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.     

Increased collagen around deformed finger nailfold capillaries in type I diabetes mellitus

Summary Quantitative finger nailfold capillary microscopy was performed in 25 patients with type I diabetes and in 27 healthy control subjects. In the last consecutive 6 patients and 7 controls of these populations, finger nailfold biopsies were taken. Measurements of loop width as an in vivo parameter for deformities of the capillary loops showed significantly higher values in diabetic patients than in controls. Histopathological examination showed markedly and significantly increased deposition of collagen in nailfold dermal papillae of the diabetic patients. The deposition of collagen was positively correlated with the number of capillary endothelial cells in the nailfold dermal papillae and with the size of the papillae in diabetic patients. It is concluded that, in addition to deformity of nailfold capillaries, collagen deposition may also be a sign of metabolic disturbance and perhaps of proliferation of capillary endothelial cells in diabetic microangiopathy.Supported by the Swiss National Fund for Scientific Research, grant number 3.904-0.86     

Tifluadom, a kappa-opiate agonist, acts as a peripheral cholecystokinin receptor antagonist

Tifluadom, a benzodiazepine kappa-opiate agonist, stereoselectively inhibited the binding of 125I-CCK to pancreatic membranes (IC50 = 47 nM). Several other opiate agonists were ineffective. Scatchard analysis indicated the inhibition of CCK binding by tifluadom was competitive in nature. Tifluadom (1 microM) did not displace 125I-CCK binding to brain tissue or 125I-gastrin binding to fundic glands. In the isolated guinea pig gallbladder, tifluadom antagonized CCK-8 induced contractions with an estimated pA2 of 6.8. These data demonstrate that tifluadom is a peripherally selective CCK antagonist. This unique action could contribute to its reported analgesic and appetite stimulatory properties.     

Atrial sympathetic and parasympathetic nerve sprouting and hyperinnervation induced by subthreshold electrical stimulation of the left stellate ganglion in normal dogs

BACKGROUND: Subthreshold electrical stimulation of the left stellate ganglion (LSG) can induce nerve sprouting and sympathetic hyperinnervation in canine ventricles. It is unclear whether a similar neural plasticity involving both sympathetic and parasympathetic innervation also exists in the atria. METHODS AND RESULTS: We applied subthreshold electrical stimulation at 20 Hz (0.45 ms pulse width) or 5 Hz (1.9 ms pulse width) to the LSG in 6 normal mongrel dogs. After 41+/-9 days, the hearts were harvested and the right and left atrium stained for synaptophysin (SYN), growth-associated protein 43 (GAP43), sympathetic nerve markers tyrosine hydroxylase (TH), and parasympathetic marker choline acetyltransferase (ChAT). Tissues from 6 additional healthy dogs were used as controls. The hearts from dogs with LSG electrical stimulation had a higher density of nerve structures immunopositive to the SYN, GAP43, TH, and ChAT (P<.01) in both right and left atria. Nerve density was equal in right and left atria. There were more TH-positive nerve structures than ChAT-positive nerve structures (P<.01) for both right and left atria. No atrial arrhythmia was observed at the second surgery. CONCLUSIONS: Continuous subthreshold electrical stimulation to the LSG induces both sympathetic and parasympathetic hyperinnervation in both right and left atria in normal dogs.     

Taurine reduces high glucose induced leukocyte–endothelial interactions via down-regulation of ICAM-1

Taurine is a semiessential amino acid and naturally occurring antioxidant. One of its main roles is to protect tissues against attack by chlorinated oxidants particularly hypochlorous acid (HOCl). It is found in high concentrations in neutrophils and previous studies showed it possesses potent antimicrobial properties and attenuates high glucose induced endothelial cell apoptosis. In humans taurine has been shown to up-regulate constitutive nitric oxide synthase (cNOS), a known cytoprotector.
No reported studies to date have looked at the possible therapeutic role of taurine in preventing diabetic endothelial dysfunction. We therefore hypothesised that taurine would attenuate the microvascular changes associated with hyperglycaemia in an animal model through alteration of leucocyte–endothelial interactions.
Male Sprague Dawley rats were randomised into control, hyperglycaemia, and taurine + hyperglycaemia groups. Taurine was gavaged (200 mg/kg) for 5 d prior to the experiment. Hyperglycaemia was established by intravenous infusion of 50% glucose. Blood glucose reached a steady state of 3 times baseline at 30 min. Using intravital microscopy leukocyte rolling, adhesion and transendothelial migration was determined in mesenteric postcapillary venules for 3 h. Intracellular adhesion molecule-1 (ICAM-1) was immunohistochemically graded using a scoring system to determine the expression in mesenteric tissue.
Taurine pretreatment significantly attenuates leukocyte-endothelial adhesion and transendothelial migration following acute hyperglycaemia but not leukocyte rolling velocity. The mechanism by which taurine protects against these effects is in part by inhibition of ICAM-1 expression .  

      

997.

