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Biomedical subjects

J He

Publications and source records attributed to J He.

At least 271 records · Page 15Linked to original sources

[Antitumor activity of howiinol (GHM-10) on L1210 cells in vitro].

Howiinol(GHM-10) is a new compound isolated from Goniothalamus howii. Previous studies showed that GHM-10 significantly inhibited the growth of cancer cells both in vitro and in vivo. In the present study, the characteristics of the inhibitory effect of GHM-10 on L1210 cells was investigated. The results showed that the IC50 of L1210 cells treated with GHM-10 for 1 h, 24 h, and 7 d was 6.85, 3.32 and 1.59 micrograms.ml-1, respectively. This outcome is in compliance with the hypothesis that GHM-10 is a cell cycle non-specific cytotoxic drug. When L1210 cells were treated with 1-2 micrograms.ml-1 of GHM-10 for 24 h, the growth rate and mitotic index were decreased and the morphology of cell nuclei changed, but the cell viability remained at the level of 96% or more, indicating that GHM-10 mainly inhibited cell proliferation. The cell cycle kinetics of L1210 cells were studied by using a flow cytometer. The results showed that the transition of cells from G1 phase to S phase was blocked to certain extent by the treatment of GHM-10 4 micrograms.ml-1 for 12 h. The fluidity of cell membrane was also increased when the L1210 cells were exposed to 2-3 micrograms.ml-1 of GHM-10 for 24 h.

Animals↗

[Clinical observation of intrachamberal anesthesia].

PURPOSE: To observe the effect in operation and influence after operation of intrachamberal anesthesia. METHODS: 2 Percent lidocaine used for intravenous injection was diluted by Bss-plus to be 0.5 percent solution. Intraocular surgery of 63 cases(76 eyes) were performed intrachamberal anesthesia by anterior chamber puncture. RESULT: All of the operations were done well, the patients didn't feel painful. Complications were not found by following up ten months. CONCLUSION: This kind of anesthesial technique was regarded to be simple, safe, and efficient. It was worthy of searching in anterior intraocular surgery.

Administration, Topical↗

Localization of HIV-1 co-receptors CCR5 and CXCR4 in the brain of children with AIDS.

The chemokine receptors CCR5 and CXCR4 are co-receptors together with CD4 for human immunodeficiency virus (HIV)-1 entry into target cells. Macrophage-tropic HIV-1 viruses use CCR5 as a co-receptor, whereas T-cell-line tropic viruses use CXCR4. HIV-1 infects the brain and causes a progressive encephalopathy in 20 to 30% of infected children and adults. Most of the HIV-1-infected cells in the brain are macrophages and microglia. We examined expression of CCR5 and CXCR4 in brain tissue from 20 pediatric acquired immune deficiency syndrome (AIDS) patients in relation to neuropathological consequences of HIV-1 infection. The overall frequency of CCR5-positive perivascular mononuclear cells and macrophages was increased in the brains of children with severe HIV-1 encephalitis (HIVE) compared with children with mild HIVE or non-AIDS controls, whereas the frequency of CXCR4-positive perivascular cells did not correlate with disease severity. CCR5- and CXCR4-positive macrophages and microglia were detected in inflammatory lesions in the brain of children with severe HIVE. In addition, CXCR4 was detected in a subpopulation of neurons in autopsy brain tissue and primary human brain cultures. Similar findings were demonstrated in the brain of adult AIDS patients and controls. These findings suggest that CCR5-positive mononuclear cells, macrophages, and microglia contribute to disease progression in the central nervous system of children and adults with AIDS by serving as targets for virus replication.

Acquired Immunodeficiency Syndrome↗

Variation in photodynamic efficacy during the cellular uptake of two phthalocyanine photosensitizers.

