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Biomedical subjects

J Han

Publications and source records attributed to J Han.

At least 37 records · Page 2Linked to original sources
PubMed2004

Genetic analysis of crown size in the first molars using SMXA recombinant inbred mouse strains.

Tooth crown size may be determined by both genetic and environmental factors. The aim of this study was to identify quantitative trait loci (QTLs) affecting dental crown size and determine whether there is genetic independence between upper and lower teeth, using SMXA recombinant inbred strains of mice. Mesiodistal and buccolingual crown diameters (MD and BL, respectively) of the upper and lower first molars (M(1) and M(1), respectively) were measured. For each trait, mean values of substrains showed a continuous spectrum of distribution. Genome-wide scan detected QTLs exceeding suggestive threshold levels for MD of M(1) (chromosomes 7, 13, and 17), BL of M(1) (chromosomes 8 and 13), MD of M(1) (chromosomes 7 and 13), and BL of M(1) (chromosomes 3 and 15). These findings suggest that tooth crown size is controlled by multiple genes, and that there is some independence of genetic control between M(1) and M(1).

Animals↗
PubMed2004

Effect of glucose concentration on the growth of normal human dermal fibroblasts in vitro.

OBJECTIVE: Glucose requirements increase in tissue repair as glucose is an energy source for cell proliferation and the formation of extracellular matrix components. Glucose concentrations in leg ulcer wound fluid are lower than in normal human serum, with a median of 0.7 mM (range: 0.3-1.2 mM). This study investigated the effect of such low concentrations on the growth of fibroblasts in vitro. METHOD: Fibroblasts from 50-year-old and 87-year-old subjects were used. Growth in medium with various concentrations of glucose was determined by a colorimetric assay and microphotography. RESULTS: Up to day 6, there were minimal differences in growth, but after day 6 a clear dose-dependent increase in growth was observed. In the lower dose range (up to 2.3 mM), growth was highly dose-dependent (r2 = 0.981), with an increase of 1.8 mM stimulating cell growth by day 10 up to 163% of the controls (p < 0.0001). Concentrations of 5.5-25.5 mM glucose stimulated cell growth by day 10 to about 210% of the controls (p < 0.0001), with little difference between these concentrations. CONCLUSION: These results suggest that glucose enhancement to cells involved in healing might serve as an adjunctive treatment for chronic wounds.

Aged↗
PubMed2003

Identification of Lps2 as a key transducer of MyD88-independent TIR signalling.

In humans, ten Toll-like receptor (TLR) paralogues sense molecular components of microbes, initiating the production of cytokine mediators that create the inflammatory response. Using N-ethyl-N-nitrosourea, we induced a germline mutation called Lps2, which abolishes cytokine responses to double-stranded RNA and severely impairs responses to the endotoxin lipopolysaccharide (LPS), indicating that TLR3 and TLR4 might share a specific, proximal transducer. Here we identify the Lps2 mutation: a distal frameshift error in a Toll/interleukin-1 receptor/resistance (TIR) adaptor protein known as Trif or Ticam-1. Trif(Lps2) homozygotes are markedly resistant to the toxic effects of LPS, and are hypersusceptible to mouse cytomegalovirus, failing to produce type I interferons when infected. Compound homozygosity for mutations at Trif and MyD88 (a cytoplasmic TIR-domain-containing adaptor protein) loci ablates all responses to LPS, indicating that only two signalling pathways emanate from the LPS receptor. However, a Trif-independent cell population is detectable when Trif(Lps2) mutant macrophages are stimulated with LPS. This reveals that an alternative MyD88-dependent 'adaptor X' pathway is present in some, but not all, macrophages, and implies afferent immune specialization.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Head and backbone of the Early Cambrian vertebrate Haikouichthys.

Agnathan fish hold a key position in vertebrate evolution, especially regarding the origin of the head and neural-crest-derived tissue. In contrast to amphioxus, lampreys and other vertebrates possess a complex brain and placodes that contribute to well-developed eyes, as well as auditory and olfactory systems. These sensory sytems were arguably a trigger to subsequent vertebrate diversifications. However, although they are known from skeletal impressions in younger Palaeozoic agnathans, information about the earliest records of these systems has been largely wanting. Here we report numerous specimens of the Lower Cambrian vertebrate Haikouichthys ercaicunensis, until now only known from the holotype. Haikouichthys shows significant differences from other fossil agnathans: key features include a small lobate extension to the head, with eyes and possible nasal sacs, as well as what may be otic capsules. A notochord with separate vertebral elements is also identifiable. Phylogenetic analysis indicates that this fish lies within the stem-group craniates. Although Haikouichthys somewhat resembles the ammocoete larva of modern lampreys, this is because of shared general craniate characters; adult lampreys and hagfishes (the cyclostomes if monophyletic) are probably derived in many respects.

