Biomedical subjects

Q Liu

Publications and source records attributed to Q Liu.

At least 415 records · Page 23Linked to original sources

PubMed1998

Comparison of interleukin-11 and epidermal growth factor on residual small intestine after massive small bowel resection.

BACKGROUND/PURPOSE: Interleukin-11 (IL-11) is a multifunctional cytokine derived from bone marrow, which has a trophic effect on small bowel epithelium. This study compares the effects of IL-11 with epidermal growth factor (EGF), a growth factor known to enhance small bowel adaptation. METHODS: Forty Sprague-Dawley rats (90 to 100 g) underwent an 85% mid-small bowel resection with primary anastomosis on day 0. Rats were divided into four treatment groups: controls (group I) received bovine serum albumin (BSA), group II received IL-11, 125 microg/kg subcutaneously (SC) twice daily, group III received EGF, 0.10 microg/g SC bid, and group IV received EGF and IL-11 in the above doses. Half of the animals (five per group) were killed on day 4 of therapy, and the rest were killed on day 8. Animals were evaluated for weight, mucosal length, and bowel wall muscle thickness on days 4 and 8, and expression of proliferating cell nuclear antigen (PCNA) in intestinal crypt and smooth muscle cells on day 8. RESULTS: There were two deaths; both were 8-day controls. Body weight was similar at day 4 and day 8. Mucosal thickness in groups II (IL-11) and group IV (IL-11 and EGF) was significantly increased at day 4 and 8 when compared with controls (group I) and EGF (group III, P < .001). Muscle thickness was significantly increased in the EGF and combined group IV compared with the BSA controls and IL-11 groups (P < .001). Thirty-two percent of the mucosal crypt cells in Group I stained positive for PCNA, whereas 51%, 53%, and 60% stained positive in groups II (IL-11), III (EGF), and IV (IL-11 and EGF), respectively. In groups I and II, 2% and 1.7% of the myocytes stained positive for PCNA, whereas 11.2% and 5.2% of the myocytes in group III and IV stained positive. CONCLUSIONS: These data suggest that IL-11 has a trophic effect on small intestinal enterocytes, causing cell proliferation and increased mucosal thickness. EGF has a more generalized effect on intestine causing proliferation of both enterocytes and myocytes. IL-11, with or without EGF, may be a useful adjunct in instances of short bowel syndrome.

Adaptation, Physiological↗

PubMed1998

Mesocaval shunt inhibits primary and metastatic hepatoma growth and enhances apoptosis.

BACKGROUND: Previous reports indicate that hepatocyte growth factor and other hepatic trophic factors reach the liver presumably by portal venous inflow and stimulate experimental hepatic tumor growth, invasion, and metastasis. This study tests this hypothesis by evaluating whether a mesocaval shunt (MCS) alters hepatic tumor growth, the mitotic rate, apoptosis, and incidence and growth of lung metastasis in rats with implanted hepatoma. METHODS: Morris hepatoma (1 x 10(5)) cells were implanted intrahepatically in 19 ACI rats. One week after implantation, 10 rats underwent MCS operation and nine controls a sham operation. Rats were killed 21 days after the operation to assess tumor volume, tumor cell mitosis, apoptosis, area of tumor necrosis, pulmonary metastases and percentage of lung tumor area. RESULTS: Mesocaval shunt induced a significant increase in the rate of tumor apoptosis (25 +/- 5 v 14 +/- 6, P < .01) and the percentage of area of tumor necrosis (29% +/- 17% v 13% +/- 8%, P < .05), a decreased tumor volume (839 +/- 1,195 v 2,909 +/- 2,572, P < .05), a reduction in tumor mitosis (70 +/- 28 v 93 +/- 11, P < .05) and decreased percentage area of pulmonary metastatic tumor (9.8 +/- 6.8 v 18.8 +/- 14, P < .05). CONCLUSION: These observations show that growth of intrahepatic tumor is influenced by portal venous inflow and suggest that MCS or other methods of regulating portal vein flow may be useful as adjunctive therapy in the treatment of advanced hepatoma.

Animals↗

PubMed1998

Surface modification of nano-apatite by grafting organic polymer.

