Studies on Water Regime and Nitrogen Metabolism of Citrus Seedlings Grown under Water Stress.
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Journal Article↗
Biomedical subjects
D Chen
Publications and source records attributed to D Chen.
A phase 1a clinical trial of LYM-1 monoclonal antibody serotherapy in patients with refractory B cell malignancies.
Ten patients with refractory B cell lymphomas were treated with weekly intravenous infusions of escalating doses of murine monoclonal antibody (MoAb) LYM-1 over four weeks. LYM-1 is a recently developed IgG2a murine MoAb that recognizes a polymorphic HLA-Dr antigen on surfaces of normal and malignant B cells but does not bind to any other normal tissues. MoAb LYM-1 has several advantages for serotherapy, since the antigen it recognizes is not shed from the cell surface and does not modulate in response to MoAb therapy. Furthermore, in vitro studies have indicated significant anti-tumour activity against lymphoma cell lines. In the current trial, dose-dependent levels of free LYM-1 were detected in the serum of all patients, but penetration of extravascular tumour tissues was poor. No significant toxicity or human anti-mouse antibody responses were observed in any patient. Clinical responses were minor and appeared to correlate with the number of infiltrating T cells seen in the initial lymphoma specimens. LYM-1 appears to be well-tolerated and has demonstrated several potential advantages as a therapeutic agent in patients with lymphoma. The mechanism of anti-tumour effect and plans for further clinical studies are discussed.
Adult↗
GB virus-C/hepatitis G virus infection in Taiwan: a virus that fails to cause a disease?
Recently, an RNA virus designated GB virus-C or hepatitis G virus (GBV-C/HGV) was identified; however, its clinical significance remains uncertain. This discovery prompted us to investigate the virological, epidemiological and clinical implications of GBV-C/HGV infection in Taiwan where chronic liver diseases and liver cancer are endemic. Our results showed that genetic heterogeneity of GBV-C/HGV isolates exists, and primers from the highly conserved 5' untranslated region of viral genome can efficiently detect GBV-C/HGV RNA. Epidemiological surveys showed that GBV-C/HGV infection is common in high-risk groups in Taiwan, and its coinfection does not aggravate the course of chronic hepatitis B or C. A prospective study of transfusion-transmitted GBV-C/HGV infection also showed GBV-C/HGV does not cause classic hepatitis in most patients. In addition, GBV-C/HGV plays a minimal role in causing fulminant hepatitis. Like hepatitis C virus, sexual transmission of GBV-C/HGV exists. The risk increases with prolonged duration of exposure. In addition, high-titered maternal viremia and mode of delivery are associated with the mother-to-infant transmission of GBV-C/HGV. Interestingly, we found that GBV-C/HGV exerts no suppression on levels of chronic hepatitis B or hepatitis C viremia, and GBV-C/HGV responds to interferon; however, ribavirin plus interferon does not induce a higher sustained response. As to the replication sites of GBV-C/HGV, our preliminary results showed liver and peripheral blood mononuclear cells are not the major sites for GBV-C/HGV replication, and thus GBV-C/HGV is not a primary hepatotropic virus. In conclusion, transfusion and exchange of body fluids indeed can transmit GBV-C/HGV; however, current lines of evidence suggest that GBV-C/HGV fails to cause a disease.
Antiviral Agents↗
The action mode of the ribosome-inactivating protein alpha-sarcin.
Based on the tertiary structure of the ribosome-inactivating protein alpha-sarcin, domains that are responsible for hydrolyzing ribosomes and naked RNA have been dissected. In this study, we found that the head-to-tail interaction between the first amino beta-strand and the last carboxyl beta-strand is not involved in catalyzing the hydrolysis of ribosomes or ribonucleic acids. Instead, a four-strand pleated beta-sheet is indispensable for catalyzing both substrates, suggesting that alpha-sarcin and ribonuclease T1 (RNase T1) share a similar catalytic center. The integrity of an amino beta-hairpin and that of the loop L3 in alpha-sarcin are crucial for recognizing and hydrolyzing ribosomes in vitro and in vivo. However, a mutant protein without the beta-hairpin structure, or with a disrupted loop L3, is still capable of digesting ribonucleic acids. The functional involvement of the beta-hairpin and the loop L3 in the sarcin stem/loop RNA of ribosomes is demonstrated by a docking model, suggesting that the two structures are in essence naturally designed to distinguish ribosome-inactivating proteins from RNase T1 to inactivate ribosomes.
Animals↗
Rapid mood change and human odors.
