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Biomedical subjects

C M Hu

Publications and source records attributed to C M Hu.

At least 19 recordsLinked to original sources

Apodemus species mice are reservoir hosts of Borrelia garinii OspA serotype 4 in Switzerland.

Among Borrelia burgdorferi sensu lato isolates, seven outer surface protein A (OspA) serotypes have been described: serotypes 1 and 2 correspond to B. burgdorferi sensu stricto and Borrelia afzelii, respectively, and serotypes 3 to 7 correspond to Borrelia garinii. In Europe, serotype 4 has never been isolated from Ixodes ricinus ticks until recently, although this serotype has been frequently isolated from cerebrospinal fluid from patients. In Europe, B. afzelii and B. burgdorferi sensu stricto were found associated with rodents and B. garinii was found associated with birds. In this study, the reservoir role of Apodemus mice for B. garinii OspA serotype 4 was demonstrated by xenodiagnosis. Apodemus mice are the first identified reservoir hosts for B. garinii OspA serotype 4.

Animals↗

Spin injection across a heterojunction: a ballistic picture.

Spin injection across heterojunctions plays a decisive role in the new field of spintronics. Within the ballistic transport regime, we state a general expression for the spin-injection rate in a heterojunction made of two ballistic electrodes. Both the spin-orbit interaction and interface scattering effect are taken into account. Our model is consistent with the well-documented results of ferromagnetic-metal junctions. It explains the recent experimental results of a dilute-magnetic-semiconductor/semiconductor junction and predicts solutions to enhance the spin-injection rate across a ferromagnetic-semiconductor junction.

Journal Article↗

Transmission of Borrelia garinii OspA serotype 4 to BALB/c mice by Ixodes ricinus ticks collected in the field.

In Europe, Borrelia garinii OspA serotype 4 has been isolated from the cerebrospinal fluid of patients but, up to now, has never been identified among culture isolates from Ixodes ricinus ticks. This information raises the question of whether OspA serotype 4 is transmitted by I. ricinus in nature. In the present study, I. ricinus nymphs collected in an area of endemicity in southern Germany were allowed to feed on mice. Cultivation of ear biopsy specimens showed that six of seven B. garinii-infected mice were infected by OspA serotype 4. In contrast, very few B. garinii OspA serotype 4 organisms were isolated directly from the ticks which infected the mice; most isolates were B. afzelii. The infected mice transmitted mainly OspA serotype 4 to xenodiagnostic ticks, preferentially in combination with B. afzelii.

Animals↗

Mechanisms underlying the induction of vasorelaxation in rat thoracic aorta by sanguinarine.

In the present study, the effect of sanguinarine (SANG) on smooth muscle was investigated in thoracic aorta isolated from rats. SANG dose-dependently relaxed the phenylephrine (PE, 3 microM)-precontracted aorta; and the concentrations to produce 50% relaxation were 3.18 +/- 0.37 and 3.42 +/- 1.14 microM, respectively, in intact and denuded aorta. These results suggest that the relaxing effect of SANG was endothelium-independent. The total contraction induced by PE was inhibited in aorta pretreated with SANG at microM concentration. Both phasic and tonic contractions induced by PE were inhibited by SANG independently, which were further supported by the fact that inositol 1,4,5-trisphosphate (IP3) formation and 45Ca2+ influx induced by 3 microM PE in denuded aorta were inhibited by SANG concentration-dependently. In addition, the vasocontraction induced by high-K+ was also inhibited by SANG, however, at higher concentrations. The inhibitory effects of SANG were reversed by dithiothreitol, a thiol reducing agent, implying that the oxidation of critical sulfhydryl groups on key molecules that regulate the smooth muscle contraction were involved. These data suggested that the inhibitory effects of SANG on PE-induced vasocontraction might involve the inhibition of IP3 formation and blockade of calcium channel.

Alkaloids↗

Ablation of uroplakin III gene results in small urothelial plaques, urothelial leakage, and vesicoureteral reflux.

