Biomedical subjects

K Hu

Publications and source records attributed to K Hu.

At least 19 recordsLinked to original sources

PubMed1995

Mechanisms of ischemic preconditioning in rat hearts. Involvement of alpha 1B-adrenoceptors, pertussis toxin-sensitive G proteins, and protein kinase C.

BACKGROUND: Ischemic preconditioning attenuates the effects of subsequent sustained ischemia by a mechanism involving adenosine and G proteins in several species. Adenosine is not involved in ischemic preconditioning of rat hearts, the mechanisms of which are poorly understood. METHODS AND RESULTS: Reduction of isometric tension development was used as an index of the effects of ischemia in isolated, Langendorff-perfused rat hearts. Two 5-minute periods of ischemia followed by 10 minutes of reperfusion attenuated the reduction of developed tension caused by 30 minutes of ischemia and 15 minutes of reperfusion. Pretreatment with pertussis toxin (PTX), depletion of norepinephrine stores with reserpine, or blockade of alpha 1-adrenoceptors with prazosin prevented the effects of ischemic preconditioning. Whereas alpha 1B-receptor blockade with chloroethylclonidine blocked ischemic preconditioning, alpha 1A-receptor blockade with 5-methylurapadil had no effect. The alpha-adrenergic agonist phenylephrine mimicked the effects of ischemic preconditioning in a concentration-dependent manner, and pretreatment with PTX prevented the action of maximally effective concentrations of phenylephrine. The protein kinase C activator phorbol 12-myristate 13-acetate mimicked and the protein kinase C inhibitors 1-(5-isoquinolinesulfonyl)-2-methylpiperazine and bisindolylmaleimide prevented ischemic preconditioning. CONCLUSIONS: Ischemic preconditioning in isolated, perfused rat hearts is caused by stimulation of alpha 1B-adrenoceptors by endogenous catecholamines through the activation of protein kinase C via a PTX-sensitive G protein. The PTX-sensitive inhibitory protein Gi, which can be activated by adenosine, muscarinic agonists, and alpha 1-adrenoceptor agonists, may play a central role in ischemic preconditioning mediated by protein kinase C across a broad range of species.

Animals↗

PubMed1995

Investigation of coronary vessels in microscopic dimensions by two- and three-dimensional NMR microscopic imaging in the isolated rat heart. Visualization of vasoactive effects of endothelin 1.

BACKGROUND: Nuclear magnetic resonance (NMR) imaging of macroscopic coronary vessels is rapidly advancing, whereas little attention has focused on development of NMR techniques for investigation of coronary microvessels. Such techniques would be of particular importance, since conventional methods to visualize coronary microvessels have specific limitations. The aim of our study was to develop two- and three-dimensional (2D and 3D) high-resolution imaging of coronary microvessels. Quantitative analysis of vessel size was performed in tomograms and applied to evaluate the vasoconstrictor effect of endothelin 1. METHODS AND RESULTS: Angiographic imaging was performed on an 11.75-T magnet by 2D and 3D gradient-echo pulse sequences. In tomograms, the validity of this method in providing correct vessel size was tested by phantom experiments. Experiments were carried out in the isolated constant-pressure-perfused rat heart with continuous registration of coronary flow and left ventricular pressure. NMR pulse sequences were pressure-triggered in mid diastole. Four groups of hearts were studied. In group 1 (n = 20), 2D imaging perpendicular and parallel to the long axis of the heart was performed. Cross sections of vessels with diameter > 140 microns were clearly detectable. In group 2 (control, n = 5) and group 3 (n = 13), tomograms perpendicular to the long axis were obtained before and after administration of vehicle (group 2) and 200 pmol endothelin 1 bolus (group 3). Vehicle had no effect on vessel cross section. Endothelin 1, which decreased global coronary flow by 47%, reduced vessel cross section by 38 +/- 19%. A weak but, on average, significant inverse correlation between area of cross section and vessel size was found. In group 4 (n = 10), 3D imaging was performed in 7 normal hearts and 3 hearts with anterior myocardial infarction. A 3D image of the entire coronary artery tree was obtained, revealing excellent agreement with anatomic studies. In infarcted rat hearts, occlusion of the left coronary artery was demonstrated. CONCLUSIONS: Visualization and quantification of coronary microvessels are feasible by NMR microscopy. NMR microscopy bears the potential of becoming a powerful tool for the investigation of the coronary microcirculation.