We demonstrate an immediate effect of airborne chemicals on human moods. We collected six groups of underarm odors, respectively, from five prepubertal girls, five prepubertal boys, five college women, five college men, five older women, and five older men. In addition, we collected odors from homes of these donors, making them a seventh group of odor. Three hundred and eight odor observers ranked the seven groups of odors of little girls, little boys, college women, college men, older women, older men, and homes by their perceived pleasantness, intensity, perceived masculinity, and age of the donors, among other qualities. On a separate task, the same odor observers assessed their depressive, hostile, and positive moods twice, once before and once a few minutes after they sniffed one of the above seven groups of odors. Exposure to underarm odors for under 2 min led to significant, rapid, and small changes in the nonclinical depressive mood of the odor observers. The mood changes were independent of the observers' perceptions of odor qualities. Odors perceived as unpleasant and intense were as likely to relieve a depressive mood as were pleasant odors.
Adolescent↗
Synaptic interactions mediating synchrony and oscillations in primate sensorimotor cortex.
The appearance of oscillatory modes of 'gamma' activity in many cortical areas of different species has generated interest in understanding their underlying mechanisms and possible functions. This paper reviews evidence from studies on primate motor cortex showing that oscillatory activity entrains many neurons during periods of exploratory manipulative behavior. These oscillatory episodes synchronize widely spread neurons in sensorimotor cortex bilaterally, including descending corticospinal neurons, as evidenced by correlated modulations in EMG activity. The resulting neural synchronization involves task-related and -unrelated neurons similarly, suggesting that it is more likely to play some global role in attention than mediating any obvious interactions involved in coordinating movements. Intracellular recordings have elucidated the strength and types of synaptic interactions between motor cortical neurons that are involved in both normal and oscillatory activity. Spike-triggered averages (STAs) of intracellular membrane potentials have revealed serial connections in the form of unitary excitatory and inhibitory post-synaptic potentials (EPSPs and IPSPs). More commonly, STAs showed large synchronous excitatory or inhibitory potentials (ASEPs and ASIPs) beginning before the trigger spike and composed of multiple unitary events. ASEPs involved synchronous activity in a larger and more widespread group of presynaptic neurons than ASIPs. During oscillatory episodes synchronized excitatory and inhibitory synaptic potentials occurred in varying proportions. EPSPs evoked by stimulating neighboring cortical sites during the depolarizing phase of spontaneous oscillations showed evidence of transient potentiation. These observations are consistent with several functional hypotheses, but fit best with a possible role in attention or arousal.
Animals↗
Gastric carcinogenesis: 2-chloro-4-methylthiobutanoic acid, a novel mutagen in salted, pickled Sanma hiraki fish, or similarly treated methionine.
The customary salting and pickling of fish in high risk gastric cancer regions were modeled to explore the relevant causative chemicals. The fish Sanma hiraki was treated with sodium chloride and sodium nitrite at pH 3. Previously, it had been found that an extract of the treated fish was mutagenic in Salmonella typhimurium TA 1535 without S9 and also that it induced glandular stomach cancer upon gavage to rats. We now demonstrate that the mutagenicity was enhanced by preincubation of the raw meat for several days before salt-nitrite treatment. HPLC techniques showed that three mutagens were present in the fish extract. One of the mutagens was found to be stable over the pH range of 1.0-9.0. This mutagen was purified by silica gel solid phase extraction, followed by a series of reverse phase HPLC steps, and was characterized by low and high resolution MS, NMR, and FT-IR. While N-nitroso compounds were generally believed to be associated with gastric carcinogenesis, it was unexpectedly found that the mutagen has the novel structure 2-chloro-4-methylthiobutanoic acid (CMBA). Based on the structure, it seemed likely that methionine might be the precursor, and this was, indeed, proven. Both salt and nitrite are essential factors for forming this mutagen. The yield of CMBA was linear for chloride concentrations from 0 to 800 mM NaCl. Of 20 amino acids reacted with nitrite and chloride at pH 3, only methionine generated a mutagen for S. typhimurium TA 1535. Tryptophan gave a product mutagenic in S. typhimurium TA 100 and TA 98, but not TA 1535, and in the case of tyrosine, the mutagen was active only for TA 100. These results suggest an important role for salt in gastric carcinogenesis and provide new approaches for exploring the formation of mutagens/carcinogens for specific target organs.
Amino Acids↗
Enoxaparin for thromboembolism prophylaxis in spinal injury: preliminary report on experience with 105 patients.
