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Biomedical subjects

K Hu

Publications and source records attributed to K Hu.

At least 55 records · Page 3Linked to original sources

Antibiotic production in relation to bacterial growth and nematode development in Photorhabdus--Heterorhabditis infected Galleria mellonella larvae.

The population of Photorhabdus luminescens C9, bacterial symbiont of the entomopathogenic nematode, Heterorhabditis megidis 90, increased rapidly to 1.2-2.6x10(9) cells g(-1) wet Galleria mellonella larvae within 24 h of nematode infection of the larvae, and maintained a relatively constant level (1.2-2.0x10(10) cells g(-1)) through the entire 14-day period of nematode development. The antibiotic, 3, 5-dihydroxy-4-isopropylstilbene, was produced by P. luminescens C9 after 24 h of nematode infection, increased rapidly at 2-5 days postinfection and remained at a level of 3000-3600 microg g(-1) wet larvae until about 21 days, decreasing gradually thereafter. The early production and continued presence of a relatively large amount of 3,5-dihydroxy-4-isopropylstilbene in the infected insect supports the hypothesis that the antibiotics produced by the bacterial symbiont help minimize competition from other microorganisms and prevents the putrefaction of the nematode-infected insect cadaver.

Animals↗

Effect of quinapril initiated during progressive remodeling in asymptomatic patients with healed myocardial infarction.

Approximately 20% of patients with healed myocardial infarction develop asymptomatic progressive left ventricular (LV) dilation and remodeling and are at increased risk for progression to symptomatic congestive heart failure and premature death. It was the goal of this study to test whether quinapril may interrupt this process and to analyze potential mechanisms. Of 138 patients with an average infarct age of 56 months, 25 had asymptomatic progressive LV dilation and were randomized in a prospective, double-blind study to placebo or quinapril. At baseline (mean +/- SEM) ejection fraction was reduced (35 +/- 3% and 39 +/- 3%) and end-diastolic volume (gated single-photon emission computed tomography) increased (104 +/- 9 and 117 +/- 12 ml/m(2)) with placebo (n = 13) and quinapril (n = 12), respectively. Progressive dilation continued in patients taking placebo (6 months: 9.4 +/- 5.2 ml/m(2), 12 months 24.6 +/- 5. 4 ml/m(2); change from baseline: p <0.05 vs baseline; p <0.05 vs 6 months), but not with quinapril (6 months: -0.9 +/- 4.0 ml/m(2); 12 months: 4.1 +/- 5.2 ml/m(2) [p <0.05] vs placebo). Wedge pressure during bicycle exercise was similar at baseline, but at 12 months tended to be lower with quinapril (17 +/- 1 mm Hg) than with placebo (24 +/- 4 mm Hg, p = 0.1673). Thus, quinapril prevented further progression of asymptomatic LV dilation and remodeling after remote myocardial infarction, possibly due to attenuation of an exercise-induced increase in LV filling pressure.

Angiotensin-Converting Enzyme Inhibitors↗

High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation.

Amyloid plaques are a neuropathological hallmark of Alzheimer's disease (AD), but their relationship to neurodegeneration and dementia remains controversial. In contrast, there is a good correlation in AD between cognitive decline and loss of synaptophysin-immunoreactive (SYN-IR) presynaptic terminals in specific brain regions. We used expression-matched transgenic mouse lines to compare the effects of different human amyloid protein precursors (hAPP) and their products on plaque formation and SYN-IR presynaptic terminals. Four distinct minigenes were generated encoding wild-type hAPP or hAPP carrying mutations that alter the production of amyloidogenic Abeta peptides. The platelet-derived growth factor beta chain promoter was used to express these constructs in neurons. hAPP mutations associated with familial AD (FAD) increased cerebral Abeta(1-42) levels, whereas an experimental mutation of the beta-secretase cleavage site (671(M-->I)) eliminated production of human Abeta. High levels of Abeta(1-42) resulted in age-dependent formation of amyloid plaques in FAD-mutant hAPP mice but not in expression-matched wild-type hAPP mice. Yet, significant decreases in the density of SYN-IR presynaptic terminals were found in both groups of mice. Across mice from different transgenic lines, the density of SYN-IR presynaptic terminals correlated inversely with Abeta levels but not with hAPP levels or plaque load. We conclude that Abeta is synaptotoxic even in the absence of plaques and that high levels of Abeta(1-42) are insufficient to induce plaque formation in mice expressing wild-type hAPP. Our results support the emerging view that plaque-independent Abeta toxicity plays an important role in the development of synaptic deficits in AD and related conditions.

