otoscopic examination. The pass rates for ABR and EOAE screening were 88.5% and 79%, respectively. On otoscopic examination, 13% (53 of 400) ears had occluding vernix obscuring the view of the tympanic membrane. Cleaning of vernix was attempted in ears that failed ABR or EOAE screening. Seventeen ears that failed ABR were cleaned, and 12 (71%) of them passed repeat ABR. Thirty-three ears that failed EOAE screening were cleaned, and 22 (67%) of them passed repeat emissions testing. Cleaning vernix increased the pass rates for ABR and EOAE screening to 91.5% and 84%, respectively. Decreased tympanic membrane mobility was found in 9% of ears that could be evaluated otoscopically. Increased failure rates for both ABR and EOAE screening were found in infant ears with decreased tympanic membrane mobility, but significance testing could not be performed because of inadequate sample size. Prevalence of occluding external canal vernix and middle ear effusion as a function of increasing infant age were studied. Implications for newborn hearing screening are discussed.

Body Fluids↗

Neuronal and transneuronal degeneration of auditory axons in the brainstem after cochlear lesions in the chinchilla: cochleotopic and non-cochleotopic patterns.

Terminal axonal degeneration in the brain following cochlear lesions was studied with the Nauta-Rasmussen method. Losses of hair cells and myelinated cochlear fibers were assessed. The cochleotopic map projected, from apex to base, on the ventral-to-dorsal axes of the cochlear nuclei. The cochleotopic correspondence was better for loss of cochlear nerve fibers and inner hair cells, than for outer hair cells. Cochlear fibers were traced to all parts of the cochlear nucleus, including the small-cell shell, also to cell-group Y and the flocculus. Terminal axonal degeneration in nuclei of the superior olivary complex, lateral lemniscus, and inferior colliculus was interpreted as transynaptic, since degenerated axons could not be traced to these locations from the cochlear nerve or trapezoid body. Moreover, biotinylated dextran amine injection in the basal turn of scala media of a normal cochlea labeled cochlear nerve fibers projecting to the high-frequency regions of the cochlear nuclei and to the flocculus, but not to more central auditory nuclei. This is the first detailed account of transynaptic degeneration in the ascending auditory pathway resulting from cochlear damage in an adult mammal. These findings are consistent with a dystrophic process depending on hair-cell loss and/or direct damage to cochlear nerve fibers.

Animals↗

Degeneration of axons in the brainstem of the chinchilla after auditory overstimulation.

The patterns of axonal degeneration following acoustic overstimulation of the cochlea were traced in the brainstem of adult chinchillas. The Nauta-Rasmussen method for axonal degeneration was used following survivals of 1-32 days after a 105 min exposure to an octave-band noise with a center frequency of 4 kHz and a sound pressure level of 108 dB. Hair-cell and myelinated nerve-fiber loss were assessed in the cochlea. The cochleotopic pattern of terminal degeneration in the ventral cochlear nucleus correlated with the sites of myelinated fiber and inner-hair-cell loss: this correlation was less rigorous with outer-hair-cell loss, especially in the dorsal cochlear nucleus. These results are consistent with a dystrophic process with a slow time course depending on hair-cell loss and/or direct cochlear nerve-fiber damage. However, in a number of cases with no damage in the apical cochlea, fine fiber degeneration occurred with a faster course in low-frequency regions in the dorsal cochlear nucleus and, transynaptically, in a non-cochleotopic pattern in the superior olive and inferior colliculus. These findings suggest that neuronal hyperactivity plays a role in the central degeneration following acoustic overstimulation, possibly by an excitotoxic process.

Acoustic Stimulation↗

Mania in children with pervasive developmental disorder revisited.

OBJECTIVE: Although a small literature of case reports suggests that mania co-occurs with pervasive developmental disorder (PDD), little is known about this overlap. The authors systematically investigated the overlap between mania and PDD in a consecutive sample of referred youths, examining its prevalence and correlates. It was hypothesized that children with PDD plus manic features have both disorders. METHOD: Subjects were consecutively referred children meeting diagnostic criteria on structured interview for PDD without mania (n = 52), the comorbid condition PDD + mania (n = 14), and mania without PDD (n = 114). All subjects were evaluated using a comprehensive diagnostic battery that included assessment of psychopathology (structured diagnostic interview and Child Behavior Checklist), cognition, and functioning. RESULTS: Of the 727 referred children, 52 met criteria for PDD, 114 met criteria for mania, and 14 met criteria for both. The 14 children with both PDD + mania represented 21% of the PDD subjects and 11% of all manic subjects. Clinical characteristics of PDD were similar in PDD subjects with and without mania, and manic features were similar in manic children with and without PDD. CONCLUSIONS: Children with PDD and mania may suffer from two disorders. Comorbid mania among patients with PDD may be more common than previously thought. Identification of the comorbid condition may have important therapeutic and scientific implications.

