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Biomedical subjects

H J Li

Publications and source records attributed to H J Li.

At least 37 records · Page 2Linked to original sources
PubMed1997

Reduced sarcolemmal dystrophin distribution and upregulation of utrophin in the cardiac and skeletal muscles of CHF-146 dystrophic hamsters.

Abnormalities in the dystrophic gene product, dystrophin, have been implicated in initiating the primary membrane defect and excessive intracellular calcium accumulation (EICA), which play fundamental pathogenic roles in hereditary muscular dystrophy (HMD). Two other cytoskeletal proteins, spectrin and utrophin, bear remarkable structural and functional homologies to dystrophin. CHF-146 strain dystrophic hamsters (DH), like patients with Duchenne muscular dystrophy (DMD), die prematurely from cardiopulmonary insufficiency, focal myonecrosis, and progressive degeneration of the cardiac and skeletal muscles with EICA. Although DH present a suitable model for HMD, there are controversies concerning their dystrophin and utrophin status. Using immunocytochemistry and Western blotting, we studied dystrophin, spectrin and utrophin anomalies in the cardiac and skeletal muscles of 6-mo-old male DH. Age- and sex-matched CHF-148 strain albino normal hamsters (NH) served as controls. Sarcolemmal dystrophin staining was much weaker and interruptive in the DH. The densitometric analysis of the immunoblots revealed that dystrophin is reduced in DH by 83% in cardiac muscle (p < 0.0001), and by 50% in skeletal muscle (p < 0.0001). We conclude that sarcolemmal dystrophin distribution is markedly reduced and discontinuous in the cardiac and skeletal muscles of DH, with simultaneous upregulation of utrophin and a varied degree of spectrin labelling. This observation suggests that reduced sarcolemmal dystrophin is associated with membrane hyperpermeability, which leads to progressive muscle degeneration via EICA and segmental necrosis in DH. As in DMD, utrophin appears to play an important compensatory role in hamster dystrophinopathy.

Animals↗
PubMed1997

[Some YAC contig construction and long range physical mapping at human X chromosome Xp11.3-21.3].

Human X chromosome short arm Xp11.3-p21.3 is an area, where several genetic disease gene loci are located. In this work, the YAC conting construction, long range physical mapping were done for this region. Some DNA probes and STS markers were used for YAC screening. Totally 77 YACs were obtained from the YAC libraries of CEPH, ICRF and ours. The size determination, 26 pairs of microsatelite STS analysis, single copy probe hybridization, Alu-PCR finger printing and long range physical mapping were conducted with these YACs. These results allowed us to map these YACs, and finally 6 YAC contigs were obtained in Xp11.3-21.3, covering about 15.3 Mb. This work will greatly facilitate the positional cloning of disease genes or the genome sequencing in this important region.

Chromosome Mapping↗
PubMed1996

Percutaneous balloon valvuloplasty for pulmonic stenosis in adolescents and adults.

BACKGROUND: Percutaneous balloon valvuloplasty has been the accepted first-line treatment for congenital pulmonic stenosis in children. Its efficacy in adolescents and adults is less well defined. METHODS: Between December 1985 and July 1995 we performed percutaneous pulmonic valvuloplasty with a single Inoue balloon catheter in 53 adolescent or adult patients 13 to 55 years of age (mean [+/- SD], 26 +/- 11). Follow-up studies were performed 0.2 to 9.8 years after the procedure (mean, 6.9 +/- 3.1) by Doppler echocardiography (in all the patients) and by cardiac catheterization and angiography (in nine patients). RESULTS: After balloon valvuloplasty, the systolic pressure gradient across the pulmonic valve decreased from 91 +/- 46 mm Hg to 38 +/- 32 mm Hg (P < 0.001), and the diameter of the pulmonic-valve orifice increased from 8.9 +/- 3.6 mm to 17.4 +/- 4.6 mm (P < 0.001). In the nine patients catheterized at follow-up, the systolic gradient decreased from 107 +/- 48 mm Hg before valvuloplasty to 50 +/- 29 mm Hg after valvuloplasty and to 30 +/- 16 mm Hg at follow-up (P < 0.001 for the comparison of the gradient before and after valvuloplasty; P < 0.001 for the comparison before valvuloplasty and at follow-up; and P < 0.05 for the comparison after valvuloplasty and at follow-up). In the same nine patients, the diameter of the pulmonic valve, as measured by right ventricular angiography, increased from 8.3 +/- 1.4 mm before valvuloplasty to 17.2 +/- 2.0 mm after valvuloplasty (P < 0.001) and to 18.4 +/- 1.4 mm at follow-up (P = 0.08). Incompetence of the pulmonic valve was noted in 7 of the 53 patients (13 percent) after balloon valvuloplasty, but it had disappeared at follow-up in all of them. CONCLUSIONS: Patients with congenital pulmonic stenosis who present in late adolescence or adult life can be treated with percutaneous balloon valvuloplasty with excellent short-term and long-term results that are similar to those in young children.