Aging↗

High-dose-rate intraoperative radiation therapy (HDR-IORT) for retroperitoneal sarcomas.

PURPOSE: Retroperitoneal sarcomas represent a formidable challenge to the treating oncologist due to their location, large size, and poor prognosis. The purpose of this study was to determine if the addition of high-dose-rate intraoperative radiation therapy (HDR-IORT) to surgery and external beam radiotherapy (EBRT) would improve the outcome in these patients. METHODS AND MATERIALS: Thirty-two patients with retroperitoneal soft tissue sarcoma were prospectively treated according to a protocol that included maximal tumor resection, HDR-IORT, and postoperative EBRT when feasible. Twelve patients presented with primary and 20 with locally recurrent disease. The tumors were high-grade in 20 patients and low-grade in 12 patients. Complete gross resection was achieved in 30 patients. HDR-IORT was given to a dose of 12-15 Gy. Additional EBRT was given to 78% of patients to a dose of 45-50.4 Gy. The two patients with gross residual disease received an additional I-125 permanent implant to a median peripheral dose of 140-160 Gy. The median follow-up was 33 months (range 1-77 mo). RESULTS: The 5-year actuarial local control rate for the whole group was 62%. For patients with primary disease, the local control rate was 74% compared to 54% in patients with recurrent disease (p = 0.4). The overall 5-year distant metastasis-free survival rate was 82%. In patients with high-grade tumors the rate was 70% vs. 100% in those with low-grade tumors. This difference was statistically significant, p = 0.05. The 5-year disease-free and overall survival rates were 55% and 45%, respectively. The most common type of post-treatment complication was gastrointestinal obstruction (18%) followed by fistula formation (9%), peripheral neuropathy (6%), hydronephrosis (3%), and wound complication (3%). CONCLUSIONS: We are encouraged by the favorable local control rate and the acceptable morbidity with this new technique applied to a challenging patient population.

Adult↗

Initial stages of tumor cell-induced angiogenesis: evaluation via skin window chambers in rodent models.

BACKGROUND: There is a paucity of information about events that follow immediately after tumor cells are triggered to initiate the process of angiogenesis (the formation of new blood vessels). Such information is relevant to the issue of when micrometastases vascularize and has implications for the accessibility of micrometastases to various treatments. In this study, we attempted to monitor events at the initiation of angiogenesis at the earliest possible stage of tumor growth in vivo. METHODS: Two different rodent mammary tumor cell lines, R3230Ac from the Fischer 344 rat and 4T1 from the BALB/c mouse, were stably transfected with a gene that encodes an enhanced version of green fluorescence protein (GFP). GFP-labeled R3230Ac or 4T1 cells (about 20-50 cells) were implanted into dorsal skinfold window chambers of Fischer 344 rats or BALB/c mice, respectively. Tumor angiogenesis was then monitored serially and noninvasively for up to 4 weeks. RESULTS: Clear evidence of modification of the host vasculature was observed when tumor mass reached approximately 60-80 cells, and functional new blood vessels were seen when tumor mass reached roughly 100-300 cells. Individual tumor cells exhibited a chemotaxis-like growth pattern toward the pre-existing host vasculature. When ex-flk1 (a soluble, truncated vascular endothelial cell growth factor receptor protein known to be antiangiogenic) was injected with the tumor cells, the initial angiogenic and tumor growth activities were inhibited considerably, indicating that angiogenesis inhibitors may halt tumor growth even before the onset of angiogenesis. CONCLUSION: Angiogenesis induced by tumor cells after implantation in the host begins at a very early stage, i.e., when the tumor mass contains roughly 100-300 cells. Identification of chemotactic signals that initiate tumor cell migration toward the existing vasculature may provide valuable targets for preventing tumor progression and/or metastases.

Animals↗

Melatonin suppression by light in euthymic bipolar and unipolar patients.