Animals↗

PubMed1995

Impairment of energy metabolism in intact residual myocardium of rat hearts with chronic myocardial infarction.

The purpose of this study was to test the hypothesis that energy metabolism is impaired in residual intact myocardium of chronically infarcted rat heart, contributing to contractile dysfunction. Myocardial infarction (MI) was induced in rats by coronary artery ligation. Hearts were isolated 8 wk later and buffer-perfused isovolumically. MI hearts showed reduced left ventricular developed pressure, but oxygen consumption was unchanged. High-energy phosphate contents were measured chemically and by 31P-NMR spectroscopy. In residual intact left ventricular tissue, ATP was unchanged after MI, while creatine phosphate was reduced by 31%. Total creatine kinase (CK) activity was reduced by 17%, the fetal CK isoenzymes BB and MB increased, while the "adult" mitochondrial CK isoenzyme activity decreased by 44%. Total creatine content decreased by 35%. Phosphoryl exchange between ATP and creatine phosphate, measured by 31P-NMR magnetization transfer, fell by 50% in MI hearts. Thus, energy reserve is substantially impaired in residual intact myocardium of chronically infarcted rats. Because phosphoryl exchange was still five times higher than ATP synthesis rates calculated from oxygen consumption, phosphoryl transfer via CK may not limit baseline contractile performance 2 mo after MI. In contrast, when MI hearts were subjected to acute stress (hypoxia), mechanical recovery during reoxygenation was impaired, suggesting that reduced energy reserve contributes to increased susceptibility of MI hearts to acute metabolic stress.

Adenosine Diphosphate↗

PubMed1995

Detection of human papillomavirus types 16, 18 DNA related sequences in bronchogenic carcinoma by polymerase chain reaction.

In studying the relationship between human papillomavirus (HPV) and bronchogenic carcinoma, "high-risk" HPV 16, 18 DNA sequences were detected in samples from 50 lung cancer patients, 18 patients with benign pulmonary diseases and 4 fetal lung tissues by polymerase chain reaction (PCR) and dot-blot hybridization with biotin-labelled probes. The results showed that HPV 16, 18 DNA related sequences were found in 32% of lung cancer specimens, with 10 cases of HPV 16, 5 cases of HPV 18 and 1 case of both types. 48.15% (13/27) of squamous cell carcinomas were shown to be positive for HPV 16, 18 DNA. In addition, two adenocarcinomas and one small cell carcinoma were positive for HPV 16 DNA. No specimens from benign diseases tissues and fetal lung tissues showed positive results. These results suggest that primary bronchogenic carcinoma is related to HPV infection.

Adenocarcinoma↗

PubMed1994

Beta-blockers in cardiac failure.

The use of beta-blocking agents in patients with heart failure is still controversial. An activated sympatho-adrenal system in heart failure may support blood pressure and cardiac index, on the other hand, it increases cardiac load and myocardial oxygen consumption, reduces myocardial oxygen supply and may contribute to the high incidence of arrhythmias and sudden death. Today there is a certain awareness about the important role of the sympatho-adrenal system in CHF. Short-term studies failed to demonstrate a benefit of beta-blockers while long-term studies have proved major haemodynamic benefit and functional improvement in most patients. The haemodynamic benefit consists of a reduction of heart rate and left ventricular filling pressure and an improvement in exercise capacity. The mechanism of these actions of beta-blockers, with the exception of lowering heart rate, remains unclear. Energy metabolism of the failing heart, which is considered to be deficient, may beneficially be influenced by chronic beta-blocker treatment. Effects of beta-blockers on prognosis in patients with heart failure are also still controversial. Most recent trials (MDC Trial, CIBIS Trial) were inconclusive concerning mortality. Aetiology of heart failure may be important; however, observations on secondary prevention post-myocardial infarction also contradict heart failure studies. Thus, further efforts are urgently needed to define the mechanism of action of beta-blockers in patients with cardiac failure and to identify more clearly patients who benefit from this type of therapy.

