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Biomedical subjects

D Liu

Publications and source records attributed to D Liu.

At least 793 records · Page 44Linked to original sources

Development of technology for linking photosensitizers to a model monoclonal antibody.

A procedure is described whereby the photosensitizer, benzoporphyrin derivative monoacid ring A (BPD-MA) was covalently linked to a model monoclonal antibody in a manner which is reproducible, quantifiable, and retains both the biological activity of the antibody and the cytotoxicity of the photosensitizer. Preliminary steps involved the linkage of BPD-MA to a modified polyvinyl alcohol (PVA) backbone, followed by conjugation to the antibody using heterobifunctional linking technology. Briefly, polyvinyl alcohol (MW ca. 10,000) was modified with 2-fluoro-1-methyl pyridinium toluene-4-sulfonate and 1,6-hexanediamine to produce side chains containing free amino groups. The free carboxyl group of BPD-MA was utilized to conjugate photosensitizer molecules to modified PVA using a standard carbodiimide reaction. Final linkage of the PVA-BPD to a model monoclonal antibody involved further substitution of the carrier with 3-mercaptopropionic acid and carbodiimide to introduce 3-4 sulfhydryl residues per carrier molecule, and introduction of sulfo-m-maleimidobenzoyl-N-hydroxysulfosuccinimide ester residues to the monoclonal (3-4 residues/molecule). Conjugation was effected by reaction of the two species at pH 5.5 for 18 h. Detailed methodology and tests for efficacy of the procedure are provided.

Antibodies, Monoclonal↗

Interactions of serum proteins with small unilamellar liposomes composed of dioleoylphosphatidylethanolamine and oleic acid: high-density lipoprotein, apolipoprotein A1, and amphipathic peptides stabilize liposomes.

Small unilamellar liposomes composed to dioleoylphosphatidylethanolamine (DOPE) and oleic acid (OA) are stabilized by incubation with normal human serum or plasma [Liu, D., & Huang, L. (1989) Biochemistry 28, 7700-7707]. The present report describes a systematic study of interactions of purified serum proteins and lipoproteins with these liposomes. Albumin destabilized liposomes by extracting OA from the liposomes, whereas immunoglobulins and lipoproteins (HDL, LDL, and VLDL) had no effect. However, HDL and, to some extent, VLDL showed a rapid stabilization activity against the lytic effect of albumin. HDL added together with or shortly after the addition of albumin completely abolished the liposome leakage and aggregation effects induced by albumin. SDS-PAGE analysis of the HDL-stabilized liposomes revealed that apolipoprotein A1 was associated with liposomes. Purified apolipoprotein A1, but not a lipid mixture resembling the lipid composition of HDL, showed comparable liposome stabilization activity as HDL. Furthermore, synthetic peptides resembling the amphipathic helices found in apolipoprotein A1 also showed strong liposome stabilization activity. Peptides which were able to form amphipathic helixes of a wedge shape were more effective stabilizers than those which could not. These data indicate that HDL plays a major role in human serum or plasma for the liposome stabilization activity. HDL exerts its activity probably by the interactions of the amphipathic helices of apolipoprotein A1 with the hydrophobic voids found on the outer surface of the highly curved, small liposomes.

Apolipoprotein A-I↗

pH-sensitive, plasma-stable liposomes with relatively prolonged residence in circulation.

Acid-sensitive liposomes composed of unsaturated phosphatidylethanolamine (PE) are efficient vehicles for cytoplasmic delivery of the target cells. We have recently shown that liposomes composed of dioleoyl-PE (DOPE) and dipalmitoyl-succinylglycerol (DPSG) retain the acid-sensitivity after exposure to human plasma. In the present work, we have extended these observations to investigate the role of ganglioside GM1 on the blood residence time of these liposomes. Small (d approximately 100 nm) unilamellar liposomes composed of DOPE and DPSG (4:1, molar ratio) became progressively less acid-sensitive when increasing amounts of GM1 were included in the lipid composition. However, partial sensitivity to acid (40-50% release of entrapped contents at pH 4) could be retained up to 5% GM1, even for liposomes which had been exposed to human plasma. Inclusion of GM1 in the lipid composition only slightly increased the release of entrapped contents in the presence of human plasma. The biodistribution of i.v. injected GM1-containing liposomes was studied by following the entrapped 125I-labeled tyraminylinulin marker in Balb/c mice. Inclusion of up to 5% GM1 showed a transient increase in the blood level and a concomitant decrease of liver and spleen uptake of liposomes. Thus, these liposomes are pH-sensitive, plasma-stable and show a relatively prolonged residence time in circulation. They are potentially significant drug carriers in vivo.

Animals↗

Mutatox test: a new test for monitoring environmental genotoxic agents.