BACKGROUND: Previous studies have suggested that bipolar patients are supersensitive to light suppression of melatonin and that this may be a trait marker for genetic vulnerability. The present study was an attempt to replicate and extend this observation. Propranolol hydrochloride effects were compared with light effects because of the documented influence of beta-adrenergic receptors on melatonin production. Nighttime levels of corticotropin and cortisol were also examined as potential trait vulnerability markers. METHODS: Melatonin levels in euthymic bipolar patients (n= 29) were tested before and after 500-lux light was administered between 2 and 4 AM and on a separate night in the dark. Results were compared with those of a group of patients with unipolar depression (n= 24) and with those of a group of non-psychiatrically ill control subjects (n= 50). Lithium effects and propranolol effects were tested in subgroups. RESULTS: No group differences were seen in light suppression among bipolar patients, unipolar patients, and controls; an analysis of the whole group did not reveal differences in propranolol effect, differences in corticotropin or cortisol levels, or evidence for a lithium effect. However, patients with bipolar I affective disorder showed the following: (1) significantly lower melatonin levels on the light night, at baseline and following light exposure; and (2) a later peak time for melatonin on the dark night. CONCLUSIONS: The general hypothesis of increased light sensitivity in bipolar patients was not supported. However, melatonin secretion abnormalities were confirmed in the subgroup with bipolar I disorder. Further assessments of circadian rhythm disruption as a vulnerability marker in bipolar illness are indicated.

Adrenocorticotropic Hormone↗

Combination treatment of murine tumors by adenovirus-mediated local B7/IL12 immunotherapy and radiotherapy.

Failure of local tumor control still poses a problem for radiotherapy and translates into reduced survival. Combining radiation with chemotherapy or other newer modalities has shown promising results. Immunological approaches to tumor therapy have found renewed interest due to improved insight into mechanisms involved in the immune response to tumors. In this paper, we studied tumor growth delay after various combination regimens of locally injected adenovirus constitutively expressing IL12 and B7.1 (AdIL12/B7.1) and fractionated radiotherapy in two nonimmunogenic murine tumor models, 4T1 and B16.F10. Effects of radiation and virus infection on surface antigen expression in these tumor lines were assessed. Mechanisms of action of AdIL12/B7.1 were studied by conducting additional experiments with and without depletion of NK-cells and/or T-cells, and by cytotoxic T-lymphocyte assays, and immunohistochemical evaluation of tumor blood vessels. Both B7.1 and IL12 were effectively expressed in both irradiated and unirradiated 4T1 and B16.F10 tumor cells but did not add significantly to radiation-induced cell killing in vitro. However, local tumor infection by AdIL12/B7.1 after irradiation significantly increases the effectiveness of radiotherapy when applied after completion of radiotherapy. The mechanism appears to be complicated, involving a host of factors that included the ability of IL12 to activate T-cells and NK-cells and to inhibit angiogenesis and the ability of radiation to induce apoptosis or necrosis among tumor cells. These data support the combination of radiotherapy with adenovirus-mediated immunotherapy and suggest that the concept of adding genetic immunotherapy after radiotherapy in a combined regimen merits further study.

Adenoviridae↗

Experimental heart failure in rats: effects on cardiovascular circadian rhythms and on myocardial beta-adrenergic signaling.

OBJECTIVES: Patients with chronic heart failure frequently show blunted circadian blood pressure profiles. The mechanisms involved in the loss of physiological day-night variation are still unclear, but a continuously active sympathetic nervous system could play a role. The present study evaluated long-term consequences of rat heart failure on cardiovascular circadian patterns in vivo, and on density and function of cardiac beta-adrenoceptor subtypes in vitro, as a marker of cardiac adrenergic drive. METHODS: Heart failure in rats was induced by coronary artery ligation leading to infarct sizes of >30% of left ventricular circumference. Blood pressure and heart rate were monitored for 10 weeks after infarction using radiotelemetry. Density and function of cardiac beta(1) and beta(2)-adrenoceptors were measured by radioligand binding and adenylyl cyclase stimulation. RESULTS: During the activity period at night blood pressure and heart rate were lower in rats with heart failure than in sham controls, leading to reduced night-day variation in the heart failure group. Depression of circadian rhythmicity in blood pressure was found over the whole study period, while that in heart rate occurred with a lag-time of several weeks. In failing left ventricles beta-adrenoceptors showed reduced high affinity agonist binding, a shift in the beta(1):beta(2) ratio towards the beta(2)-subtype, and decreased beta(1)-adrenergic stimulation of adenylyl cyclase. In right ventricles no differences were found between failing and control rats. The blunted nocturnal increase in blood pressure and heart rate as well as beta(1)-adrenergic desensitization were correlated with the severity of left ventricular dysfunction. CONCLUSIONS: Heart failure in rats leads to disturbed circadian patterns in blood pressure and heart rate, and to desensitization of cardiac beta(1)-adrenoceptors, indicating chronic sympathetic overactivity.