A decrease in the efficacy of photodynamic therapy (PDT) with phthalocyanine photosensitizers was observed for lymphoblastic murine and human cell lines as the time between the addition of the photosensitizer, aluminum phthalocyanine (AIPc), to the culture medium and exposure to light was increased from 4 h to 18 h. The total intracellular concentration of photosensitizer did not decrease significantly during this 18 h interval. For the murine cell lines, the maximum cytotoxic and mutagenic effects were observed when the time between addition of the photosensitizer and irradiation was between 1 and 4 h. The time course of the variations in efficacy did not vary greatly from one murine cell line to another, even though the cell lines differ markedly in the extent of their cytotoxic and mutagenic response. The time course of the variation was similar for cytotoxicity and mutagenicity, as well as for the induction of DNA fragmentation. The human lymphoblastic cell line, WTK1, showed less variation in survival and mutability with time than did the murine cell lines. With Pc 4 (HOSiPcOSi[CH3]2[CH2]3N[CH3]2) as the photosensitizer, the photocytotoxicity for murine L5178Y (LY)-S1 cells did not change significantly as the time between addition of Pc 4 and irradiation was increased from 2 to 18 h. However, the mutagenicity decreased by a factor of three during this interval. The mutagenicity of PDT with Pc 4 was much less in LY-S1 cells than that with AlPc. The results suggest that the variation in the efficacy observed for AlPc-induced photocytotoxicity is caused by changes in the intracellular distribution and/or the aggregation of the photosensitizer with time after its addition.

Aluminum↗

Correlation between immunoreactivity for transglutaminase K and for markers of proliferation and differentiation in normal breast tissue and breast carcinomas.

We investigated immunohistochemically localization and expression of transglutaminase K (TGK) in normal breast tissue (n = 10) and in breast carcinomas (n = 30). Transglutaminase K was compared with the staining patterns of cytokeratin 10, Ki-67, p53, estrogen and progesterone receptors in these tumors. Weak to strong membrane bound immunoreactivity to TGK was detected in 17 out of 30 breast carcinomas analyzed. TGK staining was heterogeneous with visual differences between individual tumour cells. Ninety percent of normal breast tissues revealed no immunoreactivity to TGK. Both intensity of TGK immunostaining and number of TGK-positive cells were upregulated in breast carcinomas as compared to normal breast tissue. Analyzing coexpression of TGK with cytokeratin 10, Ki-67, p53, ER and PR, no statistically significant correlation was found. Our findings indicate that: (I) TGK is upregulated in breast carcinomas as compared to normal breast tissue. (II) Upregulation of TGK in breast carcinoma is not exclusively induced by alterations of epithelial differentiation or proliferation, but by different, unknown mechanisms. (III) Upregulation of TGK in breast carcinomas may play an important role in the regulation of tumour cell invasive properties by modulating cell-matrix interactions or by facilitating the assembly of matrix and tissue remodeling.

Antibodies, Neoplasm↗

Rapid identification and isolation of zebrafish cDNA clones.

A fast and economical approach, referred to as cDNA clone tagging, was adapted to identify and isolate zebrafish cDNA clones. The basic approach was to partially sequence the coding region of size selected cDNA clones and the partial sequences were then used as tags for identifying the clones through homology search. To benefit maximally from the tagging approach, two cDNA libraries, derived from embryonic and adult fish poly(A)+ RNAs, respectively, were constructed by unidirectional cloning; conceptually, they have the potential to represent all expressed zebrafish genes. A total of 1084 clones were sequenced from the two libraries, and 511 clones were identified, based on sequence homology. These identified clones were derived from at least 261 genes, encoding 48 translational machinery proteins, 47 cytosolic proteins, 43 cytoskeletal proteins, 41 nuclear proteins, 32 membrane proteins, 22 secreted proteins, 20 mitochondrial proteins and 8 proteins with an unknown location. Of the 261 distinct cDNA clones identified, 254 were isolated for the first time in the zebrafish. These tagged cDNA clones, identified and unidentified, provide rich resources for developmental analysis as well as mapping of zebrafish genome. The long-term objective of this study is to establish a tagged zebrafish gene library that can be accessed both by hybridization screening against the plasmid DNAs and by electronic screening using the sequence information.

