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Biomedical subjects

S Yin

Publications and source records attributed to S Yin.

At least 37 records · Page 2Linked to original sources

Changes in serum leptin levels in chronic renal failure patients with metabolic acidosis.

OBJECTIVE: To examine the relationship between serum leptin levels (SLL) and metabolic acidosis in patients with chronic renal failure (CRF). DESIGN: SLL in control patients and in predialysis patients with CRF were measured and compared. SLL before and after correction of acidosis in patients with CRF were also compared. PATIENTS AND CONTROLS: Twenty-five patients with CRF (10 men and 15 women) aged 51.2 +/- 10.4 years and control patients (healthy subjects, 23 men and 25 women) aged 42.1 +/- 12.6 years were studied. INTERVENTION: Five percent sodium bicarbonate (NaHCO(3), 2 to 3 mL/kg) was intravenously infused on the morning of the first day of treatment. NaHCO(3) was taken orally at a dosage of 50 to 200 mg/kg/d for 3 to 5 days thereafter. MAIN OUTCOME MEASURE: SLL before and after NaHCO(3) treatment was measured by radioimmunoassay, and blood gas was measured before and after correction of metabolic acidosis in patients with CRF. RESULTS: SLL in the normal control group (n = 48) was 10.04 +/- 7.0 ng/mL and was realated to body mass index (BMI) (P =.0331). SLL in men (n = 23) was lower than that in female controls (n = 25, P <.01). SLL in patients with CRF (n = 25) before (plasma HCO(3)(-), 13.03 +/- 3.05 mmol/L) and immediately after improvement of metabolic acidosis (plasma HCO(3)(-), 18.35 +/- 4.21 mmol/L) was 14.52 +/- 9.27 ng/mL and 15.34 +/- 11.89 ng/mL (P >.05), respectively. SLL measured 3 to 5 days after treatment for metabolic acidosis (plasma HCO(3)(-), 20.46 +/- 4.03 mmol/L) was 19.33 +/- 14.58 ng/mL, which was significantly higher than that in the normal control group and that in acidotic patients before NaHCO(3) treatment (P <.01). CONCLUSIONS: SLL in acidotic patients with CRF were comparable to that in control subjects, and SLL was significantly increased after correction of metabolic acidosis in patients with CRF. The preliminary results suggest that hyperleptinemia in patients with CRF may be masked by metabolic acidosis and that metabolic acidosis may inhibit leptin synthesis or secretion. Further studies are needed to clarify the mechanisms.

Acidosis↗

[Effects of supplementing of calcium, iron and zinc on women's health during pregnancy].

OBJECTIVES: To determine the effects of supplementing biscuits fortified with calcium (Ca) and vitamin D (VD), iron (Fe), vitamin C (VC) and zinc (Zn) to pregnant women from the 5th month of gestation until delivery on their health, and to explore a way to improve their Ca, Fe and Zn nutritional status during pregnancy. METHODS: A total of 313 healthy and primary pregnant women were enrolled and divided into five study groups based on their order visiting the hospitals for prenatal care. Each woman of the study groups was given three pieces of biscuit fortified with VD, Ca and VD, Ca, Zn and VD (Ca + Zn + VD), Ca, Fe, VC and VD (Ca + Fe + VD), Ca, Fe, VC, Zn and VD (Ca + Fe + Zn + VD), respectively, from the 15th month of gestation until delivery (24 weeks in total) daily. The fortified levels were 10 micrograms VD, 400 mg Ca from carbonate calcium, 10 mg Zn from lactate zinc, 10 mg Fe from ferrous lactate, and 50 mg VC, respectively. A parturient women was selected from the same hospital as control after one trial subject for each study groups selected. RESULTS: The daily dietary intakes of Ca, Zn and Fe in pregnant women were only 47.7%, 54.7% and 86.7% of the Recommended Dietary Allowances for Chinese. Incidence of anemia for mid-term pregnant women was 35.2%, and Fe-supplementation could significantly improved their hemoglobin level (P < 0.05). Prevalence of anemia in the groups of Ca + Fe + Zn + VD and Ca + Fe + VD was 35.3% and 40.7%, respectively, before Fe supplementation and reduced to zero and 4.0%, respectively, after Fe supplementation. Whereas, prevalence of anemia in the other groups without Fe supplementation still kept in a relatively high level. In the groups supplemented with Ca, their plasma Ca level increased, especially with the best results in Ca + VD group. Plasma level of Zn declined with length of gestation, which could be improved by Zn supplementation. Serum level of alkaline phosphatase activity increased a little bit with length of gestation. There was no significant difference in radial and ulnar bone mineral density (BMD) between trial groups and controls two months after delivery. Maternal radial and ulnar BMD correlated significantly with their dietary Ca intakes in Ca + VD group. CONCLUSION: The best way to improve maternal nutritional status is supplementation of Ca + Fe + Zn + VitD, based on the Recommended Dietary Allowances for Chinese.