5'-Nucleotidase↗

The effect of lipid environment in purple membrane on bacteriorhodopsin.

The decay rate of the Bacteriorhodopsin (BR) photocycle intermediate M412 and proton, the proton pump efficiency (H+/M412), the ratios of M412 to other intermediates and the rotational correlation time (tauc) in purple membrane (PM) fragments treated by the zwitterionic detergent 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS) with different concentrations were studied. The results show that: (1) The largest effect of CHAPS on M412 decay rate and proton decay rate of BR, tauc of PM and the ratios of M412 to other intermediates in BR photocycle is in the range of its critical micelle concentration (CMC). This indicates that changes of the ratios of M412 to other intermediates, tauc, M412 decay and proton decay occur and are due to the variation of the lipid environment. (2) The dependency of proton yield on CHAPS concentrations is basically consistent with that of M412s%. This indicates the relation between proton pumping function and M412. These studies show the importance of maintaining a native environment.

Bacteriorhodopsins↗

Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease.

One hallmark of Alzheimer disease is the accumulation of amyloid beta-peptide in the brain and its deposition as plaques. Mice transgenic for an amyloid beta precursor protein (APP) mini-gene driven by a platelet-derived (PD) growth factor promoter (PDAPP mice), which overexpress one of the disease-linked mutant forms of the human amyloid precursor protein, show many of the pathological features of Alzheimer disease, including extensive deposition of extracellular amyloid plaques, astrocytosis and neuritic dystrophy. Active immunization of PDAPP mice with human amyloid beta-peptide reduces plaque burden and its associated pathologies. Several hypotheses have been proposed regarding the mechanism of this response. Here we report that peripheral administration of antibodies against amyloid beta-peptide, was sufficient to reduce amyloid burden. Despite their relatively modest serum levels, the passively administered antibodies were able to enter the central nervous system, decorate plaques and induce clearance of preexisting amyloid. When examined in an ex vivo assay with sections of PDAPP or Alzheimer disease brain tissue, antibodies against amyloid beta-peptide triggered microglial cells to clear plaques through Fc receptor-mediated phagocytosis and subsequent peptide degradation. These results indicate that antibodies can cross the blood-brain barrier to act directly in the central nervous system and should be considered as a therapeutic approach for the treatment of Alzheimer disease and other neurological disorders.

Alzheimer Disease↗

Antifungal, antimitotic and anti-HIV-1 agents from the roots of Wikstroemia indica.

With guidance of Pyricularia oryzae bioassay, daphnoretin (1), (+)-nortrachelogenin (2), genkwanol A (3), wikstrol A (4), wikstrol B (5) and daphnodorin B (6) were isolated from the roots of Wikstroemia indica. Compounds 1-6 induced morphological deformation of P. oryzae mycelia with MMDC values of 68.4 +/- 1.3, 31.3 +/- 1.8, 45.8 +/- 0.5, 70.1 +/- 2.4, 52.3 +/- 0.9 and 73.7 +/- 1.6 microM, respectively. Compounds 3-6 showed moderate activity against microtubule polymerization with IC50 values of 112 +/- 4, 131 +/- 3, 184 +/- 6 and 142 +/- 2 microM in vitro, respectively. Compounds 2, 3, 5 and 6 were moderately active against HIV-1 in vitro. The findings of bioactivity of 1-6 support the antifungus, antimitosis and anti-HIV-1 uses for W. indica roots.