Urothelium synthesizes a group of integral membrane proteins called uroplakins, which form two-dimensional crystals (urothelial plaques) covering >90% of the apical urothelial surface. We show that the ablation of the mouse uroplakin III (UPIII) gene leads to overexpression, defective glycosylation, and abnormal targeting of uroplakin Ib, the presumed partner of UPIII. The UPIII-depleted urothelium features small plaques, becomes leaky, and has enlarged ureteral orifices resulting in the back flow of urine, hydronephrosis, and altered renal function indicators. Thus, UPIII is an integral subunit of the urothelial plaque and contributes to the permeability barrier function of the urothelium, and UPIII deficiency can lead to global anomalies in the urinary tract. The ablation of a single urothelial-specific gene can therefore cause primary vesicoureteral reflux (VUR), a hereditary disease affecting approximately 1% of pregnancies and representing a leading cause of renal failure in infants. The fact that VUR caused by UPIII deletion seems distinct from that caused by the deletion of angiotensin receptor II gene suggests the existence of VUR subtypes. Mutations in multiple gene, including some that are urothelial specific, may therefore cause different subtypes of primary reflux. Studies of VUR in animal models caused by well-defined genetic defects should lead to improved molecular classification, prenatal diagnosis, and therapy of this important hereditary problem.

Animals↗

Antigenic conservation of an immunodominant invariable region of the VlsE lipoprotein among European pathogenic genospecies of Borrelia burgdorferi SL.

Lyme disease is caused by genetically divergent spirochetes, including 3 pathogenic genospecies: Borrelia burgdorferi sensu stricto, B. garinii, and B. afzelii. Serodiagnosis is complicated by this genetic diversity. A synthetic peptide (C(6)), based on the 26-mer invariable region (IR(6)) of the variable surface antigen of B. burgdorferi (VlsE), was used as ELISA antigen, to test serum samples collected from mice experimentally infected with the 3 genospecies and from European patients with Lyme disease. Regardless of the infecting strains, mice produced a strong antibody response to C(6), which indicates that IR(6) is antigenically conserved among the pathogenic genospecies. Twenty of 23 patients with culture-confirmed erythema migrans had a detectable antibody response to C(6). A sensitivity of 95.2% was achieved, with serum samples collected from patients with well-defined acrodermatitis chronica atrophicans. Fourteen of 20 patients with symptoms of late Lyme disease also had a positive anti-IR(6) ELISA. Thus, it is possible that C(6) may be used to serodiagnose Lyme disease universally.

Amino Acid Sequence↗

Induction of skeletal muscle contracture and calcium release from isolated sarcoplasmic reticulum vesicles by sanguinarine.

The benzophenanthrine alkaloid, sanguinarine, was studied for its effects on isolated mouse phrenic-nerve diaphragm preparations. Sanguinarine induced direct, dose-dependent effects on muscle contractility. Sanguinarine-induced contracture was partially inhibited when the extracellular Ca(2+) was removed or when the diaphragm was pretreated with nifedipine. Depletion of sarcoplasmic reticulum (SR) internal calcium stores completely blocked the contracture. Sanguinarine induced Ca(2+) release from the actively loaded SR vesicles was blocked by ruthenium red and dithiothreitol (DTT), consistent with the ryanodine receptor (RyR) as the site of sanguinarine action. Sanguinarine altered [(3)H]-ryanodine binding to the RyR of isolated SR vesicles, potentiating [(3)H]-ryanodine binding at lower concentrations and inhibiting binding at higher concentrations. All of these effects were reversed by DTT, suggesting that sanguinarine-induced Ca(2+) release from SR occurs through oxidation of critical SH groups of the RyR SR calcium release channel.

Alkaloids↗

Effects of cartap on isolated mouse phrenic nerve diaphragm and its related mechanism.

Cartap, a nereistoxin analogue pesticide, is reported to have no irritation to eyes in rabbits. However, we have demonstrated recently that cartap could actually cause acute death in rabbits via ocular exposure. Our preliminary study with isolated mouse phrenic nerve diaphragms has shown that instead of neuromuscular blockade, cartap caused muscular contracture. The objective of the study was to examine the effect of cartap on the neuromuscular junction in more detail and to investigate its possible underlying mechanism with isolated mouse phrenic nerve diaphragms and sarcoplasmic reticulum (SR) vesicles. Cartap or nereistoxin at various concentrations was added in the organ bath with isolated mouse phrenic nerve diaphragm and both nerve- and muscle-evoked twitches were recorded. Instead of blocking the neuromuscular transmission as nereistoxin did, cartap caused contracture in stimulated or quiescent isolated mouse phrenic nerve diaphragm. Both the cartap-induced muscular contracture force and the time interval to initiate the contracture were dose-dependent. The contracture induced by cartap was not affected by the pretreatment of the diaphragm with the acetylcholine receptor blocker alpha-bungarotoxin; the Na(+) channel blocker tetrodotoxin; or various Ca(2+) channel blockers, NiCl(2), verapamil, and nifedipine. On the contrary, the contracture was significantly inhibited when the diaphragm was pretreated with ryanodine or EGTA containing Ca(2+)-free Krebs solution or in combination. This suggested that both internal and extracellular Ca(2+) might participate in cartap-induced skeletal muscle contracture. Moreover, cartap inhibited the [(3)H]-ryanodine binding to the Ca(2+) release channel of SR in a dose-dependent manner. Additionally, cartap could induce a significant reduction in Ca(2+)-ATPase activity of SR vesicles at a relatively high dose. The results suggested that cartap might cause the influx of extracellular Ca(2+) and the release of internal Ca(2+), with subsequent induction of muscular contracture in the isolated mouse phrenic nerve diaphragm. Based on these findings, we propose that the acute death of rabbits following ocular exposure to cartap might have resulted from respiratory failure secondary to diaphragm contracture.

