Biomedical subjects

B Y Lin

Publications and source records attributed to B Y Lin.

At least 37 records · Page 2Linked to original sources

PubMed1994

Mechanical loading modifies ovariectomy-induced cancellous bone loss.

The object of this study was to determine the tissue level mechanism in which mechanical loading had an influence on ovariectomy-induced cancellous bone loss. Two experiments were performed: (1) 230 g female rats were divided into basal, age-related controls and right hindlimb immobilized (RHLI) group; (2) 250 g female rats were divided into basal, age-related, ovariectomized (OVX) controls and OVX combined with RHLI. The RHLI model immobilized (IM) or underloaded (UL) the right hindlimb and loaded (L) the left hindlimb compared to the right hindlimb. Both experiments lasted 60 days. Histomorphometric data was gathered from the secondary spongiosa of double fluorescent labeled proximal tibial metaphysis (PTM). The study confirmed that IM or UL induces cancellous bone loss, by decreasing bone formation, and increasing bone resorption and OVX results in cancellous bone loss, a higher bone turnover with bone resorption exceeding bone formation in the PTM. The OVX'd and immobilized (OVX + UL) PTM showed further decreased cancellous bone mass (-48%), decreased number (-43%), and decreased tissue-level bone formation rate (-54%) from that of OVX rats. However, the OVX'd and loaded (OVX + L) PTM partially prevented the OVX-induced cancellous bone loss. The cancellous bone area (+46%), number (+29%), and ratio of node to free end (+70%) were increased and percent eroded perimeter (-44%) and bone resorption rates (-30%) were decreased from OVX rats, but cancellous bone area and number were still significantly lower than those in age-related controls. We found that IM or UL accentuated cancellous bone loss in OVX rats by inhibiting bone formation and that loading partially prevented cancellous bone loss in OVX and RHLI rats by inhibiting bone resorption.

Adaptation, Physiological↗

PubMed1994

Nucleotide sequence of the genomic RNA of bamboo mosaic potexvirus.

The complete nucleotide sequence of the genomic RNA of bamboo mosaic virus (BaMV) was determined by sequencing a set of overlapping cDNA clones and by direct sequencing of the viral RNA. The RNA genome of BaMV is 6366 nucleotides long [excluding 3'poly(A) tail] and contains six open reading frames (ORFs 1 to 6) coding for polypeptides with M(r) values of 155K, 28K, 13K, 6K, 25K and 14K, respectively. The genome organization and sizes of the encoded proteins are very similar to those of other potexviruses which have been sequenced except that ORF 6 lies completely within ORF 1. The first five putative proteins of the BaMV genome show identities ranging between 44 to 59%, 26 to 49%, 30 to 53%, 15 to 35% and 20 to 30%, respectively, to the corresponding ORFs of other members of the potexvirus group. However the putative product ORF 6 shows no significant similarity to those of other potexvirus ORF products.

Amino Acid Sequence↗

PubMed1994

[Loss of heterozygosity at different chromosomes in patients with breast cancer].

The loss of heterozygosity (LOH) at chromosomes 3p24, 7q31, 16q24.3 and 17p13.1 was measured in 15 patients with breast cancer by means of polymerase chain reaction (PCR)-restriction fragment length polymorphisms (RFLP) or PCR-CA repeat analysis. In 36%, 36%, 50% and 56% of the informative cases, LOH was detected at 3p24, 7q31, 16q24.3 and 17p13.1 loci, respectively. All the LOH at 3p24 or 7q31 happened in stage II or III, 67% of the LOH at 3p24 or 7q31 happened in the cases with lymph node metastasis, and 67% of the LOH at 3p24 or 7q31 were found in estrogen receptor negative patients. This finding shows that the measurement of LOH at 3p24 and 7q31 may be an useful predicting marker for the prognosis of patients with breast cancer. The high percent of LOH at these four loci may also indicate the possibility of the existence of tumor suppressor genes for breast cancer.

Adult↗

PubMed1993

Prostaglandin E2 increased rat cortical bone mass when administered immediately following ovariectomy.