Animals↗

Tonotopic organization of auditory cortical fields delineated by parvalbumin immunoreactivity in macaque monkeys.

Tonotopic maps, obtained from single and multi-unit recordings in the primary and surrounding areas of the auditory cortex, were related to chemoarchitecture of the supratemporal plane, as delineated by immunoreactivity for parvalbumin. Neurons in the central core were sharply tuned and formed two complete tonotopic representations corresponding to the primary auditory area (AI) and the rostral (R) area. High frequencies were represented posteriorly in AI and anteriorly in R, the representation reversing in the anterior part of the core. Neurons in regions of less dense immunostaining previously described as lateral (L) and posteromedial (P-m) fields, showed broader frequency tuning. Two tonotopic representations were found in L: in an anterolateral (AL) field, corresponding to a field previously reported by others, high frequencies were represented anteriorly and low frequencies posteriorly; in a posterolateral field (PL) the trend reversed. There was a further reversal on entering P-m from the high frequency representation in PL and progressively lower frequencies tended to be represented more medially in P-m, but P-m may contain two representations reported by others. Neurons in the previously described anteromedial (A-m) and medial (M) fields of weaker immunostaining, were even more broadly tuned. A tonotopic progression from low frequency representation posteriorly to high frequency representation anteriorly was observed in the medial field. Frequency representation in A-m remains uncertain. No tonotopic representation could be demonstrated with the stimuli used in the zones of very weak parvalbumin immunostaining outside AL, PL, P-m, A-m, and M. The properties of neurons in the core and surrounding zones are likely to reflect inputs from the ventral and dorsal medial geniculate nuclei, respectively. The fields outside the core seem to be the starting points for separate streams of auditory corticocortical connections passing into association cortex.

Acoustic Stimulation↗

Effects of oral potassium on blood pressure. Meta-analysis of randomized controlled clinical trials.

OBJECTIVE: To assess the effects of supplementation with oral potassium on blood pressure in humans. DESIGN: Meta-analysis of randomized controlled trials. DATA SOURCES: English-language articles published before July 1995. STUDY SELECTION: Thirty-three randomized controlled trials (2609 participants) in which potassium supplementation was the only difference between the intervention and control conditions. DATA EXTRACTION: Using a standardized protocol, 2 of us independently abstracted information on sample size, duration, study design, potassium dose, participant characteristics, and treatment results. RESULTS: By means of a random-effects model, findings from individual trials were pooled, after results for each trial were weighted by the inverse of its variance. An extreme effect of potassium in lowering blood pressure was noted in 1 trial. After exclusion of this trial, potassium supplementation was associated with a significant reduction in mean (95% confidence interval) systolic and diastolic blood pressure of -3.11 mm Hg (-1.91 to -4.31 mm Hg) and -1.97 mm Hg (-0.52 to -3.42 mm Hg), respectively. Effects of treatment appeared to be enhanced in studies in which participants were concurrently exposed to a high intake of sodium. CONCLUSIONS: Our results support the premise that low potassium intake may play an important role in the genesis of high blood pressure. Increased potassium intake should be considered as a recommendation for prevention and treatment of hypertension, especially in those who are unable to reduce their intake of sodium.

Administration, Oral↗

Ceramide generation in response to photodynamic treatment of L5178Y mouse lymphoma cells.

Photodynamic therapy, a novel cancer treatment using a photosensitive dye and visible light, produces an oxidative stress in cells, often leading to apoptotic cell death. Because ceramide is a second messenger that has been associated with stress-induced apoptosis, we investigated a possible link between photodynamic treatment (PDT), ceramide, and apoptosis in L5178Y-R (LY-R) cells. The cells undergo rapid apoptosis, initiating within 30 min of PDT. After a dose of PDT producing a 99.9% loss of clonogenicity, LY-R cells responded by an increased production of ceramide, which reached a maximum level in 60 min. For a constant light fluence and varying concentrations of the phthalocyanine photosensitizer Pc 4 [HOSiPcOSi(CH3)2(CH2)3N(CH3)2], the ED50 for ceramide generation (46 nM) was similar to the LD50 for clonogenic cell death (40 nM). We suggest that the PDT-stimulated increase in synthesis of ceramide in LY-R cells may be coupled to PDT-induced apoptosis. When the cells were exposed to exogenous N-acetyl-sphingosine (10 microM), apoptotic changes were observed only after 12-24 h. The delayed apoptotic response to the synthetic ceramide may be due to an induction of apoptosis by a different route than the one used by PDT.