Anti-HIV Agents↗

Acceptability of baseball face guards and reduction of oculofacial injury in receptive youth league players.

GOALS: To assess the relative injury reduction effect and acceptability of face guards on batter's helmets. METHODS: A non-randomized prospective cohort study among 238 youth league baseball teams in Central and Southern Indiana during the 1997 season. Coaches, parents, and players were asked to respond to pre-season and post-season questionnaires. Approximately one half of the teams were supplied with face guard helmets (intervention); all others used this protection at their discretion (comparison). RESULTS: Parents, players, and coaches on the intervention teams reported a reduction in the incidence of oculofacial injuries compared with comparison team respondents (p=0.04). There was no reported adverse effect of face guard use on player performance. CONCLUSIONS: Helmet face guards should be required for batters to prevent facial injuries in baseball.

Attitude to Health↗

Myocardial perfusion and intracapillary blood volume in rats at rest and with coronary dilatation: MR imaging in vivo with use of a spin-labeling technique.

PURPOSE: To validate a magnetic resonance (MR) imaging technique that is not first pass and that reveals perfusion and regional blood volume (RBV) in the intact rat. MATERIALS AND METHODS: Measurement of perfusion was based on the perfusion-sensitive T1 relaxation after magnetic spin labeling of water protons. RBV was determined from steady-state measurements of T1 before and after administration of an intravascular contrast agent. The colored microsphere technique was used as a reference method for perfusion measurement. RBV and perfusion maps were obtained with the rats at rest and during administration of 3 mg of adenosine phosphate per kilogram of body weight per minute. RESULTS: At MR imaging, perfusion during resting conditions was 3.5 mL/g/min +/- 0.1 (SEM), and RBV was 11.6% +/- 0.6 (SEM). Adenosine phosphate significantly increased perfusion to 4.5 mL/g/min +/- 0.3 (SEM) and decreased mean arterial pressure from 120 mm Hg to 65 mm Hg, which implies a reduction of coronary resistance to 40% of baseline. RBV increased consistently to 23.8% +/- 0.6 (SEM). CONCLUSION: The study results show that quantitative mapping of perfusion and RBV may be performed noninvasively by means of MR imaging in the intact animal. The presented method allows determination of vasodilative and perfusion reserve, which reflects the in vivo regulation of coronary microcirculation for a given stimulus.

Adenosine↗

Evidence for functional role of epsilonPKC isozyme in the regulation of cardiac Ca(2+) channels.

Limited information is available regarding the effects of protein kinase C (PKC) isozyme(s) in the regulation of L-type Ca(2+) channels due to lack of isozyme-selective modulators. To dissect the role of individual PKC isozymes in the regulation of cardiac Ca(2+) channels, we used the recently developed novel peptide activator of the epsilonPKC, epsilonV1-7, to assess the role of epsilonPKC in the modulation of L-type Ca(2+) current (I(Ca,L)). Whole cell I(Ca,L) was recorded using patch-clamp technique from rat ventricular myocytes. Intracellular application of epsilonV1-7 (0.1 microM) resulted in a significant inhibition of I(Ca,L) by 27.9 +/- 2.2% (P < 0.01, n = 8) in a voltage-independent manner. The inhibitory effect of epsilonV1-7 on I(Ca,L) was completely prevented by the peptide inhibitor of epsilonPKC, epsilonV1-2 [5.2 +/- 1.7%, not significant (NS), n = 5] but not by the peptide inhibitors of cPKC, alphaC2-4 (31.3 +/- 2.9%, P < 0.01, n = 6) or betaC2-2 plus betaC2-4 (26.1 +/- 2.9%, P < 0.01, n = 5). In addition, the use of a general inhibitor (GF-109203X, 10 microM) of the catalytic activity of PKC also prevented the inhibitory effect of epsilonV1-7 on I(Ca,L) (7.5 +/- 2.1%, NS, n = 6). In conclusion, we show that selective activation of epsilonPKC inhibits the L-type Ca channel in the heart.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

In vivo assessment of cardiac remodeling after myocardial infarction in rats by cine-magnetic resonance imaging.