Adult↗

[Effects of supplementing calcium, iron and zinc on the fetus development and growth during pregnancy].

OBJECTIVES: The purpose of the present study is to determine the effects of supplementing the biscuits fortified with calcium (Ca), iron (Fe) and zinc (Zn) for pregnant women from the 5th month of gestation until delivery on the growth and development of fetus and to explore the best way to improve infant growth. METHODS: A total of 313 healthy and primary pregnant women were enrolled and divided into five study groups based on their order visiting the hospitals for prenatal care. Each woman of the study groups was given three pieces of biscuit fortified with VD, Ca and VD, Ca, Zn and VD (Ca + Zn + VD), Ca, Fe, VC and VD (Ca + Fe + VD), Ca, Fe, VC, Zn and VD (Ca + Fe + Zn + VD), respectively, from the 5th month of gestation until delivery (24 weeks in total) daily. The fortified levels were 10 micrograms Ca from carbonate calcium, 10 mg Zn from lactate zinc, 10 mg Fe from ferrous lactate, and 50 mg VC, respectively. A parturient women was selected from the same hospital as control after one trial subject for each study groups selected. Placenta was weighed and umbilical cord venous blood and placenta tissue samples were collected after delivery for measuring Ca and other trace elements. Body weight and height of the new-born babies were measured. RESULTS: The weight of placenta in control group (551.1 +/- 64.2) g was significantly (P < 0.05) heavier than other trial groups with Ca + Fe + Zn + VD (467.1 +/- 36.6) g, but contents of Ca and other trace elements in placenta of the control group were lower, which probably because of the lower nutrients intake of mothers in control group that would result in a compensation enlargement of placenta to get enough nutrients for fetus from mother. The Hb level in cord venous blood was significantly higher than that of maternal blood. There was no significant difference in activity of alkaline phosphatase between cord venous blood and material blood. The contents of Ca, Fe and Zn in cord venous plasma were all significantly higher than those in maternal plasma. Birth weight and height in Ca + Fe + Zn + VD group were the highest in all the groups, with birth weight of (3.53 +/- 0.33) kg, as compared with (3.28 +/- 0.54) kg in the control group. There was significant correlation between birth weight, weight for age and intake of Ca, Fe and Zn during pregnancy. CONCLUSION: Supplementation of Ca + Fe + Zn + VitD during pregnancy is the best way to improve infant development and growth, based on the current Recommended Dietary Allowances (RDA) for pregnant women.

Adult↗

[Changes in the activity of platelet L-arginine/nitric oxide pathway in hypercholesterolemia patients].