Animals↗

Astrocyte apoptosis induced by HIV-1 transactivation of the c-kit protooncogene.

HIV-1 infection of the central nervous system (CNS) frequently causes dementia and other neurological disorders. The mechanisms of CNS injury in HIV-1 infection are poorly understood. Apoptosis of neurons and astrocytes is induced by HIV-1 infection in vitro and in brain tissue from AIDS patients, but the apoptotic stimuli have not been identified. We report herein that HIV-1 infection of primary brain cultures induces the receptor tyrosine kinase protooncogene c-kit and that high levels of c-Kit expression are associated with astrocyte apoptosis. Overexpression of c-Kit in an astrocyte-derived cell line in the absence of HIV-1 induces rapid apoptotic death. The apoptotic mechanism requires the c-Kit tyrosine kinase domain. The mechanism of c-kit induction by HIV-1 involves transactivation of the c-kit promoter by the HIV-1 Nef protein. These studies demonstrate that c-Kit can induce astrocyte apoptosis and suggest that this mechanism may play a role in CNS injury caused by HIV-1 infection. We propose that c-Kit can serve dual functions as a growth factor receptor or apoptosis inducer.

Apoptosis↗

Temporal integration and duration tuning in the dorsal zone of cat auditory cortex.

The present study examined auditory cortical neurons, the responses of which depended on the duration of noise bursts. We recorded from 150 neurons with response latencies exceeding 30 msec and from 28 neurons with OFF responses to auditory stimuli in the dorsal zone of cat auditory cortex. Of 150 long-latency neurons, 132 displayed some form of duration selectivity. Seventy-eight were classified as selective for long durations. Among the long-duration-selective neurons, 30 responded only to noise burst stimuli with durations longer than a minimal threshold and were classified further as duration threshold neurons. Of 132 duration-selective neurons, 41 responded selectively to noise bursts of short duration; 13 showed maximal responses to noise bursts of a particular duration and could be regarded as duration-tuned neurons. OFF-response neurons included ones that were long-duration-selective, duration-tuned, and nonduration-selective. Duration tuning has been described previously only at the midbrain level in amphibians and bats. The present finding of sensitivity to sound duration in at least one region of cat auditory cortex indicates that this form of neural tuning may be important for hearing in all vertebrates, and for processing of sound at multiple levels in the auditory pathway. The duration tuning in the cat auditory cortex was much broader, and the best duration was distributed over a wider range than in the bat inferior colliculus. We suggest that the duration selectivity of the long-latency neurons results from integration along the time domain of a stimulus during the latent period.

Acoustic Stimulation↗

CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia.

Several members of the chemokine receptor family are used together with CD4 for HIV-1 entry into target cells. T cell line-tropic (T-tropic) HIV-1 viruses use the chemokine receptor CXCR4 as a co-receptor, whereas macrophage-tropic (M-tropic) primary viruses use CCR5 (refs 2-6). Individuals with defective CCR5 alleles exhibit resistance to HIV-1 infection, suggesting that CCR5 has an important role in vivo in HIV-1 replication. A subset of primary viruses can use CCR3 as well as CCR5 as a co-receptor, but the in vivo contribution of CCR3 to HIV-1 infection and pathogenesis is unknown. HIV-1 infects the central nervous system (CNS) and causes the dementia associated with AIDS. Here we report that the major target cells for HIV-1 infection in the CNS, the microglia, express both CCR3 and CCR5. The CCR3 ligand, eotaxin, and an anti-CCR3 antibody inhibited HIV-1 infection of microglia, as did MIP-1beta, which is a CCR5 ligand. Our results suggest that both CCR3 and CCR5 promote efficient infection of the CNS by HIV-1.