Adrenergic beta-Antagonists↗

PubMed1994

Effects of LTD4 and its specific antagonist L-660,711 in isolated rat hearts with chronic myocardial infarction.

We investigated the effects of leukotriene (LT) D4 and its novel potent and selective antagonist L-660,711 on isolated rat hearts with chronic myocardial infarction. The left coronary artery was ligated permanently or for 30 or 60 min and followed by reperfusion. Hearts were isolated and perfused in the Langendorff mode 4 days, 4 wk, or 8 wk after the operation. Dose-response curves for LTD4 (12-240 ng/min) on coronary flow were shifted to the left in rats with permanent coronary occlusion for 8 wk or with coronary occlusion for 30 or 60 min and reperfusion for 4 wk. In contrast, dose-response curves were unchanged in rats 4 days after myocardial infarction. L-660,711 shifted dose-response curves for LTD4 on coronary flow to the right in all groups. The negative inotropic and chronotropic effects of LTD4 could be markedly attenuated by L-660,711 in all groups. Our findings suggest that the effect of LTD4 is enhanced in rat hearts with chronic myocardial infarction. L-660,711 effectively antagonized the vasoconstrictor effect of exogenous LTD4.

Angiotensin I↗

PubMed1994

Effect of endurance training early or late after coronary artery occlusion on left ventricular remodeling, hemodynamics, and survival in rats with chronic transmural myocardial infarction.

BACKGROUND: Remodeling of infarcted and noninfarcted ventricular regions, infarct expansion, shape distortion, and global left ventricular (LV) dilation influence LV performance and survival. The effect of chronic exercise, initiated early or later after infarction, on remodeling, hemodynamics, and survival has not been studied. METHODS AND RESULTS: A total of 156 rats were randomized after coronary artery occlusion or sham operation to remain sedentary or to start with swim training 4 days or 21 days after coronary occlusion, which was continued over 8 weeks (6 days per week, 90 minutes per day). These intervals after coronary artery ligation were chosen because final size of infarction is well reached after 4 days; histological evolution of scar healing is still in progress, and after 21 days, histological scar healing is completed. At 8 weeks, hemodynamics were measured and LV dilation quantitated by passive pressure-volume curves. In groups with small (< or = 35%) and large (> 35%) infarcts, the area enclosed by endocardial circumference, infarct size, LV diameter, scar thickness, and septal thickness were measured in stained transverse serial LV sections to assess aneurysmal shape distortion and the response of infarcted and noninfarcted myocardia. Survival was not influenced by infarction or exercise alone. In rats with small infarcts, LV volume and shape and long-term survival were not altered by chronic exercise initiated early or late after coronary artery ligation. Mortality rose in animals with large infarction as a result of exercise (P < .0001) and was 47.6% with early exercise and 26.7% with late exercise (P < .05, early versus late). Infarct size in rats with early exercise (48 +/- 3%) was similar compared with infarct size of rats with late exercise (46 +/- 2%, P = NS compared with early exercise). Exercise did not affect LV dysfunction (assessed by systolic and end-diastolic pressures and dP/dtmax) in survivors of small and large infarctions. LV volumes increased (P < .05) in sedentary rats by large infarction (n = 13, 0.48 +/- 0.04 mL) compared with volumes after sham operation (n = 33, 0.33 +/- 0.03 mL) and with exercise (early, n = 11, 0.56 +/- 0.04 mL; late, n = 11, 0.65 +/- 0.04; P < .05 versus sedentary). In nonsurvivors from early exercise, the area enclosed by LV endocardial circumference (which corresponds to LV volume) was increased by 195%, LV diameter was increased by 60%, and scar thickness was reduced by 37% (P < .05 versus respective control). Septal thickness increased in survivors by exercise (+25%) but decreased (-28.6%) in nonsurvivors (P < .0001 versus respective control). CONCLUSIONS: Endurance training in rats after small infarction, whether started early or late after left coronary artery ligation, was well tolerated without changes in LV volume, shape, hemodynamics, and long-term survival. Endurance training in rats with large infarction decreased overall survival (P < .0001). In survivors from late exercise, training caused aggravation of global LV dilation without additional shape changes. Endurance training after large infarction caused aggravation of remodeling to a degree that was not compatible with life in 27% of the rats with late exercise and in 48% with early exercise after coronary artery ligation, despite similar exercise. This was explained by extensive remodeling that was most pronounced in nonsurvivors from early exercise. In these rats, severe global LV dilation, distortion of LV shape, scar thinning, and a paradoxic reduction of septal thickness, ie, mismatch of infarcted and noninfarcted myocardia, were observed.