Venous thromboembolism continues to be a major cause of morbidity and mortality in patients with spinal injury (SI). Recently, we reported on the effectiveness and safety of a low molecular weight heparin (LMWH), tinzaparin, in preventing deep vein thrombosis in motor-complete SI patients. Recently, another LMWH, enoxaparin, was approved by the United States Food and Drug Administration for prevention of thromboembolism in hip and knee replacement surgery. Since its approval, we have used 30 mg of enoxaparin subcutaneously every 12 h as routine prophylaxis in all hospitalized SI patients. In this retrospective study, we present an analysis of safety and efficacy of the first six months experience, during which 105 patients received the drug. No patient developed clinical evidence of thromboembolism, and none of the 60 venous ultrasound examinations showed a deep vein thrombus. Eleven patients had evidence of hemorrhage, but the LMWH was considered to have contributed to the bleeding in only three. This additional experience with enoxaparin reinforces our previous conclusion that LMWHs are safe and effective thromboprophylactic agents in SI patients.
Adolescent↗
Comparison of sperm quantity and quality in antegrade V retrograde ejaculates obtained by vibratory penile stimulation in males with spinal cord injury.
Reduced fertility in men with spinal cord injury results from the inability to ejaculate and poor semen quality. Vibratory penile stimulation can induce ejaculation in many men with spinal cord injuries, but few studies have reported the effects of repeated vibratory stimulation on quantitative semen analysis tests. Fourteen spinal cord-injured males were enrolled in a prospective study to develop a quantitative profile of antegrade and retrograde ejaculate specimens collected during repeated vibratory stimulation. Antegrade specimens were obtained in 51 (84%) and retrograde specimens were obtained in all of the 61 trials (100%). Sperm were present in 70% and 64% of the antegrade and retrograde samples, respectively. Of the patients who underwent repeated vibratory stimulation attempts, three showed marked improvement in sperm counts and characteristics with repeated vibration and five showed normal fluctuation or no change in semen quality. Overall, there was a trend toward higher sperm counts in the antegrade samples (mean, 74.1 million) than in the retrograde samples (mean, 40 million), but no statistical significance was found. Mean sperm motility, sperm progressive motility, and percent normal sperm morphology were not significantly different between antegrade and retrograde specimens. Fructose and zinc, semen markers that reflect the presence of a true ejaculate, were present in all antegrade and retrograde specimens. In conclusion, (1) both antegrade and retrograde ejaculation occur with vibratory penile stimulation, with antegrade samples containing greater numbers of sperm but retrograde samples also having significant sperm counts, (2) repeated vibration may increase sperm concentration or may result in only minimal changes reflective of normal fluctuations, and (3) vibratory stimulation results in true ejaculation, as evidenced by semen markers.
Adult↗
Measuring the impairment consequences of spinal cord injury.
The objectives of this study were to develop and validate an equal-interval measure of neurologic impairment from the International Standards for Neurological and Functional Classification of Spinal Cord Injury Patients developed by the American Spinal Injury Association. These standards were used to rate impairment at admission and discharge to Model System facilities. The results demonstrate that the standards fulfill their purpose of characterizing sensory-motor impairment. Developed was a self-scoring key that rehabilitation clinicians can use to obtain a measure of severity that combines sensory and motor level ratings and completeness classifications to describe impairment more precisely and illustrate the magnitude of reductions in impairment. This measure can be used to monitor improvement over time and compare severity across individuals or groups.
Calibration↗
From playgroup to preschool: facilitating early integration experiences.
This paper discusses community playgroup and preschool settings for non-disabled children as programme options for infants and preschoolers with a variety of physical and mental impairments. These options provide age-appropriate integration experiences which may result in benefits to parent and child, realistic developmental expectations, and a cultural expectation that social integration is a basic part of any child's education. The discussion identifies advantages to beginning integration before the age of 5 years and emphasizes the need for individualized services, ongoing staff training, support for parents, and programme evaluation.
Child, Preschool↗
Effects of daily fat or ethanol ingestion on the cholecystokinin- pancreas and the gastrin- enterochromaffin-like cell axes in rats.
BACKGROUND/AIMS: Ingestion of fat and ethanol is thought to contribute to the development of pancreatitis through the release of gut hormones, such as cholecystokinin (CCK) and gastrin. We have examined the effects of fat or ethanol on the relationships between CCK and pancreas on one hand and between gastrin and the enterochromaffin-like (ECL) cells in the stomach on the other. METHODS: In one study, rats received 2 ml of medium-chain triglycerides or water twice a day by the oral route for 12 days. In another study, rats received 2.5, 5, 10 or 20% ethanol in drinking water for 12 days. All rats were killed on day 13. RESULTS: There were no changes in either the plasma CCK concentration or the pancreatic weight and DNA content in the fat-fed rats. The serum gastrin concentration and the histidine decarboxylase (HDC) activity, HDC mRNA level and histamine content of the ECL cells were lower in fat-fed rats than in control rats. Ethanol did not affect either the plasma CCK concentration or the pancreatic weight and DNA content. The serum gastrin concentration was reduced in the rats that received 5, 10 or 20% ethanol. Also the HDC activity and histamine content of the ECL cells were reduced in the rats that received 10 and 20% ethanol. CONCLUSION: Daily ingestion of fat or ethanol for 12 days was without effects on the plasma CCK concentration and the pancreas, but reduced the serum gastrin concentration and the activity of the ECL cells in the rat.