To investigate the effects of ovariectomy and the simultaneous administration of prostaglandin E2 (PGE2) on rat tibial shaft cortical bone histomorphometry, thirty-five 3-month-old female Sprague-Dawley rats were either ovariectomized (OVX), or sham ovariectomy (sham-OVX). The OVX rats were divided into three groups and treated with 0, 1 and 6 mg PGE2/kg/day for 90 days. The double fluorescent labeled undecalcified tibial shaft cross sections (proximal to the tibiofibular junction) of all the subjects were used for histomorphometry analysis. No differences in cross-sectional area and cortical bone area were found between sham-OVX and OVX controls, but OVX increased marrow area, intracortical porosity area and endocortical eroded perimeter. Periosteal and endocortical bone formation rates decreased with aging yet OVX prevented these changes. These OVX-induced increases in marrow area and endocortical eroded perimeter were prevented by 1 mg PGE2/kg/day treatment and added bone to periosteal and endocortical surfaces and to the marrow cavity. At the 6 mg/kg/day dose level, PGE2-treated OVX rats increased total tissue area, cortical bone area, marrow trabecular bone area, minimal cortical width and intracortical porosity area, and decreased marrow area compared to basal, sham-OVX and OVX controls. In addition, periosteal bone formation was elevated in the 6 mg PGE2/kg/day-treated OVX rats compared to OVX controls. Endocortical eroded perimeter increased from basal and sham-OVX control levels, but decreased from OVX control levels in the 6 mg PGE2/kg/day-treated OVX rats. Our study confirmed that ovariectomy does not cause osteopenia in tibial shaft cortical bone in rats, but it does stimulate endocortical bone resorption and enlarges marrow area. The new findings from the present study demonstrate that PGE2 prevents the OVX-induced increases in endocortical bone resorption and marrow area and adds additional bone to periosteal and endocortical surfaces and to marrow cavity to increase total bone mass in the tibial shaft of OVX rats when given immediately following ovariectomy.

Animals↗

PubMed1993

[Studies on the establishment of malarial animal model of short-term relapse. IV. Short-term relapse in rhesus monkeys infected with sporozoites of Plasmodium cynomolgi].

The present paper reports that the short-term relapse could be artificially made by the application of the experimental method, and thus we established the monkey model of the short-term relapse. According to the experimental design, when the parasitemia was detected in rhesus monkeys infected with sporozoites of Plasmodium cynomolgi, a combined therapy of pyronaridine 6 mg/kg body weight, artemether 10 mg/kg and chloroquine 20 mg/kg once daily for 3 days was carried out to clear the erythrocytic parasite and then the short-term relapse was observed in the animal follow-up for 100 days. The combined therapy was given again when relapse occurred. One onset of relapse occurred on 47 days after therapy in monkey M194 infected with sporozoites 11 x 10(3). In M195 infected with sporozoites 55 x 10(4), relapses occurred for 3 times on 30, 37 and 51 days respectively after medication, but during a follow-up period of 200 days, no relapse was shown in M192 and M193 infected with sporozoites 50 and 55 x 10(2), respectively. The results showed that the frequency of the short-term relapse was relative to the sporozoites inoculation, and sporozoites less than 11 x 10(3) were not suitable for making short-term relapse in animal model. No long term relapse could be seen in all the 4 monkeys until 400 days. Under existing conditions that the relapse was generally explained with hypnozoite assumption, the establishment of animal model of short-term relapse could be tenable.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

[Studies on the establishment of malarial animal model of short-term relapse. III. Combined therapy with pyronaridine-artemether-chloroquine for parasitemia clearance].