The rat infarct model offers important parallels to the process of remodeling after myocardial infarction (MI) in humans. The aim of this study was to test the feasibility of cine fast low-angle shot (FLASH) magnetic resonance imaging (MRI) for assessment of the infarcted and noninfarcted rat heart and to compare the results with established methods. In group A, MRI was done 8-16 weeks after MI on a 7-T scanner using an electrocardiogram-triggered cine-FLASH sequence. We determined left ventricular (LV) volumes and mass, wall thickness, MI size, cardiac output, and ejection fraction. Afterward, MI size was histologically determined. In group B, after MRI eight controls and eight rats 16 weeks after MI underwent conventional hemodynamic measurements for determination of cardiac output, LV volumes, and ejection fraction by electromagnetic flowmeter and pressure-volume curves. LV wet weight was determined. In group A, MRI-acquired MI size (18.5 +/- 2%) was smaller than histology (22.8 +/- 2.5%, p < 0.05) with close correlation (r = 0.97). In group B, agreement in LV mass was found between MRI and wet weight (controls, 537.6 +/- 19.6 vs. 540.3 +/- 18.4 mg; MI, 865.1 +/- 39.2 vs. 865.1 +/- 41.3 mg; for the difference p = ns, r = 0.97, p < 0.05) and in the MRI and flowmeter measurements (cardiac output, controls 73.1 +/- 2.9 vs. 75.2 +/- 2.6 ml/min; MI 82.4 +/- 5.2 vs. 81.9 +/- 3.7 ml/min; for the difference p = ns, r = 0.80, p < 0.05). End-diastolic volume by MRI differed from pressure-volume curves with good correlation (controls, 343.9 +/- 8.4 vs. 262.7 +/- 12.8 microl; MI, 737.0 +/- 70.5 vs. 671.1 +/- 64.1 microl; p < 0.05 each, r = 0.96, p < 0.05). Cine-FLASH-MRI is a valuable diagnostic tool applicable to the rat model of MI. Being noninvasive and exact, it offers new insights in the remodeling process after MI because serial measurements are possible.

Animals↗

Radiotherapy in the management of plasma cell tumors.

Most patients with plasma cell tumors receive radiation therapy at some time during the course of their disease. Plasma cell tumors are radio-responsive, but the systemic nature of the disease in most patients limits the application of localized irradiation. In patients with solitary plasmacytomas (osseous and non-osseous), radiation therapy is the primary treatment modality. It provides excellent local control that may translate into a long remission and even cure. Adequate dose and careful anatomic planning are essential. In patients with multiple myeloma, effective palliation of pain can be achieved with relatively small fields and low doses of radiation. Hemibody irradiation has been shown to provide cost-effective palliation but is associated with toxicity and has failed to contribute to a more definitive therapeutic approach. Hemibody irradiation is rarely used today. Total-body irradiation is often employed in conditioning regimens prior to autologous or allogeneic stem-cell transplantation for multiple myeloma. However, the magnitude of its contribution to the efficacy of high-dose programs in multiple myeloma remains to be studied. This article explores the rationale for and various aspects of providing effective radiotherapy in patients with plasma cell tumors.

Humans↗

An enzymologic study on bone marrow cells in patients with aplastic anemia treated by supplementing the kidney and removing blood stasis.

The content of cytochrome oxidase (CCO), succinate dehydrogenase (SDH) and neutrophil alkaline phosphatase (NAP) in bone marrow cells in 68 cases of aplastic anemia before and after treatment was determined by computerized graphical analysis and compared with that of normal volunteers (control group). The significantly lowered CCO and SDH levels and the markedly increased NAP content before treatment (P < 0.01) became approximately normal after that of supplementing the kidney and removing blood stasis (P > 0.05).

Adolescent↗

[Cleft palate repair of infants with 32 cases].

OBJECTIVE: To search a proper time for cleft palate repair. METHODS: Thirty-two patients with unilateral and bilateral cleft palate, aged from 25 days to 3 months, were undergoing the cleft palate repair. The surgical risk was analyzed perioperatively. The speech function and the maxillary development were also evaluated after the operation. RESULTS: All of the cases were successfully repaired with less bleeding, quicker recovery, shorter operative time and less psychological injury. The speech function and the maxillary development were very well. CONCLUSION: A patient, even under 3 months age, could also be a good candidates for cleft palate repairing when the general condition was good.

Age Factors↗