Animals↗
PubMed2003

Use of levetiracetam in a population of patients aged 65 years and older: a subset analysis of the KEEPER trial.

Levetiracetam (Keppra) was evaluated in a subset of patients aged >/=65 years (n=78) enrolled in a large (n=1030) open-label, phase IV trial (the KEEPER trial). A 4-week dose adjustment was followed by a 12-week evaluation period. An overall median reduction in partial seizures of 80.1% (n=65) was observed. Overall, 76.9% of patients were >/=50% responders, 56.9% were >/=75% responders, and 40.0% were 100% responders. Levetiracetam was well tolerated, with 42.3% of patients reporting one or more adverse events. A total of 15 patients (19.2%) experienced an adverse event that led to discontinuation. Somnolence (n=13,16.7%) and dizziness (n=7,9.0%) were the most commonly reported adverse events. Despite the limitations of the open-label study design, these data provide information regarding the use of levetiracetam as add-on therapy for the treatment of partial-onset seizures in patients >/=65 years of age, including those requiring concomitant medications.

Age Factors↗
PubMed2003

26-Week repeated oral dose toxicity study of the new quinolone antibacterial DW-116 in Sprague-Dawley rats.

The purpose of this study is to investigate the potential subchronic toxicity of DW-116 by a 26-week repeated oral dose in Sprague-Dawley rats. The test article, DW-116, was administered daily by gavage to male and female rats at dose levels of 0, 5, 25 and 125 mg/kg/day. At the end of the treatment period, 12 rats/sex/group were sacrificed, while six extra rats/sex in the vehicle control and highest dose groups were sacrificed after a 4-week recovery. During the test period, clinical signs, mortality, body weights, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weights and histopathology were examined. There was no treatment-related mortality. An increase in the incidence of post-dosing salivation was observed in both sexes of the highest dose group. At the scheduled autopsy, an increase in the liver weight was observed in males of the highest dose group in a dose-dependent manner. Hematological investigations revealed a dose-dependent increase in the total white blood cell (WBC) and lymphocyte counts in males treated with the 125 mg/kg dose. Total bilirubin and alanine aminotransferase (ALT) values were also increased in males at the same dose. These effects were completely reversible during the recovery period. There were no adverse effects on body weight, food and water consumption, ophthalmoscopy, urinalysis, necropsy findings and histopathology in any treatment group. Based on these results, it was concluded that the 26-week repeated oral dose of DW-116 caused increases in the liver weight, WBC counts, total bilirubin and ALT values in males at a dose level of 125 mg/kg/day. The target organ was determined to be the liver and WBC in males, but not in females. The no-observed-adverse-effect level (NOAEL) was considered to be 25 mg/kg/day for males and 125 mg/kg/day for females.

Administration, Oral↗
PubMed2003

The KEEPER trial: levetiracetam adjunctive treatment of partial-onset seizures in an open-label community-based study.

PURPOSE: Three randomized, placebo-controlled trials have demonstrated the safety and efficacy of levetiracetam, a new antiepileptic medication, as add-on therapy for partial-onset seizures. The purpose of this study was to gather additional safety and efficacy data on levetiracetam in the real-world setting of community-based practice. METHODS: This was a phase IV prospective, open-label, multicenter, community-based trial. A total of 1030 patients (intent-to-treat (ITT) population) at least 16 years old (mean, 42.2 years) with partial-onset seizures were enrolled by over 300 investigators. Patients whose partial-onset seizures were inadequately controlled on their current medications had levetiracetam 500 mg bid added to their regimens. The levetiracetam dose was increased by 500 mg bid at the end of weeks 2 and 4 to a maximum dose of 1500 mg bid, unless the patient had been seizure-free during the preceding 2-week period. The dose was then to remain the same for 12 weeks. The main outcome measures were reduction in seizure frequency, global evaluation scale (GES), and adverse events. RESULTS: During the 16 weeks of the trial, 57.9% (542/936) experienced at least a 50% reduction in the frequency of partial-onset seizures, 40.1% (375/936) experienced at least a 75% reduction, and 20% (187/936) demonstrated a 100% seizure reduction. During the last 6 weeks of the study, 66.7% (500/750) experienced at least a 50% reduction in the frequency of partial seizures, 52.4% (393/750) experienced at least a 75% reduction, and 42.1% (316/750) demonstrated a 100% seizure reduction. On the investigator-completed clinical impression rating (GES), 74.3% (734/988) of patients were considered improved, with 37% of patients showing marked improvement. The most common adverse events were somnolence, dizziness, asthenia, and headache; these events were predominantly mild-to-moderate in nature. CONCLUSIONS: These results provide further evidence regarding the efficacy and safety of levetiracetam as adjunctive treatment for partial-onset seizures.