Since surface properties of hydroxyapatite (HA) play an important role in its performance, surface modification of HA has gained much attention from researchers. Silane coupling agents have been the focus of the research. In this study, an effective surface modification method was developed using hexamethylene diisocyanate as a coupling agent. Polyethylene glycol (Mw = 1500) was successfully coupled to the surface of nano-size apatite particles (nano-apatite). Various methods were used to characterize the surface-modified nano-apatite. Infra-red spectra confirmed the existence of a layer of polymer with both urethane and ether linkage on the surface of nano-apatite. The amount of grafted polymer as determined by total organic carbon analysis (TOC) and thermal gravimetric analysis (TGA) was about 20% in weight. Solid 1H MAS NMR spectra indicated that the amount of hydroxyl groups of nano-apatite was decreased by 7.7% after surface grafting reaction. It is concluded that the surface hydroxyl groups of nano-apatite have the reactivity towards isocyanate groups.

Carbon↗

PubMed1998

More than one way to splice an RNA: branching without a bulge and splicing without branching in group II introns.

Domain 6 (D6) of group II introns contains a bulged adenosine that serves as the branch-site during self-splicing. In addition to this adenosine, other structural features in D6 are likely to contribute to the efficiency of branching. To understand their role in promoting self-splicing, the branch-site and surrounding nucleotides were mutagenized. Detailed kinetic analysis on the self-splicing efficiency of the mutants revealed several interesting features. First, elimination of the branch-site does not preclude efficient splicing, which takes place instead through a hydrolytic first step. Second, pairing of the branch-site does not eliminate branching, particularly if the adenosine is involved in a mispair. Third, the G-U pairs that often surround group II intron branch-points contribute to the efficiency of branching. These results suggest that there is a strong driving force for promoting self-splicing by group II introns, which employ a versatile set of different mechanisms for ensuring that splicing is successful. In addition, the behavior of these mutants indicates that a bulged adenosine per se is not the important determinant for branch-site recognition in group II introns. Rather, the data suggest that the branch-site adenosine is recognized as a flipped base, a conformation that can be promoted by a variety of different substructures in RNA and DNA.

Adenosine↗

PubMed1998

Polyacids as bonding agents in hydroxyapatite polyester-ether (Polyactive 30/70) composites.

A previously developed method to improve the interface between hydroxyapatite (HA) and a polyester-ether (Polyactive 70/30) by using polyacrylic acid or poly(ethylene-co-maleic acid) has been applied to HA/Polyactive 30/70 composites noting that polyactive 30/70 contains less polyethylene glycol (PEG) segments and a higher concentration of rigid poly(butylene terephthalate) (PBT) segments. The mobility of the PEG segments is significantly affected by the existence of a high concentration of rigid PBT segments. Our experimental results show that this method is indeed suitable for making HA/Polyactive 30/70 composites. The hydrogen bond/dipole interaction forming ability of the PEG segment is not affected by the existence of relatively large amounts of PBT segments. By using these coupling agents, the mechanical properties of the composite can be significantly improved both in dry and wet states. A fractographical study of the fracture surfaces revealed that the surface modified HA particles maintain better contact at fracture. It also showed that larger HA particles may initiate cracks and that such particles may be responsible for a decrease in the tensile strength of the composites.

Journal Article↗

PubMed1998

Preparation of bioactive microporous titanium surface by a new two-step chemical treatment.

Microporous oxide layers allowing fast deposition of calcium phosphate layers (CPLs) were formed on commercially pure titanium (c.p.Ti) after the application of a newly developed two-step chemical treatment. The micropores were of submicrometre size. The two-step treatment was carried out by etching c.p.Ti samples with HCl and H2SO4 first and then treating them in boiling 0.2 N NaOH solution at 140 degrees C for 5 h. Conformal CPLs, about 20 microm thick, were deposited on the two-step treated c.p.Ti surface by means of a two-day immersion in an in vitro supersaturated calcification solution. The CPL was characterized to be mainly composed of two sublayers, i.e. an outside loose octacalcium phosphate crystal sublayer and an inside dense carbonated apatite sublayer. A scratching test indicated that the apatite sublayer was strongly bonded to the c.p.Ti substrate. Moreover, it was observed that the untreated or single-step treated c.p.Ti surfaces are not only morphologically different from one another but significantly different from the two-step treated one, in that no precipitation was observed on them up to 14 d immersion in the same calcification solution. It is indicated that the two-step chemical treatment is a simple and easily controllable method to prepare bioactive titanium surfaces and subsequently to induce the rapid precipitation of conformal and adherent CPL from in vitro supersaturated calcification solutions.