OBJECTIVE: To investigate the changes of the platelet L-arginine (L-Arg)/nitric oxide (NO) pathway in hypercholesterolemia patients. METHODS: The platelet NO production in 21 hypercholesterolemia (HC) patients and 26 normal individuals was assayed by spectrum, the NOS activity and the transportation of L-Arg were determined by (3)H-labelled L-Arg. RESULTS: The NO production in hypercholesterolemic platelets [(24.06 +/- 3.70) nmol/10(8) platelets] was decreased significantly as compared with normal controls [(28.39 +/- 4.45) nmol/10(8) platelets] (P < 0.01), and so did the NOS activity [(1.46 +/- 0.47) pmol/10(8) platelets] vs (1.81 +/- 0.50) pmol/10(8) platelets]. The transportation of L-Arg by hypercholesterolemia platelets also decreased significantly than that by normal controls. The Vmax in the former [(46.84 +/- 3.39) pmol x (10(7) platelets)(-1) x min(-1)] was significantly lower than that in the latter [(53.89 +/- 3.45) pmol x (10(7) platelets)(-1) x min(-1)]. There was no difference between the two groups in K(d) (P > 0.05). CONCLUSIONS: The activity of the L-arg/NO pathway in hypercholesterolemia platelets is decreased significantly as compared with normal controls, implying that it is probably one of the reasons for the hyperactivity of hypercholesterolemia platelets.

Adult↗

[Posterior semicircular canal occlusion with microwave assisted technique in guinea pigs].

OBJECTIVE: To study the effectiveness of posterior semicircular canal occlusion with microwave assisted technique. METHOD: Posterior semicircular canal occlusion with microwave assisted technique was performed in 20 guinea pigs. Electronystagmography (ENG) and auditory brainstem response (ABR) were recorded preoperatively and postoperatively. Morphological changes were observed under light microscopy. RESULT: Left and right nystagmus returned symmetrical on the 3rd postoperative day. Two ears showed normal symmetrical nystagmus to icc-water stimulation on preoperation and the 30th postoperative day. There were no significant changes of the thresholds of ABR before and after surgery. Histopathological findings revealed that posterior semicircular canal was completely occluded, and that Organ of Corti and crista ampullaris were normal. CONCLUSION: Posterior semicircular occlusion with microwave technique is suggested as an effective and safe treatment for the benign paroxysmal positional vertigo.

Animals↗

Minor groove interactions at the DNA polymerase beta active site modulate single-base deletion error rates.

The structures of open and closed conformations of DNA polymerase beta (pol beta) suggests that the rate of single-nucleotide deletions during synthesis may be modulated by interactions in the DNA minor groove that align the templating base with the incoming dNTP. To test this hypothesis, we measured the single-base deletion error rates of wild-type pol beta and lysine and alanine mutants of Arg(283), whose side chain interacts with the minor groove edge of the templating nucleotide at the active site. The error rates of both mutant enzymes are increased >100-fold relative to wild-type pol beta. Template engineering experiments performed to distinguish among three possible models for deletion formation suggest that most deletions in repetitive sequences by pol beta initiate by strand slippage. However, pol beta also generates deletions by a different mechanism that is strongly enhanced by the substitutions at Arg(283). Analysis of error specificity suggests that this mechanism involves nucleotide misinsertion followed by primer relocation, creating a misaligned intermediate. The structure of pol beta bound to non-gapped DNA also indicates that the templating nucleotide and its downstream neighbor are out of register in the open conformation and this could facilitate misalignment (dNTP or primer terminus) with the next template base.

Alanine↗

Apoptosis induced by the nuclear death domain protein p84N5 is associated with caspase-6 and NF-kappa B activation.