Adolescent↗
PubMed2003

Endoscopic hemoclipping using a transparent cap in technically difficult cases.

BACKGROUND AND STUDY AIMS: Technical difficulties have been experienced in endoscopic hemoclipping on the posterior wall of the body of the stomach because the angle of approach is tangential. It has been suggested that the use of a transparent cap on the tip of the endoscope could help to solve this problem. The purpose of this study was to examine the efficacy of endoscopic hemoclipping using a transparent cap over the tip of the endoscope. PATIENTS AND METHODS: A total of 74 patients with a bleeding peptic ulcer or stigmata of recent hemorrhage underwent endoscopic hemoclipping. Technical difficulty in hemoclipping was experienced in 18 patients and the transparent cap was used in these cases. We therefore conducted a nonrandomized prospective study to compare bleeding control with the hemoclip with and without the aid of a transparent cap. RESULTS: There were no statistically significant differences between the patients treated with the cap and those treated without the cap with regard to the initial hemostasis rate (94.4 % vs. 91.1 %), the rebleeding rate (11.7 % vs. 11.8 %), or the permanent hemostasis rate (94.4 % vs. 96.4 %). CONCLUSIONS: Although there was no statistically significant difference between patients treated with or without a transparent cap, hemoclipping with the aid of the cap made it possible to clip a lesion too tangential to be clipped without it. However, this study did not compare conventional hemoclipping with hemoclipping using a cap because the cap was only used in cases in which conventional clipping had failed.

Duodenal Ulcer↗
PubMed2003

TGF-beta signaling and its functional significance in regulating the fate of cranial neural crest cells.

Members of the transforming growth factor-beta (TGF-beta) superfamily regulate cell proliferation, differentiation, and apoptosis, and control the development and maintenance of most tissues. TGF-beta signal is transmitted through the phosphorylation of Smad proteins by TGF-beta receptor serine/threonine kinase. During craniofacial development, TGF-beta may regulate the fate specification of cranial neural crest cells. These cells are multipotent progenitors and capable of producing diverse cell types upon differentiation. Here we summarize evidence that TGF-beta ligands and their signaling intermediates have significant roles in patterning and specification of cranial neural crest cells. The biological function of TGF-beta is carried out through the regulation of transcriptional factors during embryogenesis.

Animals↗
PubMed2002

Prevention of autoimmune diabetes by immunogene therapy using recombinant vaccinia virus expressing glutamic acid decarboxylase.

AIMS/HYPOTHESES: Type I (insulin-dependent) diabetes mellitus results from T-cell-mediated autoimmune destruction of pancreatic beta cells. Among the beta-cell autoantigens that have been implicated in triggering of beta-cell-specific autoimmunity, glutamic acid decarboxylase (GAD) is a strong candidate in both humans and the NOD mouse. We aimed to determine whether treatment with a recombinant vaccinia virus expressing GAD (rVV-GAD65) could prevent the development of diabetes in NOD mice. METHODS: Three-eight-to-nine-week-old female NOD mice were injected with various doses of rVV-GAD65 or rVV-MJ601as a control. We then examined the incidence of diabetes, T-cell proliferative response to GAD, amounts of anti-GAD IgGs, cytokine production and generation of regulatory cell populations. RESULTS: Administration of rVV-GAD65 to NOD mice prevented diabetes in an age-dependent and dose-dependent manner. Splenic T cells from rVV-GAD65-treated mice did not proliferate in response to GAD65. The amount of IgG1 was increased, whereas IgG2a amounts did not change in rVV-GAD65-treated NOD mice. The production of interleukin-4 increased, whereas the production of interferon-gamma decreased in rVV-GAD65-treated mice after stimulation with GAD. Furthermore, splenocytes from rVV-GAD65-treated NOD mice prevented the transfer of diabetes by splenocytes from acutely diabetic NOD mice in NOD. scid recipients. CONCLUSION/INTERPRETATION: Immunogene therapy using a recombinant vaccinia virus expressing GAD results in the prevention of autoimmune diabetes in NOD mice by the induction of immunological tolerance through active suppression of effector T cells, and this treatment might have therapeutic value for the prevention of Type I diabetes.