Adolescent↗
PubMed1993

The beta-thalassemia frameshift at codon 8 (-AA) observed in four Chinese of the Uygur nationality.

During a survey for beta-thalassemia in Kashi City, Xinjiang Province, P.R. China, four unrelated Uygur students were identified as heterozygotes for the beta-thalassemia frameshift at codon 8 (-AA). Detection was with the polymerase chain reaction combined with allele-specific oligonucleotide hybridization. This beta-thalassemia allele has not been observed in the Chinese population before and might be rather specific for the Uygur nationality.

Asian People↗
PubMed1992

Dystrophin cytochemistry in mdx mouse muscles injected with labeled normal myoblasts.

A new technique enables correlation of dystrophin expression with the location of donor versus host nuclei in the same sections of mdx mouse muscle injected with normal myoblasts. Myoblasts from C57BL/6J mice or from humans were labeled with 0.01% fluoro-gold (FG) in Dulbecco's Modified Eagles Medium (DMEM) for 16 h at 37 degrees C before myoblast transfer. About 3 x 10(4) myoblasts were injected into the quadriceps muscles of mdx mice immunosuppressed with cyclosporine A (CsA). At 11, 21, or 25 days after myoblast transfer, injected muscles were dissected out and sectioned. These mouse sections were processed for dystrophin and then labeled with a fluorescent nucleus counterstain, 5 micrograms% Hoechst 33342 in phosphate-buffered saline (PBS), for 10 min at room temperature. Fluoro-gold labeling corresponding with Hoechst 33342 staining indicated survival of normal nuclei in dystrophic muscle. Dystrophin was found in the sarcolemma of myofibers containing FG-labeled nuclei but not of myofibers containing only Hoechst 33342-labeled nuclei. Control muscle samples showed neither FG labeling nor dystrophin. This study demonstrates that the donor human and mouse myoblasts survived and developed in host mouse muscles for at least 25 days after myoblast transfer, and that the localization of their normal nuclei correlates with dystrophin expression in muscle fibers of immunosuppressed mdx host mice.

Animals↗
PubMed1992

Feasibility, safety, and efficacy of myoblast transfer therapy on Duchenne muscular dystrophy boys.

Five billion normal myoblasts were injected into each of 21 Duchenne muscular dystrophy (DMD) boys aged 6-14 yr to assess the feasibility, safety, and efficacy of the Phase II myoblast transfer therapy (MTT). The Phase II study was designed to strengthen muscles of both lower limbs. Forty-eight intramuscular injections transferred the myoblasts into 22 major muscles at 55.6 x 10(6)/mL in 10 min under general anesthesia. Eleven boys had received 8 million myoblasts each 1 yr ago in the Phase I MTT. In the Phase II study, eight of them had their myoblasts subcultured from reserves frozen 1 yr ago. The donor myoblasts for each of the remaining boys were cultured from satellite cells derived from a 1-g muscle biopsy of a normal male who might or might not be histocompatible with the recipient. The immunosuppressant cyclosporine (Cy) is being administered to recipients for 6 mo after MTT to facilitate donor cell survival. There was no evidence of an adverse reaction to MTT or Cy as determined by serial laboratory evaluations including electrolytes, creatinine, and urea. Early objective functional tests using the KinCom Robotic Dynamometer were conducted on 13 subjects aged 6 to 13 before MTT and at 3 mo after MTT. Of the 69 muscle groups (knee extensors, knee flexors, plantar flexors) tested for isometric force generation in these subjects, 43% showed mean increase of 41.3% +/- 5.9 SEM, 38% showed no change, and 19% showed continuous force reduction of 23.4% +/- 3.1 SEM. The remaining subjects await the 3-mo post-MTT evaluation. The results indicate that 1) MTT is safe; 2) MTT increases muscle strength in DMD: 81% of the muscles tested showed either increase in strength or did not show continuous loss of strength; 3) more than 5 billion myoblasts can be cultured from 1 g normal muscle biopsy, providing unprecedented numbers of cells for MTT; 4) myoblasts, frozen over 1 yr, retain the ability to proliferate from 10 million to 5 billion, and to form normal myofibers; 5) injections of 5 billion myoblasts have not provoked any immunological rejection symptoms in the Phase II subjects, 11 of whom received 8 million myoblasts in the Phase I MTT a year ago; 6) it is safe to perform multiple injections of myoblasts into lower limb muscles without formation of emboli; and 7) donor cell rejection by the recipient can be prevented with Cy when properly managed.

Adolescent↗
PubMed1992

Types of thalassemia among patients attending a large university clinic in Kuala Lumpur, Malaysia.