Bipolar Disorder↗

DNA bending is induced by binding of the glucocorticoid receptor DNA binding domain and progesterone receptors to their response element.

Circular permutation analysis was used to determine the degree of DNA bending induced by binding of the glucocorticoid receptor (GR) DNA binding domain (DBD), the human progesterone receptor (PR) DBD, PR-A:A and PR-B:B homodimers, and PR-A:B heterodimers to the glucocorticoid response element/progesterone response element (GRE/PRE). The bending angles induced by the GR DBD and the PR DBD were approximately 28 degrees and 25 degrees, respectively. The PR-B:B and PR-A:A homodimers and the PR-A:B heterodimers all induced similar DNA bending angles of 72-77 degrees. The substantially greater DNA bend induced by full-length PR compared to the PR DBD indicates that sequences outside the classic zinc finger DNA binding domain may play an important role in the interaction of PR with the GRE/PRE. Because PR-A:A and PR-B:B homodimers and the PR-A:B heterodimers induce similar DNA bends, the different abilities of the PR-A and PR-B isoforms to activate transcription are not due to differences in their abilities to distort DNA structure.

Binding Sites↗

New antihepatotoxic cerebroside from Lycium chinense fruits.

Two cerebrosides isolated from Lycium chinense fruits have been characterized as 1-O-beta-D-glucopyranosyl-(2S, 3R,4E,8Z)-2-N-palmitoyloctadecasphinga-4,8-dienine+ ++ (1) and 1-O-beta-D-glucopyranosyl -(2S,3R,4E,8Z)-2-N-(2'-hydroxypalmitoyl)octadecasph inga-4,8-dienine (2). While 2 is already known, the structure of 1 was determined by spectral and chemical studies. Incubation of CCl4-intoxicated hepatocytes with 1 and 2, respectively, significantly reduced the levels of glutamic pyruvic transaminase (GPT) and sorbitol dehydrogenase (SDH) released by injured cells.

Animals↗

Effect of chronic prolactin infusion on pituitary prolactin and hypothalamic proopiomelanocortin.

Although there is evidence that endogenous opioids, and in particular beta-endorphin (beta-EP), may mediate some of the suppressive effects of hyperprolactinemia on the hypothalamic-pituitary-gonadal (HPG) axis, there is controversy about the effects of prolactin (PRL) on beta-EP and its precursor, proopiomelanocortin (POMC), in the hypothalamus. In this study we have therefore examined the effects of chronic peripheral and intracerebroventricular (i.c.v.) infusion of ovine PRL on POMC gene expression and beta-EP levels in the medial basal hypothalamus (MBH) of castrated male and female rats. Endogenous pituitary and plasma PRL levels were determined by RIA with an antiserum to rat PRL which does not crossreact with oPRL. Suppression of endogenous rPRL levels was used as a confirmation of the biological effectiveness of the infused oPRL. POMC mRNA was measured in the MBH by solution hybridization assay. In the first experiment oPRL (5 microg/microl/h) or vehicle was infused for 2 weeks by osmotic minipump into the right lateral ventricle of ovariectomized rats. The mean plasma concentration of rPRL declined from 3.7+/-1.0 ng/ml in the controls to 1.4+/-0.13 ng/ml in the oPRL infused animals (P<0.05); pituitary rPRL content similarly decreased from 39.1+/-4.6 microg to 20.4+/-3.7 microg (P<0.02). There was no significant change in the concentration of POMC mRNA or beta-EP in the MBH of the oPRL treated animals. In the second experiment oPRL was infused for 1 week into the third ventricle of orchiectomized rats. Again despite a fall in endogenous PRL levels, there was no significant change in POMC or beta-EP in the MBH. In the third experiment oPRL was infused subcutaneously into orchiectomized rats for 2 weeks. Mean plasma oPRL levels were 150+/-7.3 ng/ml after 1 week and 58+/-7.5 ng/ml after 2 weeks. Pituitary rPRL content was again suppressed in the oPRL treated animals but no change in POMC or beta-EP was detected in the MBH. We conclude that oPRL can be infused both peripherally and centrally for up to 2 weeks with resulting suppression of endogenous pituitary PRL content and release. Under these conditions no effects on the concentrations of POMC mRNA or beta-EP could be demonstrated in the hypothalamus. These results suggest that either PRL has nongenomic effects on hypothalamic beta-EP or that endogenous opioids other than beta-EP mediate the suppressive effects of PRL on the HPG axis.