To establish a Plasmodium cynomolgi-monkey model of short-term relapse, different antimalarials have been used to inhibit recrudescence so as to elude the confusion between the two different onsets. When a single dose of effective schizonticides pyronaridine, artemether or chloroquine was administered, recrudesence readily occurred. This paper reports the results of the combined therapy with the above three drugs. Seven rhesus monkeys from Guangxi Autonomous Region infected with Plasmodium cynomolgi from Vietnam by blood transmission were rapidly cured by combined therapy with pyronaridine 6 mg/kg-artemether 100 mg/kg-chloroquine 10 mg/kg (PAC-1) once daily for 3 days. The average time of parasite clearance was 3.43 +/- 0.89 d and the curvilinear regression equation of parasite density after treatment was Y = 10(3.94-0.83X). Severe side effects of the gastrointestinal tract occurred during the course of treatment, though no recrudescence was found after 300-400 days. To reduce the side effects, another test was carried out in 3 monkeys and the dosage regimen was modified to pyronaridine 6 mg/kg-artemether 10 mg/kg-chloroquine 20 mg/kg (PAC-2) once daily for 3 days. There was no obvious side effect in the tested monkeys and the parasites were cleared during a mean time of 2.67 +/- 0.58 d and the curvilinear regression equation of parasite density was Y = 10(3.7-1.46X). No recrudescence was detected in the animals during a follow-up of 180 days. The study shows that PAC-2 regimen of the combined therapy is effective for parasitemia clearance and might be adopted for establishment of the monkey model of short-term relapse.

Animals↗

PubMed1992

Tamoxifen stimulates human papillomavirus type 16 gene expression and cell proliferation in a cervical cancer cell line.

The widely adopted use of tamoxifen as a chemotherapeutic agent is primarily based on its inhibition of cancer cell growth. However, we report that tamoxifen at low concentrations (10(-9) and 10(-11) M) causes stimulation of cell proliferation in a cervical cancer cell line, SFR. The facts that SFR cells do not contain estrogen receptors and are estrogen nonresponsive imply the existence of an antiestrogen-specific binding protein and suggest that the effect of tamoxifen is possibly mediated through a pathway other than estrogen receptors. Tamoxifen at low concentrations stimulated human papillomavirus type 16 (HPV-16) gene transcription and E7 protein production. Levels of HPV-16 mRNA and E7 protein reached a peak at approximately 2-4 h after tamoxifen treatment, persisted for several hours, and subsequently decreased to their prestimulation levels by about 24 h after treatment. Our results indicate for the first time that tamoxifen stimulates cell proliferation of cervical cancer cells, and we suggest that the enhanced HPV-16 mRNA and E7 protein levels are probably responsible.

Cell Division↗

PubMed1992

IL-12 augments antigen-dependent proliferation of activated T lymphocytes.

Ag-dependent T cell activation requires multiple transmembrane signals including activation of Ag-specific T cell receptor in combination with signals delivered through cytokine receptors. IL-12 is a heterodimeric cytokine involved in the regulation of NK and T lymphocyte responses. In examining the role of IL-12 in T cell activation, we found a direct relationship between Ag stimulation and IL-12-induced proliferation. Unlike IL-2, which induced proliferation of CTL either in the presence or absence of a CD3/TCR co-signal, IL-12 mediated proliferation of CTL only when the cells were recently co-stimulated with alloantigen or solid-phase anti-CD3 antibody. After culture in the absence of alloantigen or anti-CD3 for 7 to 14 days, these CTL lost the ability to proliferate to IL-12 alone. Under these conditions, however, IL-12 synergized with low-dose IL-2 to induce CTL proliferation. Restimulation with alloantigen or solid-phase anti-CD3 restored the ability of the CTL to proliferate to IL-12 alone. Not all Ag signals resulted in IL-2 independent proliferation to IL-12. For example, CTL with specificity for influenza matrix peptide proliferated best when co-cultured with peptide Ag presented on self MHC and a combination of IL-2 and IL-12. This evidence suggests that IL-12 may be useful in expanding an Ag-specific T cell population, as the culture of CTL with IL-12 and low-dose IL-2 leads to proliferation only in response to an Ag co-signal.

Amino Acid Sequence↗

PubMed1992

Adaptation of cancellous bone to aging and immobilization in growing rats.