Journal Article↗

PubMed1998

Confidence-accuracy inversions in scene recognition: a remember-know analysis.

S. E. Clark (1997) offered a modified signal-detection explanation of the confidence-accuracy inversions observed in E. Tulving's (1981) experiments. In addition to replicating E. Tulving (1981), we had participants make "remember-familiar" judgments. Confidence and accuracy dissociated across subjective reports. Response confidence differed only for judgments based on familiarity, whereas accuracy differed only for "remember" responses. S. E. Clark's model does not predict this, nor can it mimic "remember" performance across all conditions. We propose that although "knowing" can be accommodated within an equal variance signal-detection account, "remembering" is governed by contextual constraints that influence the distinctiveness of information upon which participants rely during reports. The current paradigm is a pictorial analogue to H. L. Roediger and K. B. McDermott's paradigm (1995) in that participants claim to explicitly remember thematically related items that were not actually seen during study.

Humans↗

PubMed1998

A novel DNA-binding motif shares structural homology to DNA replication and repair nucleases and polymerases.

A novel class of DNA-binding domains has been established from at least sixteen recently identified DNA-binding proteins. The three-dimensional structure of one of these domains, Mrf-2, has been solved using NMR methods. This structure is significantly different from known DNA-binding domain structures. The mechanism of DNA recognition by this motif has been suggested based on conserved residues, surface electrostatic potentials and chemical shift changes. This new DNA-binding motif shares structural homology with T4 RNase H, E. coli endonuclease III and Bacillus subtilis DNA polymerase I. The structural homology suggests a mechanism for substrate recognition by these enzymes.

Amino Acid Sequence↗

PubMed1998

Superoxide and endothelium-dependent constriction to flow in porcine small pulmonary arteries.

1. The aim of this study was to determine the response of porcine small pulmonary arteries to intralumenal flow and to identify the cellular mechanisms and potential mediators involved in the response. 2. Porcine small pulmonary arteries were isolated from a branch of the main intrapulmonary artery of the lower lung lobe and studied in a perfusion myograph system that allowed independent control of transmural pressure and intralumenal flow. At a transmural pressure of 20 mmHg, the baseline internal diameter (BID) of the arteries was 251.2+/-16.1 microm (n=16). 3. Under quiescent conditions or during constriction with U46619 to approximately 60% of BID, intralumenal flow caused reversible constriction in arteries with endothelium (in the presence of U46619, flow decreased diameter from 60.0+/-2.5% to 49.5+/-3.0% BID at 10 microl min(-1), n=16, P<0.05) but no change in diameter of arteries without endothelium. 4. In the presence of superoxide dismutase (SOD, 150 u ml(-1)), the response to flow was converted from constriction to vasodilatation (in presence of U46619 and SOD, flow increased diameter from 54.2+/-3.4% to 76.7+/-4.5% BID at 10 microl min(-1), n=10, P<0.05). Inhibition of NO synthase with L-NAME (3 x 10(-5) M) abolished the flow-induced vasodilatation occurring in the presence of SOD and the flow-induced constriction occurring in the absence of SOD. In arteries with endothelium, L-NAME (3 x 10(-5) M) caused significant vasoconstriction, whereas SOD did not alter vasomotor tone. 5. Acetylcholine (10(-8) to 10(-6) M) caused endothelium-dependent relaxation of small pulmonary arteries that was not significantly affected by SOD (150 u ml(-1)) but was inhibited by L-NAME (3 x 10(-5) M). 6. These results suggest that in small, porcine, isolated pulmonary arteries, intralumenal flow increases the production of NO but this is obscured by the generation of superoxide which causes vasoconstriction.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1998

High prevalence of Plasmodium malariae and Plasmodium ovale in malaria patients along the Thai-Myanmar border, as revealed by acridine orange staining and PCR-based diagnoses.