Animals↗

Genetic diversity of Borrelia burgdorferi sensu lato isolates obtained from Ixodes ricinus ticks collected in Slovakia.

In Europe, Borrelia burgdorferi sensu lato is diverse, including B. burgdorferi s.s., B. garinii, B. afzelii, B. valaisiana and B. lusitaniae. In this study, we focused on the distribution of the different B. burgdorferi species among Ixodes ricinus adult ticks collected in an endemic area within Slovakia. We compared results of prevalence of B. burgdorferi infection in ticks obtained by immunofluorescence (IF) and by isolation. Isolates were characterized by restriction fragment length polymorphism (RFLP) of the rrf-rrl intergenic spacer genes using MseI. Using immunofluorescence we observed that 56/114 (49%) ticks were infected by B. burgdorferi s.l. Males were found to be more often infected (32/57, 56%) than females (24/57, 42%) but the difference was not significant (p = 0.1895). From the same 114 ticks a total of 37 isolates were obtained: 19 from males (33%) and 18 from females (32%). The RFLP identification revealed 25 B. afzelii (68%), 5 B. garinii (14%), 5 B. valaisiana (14%) and 2 B. lusitaniae (5%). The infection in ticks was more often detected by IF than by isolation (p = 0.0153) and isolation success was higher when the infection degree in ticks was high (p = 0.0397). The infection prevalence observed in this area is among the highest observed in Europe.

Animals↗

Infection of Ixodes ricinus (Acari: Ixodidae) by Borrelia burgdorferi sensu lato in North Africa.

Free-living adult Ixodes ricinus L, were collected in Amdoun, situated in the Kroumiry mountains in northwestern Tunisia (North Africa). Using direct fluorescence antibody assay, the infection rate of field-collected I. ricinus by Borrelia burgdorferi sensu lato was 30.5% (n = 72). No difference in infection rate was observed between male and female ticks. Spirochetes that had been isolated from I. ricinus from Ain Drahim (Kroumiry Mountains) in 1988 were identified as Borrelia lusitaniae (formerly genospecies PotiB2). This is the first identification of a genospecies of Borrelia burgdorferi sensu lato from the continent of Africa.

Africa, Northern↗

Immunization with a polyvalent OspA vaccine protects mice against Ixodes ricinus tick bites infected by Borrelia burgdorferi ss, Borrelia garinii and Borrelia afzelii.

Sequence variability of the outer surface protein (Osp) A among Borrelia burgdorferi sl species suggests that a monovalent OspA vaccine may not protect against the various Borrelia present in Eurasia. Here, we confirmed that a monovalent recombinant OspA (rOspA) vaccine does not protect mice against Ixodes ricinus mediated infection with B. burgdorferi ss, Borrelia garinii and Borrelia afzelii. However, when mice were vaccinated with a cocktail of various rOspA from these three species, they were protected, and all challenge ticks that fed on them were cleared of their spirochetes. These results showed that a multiple OspA antigens vaccine, compatible with human use, was very efficient at protecting mice against B. burgdorferi ss, B. garinii, and B. afzelii.

Animals↗

Apodemus sp. rodents, reservoir hosts for Borrelia afzelii in an endemic area in Switzerland.