Two-and-half-month-old female rats were subjected to right hindlimb immobilization or served as controls for 0, 1, 2, 8, 14, and 20 weeks. The right hindlimb was immobilized by bandaging it against the abdomen, thus unloading it. Cancellous bone histomorphometry was performed on microradiographs and double-fluorescent labeled 20 microns sections of the distal femoral metaphyses. Primary spongiosa bone loss occurred rapidly by 2 weeks, and secondary spongiosa bone loss occurred rapidly by 8 weeks of immobilization, and then equilibrated at 60% less bone mass than age-related controls. The negative bone balance induced by immobilization was caused by transient increase in bone resorption, decrease in bone formation, and longitudinal bone growth. The dynamic data of secondary spongiosa cancellous bone showed that percent eroded perimeter was transiently elevated by 55 to 82% between 1 and 8 weeks, percent labeled perimeter was transiently depressed by 32% to 50% between 1 and 14 weeks, mineral apposition rate was depressed by 23% and 19% at 1 and 2 weeks, and bone formation rate-bone area referent was transiently depressed by 35% and 59% at 1 and 2 weeks. All the above parameters were at age-related control levels by 20 weeks of immobilization. However, bone formation rate-tissue area referent was depressed (-65%) throughout the study. Immobilization depressed completely longitudinal bone growth by 2 weeks and remained so. Only 0.65 mm of new metaphysis was generated in the immobilized versus 2.1 mm in controls during the study period. The immobilization induced an early cancellous bone loss which equilibrated at a new steady state with less bone and a normal (age-related control) bone turnover rate. When these findings were compared to an earlier study of 9-month-old virgin females subjected to right hindlimb immobilization up to 26 weeks, we found the adaptive responses of the cancellous bone were identical except that they occurred earlier and equilibrated sooner in younger rats.

Aging↗

PubMed1992

Prostaglandin E2 alleviates cyclosporin A-induced bone loss in the rat.

Cyclosporine A (CsA) administered to the male and female rat produces high-turnover osteopenia. Prostaglandins have both bone-resorbing and bone-forming properties, but administration of prostaglandin E2 (PGE2) to the rat in vivo produces a net increase in cancellous bone. To investigate the effects of PGE2 on CsA-induced alteration in bone mass, 43 male Sprague-Dawley rats (9 weeks old) were administered 15 mg/kg of CsA by oral gavage and/or 6 mg/kg of PGE2 by subcutaneous injection daily for 21 days according to the following protocol: group A was an age-matched control; group B received CsA only; group C received PGE2 only; and group D received CsA and PGE2. Serum was assayed on days 0, 7, 14, and 21 for bone gla protein (BGP), PTH, and 1,25-dihydroxyvitamin D [1,25-(OH)2D]. A computerized image analysis system was used for bone histomorphometry of the proximal tibial metaphysis after double tetracycline labeling. Compared to control animals (group A), treatment with CsA alone (group B) and PGE2 alone (group C) significantly elevated BGP levels. Combination therapy (group D) resulted in BGP levels that were significantly higher on days 7 and 14 than with either agent alone. 1,25-(OH)2D was significantly elevated in the CsA group only (group B). Therapy with CsA alone (group B) resulted in a significant osteopenia. The concurrent administration of PGE2 with CsA (group D) alleviated the altered bone mass induced by CsA alone by adding a significant amount of additional bone. This report confirms and extends the current knowledge of the different effects of CsA and PGE2 on bone mineral metabolism and demonstrates that PGE2 can alleviate the deleterious effects of CsA on bone.

Administration, Oral↗

PubMed1992

Prostaglandin E2 prevents bone loss and adds extra bone to immobilized distal femoral metaphysis in female rats.

The object of this study was to determine whether prostaglandin E2 (PGE2) can prevent disuse (underloading)-induced cancellous bone loss. Thirteen-month-old retired female Sprague-Dawley breeders served as controls or were subjected to right hindlimb immobilization by bandaging and simultaneously treated subcutaneously daily with 0, 1, 3, or 6 mg PGE2/kg/d for two and six weeks. Histomorphometric analyses were performed on the cancellous bone using double-fluorescent labeled, 20 micron thick, undecalcified distal femoral metaphysis sections. We found that PGE2 administration not only prevented diuse-induced bone loss, but also added extra bone to disuse cancellous bone in a dose-response manner. PGE2 prevented the disuse-induced osteopenia by stimulating more bone formation than resorption and shortening the period of bone remodeling. It activated woven bone formation, stimulated lamellar bone formation, and increased the eroded bone surface above that caused by disuse alone. While underloading increased the remodeling period (sigma), PGE2 treatment of underloaded bone shortened the time for osteoclastic bone resorption and bone remodeling, and thus reduced the remodeling space. The study shows that PGE2 is a powerful anabolic agent that prevents disuse-induced osteopenia and adds extra bone to these same bones.