Animals↗
Vascular endothelial growth factor/vascular permeability factor enhances vascular permeability via nitric oxide and prostacyclin.
BACKGROUND: Vascular endothelial growth factor (VEGF), an endothelial cell mitogen that promotes angiogenesis, was initially identified as a vascular permeability factor (VPF). Abundant evidence suggests that angiogenesis is preceded and/or accompanied by enhanced microvascular permeability. The mechanism by which VEGF/VPF increases vascular permeability (VP), however, has remained enigmatic. Accordingly, we used an in vivo assay of VP (Miles assay) to study the putative mediators of VEGF/VPF-induced permeability. METHODS AND RESULTS: VEGF/VPF and positive controls (platelet-activating factor [PAF], histamine, and bradykinin) all increased vascular permeability. Prior administration of the tyrosine kinase inhibitors genistein or herbimycin A prevented VEGF/VPF-induced permeability. Placenta growth factor, which binds to Flt-1/VEGF-R1 but not Flk-1/KDR/VEGF-R2 receptor tyrosine kinase, failed to increase permeability. Other growth factors such as basic fibroblast growth factor (FGF), acidic FGF, platelet-derived growth factor-BB, transforming growth factor-beta, scatter factor, and granulocyte macrophage-colony stimulating factor (8 to 128 ng) failed to increase permeability. VEGF/VPF-induced permeability was significantly attenuated by the nitric oxide (NO) synthase inhibitors N(omega)-nitro-L-arginine (10 mg/kg) or N(omega)-nitro-L-arginine methyl ester (20 mg/kg) and the cyclooxygenase inhibitor indomethacin (5 mg/kg). The inactive enantiomer N(omega)-nitro-D-arginine methyl ester (20 mg/kg) did not inhibit VEGF/VPF-induced permeability. In vitro studies confirmed that VEGF/VPF stimulates synthesis of NO and prostaglandin metabolites in microvascular endothelial cells. Finally, NO donors and the prostacyclin analogue taprostene administered together but not alone reproduced the increase in permeability observed with VEGF/VPF. CONCLUSIONS: These results implicate NO and prostacyclin produced by the interaction of VEGF/VPF with its Flk-1/KDR/VEGF-R2 receptor as mediators of VEGF/VPF-induced vascular permeability. Moreover, this property appears unique to VEGF/VPF among angiogenic cytokines.
Animals↗
Age-dependent impairment of angiogenesis.
BACKGROUND: The effect of aging on angiogenesis in ischemic vascular disease has not been studied. Accordingly, we investigated the hypothesis that angiogenesis is impaired as a function of age. METHODS AND RESULTS: Forty days after the resection of 1 femoral artery, collateral vessel development was significantly impaired in old (aged 4 to 5 years; n=7) versus young (aged 6 to 8 months; n=6) New Zealand White (NZW) rabbits on the basis of reduced hindlimb perfusion (ischemic: normal blood pressure ratio=0.58+/-0.05 versus 0.77+/-0.06; P<0.005), reduced number of angiographically visible vessels (angiographic score=0.48+/-0.05 versus 0.70+/-0.05; P<0.01), and lower capillary density in the ischemic limb (130.3+/-5.8/mm2 versus 171.4+/-9.5/mm2; P<0.001). Angiogenesis was also impaired in old (aged 2 years) versus young (aged 12 weeks) mice as shown by reduced hindlimb perfusion (measured by laser Doppler imaging) and lower capillary density (353.0+/-14.3/mm2 versus 713.3+/-63.4/mm2; P<0.01). Impaired angiogenesis in old animals was the result of impaired endothelial function (lower basal NO release and decreased vasodilation in response to acetylcholine) and a lower expression of vascular endothelial growth factor (VEGF) in ischemic tissues (by Northern blot, Western blot, and immunohistochemistry). When recombinant VEGF protein was administered to young and old rabbits, both groups exhibited a significant and similar increase in blood pressure ratio, angiographic score, and capillary density. CONCLUSIONS: Angiogenesis responsible for collateral development in limb ischemia is impaired with aging; responsible mechanisms include age-related endothelial dysfunction and reduced VEGF expression. Advanced age, however, does not preclude augmentation of collateral vessel development in response to exogenous angiogenic cytokines.