Adult↗

Cerebellar infarction and atrophy in infants and children with a history of premature birth.

BACKGROUND AND OBJECTIVE: We wished to determine the pattern of cerebellar disease in children with a history of premature birth and early ultrasound evidence of intraventricular haemorrhage and/or parenchymal lesions of the cerebral hemispheres. MATERIALS AND METHODS: MRI findings for all premature infants examined in a 3-year period (73 patients) were reviewed to determine the nature and frequency of lesions of the cerebellum and the results were correlated with clinical data. RESULTS: Six cases of unilateral cerebellar infarction were identified. These involved the posterior inferior cerebellar territory in each case (as well as other territories in two cases). A case of generalised cerebellar atrophy and three cases of unilateral cerebellar hemisphere atrophy were identified as well. In nine of these ten cases abnormalities were also seen elsewhere in the brain. CONCLUSION: The literature describes cerebellar infarction in infants and children as rare, but this study shows that it is not unusual following perinatal haemorrhagic/ischaemic anoxic injury. It is suggested that cerebellar atrophy may also occur as a result of vascular disease.

Arteries↗

Blood flow in the carotid artery during breath-holding in relation to diving bradycardia.

The present study investigated the mechanism of diving bradycardia. A group of 14 healthy untrained male subjects were examined during breath-holding either out of the water (30-33 degrees C), in heat-out immersion, or in whole-body submersion (27-29 degrees C) in a diving pool. Blood velocity, blood volume flow in the carotid artery, diastolic blood pressure and electrocardiogram were measured and recorded during the experiments. The peak blood velocity increased by 13.6% (P < 0.01) and R-wave amplitude increased by 57.1% (P < 0.005) when the subjects entered water from air. End-diastolic blood velocity (Ved) in the carotid artery increased significantly during breath-holding, e.g. Ved increased from 0.20 (SD 0.02) m.s-1 at rest to 0.33 (SD 0.04) m.s-1 (P < 0.001) at 50.0 s in breath-hold submersion to a 2.0-m depth. Blood volume flow in the carotid artery increased by 26.6% (P < 0.05) at 30 s and 36.6% (P < 0.001) at 40 s in breath-hold submersion to a 2.0-m depth. Diastolic blood pressure increased by 15.4% (P < 0.01) at 60 s during breath-holding in head-out immersion. Blood volume flow, Ved and diastolic blood pressure increased significantly more and faster during breath-holding in submersion than out of the water. There was a good negative correlation with the heart rate: the root mean square correlation coefficient r was 0.73 (P < 0.001). It was concluded that an increased accumulation of blood in the aorta and arteries at end-diastole and decreased venous return, caused by an increase in systemic peripheral resistance during breath-holding, underlies diving bradycardia.

Adult↗

Epidemiology and prevention of hypertension.

At least 43 million (24%) adults in the general population of the United States have hypertension. The prevalence of hypertension increases with age and is higher among African-Americans compared to other ethnic groups. During the past several decades, the prevalence of hypertension in the general population of the United States has declined and the proportion of hypertensives who are aware of their high blood pressure, as well as the portion who are being treated and controlled has improved. Hypertension is the most important modifiable risk factor for coronary heart disease, stroke, congestive heart failure, and end-stage renal disease. To achieve the final goal of eliminating all blood pressure-related disease in the community, detection and treatment of hypertension must be complemented by equally energetic approaches directed at primary prevention of hypertension. A small downward shift in the entire distribution of blood pressure in the general population will not only reduce the incidence of hypertension, but substantially diminish the burden of blood pressure in the general population.

Adult↗

DNA inoculation with a plasmid vector carrying the hepatitis E virus structural protein gene induces immune response in mice.