Aging↗

PubMed1992

High level expression on a chimeric anti-ganglioside GD2 antibody: genomic kappa sequences improve expression in COS and CHO cells.

We report a flexible strategy for the high level expression of a recombinant human monoclonal antibody (mAb) in Chinese hamster ovary (CHO) cells, initially using COS monkey kidney cell transfections to evaluate rapidly modifications to immunoglobulin (Ig) DNA constructs. Using sequential transfections with two amplifiable markers, we generated CHO cell lines and clones that secrete 80-110 micrograms/10(6) cells/24 hours of a mouse-human chimeric IgG1 kappa mAb. This cellular productivity is considerably greater than most murine hybridomas and transfected myelomas. Our data also demonstrate that genomic kappa sequences can improve mAb expression in COS and CHO cells. As a paradigm, we focused our expression studies on a human chimeric form of 3F8, a murine mAb that binds to ganglioside GD2 on neuroblastoma and melanoma tumor cells.

Animals↗

PubMed1992

Cloning and mapping of the alpha-adducin gene close to D4S95 and assessment of its relationship to Huntington disease.

The genetic defect underlying Huntington's disease (HD) has been mapped to 4p16.3. Refined localization using recombinant HD chromosome analysis and allelic association analyses have identified two distinct candidate regions. Using a cDNA hybrid selection procedure we have cloned the gene for alpha-adducin, a subunit of a cytoskeletal protein crucial for spectrin-actin membrane plasticity. This gene maps to the proximal 2.2 Mb candidate region within 20 kb of D4S95. Alleles of markers at this locus have been shown to exhibit significant linkage disequilibrium with HD. A 4 kb alpha-adducin transcript was identified which is abundantly expressed in the caudate nucleus, the site of major neuronal loss in HD. Sequencing of the brain alpha-adducin cDNA from two HD patients and an age-matched control did not detect any sequence alterations specific to HD. However, we identified in brain cDNA of both patients and control samples, two alternately spliced brain exons, not previously described in the erythrocyte cDNA. A 93 bp exon is inserted in frame between codon 471 and 472 while a 34 bp exon inserted within codon 621 disrupts the frame and introduces a stop codon after 11 novel amino acids. The mapping of the adducin gene adjacent to D4S95 and its pattern of expression, as well as its potential for distinct alternately spliced variants, reinforces the necessity to accurately assess the role of the expression of this gene in the pathogenesis of HD.

Amino Acid Sequence↗

PubMed1992

[Studies on the establishment of malarial animal model of short-term relapse. II. The phenomenon of sustained special ring form parasitemia in Plasmodium cynomolgi infection].

Our previous report that the EE merozites of Plasmodium cynomolgi from Vietnam continuously released from the liver to the blood circulation was further demonstrated in this report. Monkeys were given pyronaridine 24 mg/kg.d x 6 after being inoculated intravenously with 32 x 10(5) sporzoites of P. cynomolgi. Thick blood film examination was conducted two times daily till the day when trophozoites were detected. Under the residual action of blood schizontocied, a special ring form parasitemia at low patasite-density was detected for more than 30 days. As the ring forms of P. cynomolgi were demonstrated to be susceptible to pyronaridine in our previous experiments, it might be inferred that these ring forms derived from EE merozites released not for once but continuously for 30 days or longer.

Aminoquinolines↗

PubMed1992

[Studies on the establishment of malarial animal model of short-term relapse. I. Asynchronous growth of exoerythrocytic schizonts of Plasmodium cynomolgi].