Aging↗
Neuromuscular block by antibiotics: polymyxin B.
Characteristics of neuromuscular block produced by polymyxin B (PXB) were examined in 12 anesthetized cats, using sciatic nervetibialis anticus muscle preparations. The ED50 was 6.7 (+/- 1.4, SD) PXB base/kg body weight. The ED95 was 10.8 (+/- 2.4) mg/kg. Spontaneous recovery from 25 percent of control to 75 percent of control required 72 (+/- 16) minutes. During a 50 percent block, train-of-four twitches elicited at 2 Hz faded with a train-of-four ratio of 0.42 (+/- 0.13), but the tetanus did not fade. Edrophonium Cl, neostigmine methylsulfate, and pyridostigmine Br at sub-clinical dosages weakly antagonized the block but enhanced the block at anti-curare dosages. All 3 cholinesterase inhibitors were short acting, lasting 10 to 15 minutes, and noncumulative on repeated injection. The potency ratio was approximately 20:10:1 in the order of edrophonium, neostigmine, and pyridostigmine on a weight-for-weight basis. Calcium partially antagonized the block. The authors conclude that neuromuscular blocks produced by various antibiotics differ from each other and from that produced by other groups of neuromuscular blocking agents, including curare.
Animals↗
The role of the allergist in Lyme disease.
The allergist may frequently be involved with cases of Lyme disease. There are at least three reasons for this. First, the major symptom is often a rash that brings into the differential diagnosis several diseases that the allergist is likely to have expertise in; therefore, the allergist's role as a diagnostician is very important. The second reason is that the Borrelia burgdorferi (Bb) infection is treated with antibiotics and the patients may frequently develop reactions that may be immune-mediated. The allergist's expertise in diagnosis and management of allergic reactions is important. The third reason is that there is no established laboratory diagnostic test so that the clinician must use the existing tests, most often serologic, with their limitations, in the context of a history and physical. The allergist as an immunologist can be very helpful in the proper interpretation of the test results. The differential of the rash and the immune response to the infecting agent is described.
Allergy and Immunology↗
Transmission electron microscopic study of the hemorrhagic spots in patients with epidemic hemorrhagic fever in the early stage.
Epidemic hemorrhagic fever (EHF) virus particles were found in the squamous epithelial cells and the capillary endothelial cells of the petechial spots located on the mucous membrane of the soft palate in 3 patients with severe early-stage EHF with transmission electron microscopy. The virus particles were round or oval in shape, about 100 nm in diameter, with a two-layer lipid envelope from which spikes were protruding. The nucleocapsid of the virus appeared to be hollow microfilamentoid or dense granules. Meanwhile, budding virus particles with a diameter of 80 nm were found in the enlarged Golgi apparatus. The infected cells displayed an enlarged and proliferating Golgi apparatus. The morphological characteristics of the viron mentioned above coincided with those of the virus particles of the family Bunyaviridae. This study is the first to demonstrate that the squamous epithelial cells on the mucous membrane of the soft palate are the target cells of EHF infection and to provide subcellular morphological evidence of petechial hemorrhage at the soft palate.
Adult↗
Rheologic and hemodynamic characteristics of red cells of mouse, rat and human.
The present study compares hematologic, rheologic and hemodynamic characteristics of red cells from mouse, rat and human. Red cells in these species are biconcave discs that show significant differences in diameter and mean corpuscular volume (MCV). However, differences in mean corpuscular hemoglobin concentration (MCHC) are not significant. Viscosity measurement of washed red cell suspensions (in each case the medium osmolarity adjusted to match plasma osmolarity) showed significant interspecies differences at shear rates of 37.5 and 750 sec-1 as follows: Human > rat > mouse. Hemodynamic and microcirculatory behavior of these red cells was investigated in the artificially perfused ex vivo mesocecum vasculature of the rat. Hemodynamic measurements in the whole ex vivo mesocecum preparation revealed maximal increase in the peripheral resistance unit (PRU) for the human red cells followed by the rat and mouse red cells, respectively at a hematocrit (Hct) of 40%. Further, measurements of red cell velocities (Vrbc) in single arterioles of the mesocecum vasculature, during sustained perfusion with washed red cell suspensions, showed that at any given perfusion pressure (Pa), Vrbc for both mouse and rat red cells was higher than that for human red cells, while Vrbc for mouse red cells was higher than that for the rat. These results demonstrate that the microvascular flow behavior of these red cells is likely to be influenced by both physical and rheologic characteristics.
Animals↗