We have identified the beta-thalassemia mutations in 59 patients with thalassemia major and 47 patients with Hb E-beta-thalassemia, and the deletional and nondeletional alpha-thalassemia determinants in 23 out of 24 patients with Hb H disease. All persons were attending the Haematology Clinic at the National University of Malaysia in Kuala Lumpur (Malaysia). Most patients (76) were of Malay descent, while 52 patients were Chinese, and two came from elsewhere. The most frequently occurring beta-thalassemia alleles among the Malay patients were IVS-I-5 (G----C) and G----A at codon 26 (Hb E), while a few others were present at lower frequencies. The Chinese patients carried the mutation characteristic for Chinese [mainly codons 41/42 (-TTCT) and IVS-II-654 (C----T)]; Malay mutations were not observed among Chinese and Chinese mutations were virtually absent in the Malay patients. The large group of patients with Hb E-beta-thalassemia and different beta-thalassemia alleles offered the opportunity of comparing hematological data; information obtained for patients with Hb E-beta-thalassemia living in other countries was included in this comparison. Twenty-three patients with Hb H disease carried the Southeast Asian (SEA) alpha-thalassemia-1 deletion; 13 had the alpha CS alpha (Constant Spring) nondeletional alpha-thalassemia-2 determinant, while the deletional alpha-thalassemia-2 (-3.7 or -4.2 kb) was present in 10 subjects. The --/alpha CS alpha condition appeared to be the most severe with higher Hb H values. Both deletional and nondeletional types of alpha-thalassemia-2 were seen among Malay and Chinese patients.

Academic Medical Centers↗
PubMed1991

Myoblast transfer therapy for Duchenne muscular dystrophy.

A randomly selected extensor digitorum brevis (EDB) muscle in each of three Duchenne muscular dystrophy (DMD) boys aged 9 to 10 was injected with approximately 8 x 10(6) myoblasts. The contralateral EDBs were sham-injected with carrier solution. Donor myoblasts were derived from cell culture of muscle biopsies from the normal ward or normal brothers of the recipients. Cyclosporine (CsA) treatment began two days before myoblast injection and continued for three months. Three days prior to myoblast injection and three months after, the isometric twitch and maximum voluntary contraction of the left and the right EDBs were measured. Myoblast-injected EDBs showed increases in tensions whereas sham-injected EDBs showed reductions. Both immunocytochemical staining and immunoblot revealed dystrophin in the myoblast-injected EDBs. Dystrophic characteristics such as fiber splitting, central nucleation, phagocytic necrosis, variation in fiber shape and size, and infiltration of fat and connective tissues were less frequently observed in these muscles. Sham-injected EDBs exhibited significant structural and functional degeneration and no dystrophin. Throughout the study, there was no sign of erythema, swelling or tenderness at the injection sites. Serial laboratory evaluation including electrolytes, creatinine, and urea did not reveal any significant changes before or after myoblast transfer. We conclude that myoblast transfer therapy is a safe and efficacious procedure to improve the biochemistry, structure, and function of degenerative EDB muscles in DMD.

Cells, Cultured↗
PubMed1991

Vital marker for muscle nuclei in myoblast transfer.

A new method is developed using Fluoro-Gold (FG) as a vital stain to label the nuclei of donor myoblasts in myoblast transfer studies. In vitro incubation with 0.01% FG for 16 h resulted in 100% nuclei labelling. Intensive fluorescence persisted following 9 days of subculture, when the human myoblasts were injected into the quadriceps of mouse recipients immunosuppressed with cyclosporine. Injected muscles showed mosaicism of host and donor nuclei 25 days after injection, indicating (i) survival and fusion among donor myoblasts, and (ii) fusion between host and donor cells. FG labelling was not observed in control muscles injected with an equal volume of FG-labelled dead myoblasts, 0.01% FG medium, or phosphate-buffered saline.

Adult↗
PubMed1990

Abnormal hemoglobins in the Silk Road region of China.

A review is presented of the occurrence of 24 abnormal hemoglobins (13 alpha-chain variants and 11 beta-chain variants) in populations in the Silk Road area of Northwestern China. Most frequently occurring were Hb D-Punjab [beta 121(GH4)Glu----Gln] in Uygurs, Kazaks, and Khalkhas, Hb G-Taipei [beta 22(B4)Glu----Gly] in persons of the Han nationality, and Hb G-Coushatta [beta 22 (B4)Glu----Ala] in the Uygurs, Kazaks, Hans, and related nationalities. The data suggest that these variants likely originated in Central Asia, in the Han nationality of China, and in the minorities of northern China, respectively. Other variants occurred at considerably lower frequencies and were imported from other countries or arose as independent mutations. Two variants [Hb Tashikuergan or alpha 19(AB1)Ala----Glu; Hb Tianshui or beta 39(C5) Gln----Arg] were observed for the first time. The data from this study of the many variants support the movements of various populations in this area, as reported in numerous historical documents.

China↗