In this study, Yamaska River water and Milli-Q water and organically extracted sediment extracts were used to evaluate the sensitivity of a new genotoxicity screening test, the Mutatox test. Also in this study, the samples were tested for acute and chronic toxicity using the following screening test procedures: Microtox, Daphnia magna, Ceriodaphnia reticulata and ATP-TOX Systems. The Mutatox test is based on the use of a dark mutant strain of Photobacterium phosphoreum and is sensitive to chemicals which are (1) DNA damaging agents (2) DNA intercalating agents, (3) DNA synthesis inhibitors and (4) direct mutagens. In this study, the Mutatox test was found to be a simple-to-perform sensitive procedure which added greater scope to the battery of tests approach. Preliminary indications are that this procedure may prove to be one of the more responsive and valuable tests in the 'battery of tests' approach to environmental screening.

Journal Article↗

Combined insulin-glibenclamide therapy of NIDDM patients in primary health care. A follow-up study of its compliance and efficacy and a review of the literature.

Twenty non-insulin-dependent diabetic (NIDDM) patients with secondary failure to sulphonylureas were given combined insulin-glibenclamide therapy. After discharge they were followed for the following 12 months at different primary care centres. In the 19 patients who completed the combined therapy, the mean glycosylated haemoglobin A1c (HbA1c) level decreased from 11.2 +/- 0.5% to 9.1 +/- 0.3% at 2 months (p less than 0.001), and remained at 9.1 +/- 0.4% at 12 months. The reduction of HbA1c was positively correlated with the HbA1c value and inversely with the initial body weight (both p less than 0.05). There was a slight rise in the body mass index (BMI) from 26.9 +/- 0.9 to 28.2 +/- 0.7 at 12 months (p less than 0.001), which was inversely correlated with the BMI value at 0 month (p less than 0.05). The insulin doses were similar at 2 and 12 months. A review of the literature since 1985 identified ten double-blind, controlled studies on combined insulin-sulphonylurea therapy, comprising 156 NIDDM patients followed for 8-52 weeks. Improved glycaemic control and endogenous insulin secretion were documented in nine of these studies in parallel with a decrease of insulin requirement in six studies. We conclude from our own experience and the literature that combined insulin-glibenclamide therapy is an efficient and compliant therapeutic regimen.

Aged↗

[Restriction fragment length differences (RFLDs) of genomic DNA from different geographical strains of Anopheles sinensis and Anopheles anthropophagus].

Total DNA was extracted from three geographical strains of Anopheles sinensis and two geographical strains of Anopheles anthropophagus and digested respectively with three restriction endonucleases (Bgl II, Hae III and Pst I). The restriction fragment length differences (RFLDs) of repetitive DNA detected after agarose gel electrophoretic separation and ethidium bromide staining were compared among the above-mentioned geographical strains of both An. sinensis and An. anthropohagus. The results indicated that the band patterns are species- specific and strain-specific, their main bands being similar while their minor bands being distinctly different. Pst I digestion produced unique fragments for three geographical strains of An. sinensis while Bgl II digestion produced unique fragments for two geographical strains of An. anthropophagus. In view of the variation in repetitive DNA of different geographical strains of both An. sinensis and An. anthropophagus presented, the RFLDs could be used as a means to distinguish various closely related geographical strains of anopheline mosquitoes.

Animals↗

Micro-vitreous surgery combined with scleral encircling for the management of complex retinal detachment.

50 cases (50 eyes) of various complex retinal detachments (RD) were treated with a combination of vitrectomy, membrane peeling, intraocular air tamponade and scleral encircling. RD with opaque media, RD with proliferative vitroretinopathy, traction RD due to trauma or other factors, RD with posterior breaks, and giant tears were included. During the follow-up periods of 3-12 months, 27 cases (54%) obtained anatomic reattachment, 23 failed (46%). Of the successful case, 24 eyes achieved improvement, 2 eyes remained unchanged, and one eye became worse in their vision. The surgery complications were: retinal haemorrhage, choroidal haemorrhage, iatrogenic tears, and the development of cataract.

Adolescent↗

[Antimutagenicity screening of water extracts from 102 kinds of Chinese medicinal herbs].

Our observation shows that out of 102 kinds of Chinese medicinal herbs tested, 17 have remarkable antimutagenic effect on the mutation induced by aflatoxin B1, in Ames test. Among the 17 herbs Glycyrrhiza uralensis, Bupleurm chinense, Portulaca grandiflora and Cnidium monnieri have been found in other tests to be effective against mutagenesis induced by cyclophosphamide in mice.

Animals↗

Trauma outcome analysis of two Canadian centres using the TRISS method.