Animals↗

Hepatitis G virus infection: clinical characteristics and response to interferon.

A new member of the Flaviviridae family has recently been cloned and completely sequenced. The new virus, tentatively named hepatitis G virus (HGV) and known to be closely related to GB virus C (GBV-C), is transmitted by blood and blood products, intravenous drug use and other behaviour associated with a high risk of parenteral exposure to blood. The association of the virus with hepatitis is demonstrated by the presence of raised liver transaminase (alanine aminotransferase, ALT) levels in patients infected with HGV in the absence of other identifiable causes of hepatitis. No patient sera from groups exposed to blood and blood products were found to be positive when tested for the presence of GBV-A or GBV-B sequences, two other recently described flaviviruses. Forty-five per cent of the HGV-infected patients investigated had normal ALT suggesting the existence of a normal carrier state. Persistent infection of up to 13 years duration was observed. Co-infection with hepatitis B or hepatitis C viruses (HBV and HCV) was commonly seen presumably because of shared risk factors. None of five patients with fulminant hepatic failure was positive for HGV infection. The virus is sensitive to interferon-alpha, but sustained responses were not seen with the treatment regimens used for HBV and HCV. Viral titres increased during immunosuppression following liver transplantation and the higher levels of viraemia were in one case accompanied by elavated ALT. Whether HGV (GBV-C) replicates in the liver in some or all cases remains to be established. Preliminary data suggest that it is present within peripheral blood lymphocytes.

Antiviral Agents↗

XBMP-1B (Xtld), a Xenopus homolog of dorso-ventral polarity gene in Drosophila, modifies tissue phenotypes of ventral explants.

Previously we have isolated a Xenopus cDNA homolog of bone morphogenetic protein-1 (XBMP-1A). In the present report we describe a new cDNA clone called XBMP-1B (or Xtld) from a Xenopus embryonic library. Sequence analysis indicates that these two clones share an indentical N-terminal sequence, including a region of metalloprotease domain, three copies of a repeat first found in complement proteins C1r/s and an epidermal growth factor (EGF)-like sequence. XBMP-1B protein has an additional copy of an EGF-like sequence followed by two copies of complement 1 r/s repeat in the C-terminus. The overall protein structure predicted from the XBMP-1B sequence reveals that it encodes a protein homologous to Drosophila tolloid. Three XBMP-1 transcripts (2.9, 5.2 and 6.6 kb) were detected by northern blot analysis. However, the 2.9 kb transcript hybridized specifically with XBMP-1A and the 5.2 and 6.6 kb transcripts hybridized with XBMP-1B. In Drosophila, a major function of tolloid is to augment the activity of the decapentaplegic gene product, a close relative of tumor growth factor (TGF)-beta superfamily members, BMP-2/4. Although XBMP-1 and XBMP-4 are detected in various adult tissues of Xenopus, the expression pattern of these two genes was not tightly correlated. In the embryo, the expression of XBMP-1 increased gradually from the morula to the swimming tadpole stages. Injection of XBMP-1B RNA into the ventral blastomeres at the 4-cell stage caused an elongation of the ventral marginal zone explants and converted globin-positive blood cells to mesenchymal and muscle tissues at later stages. It was shown that XBMP-1A was less active and a 1A mutant lacking the signal sequence was inactive. Further studies revealed that injection of XBMP-1B RNA into the ventral marginal zone induced up-regulation of dorsal marginal zone markers, such as goosecoid and chordin, at the gastrulation stage. These data indicate that XBMP-1 may have a role in determining dorso-ventral patterning in Xenopus, but in a different way from the dpp/tolloid system demonstrated in Drosophila.

Amino Acid Sequence↗