The prevalence of the four human malaria parasites was investigated among malaria patients at northern, central and southern towns in Thailand along the border with Myanmar between September 1995 and May 1996. Thin smears obtained from 548 Thai and Burmese patients were reviewed by an acridine orange staining method, and many mixed infections with two to four species, including P. malariae and P. ovale, were detected. These diagnostic results were compared with those by two PCR-based diagnoses, microtitre plate hybridization (MPH) and a nested PCR method, both of which targets the same, species-specific regions in the 18S rRNA genes. In both PCR diagnoses, many P. malariae and P. ovale infections were also detected. Detection sensitivity of P. malariae infection was higher in nested PCR than MPH, and a total prevalence of P. malariae infection estimated by nested PCR reached 24.3% (133/548). In 16 of them, the size of PCR products amplified by the P. malariae-specific primer was about 20-bp shorter than the expected size of 115-bp. Four of 16 possessed two different bands with normal and shorter sizes, suggesting that P. malariae isolates may be separated into two types, and that those with shorter products may be new variant form (s) with a nucleotide deletion in the target region. On the other hand, 21 P. ovale infections (3.8%) were detected by nested PCR, but four of them were MPH-negative because of the sequence variation at the probe region. These results indicated that the prevalence of P. malariae and P. ovale along the Thai-Myanmar border may be substantially higher than previously reported.

Acridine Orange↗

PubMed1998

Endomorphin-stimulated [35S]GTPgammaS binding in rat brain: evidence for partial agonist activity at mu-opioid receptors.

Endomorphin-1 is a peptide whose binding selectivity suggests a role as an endogenous ligand at mu-opioid receptors. In the present study, the effect of endomorphin-1 on mu receptor-coupled G proteins was compared with that of the mu agonist DAMGO by using agonist-stimulated [35S]GTPgammaS binding in rat brain. [35S]GTPgammaS autoradiography revealed a similar localization of endomorphin-1- and DAMGO-stimulated [35S]GTPgammaS binding in areas including thalamus, caudate-putamen, amygdala, periaqueductal gray, parabrachial nucleus, and nucleus tractus solitarius. Naloxone blocked endomorphin-1-stimulated labeling in all regions examined. Although the distribution of endomorphin-1-stimulated [35S]GTPgammaS binding resembled that of DAMGO, the magnitude of endomorphin-1-stimulated binding was significantly lower than that produced by DAMGO. Concentration-effect curves of endomorphin-1 and DAMGO in thalamic membranes confirmed that endomorphin-1 produced only 70% of DAMGO-stimulated [35S]GTPgammaS binding. Differences in maximal stimulation of [35S]GTPgammaS binding between DAMGO and endomorphin-1 were magnified by increasing GDP concentrations, and saturation analysis of net endomorphin-1-stimulated [35S]GTPgammaS binding revealed a lower apparent Bmax value than that obtained with DAMGO. Endomorphin-1 also partially antagonized DAMGO stimulation of [35S]GTPgammaS binding. These results demonstrate that endomorphin-1 is a partial agonist for G protein activation at the mu-opioid receptor in brain.

Animals↗

PubMed1998

Feasibility of stent placement above the sphincter of Oddi ("inside-stent") for patients with malignant biliary obstruction.

BACKGROUND AND STUDY AIMS: Animal studies suggest that placement of endobiliary stents wholly above the papilla (the "inside-stent") prolongs the duration of stent patency. We reviewed the cholangiographic characteristics of patients with malignant obstructive jaundice in order to evaluate the feasibility of this approach and to assist in the design of a new stent. PATIENTS AND METHODS: A review was conducted of 270 patients who had undergone endoscopic retrograde cholangiopancreatography (ERCP) for malignant obstructive jaundice at our hospital, to determine the relative frequencies of the types of cancers. The ERCP films of 59 relevant consecutive patients with malignant obstructive jaundice were studied to determine the length of the stricture, the distance between the stricture and the papilla, and the angulation of the common duct. RESULTS: The most frequent primary cancers causing malignant obstructive jaundice were pancreatic cancer (57%), biliary cancer involving the hilum (19%, including metastatic disease), nonhilar biliary cancer (14%), and papillary cancer (10%). The length between the lower end of the stricture and the sphincter was more than 2 cm for all hilar biliary cancer, representing two-thirds of nonhilar biliary cancer cases, while it was less than 1 cm for most pancreatic cancers. There was an average angulation of 30-40 degrees in the axis of the distal common bile duct. CONCLUSIONS: For most biliary cancers, the stricture is high enough to allow the placement of a stent fully above the papilla, but this is not possible for most pancreatic cancers (or any papillary cancers). An "inside-stent" approach would be possible in about one-third of patients with malignant obstructive jaundice if a clearance length of over 2 cm between the stricture and the sphincter is required, and in about 45% of patients if a minimum clearance of 1 cm is required. A 30-40 degrees flexion in the distal part of the stent would approximate the average angulation in the axis of the common bile duct and help to prevent dislocation.