In this retrospective study, the TRISS method of trauma care analysis is used to compare trauma care at the Hamilton General Hospital (HGH) and the Ottawa Civic Hospital (OCH) with the standards reported in the Major Trauma Outcome Study (MTOS). A total of 274 adult patients with multiple-system injuries were studied; their demographic data, Trauma Scores (TS) on arrival to the Emergency Room, and Injury Severity Scores (ISS) were reviewed. The TRISS scores and Z and M statistics were then calculated. In the Hamilton group, 106 consecutive patients from April through July 1987 were studied. The majority of patients (72%) were male, and the median age was 26 years. The majority of patients (96.2%) sustained blunt trauma, with motor vehicle accidents (MVA) being the most common (76.4%) mechanisms of injury. Fifty-four (51%) of the patients were transferred from outlying hospitals. The Z and M statistics were -0.05 and 0.92, respectively. In the Ottawa group, 168 consecutive patients from April 1987 through October 1988 were studied. The majority of patients (73%) were male, and the median age was 39 years. Blunt trauma accounted for the majority (91.7%) of injuries, with MVAs being responsible for 58% of injuries. Most patients (63.5%) were transferred from regional hospitals. The Z and M statistics were 1.20 and 0.56, respectively. We conclude that the survival statistics of trauma patients treated at both centres are comparable to those of trauma patients in the MTOS.

Adult↗

Role of cholesterol in the stability of pH-sensitive, large unilamellar liposomes prepared by the detergent-dialysis method.

Large unilamellar liposomes prepared by an octyl glucoside-dialysis method were examined for stability at 37 degrees C in the presence or absence of human plasma, using the release of the entrapped calcein as a fluorescence marker. The liposomes were acid-sensitive as they were composed of dioleoylphosphatidylethanolamine, oleic acid and cholesterol. The stability of the liposomes in the absence of plasma was significantly enhanced with increasing cholesterol content. However, the maximal calcein release at pH 5 decreased linearly with increasing cholesterol content of the liposome, indicating that cholesterol had reduced the acid-sensitivity of the liposomes. In the presence of human plasma, calcein release exhibited a biphasic behavior with a fast (plasma-sensitive) and a slow (plasma-resistant) component. Inclusion of cholesterol in the liposomes resulted in an increased proportion of the plasma-resistant component. Liposomes pretreated with human plasma, after removal of excess plasma and the released calcein by gel-filtration, showed a remarkable stability both in the presence and absence of human plasma. The acid-sensitivity of the plasma-treated liposomes with 40% cholesterol was the same as that of the untreated liposomes. These results are discussed in terms of the mechanism by which these liposomes deliver their contents to the cytoplasm of the cells via the endocytic pathway, a known biological activity of the type of liposome described here.

Blood↗

A modified fascia needle.

A new fascia needle has been designed. It is considerably easier to handle and does not have any of the problems surgeons typically encounter with the Wright needle.

Humans↗

The detection of an antibody against IgA allotype A2M 2 and a study of the Am genetic marker among the Han Chinese population.

The serum of a woman was found by the Ouchterlony double-diffusion and the hemagglutination inhibition (HAI) methods to have immunoglobulin A (IgA) deficiency. Further investigation using the hemagglutination (HA) test with red cells coated with IgA myeloma proteins of different specificities showed that the serum agglutinated only IgA2-, A2M-1, and A2M 2-coated cells. The patterns of the HAI test with a reference panel confirmed the presence of two specificities. One was anti-IgA2 and the other was a rare antibody against the allotype A2M 2. The anti-A2M 2 was used for population studies. Testing of the Han Chinese population, including family studies, confirms that A2M.1 and A2M.2 have an autosomal dominant mode of inheritance and are controlled by a codominant allele. The distribution of the two Am genetic markers among the Han Chinese population demonstrated A2M.1 with a gene frequency of 0.553 and A2M.2 with a gene frequency of 0.447 (chi 2 = 0.145, 0.80 greater than p greater than 0.70).

Alleles↗

The central projections of the great auricular nerve primary afferent fibers--an HRP transganglionic tracing method.

A study of the central distribution of the primary afferent fibers of the great auricular nerve (GAN) was made in 18 rabbits by means of transganglionic transport of horseradish peroxidase (HRP). HRP applied to the cut central end of the GAN was detected ipsilaterally in the dorsal root ganglion cells (segments C2-C3) and the superior cervical ganglion cells. The transganglionically labeled fibers were seen in the dorsal column of the upper 4 cervical segments and in the cranial nerve nuclei of the medulla oblongata. The afferent projections were rather strong in the regions of laminae I-V of C2, the caudal subnucleus of the nucleus of the spinal tract of the trigeminal nerve (NVSpc), the solitary nucleus (SN), the medial and lateral cuneate nuclei, etc. The results showed that the primary afferent impulses of the GAN and the peripheral nerves which supply the head, face, trunk and viscera might converge on the upper cervical cord, the NVSpc and the SN, and play a certain role of modulation on the transmission of somaticovisceral sensations, especially pain.

Afferent Pathways↗