Borrelia burgdorferi is maintained in nature in transmission cycles alternatively involving ticks and reservoir hosts. Small rodents like Apodemus mice and Clethrionomys voles are the primary reservoir of Lyme disease in Europe. In this study, we analyzed by SDS-PAGE and Western blot 20 borrelial isolates from xenodiagnostic ticks fed on four Apodemus sp. mice captured in the Staatswald forest (Switzerland). All isolates but one showed a homogeneous protein pattern expressing an outer surface protein, (Osp) A of 32 kDa and an OspB of 35 kDa and reacted with monoclonal antibody (mAb) I 17.3 specific for B. afzelii. One isolate expressed an OspA of 32.5 kDa and an OspB of 35 kDa and did not react with species-specific mAbs I 17.3, D6 and H3TS, but was shown to belong to B. afzelii by Southern blot analysis. The possibility exists that non-cultivatable borreliae are present in xenodiagnostic ticks. However, our results clearly show that Apodemus sp. are reservoir hosts for B. afzelii, since this genospecies is transmitted from Apodemus sp. to feeding larval ticks.

Animals↗

Borrelia burgdorferi in rodents (Apodemus flavicollis and A. sylvaticus): duration and enhancement of infectivity for Ixodes ricinus ticks.

Ixodes ricinus is an important vector of Borrelia burgdorferi in Europe, and small rodents (Apodemus flavicollis, A. sylvaticus and Clethrionomys glareolus) are important sources for infecting ticks. In this study, we examined their reservoir role by studying the duration of their infectivity for ticks. A. flavicollis and A. sylvaticus mice captured in nature were exposed to uninfected I. ricinus larvae at different times after their capture: 10 days, and 2, 7, 11, 14 and 40 months. Ticks were examined for spirochaetes after moulting using direct immunofluorescence. All animals remained infective for ticks their life long but the efficiency of transmission from hosts to ticks varied from one individual to the other, presenting a three-fold variation (26.5% to 81.4%). Rodents continously exposed to successive infestations by larval I. ricinus ticks over a period of one month showed an enhancement of infectivity for larval ticks during this period.

Animals↗

Comparison in the immunological properties of Borrelia burgdorferi isolates from Ixodes ricinus derived from three endemic areas in Switzerland.

Borrelia burgdorferi isolates were obtained from Ixodes ricinus from three sites in Switzerland. They were examined by SDS-PAGE and immunoblotting. The phenotypes, in respect of three outer surface proteins (Osp), differed between the sites of collection. In site 1, most isolates had an OspA of 31 kDa and an OspB of 34 kDa; in site 2, isolates presenting an OspA of 33 kDa dominated and in site 3, the isolates with an OspA of 32 kDa and an OspB of 35 kDa were most frequent. This distribution differed significantly. About half of the isolates from sites 1 and 3 reacted with anti-OspA monoclonal antibody H5332 compared to 29% from site 2. Site 1 isolates reacted significantly more frequently (81%) with another anti-OspA monoclonal antibody LA-31 than isolates from site 3 (P < 0.0001). These findings have implications for the epidemiology of Lyme borreliosis, for the further development of serodiagnostic reagents and for the development of a vaccine.

Animals↗

[Diagnostic value of MRI in non-traumatic osteonecrosis of femoral head at early stage].

To determine whether magnetic resonance imaging (MRI) can demonstrate the early stage changes of avascular necrosis of the femoral head that are not detectable radiographically. Clinical examinations, radiography and MRI were performed in twenty-six patients (thirty hips) at high risk. On the basis of the pathological findings of core biopsies, the results demonstrate that MRI had an accuracy of 96.7% in diagnosing pre-radiologic stage necrosis of the femoral head in this series.

Adult↗

[A newly designed multifunctional intramedullary decompressor and its clinical application].

A newly designed multifunctional intramedullary decompressor has been introduced in this paper. It has the following functions: (1) intramedullary decompression of femoral head; (2) curettage of necrotic bone; (3) biopsying (4) taking out iliac bone and placing bone graft; (5) taking out broken snail. Thirty four cases of 46 avascular necrotic femoral heads have been treated by using this decompressor, all cases had satisfactory results 18 weeks after operation.

Femur Head↗

[Sequence of light chain variable region gene of a monoclonal antibody to human hepatocarcinoma].

The isolation of the rearranged immunoglobulin genes from a hybridoma cell line, which is a prerequisite for the construction of a recombinant antibody, can easily be achieved by PCR. We have determined the nucleotide sequence of the variable region of L chain of a high affinity monoclonal antibody HAb27 directed to human hepatocarcinoma. Analysis of the nucleotide sequence of the light chain V region of HAb27 revealed that the V kappa sequence was 85% identical to germline V kappa Ox1 sequence.

Amino Acid Sequence↗