Bile Duct Neoplasms↗

PubMed1998

A surface-based approach to DNA computation.

A scalable approach to DNA-based computations is described. Complex combinatorial mixtures of DNA molecules encoding all possible answers to a computational problem are synthesized and attached to the surface of a solid support. This set of molecules is queried in successive MARK (hybridization) and DESTROY (enzymatic digestion) operations. Determination of the sequence of the DNA molecules remaining on the surface after completion of these operations yields the answer to the computational problem. Experimental demonstrations of aspects of the strategy are presented.

Automation↗

PubMed1998

DNA computing on surfaces: encoding information at the single base level.

The feasibility of encoding a bit (0 or 1) of information for DNA-based computations at the single nucleotide level is evaluated, particularly with regard to the efficiency and specificity of hybridization discrimination. Hybridization experiments are performed on addressed arrays of 32 (2(5)) distinct oligonucleotides immobilized on chemically modified glass and gold surfaces with information encoded in a binary (base 2) format. Similar results are obtained on both glass and gold surfaces and the results are generally consistent with thermodynamic calculations of matched and mismatched duplex stabilities. It is found that under the conditions required to obtain single nucleotide specificity in the hybridization process, hybridization efficiency is low, compromising the utility of single nucleotide encoding for DNA computing applications in the absence of some additional mechanism for increasing specificity. Several methods are suggested to provide such increased discrimination.

Base Composition↗

PubMed1998

Effect of green tea on p53 mutation distribution in ultraviolet B radiation-induced mouse skin tumors.

In the present study, administration of green tea to SKH-1 mice, via the drinking fluid, was found to significantly reduce the incidence and volume of ultraviolet B (UVB) radiation-induced skin tumors. Thirty-six skin tumors induced by UVB and 32 skin tumors induced by UVB, in mice treated with green tea in their drinking water, were collected and examined for the presence of mutations in the p53 gene. Polymerase chain reaction products from p53 exons 5-8 were screened by single-strand conformation polymorphism and direct sequence analyses. Eight of 36 UVB-induced tumors contained nine p53 mutations, with four in exon 5 and five in exon 8. In contrast, nine of 32 UVB-induced tumors in mice treated with green tea contained 11 p53 mutations, with two in exon 5, five in exon 6 and four in exon 8. All of the p53 mutations occurred at dipyrimidine sequences. These results were further corroborated by p53 immunohistochemistry. The most frequent mutations were C-->T or T-->C transitions, which are consistent with the genetic alterations caused by UVB exposure. Interestingly, mutations found in exon 6 of the p53 gene occurred only in tumors from the UVB/green tea group. Thus, the tumors observed in UVB/green-tea-treated mice have a different exon distribution of p53 mutations than tumors obtained from mice treated with UVB alone.

Animals↗

PubMed1998

No cross-tolerance between S-nitrosocaptopril and nitroglycerin in dog coronary arteries in vivo.