Although the mechanisms involved in responses to extracellular or mitochondrial apoptotic signals have received considerable attention, the mechanisms utilized within the nucleus to transduce apoptotic signals are not well understood. We have characterized apoptosis induced by the nuclear death domain-containing protein p84N5. Adenovirus-mediated N5 gene transfer or transfection of p84N5 expression vectors induces apoptosis in tumor cell lines with nearly 100% efficiency as indicated by cellular morphology, DNA fragmentation, and annexin V staining. Using peptide substrates and Western blotting, we have determined that N5-induced apoptosis is initially accompanied by activation of caspase-6. Activation of caspases-3 and -9 does not peak until 3 days after the peak of caspase-6 activity. Expression of p84N5 also leads to activation of NF-kappaB as indicated by nuclear translocation of p65RelA and transcriptional activation of a NF-kappaB-dependent reporter promoter. Changes in the relative expression level of Bcl-2 family proteins, including Bak and Bcl-Xs, are also observed during p84N5-induced apoptosis. Finally, we demonstrate that p84N5-induced apoptosis does not require p53 and is not inhibited by p53 coexpression. We propose that p84N5 is involved in an apoptotic pathway distinct from those triggered by death domain-containing receptors or by p53.

Adenoviridae↗

[Study on the absorption of environmental contaminants in low-level exposure by pharmacokinetic analysis].

A dynamic generating toxic gas system and a nose-only exposure system were used for the pharmacokinetic study of inhaled environmental contaminants for benzene, toluene, xylene, ethylbenzene, chlorobenzene, styrene, isopropyl benzene, tetrachloroethylene, nonane and methylcyclohexane in male guinea pig. The change of these substances in blood with time was determined simultaneously by solid phase micro-extraction(SPME) gas chromatography (GC). The results showed that the fraction of absorption of benzene at low (121 micrograms/m3) exposure was 4.8 times higher than that at high(12.1 mg/m3) exposure. The pharmacokinetics of these substances were evaluated by using linear compartment models. The data showed that more styrene was absorbed than tetrachloroethylene at low-exposure. The metabolic elimination of these compounds at various exposure concentrations was extrapolated by using estimated pharmacokinetic parameters. Moreover, not only should the differences in absorption quantities be considered in evaluation of potential risk assessment, the metabolic elimination rates should also be considered although the exposure concentrations in gas for all chemicals were equal. The data presented in this paper was fundamental data used for risk assessment.

Air Pollutants↗

Validation of biomarkers in humans exposed to benzene: urine metabolites.

BACKGROUND: The present study was conducted among Chinese workers employed in glue- and shoe-making factories who had an average daily personal benzene exposure of 31+/-26 ppm (mean+/-SD). The metabolites monitored were S-phenylmercapturic acid (S-PMA), trans, trans-muconic acid (t,t-MA), hydroquinone (HQ), catechol (CAT), 1,2, 4-trihydroxybenzene (benzene triol, BT), and phenol. METHODS: S-PMA, t,t-MA, HQ, CAT, and BT were quantified by HPLC-tandem mass spectrometry. Phenol was measured by GC-MS. RESULTS: Levels of benzene metabolites (except BT) measured in urine samples collected from exposed workers at the end of workshift were significantly higher than those measured in unexposed subjects (P < 0.0001). The large increases in urinary metabolites from before to after work strongly correlated with benzene exposure. Concentrations of these metabolites in urine samples collected from exposed workers before work were also significantly higher than those from unexposed subjects. The half-lives of S-PMA, t,t-MA, HQ, CAT, and phenol were estimated from a time course study to be 12.8, 13.7, 12.7, 15.0, and 16.3 h, respectively. CONCLUSIONS: All metabolites, except BT, are good markers for benzene exposure at the observed levels; however, due to their high background, HQ, CAT, and phenol may not distinguish unexposed subjects from workers exposed to benzene at low ambient levels. S-PMA and t,t-MA are the most sensitive markers for low level benzene exposure.

Acetylcysteine↗

Performance of a 2D image-based anthropometric measurement and clothing sizing system.