Small-signal analysis of response of mammalian muscle spindles with fusimotor stimulation and a comparison with large-signal responses.     

W J Chen  R E Poppele 《Journal of neurophysiology》1978,41(1):15-27

1. Response dynamics of primary and secondary muscle spindle endings to small-amplitude sinusoidal stretches were found to be unaltered by tonic repetitive stimulation of fusistatic or fusidynamic fibers. 2. Overall sensitivity of these receptors is decreased by fusistatic stimulation and either unchanged, increased, or decreased by fusidynamic stimulation at rates of 75/s or greater. 3. In the case of primary endings, the results obtained with small-amplitude sinusoidal stretches are not compatible with the response of these receptors to large-amplitude ramp stretches. The difference is explained by dependence of receptor dynamics on stretch amplitude. Fusistatic stimulation tends to prevent those changes in dynamics, whereas fusidynamic stimulation tends to enhance them. 4. In the case of secondary endings, the results obtained with small- and large-amplitude stretches appear to be compatible with a linear model for this receptor (i.e., one with dynamics independent of input parameters). 5. By modulating the frequency of stimulation applied to fusimotor fibers and comparing the resulting afferent response to the receptor response to stretch dynamic characteristics of intrafusal muscle contraction can be deduced. The results suggest that the dynamics of fusiastatic and fusidynamic contraction are the same and, furthermore, that they are the same as those of extrafusal muscle. We note that the result is incompatible with measurements of the time course of twitch and tetanus development and suggest, therefore, that muscle dynamics are a function of contractile state.     

998.

A new haplogroup pattern displayed in Fujian Han in China   总被引：1，自引：0，他引：1  

Yu M  Zhang Y  Xue Y  Chen F  Wang Q  Huang X  Wang B  Yu Y  Liu A  Ma L  Shi R  Lu F  Shi Z  Zhang Y  Cheng W  Ai Q  Xu F  Huang C  Chen B  Yang H  Kang X  Sun Y  Zhang G  Li P  Fu S 《Journal of human genetics》2002,47(2):95-98

Human Y-chromosomal binary polymorphisms have been considered to preserve the paternal genetic legacy and provide evidence on human evolution and the genetic relationships among and demographic history of different populations. To reveal the genetic origin and immigration of the Fujian Han, 13 binary markers on the Y chromosome were used to screen Fujian Han by allele-specific polymerase chain reaction. The results indicated that the M₉G marker was highly prevalent (96.20%), suggesting a significant genetic drift. In addition, M₁₂₂C frequency was only 22.78%, and M₄₅A and M₁₀₃T were default. The distinctive haplogroup frequencies (H₁, H₅, and H_6/7/8) imply that the haplogroup pattern is a relatively ancestral and interim type. Received: October 13, 2001 / Accepted: December 3, 2001     

999.

Determinants of rotavirus stability and density during CsCl purification.     

D Y Chen  R F Ramig 《Virology》1992,186(1):228-237

The stability of rotavirus infectivity during CsCl gradient purification and subsequent storage was examined using our standard SA11 wild type (SA11-Cl3), the SA11 4F variant (SA11-4F), bovine rotavirus B223, and a panel of bi- and triparental reassortants derived from these parental viruses. Viral stability was determined by the recovery of infectivity at each step during a standard CsCl purification protocol. SA11-4F was the most stable parent (91-93% recovery), SA11-Cl3 had intermediate stability (10-21% recovery), and B223 was least stable (0.5-7% recovery). Among the reassortants, the recovery varied from 0.5 to 88.6% of the initial infectivity and was determined primarily by the parental origin of genome segment 4. The greatest loss of infectivity occurred during Freon extraction, with smaller losses during the CsCl gradient, and the smallest loss during the virus pelleting step. Comparison of the stability of viruses grown in the presence or absence of exogenous trypsin revealed that, in general, viruses grown in the absence of trypsin were more stable during purification. During 4-5 months storage at 4 degrees, the differences in stability of parental and reassortant viruses were not as dramatic as during purification and were not significantly affected by the presence or absence of trypsin during growth. However, survival during storage was as low as 4% and as high as 100% and was also primarily dependent on the parental origin of genome segment 4. It was noted that bovine rotavirus B223 had higher density in CsCl than either SA11-Cl3 or SA11-4F. The observation of heterogeneity in density was investigated using reassortants. These results indicated that all reassortants had intermediate density and suggested that physical interactions among the structural proteins were responsible for the heterogeneity in density. The possible roles of viral structural proteins in rotavirus stability and the relationship between the stability and the density are discussed.     

1000.

Gm allotypes in blacks with systemic lupus erythematosus   总被引：3，自引：0，他引：3  

J A Fedrick  J P Pandey  Z Chen  H H Fudenberg  S K Ainsworth  R L Dobson 《Human immunology》1983,8(2):177-181

Serum samples were collected from 328 healthy American Blacks and from 61 American Blacks with systemic lupus erythematosus (SLE). Sera were typed for the Gm1,2,3,5,6,13,17, and 21 allotypes as well as for the Km(1) allotype. The frequency of Gm phenotype 1,17;5,6,13 was significantly increased in the SLE patients (p = 0.0001, RR = 3.19, EF = 0.29). Our data suggest the existence of at least two immunoglobulin allotype associated genes that somehow interact to increase susceptibility to SLE in Blacks. To our knowledge, this is the first report of an association of Gm and SLE in Blacks.     