S-Nitrosocaptopril (S-NO-Cap), a nitrate and an angiotensin-converting enzyme (ACE) inhibitor, may be produced after coadministration of nitroglycerin (NTG) and captopril (CAP). We synthesized S-NO-Cap and investigated its in vivo tolerance. In open-chest dogs, S-NO-Cap [300 microg; intracoronary (i.c.)] and NTG (50 microg, i.c.) increased coronary blood flow (CBF) similarly (8.0 vs. 9.0 ml/min; p = NS; n = 5). After a 2-h i.c. NTG infusion at high dose (1.32 micromol/min), NTG (50 microg, i.c.) had no significant effect on CBF, whereas S-NO-Cap (300 microg, i.c.) still produced an attenuated increase in CBF (4.9 ml/min; p < 0.05 vs. control). On the other hand, after a 2-h i.c. infusion of S-NO-Cap (1.32 micromol/min), the CBF response to S-NO-Cap (300 microg) showed no attenuation, whereas that to NTG (50 microg) was potentiated (8.8 vs. 12.6 ml/min; p < 0.05; n = 6). Under basal conditions, S-NO-Cap (30-300 microg, i.c.) increased CBF dose dependently, whereas CAP (30-300 microg, i.c.) had no effect on CBF, suggesting that S-NO-Cap dilates coronary vessels by a nitrate action but not by an ACE-inhibitory action. In nonsurgical dogs, 2-h intravenous (i.v.) infusion of S-NO-Cap (1.32 micromol/min) had a stable hypotensive effect, whereas that of NTG (1.32 micromol/min) gradually attenuated the effect. Plasma NO3-, an oxidative product of nitric oxide (NO), increased after both infusions, suggesting that S-NO-Cap may act partially as an NO donor, similarly to NTG. Plasma ACE activity was reduced after an S-NO-Cap infusion (5.84 vs. 4.10 IU/L; p < 0.01; n = 5), and plasma aldosterone was markedly increased after NTG infusion relative to that after S-NO-Cap infusion (243.0 vs. 38.6 pg/ml; p < 0.05). Plasma norepinephrine increased after both infusions (393.6 vs. 289.0 pg/ml; p = NS). As judged by the increase in CBF, whereas S-NO-Cap showed partial tolerance with NTG, no tolerance was found with S-NO-Cap itself. The in vivo coronary vascular response to S-NO-Cap may, therefore, be partially reduced by activation of the adrenergic or renin-angiotensin-aldosterone systems or both induced by NTG, because S-NO-Cap showed no cross-tolerance with NTG in our earlier in vitro study.

Aldosterone↗

PubMed1998

Two transcription factors, DREB1 and DREB2, with an EREBP/AP2 DNA binding domain separate two cellular signal transduction pathways in drought- and low-temperature-responsive gene expression, respectively, in Arabidopsis.

Plant growth is greatly affected by drought and low temperature. Expression of a number of genes is induced by both drought and low temperature, although these stresses are quite different. Previous experiments have established that a cis-acting element named DRE (for dehydration-responsive element) plays an important role in both dehydration- and low-temperature-induced gene expression in Arabidopsis. Two cDNA clones that encode DRE binding proteins, DREB1A and DREB2A, were isolated by using the yeast one-hybrid screening technique. The two cDNA libraries were prepared from dehydrated and cold-treated rosette plants, respectively. The deduced amino acid sequences of DREB1A and DREB2A showed no significant sequence similarity, except in the conserved DNA binding domains found in the EREBP and APETALA2 proteins that function in ethylene-responsive expression and floral morphogenesis, respectively. Both the DREB1A and DREB2A proteins specifically bound to the DRE sequence in vitro and activated the transcription of the b-glucuronidase reporter gene driven by the DRE sequence in Arabidopsis leaf protoplasts. Expression of the DREB1A gene and its two homologs was induced by low-temperature stress, whereas expression of the DREB2A gene and its single homolog was induced by dehydration. Overexpression of the DREB1A cDNA in transgenic Arabidopsis plants not only induced strong expression of the target genes under unstressed conditions but also caused dwarfed phenotypes in the transgenic plants. These transgenic plants also revealed freezing and dehydration tolerance. In contrast, overexpression of the DREB2A cDNA induced weak expression of the target genes under unstressed conditions and caused growth retardation of the transgenic plants. These results indicate that two independent families of DREB proteins, DREB1 and DREB2, function as trans-acting factors in two separate signal transduction pathways under low-temperature and dehydration conditions, respectively.

Adaptation, Physiological↗

PubMed1998

Comparative efficacy of trovafloxacin in experimental endocarditis caused by ciprofloxacin-sensitive, methicillin-resistant Staphylococcus aureus.

The new fluoroquinolone trovafloxacin was tested against a ciprofloxacin-sensitive, methicillin-resistant Staphylococcus aureus strain in the rabbit model of endocarditis. Trovafloxacin was more effective than vancomycin (CFU/g of vegetation, 2.65 +/- 1.87 versus 4.54 +/- 2.80 [mean +/- standard deviation]; P < 0.05) or ampicillin-sulbactam plus rifampin (4.9 +/- 1.1 CFU/g). The addition of ampicillin-sulbactam to trovafloxacin tended to reduce titers further.

Animals↗