Two-dimensional, image-based anthropometric measurement systems offer an interesting alternative to traditional and three-dimensional methods in applications such as clothing sizing. These automated systems are attractive because of their low cost and the speed with which they can measure size and determine the best-fitting garment. Although these systems have appeal in this type of application, not much is known about the accuracy and precision of the measurements they take. In this paper, the performance of one such system was assessed. The accuracy of the system was analyzed using a database of 349 subjects (male and female) who were also measured with traditional anthropometric tools and techniques, and the precision was estimated through repeated measurements of both a plastic mannequin and a human subject. The results of the system were compared with those of trained anthropometrists, and put in perspective relative to clothing sizing requirements and short-term body changes. It was concluded that image-based systems are capable of providing anthropometric measurements that are quite comparable to traditional measurement methods (performed by skilled measurers), both in terms of accuracy and repeatability.

Anthropometry↗

Adenovirus-mediated N5 gene transfer inhibits tumor cell proliferation by induction of apoptosis.

Gene therapy designed to initiate apoptotic cell death provides a potentially effective method to treat cancer. A prerequisite for this approach is the identification of genes that function in distinct apoptotic pathways. Although apoptotic pathways initiated by receptors such as tumor necrosis factor receptor-1 are well characterized, little is known about apoptotic pathways initiated within the nucleus in response to genotoxic stress. We have demonstrated previously that the nuclear, death domain-containing protein p84N5 can induce apoptosis upon transfection into cells, suggesting that it may play a role in an apoptotic pathway initiated within the nucleus. To test the possibility that N5 could be used in the gene therapy of cancer, we have generated a recombinant adenovirus engineered to express N5 and tested the effects of viral infection on the growth and tumorigenicity of tumor cells. N5 adenovirus infection significantly reduced the proliferation and tumorigenicity of breast, ovarian, and osteosarcoma tumor cell lines. Reduced proliferation and tumorigenicity were mediated by an induction of apoptosis as indicated by DNA fragmentation in infected cells. The results suggest that the N5 cDNA is a candidate for the gene therapy of cancer.

Adenoviridae↗

Benzene and lymphohematopoietic malignancies in China.

While this study is larger than previous investigations and includes workers with a wide range of exposures to benzene, the estimates of risk, as measured by statistical confidence intervals, are still fairly broad, and would benefit from the larger numbers that could be provided by continued follow-up of this population. Nevertheless, the study confirms earlier findings of increased risk for ANLL and aplastic anemia among benzene-exposed workers, provides the first substantial evidence that MDS is linked to benzene exposure, and provides evidence that benzene increases risk for ANLL/MDS at lower levels of exposure than had previously been demonstrated. Currently we are evaluating the potential for extending the follow-up of workers included in this study. A new study would include expanded data collection for cases of hematopoietic malignancy and related disorders and for an appropriate control series.

Adult↗

Genotoxic markers among butadiene polymer workers in China.

While 1,3-butadiene is carcinogenic in rodents, cancer causation in humans is less certain. We examined a spectrum of genotoxic outcomes in 41 butadiene polymer production workers and 38 non-exposed controls, in China, to explore the role of butadiene in human carcinogenesis. Because in vitro studies suggest that genetic polymorphisms in glutathione S-transferase enzymes influence genotoxic effects of butadiene, we also related genotoxicity to genetic polymorphisms in GSTT1 and GSTM1. Among butadiene-exposed workers, median air exposure was 2 p.p.m. (6 h time-weighted average), due largely to intermittent high level exposures. Compared with unexposed subjects, butadiene-exposed workers had greater levels of hemoglobin N-(2,3,4-trihydroxybutyl)valine (THBVal) adducts (P < 0.0001) and adduct levels tended to correlate, among butadiene-exposed workers, with air measures (P = 0.03). Butadiene-exposed workers did not differ, however, from unexposed workers with respect to frequency of uninduced or diepoxybutane-induced sister chromatid exchanges, aneuploidy as measured by fluorescence in situ hybridization of chromosomes 1, 7, 8 and 12, glycophorin A variants or lymphocyte hprt somatic mutation. Also among the exposed, greater THBVal levels were not associated with increases in uninduced sister chromatid exchanges, aneuploidy, glycophorin A or hprt mutations. Butadiene-exposed workers had greater lymphocyte (P = 0.002) and platelet counts (P = 0.07) and lymphocytes as a percentage of white blood cells were moderately correlated with greater THBVal levels (Spearman's phi = 0.32, P = 0.07). Among butadiene-exposed workers, neither GSTM1 nor GSTT1 genotype status predicted urinary mercapturic acid butanediol formation, THBVal adducts, uninduced sister chromatid exchanges, aneuploidy or mutations in the glycophorin A or hprt genes. Overall, the study demonstrated exposure to butadiene in these workers, by a variety of short-term and long-term measures, but did not show specific genotoxic effects, at the chromosomal or gene levels, related to that exposure.