A monkey was infected with sporozoites of Plasmodium cynomolgi from Vietnam. Parasitemia was detected on the 8th day with a starting density of 17/100 white blood cells. 22 hours after that time, many EE schizonts appeared with an average density of 3.74 +/- 0.66 per mm3 hepatic tissue in liver biopsy specimens from the monkey. Most of the EE schizonts were immature and grew at an uneven rate, having an average diameter of 34.22 +/- 7.28 microns but some of them even remained 15.75 +/- 2.47 microns in diameter similar to the EE schizonts on the 6th day. The results showed that the EE schizonts of Plasmodium cynomologi were asynchronous in growth. The authors suggest that the release of merozoites from liver might be a successive process for many times, and not to be completed at a time.

Animals↗

PubMed1991

Genomic organization and complete sequence of the human gene encoding the beta-subunit of the cGMP phosphodiesterase and its localisation to 4p 16.3.

As part of the search for the Huntington disease (HD) gene we have cloned and sequenced 34 kb of genomic DNA containing the full-length gene for the beta-subunit of the human cGMP phosphodiesterase (beta-cGMP PDE). This gene is localized to 4p16.3 about 700 kb proximal to the 4p telomere and represents the most telomeric gene characterized on 4p to date. We show that this gene is comprised of 22 exons spanning approximately 43 kb of genomic DNA. We also provide 400 bp immediately 5' to the putative initiator methionine and 700 bp of 3' flanking sequences. Northern blot analysis of several human tissues revealed a highly abundant 3.5 kb transcript and a minor signal of 4.5 kb in retinal tissue. Alignment of the deduced amino acid sequence to the previously identified beta-subunits of the cGMP PDEs of mouse and cow demonstrates highly significant similarities and, therefore, confirms the identity of the cloned gene. A defect in the beta-subunit of the cGMP PDE gene has been shown recently to be the cause for the retinal degeneration in the rd mouse. The cloning of the human homolog and the knowledge of its genomic organization with exon/intron boundaries will allow rapid assessment of the role of this gene in the causation of human retinopathies.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed1990

[Study on the exoerythrocytic forms of Plasmodium yoelii yoelii in rats and mice].

SD rats and three strains of mice were infected with Plasmodium yoelii yoelii By265 strain by intravenous inoculation of sporozoites via tail vein. Liver tissues were taken 42 hours after infection and serial sections were made and stained by Colophonium-Giemsa method for microscopic examination. The ratio of the average value of major diameter/minor diameter of exoerythrocytic(EE)schizonts of Plasmodium yoelii yoelii in rats and mice of ICR/JCL, C57BL, KM strains was 35.81 +/- 4.56 microns/29.72 +/- 4.08 microns, 28.08 +/- 4.66 microns/23.66 +/- 4.44 microns, 28.14 +/- 4.16 microns/23.63 +/- 3.77 microns, 23.80 +/- 2.42 microns/21 +/- 0 microns, respectively. The results showed that the development of EE schizonts of Plasmodium yoelii yoelii was not synchronous. The EE schizonts in the rat liver were surrounded by Kupffer cells, monocytes and monocyte-derived macrophages. Since the parasitemia disappeared rapidly in rats, and EE schizonts were not well developed in KM strain, it may be considered that ICR/JCL and C57BL strains are more suitable as vertebrate host in Plasmodium yoelii yoelii-Anopheles stephensi system model (Figs. 1-9).

Animals↗

PubMed1990

Experimental studies on combinations of pyronaridine/primaquine versus chloroquine/primaquine.

The toxicity of combined use of blood schizontocide pyronaridine (PND) and primaquine (PQ) in mice and rats was significantly lower than that of chloroquine (CQ) plus primaquine (PQ). PND 1/2 LD50 (ca 600 mg/kg) in combination with PQ reduced the toxic action of PQ in mice, while CQ 1/2 LD50 (ca 300 mg/kg) plus PQ produced synergistic toxic effect. In animal models such as Plasmodium yoelii sporozoite infection in mice and P. cynomolgi sporozoite infection in rhesus monkeys, the tissue schizontocidal action of PQ was not affected by PND. Therefore, clinical evaluation of PND/PQ in comparison with CQ/PQ in treating vivax malaria is suggested.

Animals↗