Animals↗

PubMed1994

[An experimental study of the auditory brainstem implant in guinea pigs].

In order to examine the characteristics of the auditory brainstem implant, an animal model with electrical stimulation of the cochlear nucleus in guinea pigs was created. Middle latency response (MLR) to pulsatile electrical stimulation of the cochlear nucleus was recorded from the auditory cortex with bipolar plantinumiridium electrodes and stereotaxic technique. The electrically and acoustically generated MLRs have a similar morphology though there are little differences in the latencies, wave intervals and dynamic ranges. The results indicated that the central auditory pathways can be activated by means of electrical stimulation. The safety of the brain tissue to the electrical stimulation are also discussed.

Acoustic Stimulation↗

PubMed1994

[Indications for ACE inhibitors in the postinfarct period].

Prognosis of patients post-myocardial infarction depends largely on the degree of left ventricular dysfunction, which results from loss of contractile tissue and remodeling of infarcted and surviving myocardium. This remodeling process may result in chronically progressive dysfunction and ultimately in heart failure. Next to mechanical determinants humoral control of hypertrophy, dilatation and qualitative changes of surviving myocardium are discussed. A major determinant of the extent of remodeling is infarct size. Efficacy of angiotensin-converting enzyme (ACE) inhibitors on infarct size was tested in animal experiments with conflicting results. Recent clinical studies also report beneficial (GISSI-3 and ISIS-4) or no (CONSENSUS II) effects on survival post-myocardial infarction when ACE-inhibitors were used in the acute phase. Up to date it remains unsettled which patients may benefit from acute therapy with ACE-inhibitors. Three days after myocardial infarction hemodynamically stable patients with heart failure may be treated with ACE-inhibitors (AIRE study). Prognosis may be improved and manifestation of heart failure prevented or delayed also in patients without heart failure treated in this phase of myocardial infarction with ACE-inhibitors (SAVE study). Prevention of heart failure may also be observed in patients treated later (at least 4 weeks) after myocardial infarction (SOLVD prevention arm). It is essential for this indication that patients are carefully selected for treatment depending on left ventricular function. Duration of treatment in patients with severe left ventricular dysfunction probably has to be lifelong, the doses of ACE-inhibitors used have to be relatively high (e.g. 3 x 50 mg captopril or 2 x 10 mg enalapril).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1993

Effect of acupuncture on weight loss evaluated by adrenal function.

In order to understand the relationship between patients' adrenal function and simple obesity and effect of acupuncture on it, the obesity indices, lipid indices, fasting blood-glucose, noradrenaline, dopamine, adrenalin and cortisol were observed. The results indicated that patients with simple obesity had hypofunction of the sympathetic-adrenal system and the hypothalamus-pituitary-adrenal system. Acupuncture treatment not only affected weight loss but also enhanced functioning of the two systems, suggesting that the effect of acupuncture on weight loss may be produced by enhancing the functions of both the sympathetic-adrenal system and the hypothalamus-pituitary-adrenal system.

Acupuncture Therapy↗

PubMed1992

Transcription of the hypersensitive site HS2 enhancer in erythroid cells.