Adult↗

Calorigenic actions of leptin are additive to, but not dependent on, those of thyroid hormones.

We examined a possible mechanistic interaction between leptin and thyroid hormones in rats with hypothyroidism induced by thyroidectomy (TX) and propylthiouracil administration. In study 1, the TX rats were treated by vehicle (V, n = 9) or by recombinant murine leptin (L, 0.3 mg. kg(-1). day(-1), n = 9) or were pair-fed (PF, n = 9) against L. In study 2, the TX rats were all given 3, 3'5'-triiodo-L-thyronine (T(3)) replacement (T, 5 microg. kg(-1). day(-1)) to correct hypothyroidism. They were then subdivided into three groups, namely, vehicle (T+V, n = 9), leptin (T+L, n = 10), and pair-feeding (T+PF, n = 9), similar to study 1 except for T(3) (T). Reduced food consumption and weight gain in the TX rats were reversed by T(3) replacement. Leptin suppressed food intake in the TX rats regardless of T(3) replacement. O(2) consumption (VO(2)) and CO(2) production (VCO(2)) were reduced in TX rats (P < 0.05 vs. normal) but were normalized by either T(3) or leptin treatment. T+L additively increased VO(2) and VCO(2) (P < 0.05 vs. TX, T(3), and L). The respiratory exchange ratio was unaltered in TX rats, with and without T(3), but was significantly reduced by L or T+L treatments. These results indicate that the metabolic actions of leptin are not dependent on a normal thyroid status and that the effects of leptin and T(3) on oxidative metabolism are additive.

Animals↗

Laryngeal reflexomyographic responses in rabbits: a neurolaryngological study of glottal movement.

The role of the laryngeal reflex in glottal movement has been reported, but its mechanism remains unclear. To further investigate the neurophysiological characteristics of glottal movement, we recorded the laryngeal reflexomyographic responses (LRMRs) to electrical stimulation of the superior laryngeal nerve (SLN) in rabbits. The procedure involved simultaneous recording of the LRMRs from the thyroarytenoid muscles by means of bipolar hooked wire electrodes after electrical stimulation to the SLN. The results demonstrated characteristic patterns of the responses, consisting of R1 and R2, similar to those found in humans. The R1 response was obtained with a latency of 10.7 +/- 0.78 ms. The ipsilateral R2 response was obtained with a latency of 43.76 +/- 4.67 ms in all rabbits, and the contralateral R2 response with a latency from 42.6 to 50.2 ms in 4 rabbits. It was concluded that LRMRs may serve as a potential central laryngeal function test in the investigation of glottal movement control.

Animals↗

Critical evaluation of neurolaryngological disorders.

Otolaryngological examinations, videostroboscopic image analysis, and laryngeal electromyography were used as a test battery for a critical evaluation in 80 patients. Vocal fold movements were categorized into mobility, restricted mobility, immobility with different positions, and overactive movement. Laryngeal electromyographic examinations were conducted in all patients, and the results were classified into normal, neuropathic, and myopathic patterns. The electromyographic data were integrated with videostroboscopic findings, interpreted with knowledge of biomechanical and electrophysiological mechanisms of the larynx, and correlated clinically with underlying diseases. It is suggested that neurolaryngological procedures are most clinically useful when dictated by a decision-making algorithm.