The plasmid construct, pJHEV, containing the full-length open reading frame 2 (ORF-2) of hepatitis E virus (HEV) gene, expresses the HEV structural protein ORF-2 in Cos-7 cells under the control of a hCMV promoter. No ORF-2 protein could be detected in Cos-7 cells transfected with either vector alone or with a vector containing the ORF-2 of HEV in the incorrect orientation. The successful construct was further tested in BALB/c (H-2d) mice for the induction of an ORF-2 specific immune response. Intramuscular (i.m.) immunization of mice pretreated 24 h earlier with bupivacaine with the naked DNA construct elicited a humoral immune response in 80% and 100% of two separate groups of mice, respectively. No anti-ORF-2 responses were observed in mice immunized with the vector only. Sera from mice injected with pJHEV specifically recognized HEV ORF-2 structural protein expressed in recombinant baculovirus in an enzyme-linked-immunosorbent assay (ELISA) and Western blot. Anti-ORF-2 serum titers peaked at ca 1:5000 in the ELISA and 1:1000 in the Western blot. These titers have remained constant for over 12 months after the last boost of pJHEV. To our knowledge, this is the first report of the use of DNA-based immunization for the generation of an immune response to a HEV structural protein.

Animals↗

Protein-binding high-performance frontal analysis of (R)- and (S)-warfarin on HSA with and without phenylbutazone.

Applicability of high-performance frontal analysis (HPFA) to the stereoselective study of drug-drug interaction upon plasma protein binding has been investigated. Racemic warfarin and phenylbutazone were used as model drugs. An on-line HPFA/HPLC system consisting of a HPFA column (diol-silica column), an extraction column, and a chiral separation column was developed, and human serum albumin solution containing racemic warfarin and/or phenylbutazone was injected directly to the HPFA column. When the injection volume was large enough, the binding equilibrium in the sample solution was reproduced in the column, and consequently a plateau region appeared on the chromatogram. This plateau region contains unbound drug(s). A given volume of eluent in the plateau part was transferred into the extraction column by column-switching. The concentrated drug(s) was then transferred to the chiral separation column to determine the unbound concentrations of the enantiomers and/or the competitor. The results agreed with those obtained by a conventional ultrafiltration-HPLC method. The influence of phenylbutazone upon the protein binding of warfarin is enantioselective. In warfarin and human serum albumin mixed solution, the unbound concentration of (R)-warfarin was 1.22 times higher than that of the S-isomer. By addition of phenylbutazone, the unbound concentration of (S)-warfarin increased more than that of (R)-warfarin, resulting in the reversed enantioselectivity, i.e., the unbound concentration of (S)-warfarin became 1.19 times larger than that of (R)-warfarin. The present method was also applicable to human plasma samples.

Chromatography, High Pressure Liquid↗

Cytokine expression in the alkali-burned cornea.

PURPOSE: This study investigated the cytokine expression profile in alkali-burned mouse corneas, in order to elucidate the mechanisms of corneal damage and repair. METHODS: The cytokines expressed in alkali-burned corneas were identified by polymerase chain reaction (RT-PCR), then quantitated using ELISA. Based on the ELISA results, immunohistochemical analyses were performed to localize cytokine expression. RESULTS: Among the ten cytokines examined, IL-1 (IL-1 beta), IL-6, IL-10 and TNF-alpha mRNA were expressed in alkali-burned corneas. Quantitation revealed that IL-alpha and IL-6 were strongly induced in the early stages of alkali burn, peak production of IL-1 alpha (53.2 pg/cornea) and IL-6 (23.6 pg/cornea) occurring at days 3 and 7, respectively. The production of IL-10 and TNF-alpha was not significantly elevated during the 42 day period after burn. Immunohistochemical analyses revealed that both IL-1 alpha and IL-6 were mainly localized in regenerating epithelial basal cells. CONCLUSIONS: IL-1 alpha and IL-6 levels in the cornea are dramatically elevated in the regenerated epithelium during the early stages of alkali burn, and may play an important role in associated corneal damage and repair.

Alkalies↗