In the human genome, the erythroid-specific hypersensitive site HS2 enhancer regulates the transcription of the downstream beta-like globin genes 10-50 kilobases away. The mechanism of HS2 enhancer function is not known. The present study employs RNA protection assays to analyze the transcriptional status of the HS2 enhancer in transfected recombinant chloramphenicol acetyltransferase (CAT) plasmids. In erythroid K562 cells in which the HS2 enhancer is active, the HS2 sequence directs the synthesis of long enhancer transcripts that are initiated apparently from within the enhancer and elongated through the intervening DNA into the cis-linked CAT gene. In nonerythroid HL-60 cells in which the HS2 enhancer is inactive, long enhancer transcripts are not detectable. Splitting the HS2 enhancer between two tandem Ap1 sites abolishes the synthesis of a group of long enhancer transcripts and results in loss of enhancer function and transcriptional silencing of the cis-linked CAT gene. In directing the synthesis of RNA through the intervening DNA and the gene by a tracking and transcription mechanism, the HS2 enhancer may (i) open up the chromatin structure of a gene domain and (ii) deliver enhancer binding proteins to the promoter sequence where they may stimulate the transcription of the gene at the cap site.

Base Sequence↗

PubMed1989

Transmitter neurochemistry of the efferent neuron system innervating the labyrinth.

It is likely that several mechanisms contribute to the efferent control of cochlear and vestibular function. Different effects are probably mediated by different neuronal transmitters. In spite of a number of transmitter candidates, it is still widely assumed that the entire efferent system can be globally characterized as cholinergic. We attempted to label retrogradely identified efferent neurons in the brainstem with a monoclonal antibody against choline acetyltransferase (ChAT), the acetylcholine (ACh) synthesizing enzyme. Only a portion of the vestibular efferents could thus be shown to be cholinergic in the rat. Medial cochlear efferents, terminating under outer hair cells, may also be cholinergic since they stain intensely for acetylcholine esterase (AChE) after pre-treatment with the AChE inhibitor diisopropylfluorophosphate (DFP). The lateral cochlear efferents terminating under inner hair cells, as well as more than half of the vestibular efferent neuron population, reacted negatively with either method designed to identify cholinergic neurons. Half of the lateral olivo-cochlear neuron population filled retrogradely with tritiated gamma-amino butyric acid [( 3H]-GABA). These cells were similar in size and distribution to neurons staining for the GABA synthesizing enzyme glutamic acid decarboxylase (GAD). Retrograde transport of [3H]-aspartate from the inner ear to the brainstem was seen in half of the lateral olivocochlear population, as well as in part of the efferent vestibular population in group E and in the caudal pontine reticular nucleus (CPR). Since various peptides have also been located in efferent neurons, this system is chemically diversified. Several distinct mechanisms of efferent control with presumably differing functions must, therefore, exist.

Acetylcholinesterase↗

PubMed1989

Activation of the GM-CSF promoter by HTLV-I and -II tax proteins.

Production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by normal T lymphocytes requires activation by antigen, mitogen or lectin, whereas T-cell lines transformed by human T-cell leukemia virus type I (HTLV-I) or type II (HTLV-II) constitutively produce high levels of GM-CSF. Using transient cotransfection assays, we demonstrate that introduction of the tax gene of either HTLV-I or HTLV-II is sufficient to activate GM-CSF promoter constructs in an unstimulated T-cell line. The GM-CSF 5' flanking sequences previously shown to be sufficient for GM-CSF induction following T-cell activation are also sufficient for activation by the HTLV tax proteins. The sequences required for trans-activation of GM-CSF are distinct from those required for the activation of other T-cell-inducible genes (IL-2R alpha, IL-2) by tax, suggesting that tax can have pleiotropic effects on gene expression in T cells. Constitutive GM-CSF production by HTLV-infected T cells may therefore be due to trans-activation of its promoter by tax. Expression of GM-CSF by HTLV-I infected lymphocytes may be important in the granulocytosis and eosinophilia frequently seen in patients with HTLV-I-induced adult T-cell leukemia/lymphoma.

Animals↗

PubMed1989

Electrophysiology of the electrically and mechanically damaged cochlea.