Adoptive Transfer↗
PubMed2002

Subchronic toxicity of plant sterol esters administered by gavage to Sprague-Dawley rats.

The purpose of this study was to investigate the potential subchronic toxicity of plant sterol esters by a 13-week repeated oral dose in Sprague-Dawley rats. The test article was administered once daily by gavage to male and female rats at dose levels of 0, 1000, 3000 and 9000 mg/kg/day for 13 weeks. At the end of treatment period, 10 rats/sex/group were sacrificed, while six rats/sex in the negative control and highest dose groups were sacrificed after a 4-week recovery period. During the test period, clinical signs, mortality, body weights, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weights and histopathology were examined. Slight decreases in body weight gain were noted at lower doses but were only statistically different from the control animals in the highest dose group. In histopathological examinations, an increase in the incidence of cardiomyopathy with mononuclear cell infiltration was observed in males of the 9000 mg/kg group. Decreased body weight gain and increased incidence of cardiomyopathy observed in the highest dose group were not recovered until the end of the recovery period. There were no adverse effects on mortality, clinical signs, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, necropsy findings and organ weights in any treatment group. Based on these results, it was concluded that the 13-week repeated oral dose of plant sterol esters resulted in the suppression of body weight gains in both sexes and cardiomyopathy in males at a dose level of 9000 mg/kg/day. The target organ was determined to be heart in males, but not in females. The no-observed-adverse-effect level (NOAEL) was considered to be 3000 mg/kg/day for both sexes.

Administration, Oral↗
PubMed2002

Free radical scavenging effect of Diospyros kaki, Laminaria japonica and Undaria pinnatifida.

Diospyros kaki folium, Laminaria japonica thallus and Undaria pinnatifida thallus have been used traditionally in Korea to promote maternal health. The scavenging activity against DPPH (1,1-diphenyl-2-picrylhydrazyl) radicals of the methanol extracts of these plants were investigated. The extract of D. kaki was found to be the most potent, with an IC(50) value of 0.11 mg/ml.

Biphenyl Compounds↗
PubMed2002

Acipimox stimulates leptin production from isolated rat adipocytes.

Acipimox is a nicotinic acid-derived antilipolytic drug devoid of major side effects, and has been used in a number of human trials. This work reports the effects of Acipimox on leptin production from isolated rat adipocytes, in comparison with nicotinic acid and insulin. For cells isolated from normal animals, all these three reagents stimulated leptin release to a similar extent. Acipimox and nicotinic acid were more potent than insulin in stimulating leptin release from cells isolated from diabetic animals, probably because of impaired insulin sensitivity in cells from these diseased animals. Co-incubation of Acipimox with norepinephrine or dibutyryl cAMP diminished its stimulatory effects on leptin release, in parallel with increased lipolysis, suggesting that intracellular free fatty acids play an important role in mediating leptin production in adipocytes.

Adipocytes↗
PubMed2001

Primitive deuterostomes from the Chengjiang Lagerstätte (Lower Cambrian, China).

Cambrian fossil-Lagerstätten (sites of exceptional fossil preservation), such as those from Chengjiang (Lower Cambrian) and the Burgess Shale (Middle Cambrian), provide our best window into the Cambrian 'explosion'. Such faunas are known from about 40 localities, and have yielded a widely disparate series of taxa ranging from ctenophores to agnathan fish. Recent excavations of the Chengjiang fossil-Lagerstätte, known from a series of sites near Kunming in Yunnan, south China, have resulted in the discovery of several new forms. In conjunction with material described earlier, these provide evidence for a new group of metazoans, the vetulicolians. Several features, notably a series of gill slits, suggest that this group can throw light on an early stage of deuterostome diversification.

Animals↗