Adolescent↗

Transcriptional regulation of human 11beta-hydroxylase (hCYP11B1).

Steroid 11beta-hydroxylase is a mitochondrial enzyme that catalyzes the conversion of deoxycortisol to cortisol. The gene encoding human 11beta-hydroxylase (hCYP11B1) is expressed in the adrenal cortex under the control of circulating levels of ACTH. The current study was undertaken to define the cis-regulatory elements and transacting factors that regulate hCYP11B1 transcription. The hCYP11B1 5'-flanking DNA was studied using transient transfection of luciferase reporter constructs in NCI-H295R human adrenocortical cells. A cAMP analogue ((Bu)2cAMP) increased expression of a construct containing -1102 bp of hCYP11B1 5'-flanking DNA (pB1-1102). An element at position -71/-64 (TGACGTGA, previously termed Ad1) resembling a consensus cAMP response element (CRE) was required for maximal induction by cAMP. The Ad1 element bound several transcriptional factors in electrophoretic mobility shift assays, including CRE-binding protein, activating transcription factor-1 (ATF-1), and ATF-2, but only the ATF-2 complex migrated similarly to a complex seen using H295R nuclear extract. In addition, Western analysis of H295R and adrenal lysates demonstrated expression of high levels of ATF-2 and ATF-1. CRE-binding protein levels varied among the strains of H295R cells tested. Transcription of CYP11B1 also appeared to be regulated by steroidogenic factor-1 (SF-1). Luciferase reporter gene activity was increased after cotransfection with expression vectors containing SF-1. An element in hCYP11B1 at positions 242/-234 (CCAAGGCTC), previously termed Ad4, was required for maximal induction by SF-1 and was found to bind SF-1 in electrophoretic mobility shift assays. The key role for SF-1 in hCYP11B1 transcription is in contrast to its lack of an effect on expression of the hCYP11B2 (aldosterone synthase) isozyme. The differential effects of SF-1 on transcription of hCYP11B1 and hCYP11B2 may be one of the mechanisms controlling differential expression of these isozymes within the zonae fasciculata and glomerulosa of the human adrenal cortex.

Adrenal Glands↗

Biological repair of thyroid cartilage defects by osteogenic protein-1 (bone morphogenetic protein-7) in dog.

The efficacy of human recombinant osteogenic protein-1 (OP-1; bone morphogenetic protein-7) in regeneration of dog larynx was examined by treating thyroid cartilage defects (1.5 cm2) in dogs with thyroid allografts covered with host perichondrium or fascia. Prior to implantation allografts were frozen, thawed and demineralized. The treatment groups were as follows: I--Allograft control implant (n = 3); II--Implants coated with 500 micrograms OP-1 (n = 4); III--Implants coated with 100 micrograms OP-1 (n = 3); IV--Implants coated with 500 micrograms OP-1 and covered with neck fascia (n = 3); and V--Implants extracted with 1 M NaCl and guanidine hydrochloride, and coated with 500 micrograms OP-1 (n = 4). Dogs were sacrificed four months following surgery. Each larynx was removed, carefully dissected and a three-dimensional reconstruction of the defect area was performed on serial sections. The results revealed that the implants of control dogs remained intact with no apparent reduction in size and new tissue formation. OP-1 enriched thyroid allografts, dose dependently induced bone, cartilage and ligament-like structures comprising up to 80% of the total regenerated defect area. Boundaries of the defects healed by formation of new bone when bone resided within the old thyroid cartilage layers. Old cartilage not containing bone within its layers healed by complete integration with newly formed cartilage. Both new bone and cartilage were embedded into layers of new ligament-like tissue which expressed specific morphologic and molecular markers. The three newly formed tissues were tightly connected into a "bone-cartilage-ligament continuum" of tissues, suggesting that OP-1 served as a multiple tissue morphogen in this specific microenvironment.

Animals↗