Electrical and mechanical stimuli were used in an attempt to cause cochlear deafness in a preparation with a rich supply of afferent cochlear neurons. Hearing sensitivity was assessed by electrocochleography and neuron survival was estimated by evaluating electrically induced auditory brainstem responses (EABR). Charge balanced sinusoidal alternating currents between 1 and 30 kHz for up to 15 hours produced a limited high frequency hearing loss when applied through the intact round window. A similar permanent threshold shift (PTS) could be induced by mechanical irritation with a scala tympani electrode through a round window fenestration. There is a summation of electrical and mechanical damage; however, complete deafness never occurred and the EABR provided no evidence for a major retrocochlear damage. These results suggest that deafness associated with perilymph leakage or induced during certain types of ear surgery should not be accepted as inevitable.

Animals↗

PubMed1989

Analogue signal representation in the medial superior olive of the cat.

Temporal sound processing is likely to depend upon a delay line at a low level in the auditory pathways. We searched for such a delay line in the medial superior olivary nucleus of anesthetized cats. A remarkably pure sinusoidal neurophonic field potential could be recorded in the center of the MSO which was localized electrophysiologically as the point of the field potential polarity reversal and histologically by microinjection WGA-HRP through the recording microelectrode. Fourier analysis of the neurophonic potentials revealed increasing degradation by distortion products with distance from the MSO center. Neurophonic tuning curves indicated a similar frequency selectivity for individual recording sites as predicted by cochlear filter functions. Cross correlation of neurophonics recorded at different positions along the medio-lateral axis demonstrated the presence of a delay line, extending to over 0.6 ms. It is concluded that delay lines required for directional hearing and complex tone identification exist in the MSO.

Acoustic Stimulation↗

PubMed1988

Retrograde transport of [3H]-GABA by lateral olivocochlear neurons in the rat.

Injection of [3H]-gamma aminobutyric acid (GABA) into the perilymphatic space of the rat's inner ear resulted in retrograde labeling of a portion of the small efferent olivocochlear neurons within the lateral superior olivary nucleus (LSO). These cells were of similar size as LSO neurons stained immunohistochemically with antibodies to the GABA synthesizing enzyme glutamic acid decarboxylase (GAD). They were of fusiform shape, but smaller than principal LSO cells, which did not stain for GAD and did not accumulate [3H]-GABA. Other efferent cochlear and vestibular neurons were not labeled.

Animals↗

PubMed1988

Histopathology of chloroform-induced inner ear damage.

Inner ear function loss was caused in guinea pigs and rats by injecting chloroform into the middle ear. After symptoms for cochlear and vestibular deficit had been registered, the animals were permitted to survive for one day to five months. Ear histopathology was then studied in celloidin sections. In both species, hair cells and afferent nerve fibers were intact at all survival times. The acute stage of functional loss in guinea pigs was associated with inner ears of normal histological appearance. Within days after chloroform injection a severe otitis media developed which led to fibrous occlusion of the round window and eventually to new bone growth in the middle ear space around the otic capsule. A secondary labyrinthitis was also observed, resulting in endolymphatic hydrops at longer survival times. Different histopathological changes were seen in rats. The tectorial membrane appeared swollen in all cases, the swelling being more severe in more apical turns at longer survival times. It is concluded that only secondary sequela of the initial functional insult can be detected by standard light microscopic histopathology. Chloroform does not cause a chemical labyrinthectomy as previously assumed, although it is severely ototoxic.

Animals↗

PubMed1987

Electrophysiological evaluation of chloroform-induced inner ear damage.

Local placement of chloroform in either the external or the middle ear has been previously reported to induce a chemical labyrinthectomy. In order to examine the value of this effect as a research tool, we injected chloroform into the middle ears of guinea pigs and rats. Cochlear damage was assessed by electrocochleography (ECochG) and auditory brainstem response (ABR) audiometry. Both species developed complete deafness within a few hours after instillation of the chloroform. The deafness was permanent in the guinea pigs, whereas there was a partial recovery of auditory function in the rats. The survival rate of the auditory nerve fibers was estimated by measuring the ABR evoked by electrical stimulation via the scala tympani (EABR). A normal EABR recruitment pattern suggested that the main chloroform effect was located peripheral to the afferent axons. In conclusion, chloroform must be considered a severely ototoxic agent when applied locally.

Animals↗