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Small-signal analysis of response of mammalian muscle spindles with fusimotor stimulation and a comparison with large-signal responses.

1. Response dynamics of primary and secondary muscle spindle endings to small-amplitude sinusoidal stretches were found to be unaltered by tonic repetitive stimulation of fusistatic or fusidynamic fibers. 2. Overall sensitivity of these receptors is decreased by fusistatic stimulation and either unchanged, increased, or decreased by fusidynamic stimulation at rates of 75/s or greater. 3. In the case of primary endings, the results obtained with small-amplitude sinusoidal stretches are not compatible with the response of these receptors to large-amplitude ramp stretches. The difference is explained by dependence of receptor dynamics on stretch amplitude. Fusistatic stimulation tends to prevent those changes in dynamics, whereas fusidynamic stimulation tends to enhance them. 4. In the case of secondary endings, the results obtained with small- and large-amplitude stretches appear to be compatible with a linear model for this receptor (i.e., one with dynamics independent of input parameters). 5. By modulating the frequency of stimulation applied to fusimotor fibers and comparing the resulting afferent response to the receptor response to stretch dynamic characteristics of intrafusal muscle contraction can be deduced. The results suggest that the dynamics of fusiastatic and fusidynamic contraction are the same and, furthermore, that they are the same as those of extrafusal muscle. We note that the result is incompatible with measurements of the time course of twitch and tetanus development and suggest, therefore, that muscle dynamics are a function of contractile state.     

A new haplogroup pattern displayed in Fujian Han in China

Human Y-chromosomal binary polymorphisms have been considered to preserve the paternal genetic legacy and provide evidence on human evolution and the genetic relationships among and demographic history of different populations. To reveal the genetic origin and immigration of the Fujian Han, 13 binary markers on the Y chromosome were used to screen Fujian Han by allele-specific polymerase chain reaction. The results indicated that the M₉G marker was highly prevalent (96.20%), suggesting a significant genetic drift. In addition, M₁₂₂C frequency was only 22.78%, and M₄₅A and M₁₀₃T were default. The distinctive haplogroup frequencies (H₁, H₅, and H_6/7/8) imply that the haplogroup pattern is a relatively ancestral and interim type. Received: October 13, 2001 / Accepted: December 3, 2001     

Determinants of rotavirus stability and density during CsCl purification.

The stability of rotavirus infectivity during CsCl gradient purification and subsequent storage was examined using our standard SA11 wild type (SA11-Cl3), the SA11 4F variant (SA11-4F), bovine rotavirus B223, and a panel of bi- and triparental reassortants derived from these parental viruses. Viral stability was determined by the recovery of infectivity at each step during a standard CsCl purification protocol. SA11-4F was the most stable parent (91-93% recovery), SA11-Cl3 had intermediate stability (10-21% recovery), and B223 was least stable (0.5-7% recovery). Among the reassortants, the recovery varied from 0.5 to 88.6% of the initial infectivity and was determined primarily by the parental origin of genome segment 4. The greatest loss of infectivity occurred during Freon extraction, with smaller losses during the CsCl gradient, and the smallest loss during the virus pelleting step. Comparison of the stability of viruses grown in the presence or absence of exogenous trypsin revealed that, in general, viruses grown in the absence of trypsin were more stable during purification. During 4-5 months storage at 4 degrees, the differences in stability of parental and reassortant viruses were not as dramatic as during purification and were not significantly affected by the presence or absence of trypsin during growth. However, survival during storage was as low as 4% and as high as 100% and was also primarily dependent on the parental origin of genome segment 4. It was noted that bovine rotavirus B223 had higher density in CsCl than either SA11-Cl3 or SA11-4F. The observation of heterogeneity in density was investigated using reassortants. These results indicated that all reassortants had intermediate density and suggested that physical interactions among the structural proteins were responsible for the heterogeneity in density. The possible roles of viral structural proteins in rotavirus stability and the relationship between the stability and the density are discussed.     

Gm allotypes in blacks with systemic lupus erythematosus

Serum samples were collected from 328 healthy American Blacks and from 61 American Blacks with systemic lupus erythematosus (SLE). Sera were typed for the Gm1,2,3,5,6,13,17, and 21 allotypes as well as for the Km(1) allotype. The frequency of Gm phenotype 1,17;5,6,13 was significantly increased in the SLE patients (p = 0.0001, RR = 3.19, EF = 0.29). Our data suggest the existence of at least two immunoglobulin allotype associated genes that somehow interact to increase susceptibility to SLE in Blacks. To our knowledge, this is the first report of an association of Gm and SLE in Blacks.