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.     

The levels and bactericidal capacity of antibodies directed against the UspA1 and UspA2 outer membrane proteins of Moraxella (Branhamella) catarrhalis in adults and children

The UspA1 and UspA2 proteins from Moraxella catarrhalis share antigenic epitopes and are promising vaccine candidates. In this study, the levels and bactericidal activities of antibodies in sera from healthy adults and children toward UspA1 and UspA2 from the O35E strain were measured. Human sera contained antibodies to both proteins, and the levels of immunoglobulin G (IgG) antibodies were age dependent. Adult sera had significantly higher titers of IgG than child sera (P < 0.01). The IgG3 titers to the UspA proteins were higher than the IgG1 titers in the adults' sera, while the IgG1 titers were higher than the IgG3 titers in the children's sera (P < 0.05). The IgG antibodies in the sera from 2-month-old children appeared to be maternally derived, since the mean titer was significantly higher than that in sera from 6- to 7-month-old children (P < 0.05). Serum IgA antibodies to both UspA1 and UspA2 were low during the first 7 months of age but thereafter gradually increased along with the IgG titers. Analysis of sera absorbed with UspA1 or UspA2 showed that the antibodies to UspA1 and UspA2 were cross-reactive with each other and associated with serum bactericidal activity. Examination of affinity-purified human antibodies confirmed that naturally acquired antibodies to UspA1 and UspA2 were bactericidal and cross-reactive. These results support using UspA1 and UspA2 in a vaccine to prevent M. catarrhalis infections.     

Progressive decrease of proinsulin secretion in sulphonylurea-treated type 2 diabetes

Progressive deterioration of beta-cell function is proposed as a disease-related factor of sulphonylurea (SU) failure in type 2 diabetes. If it gradually worsens over time then disease duration may mirror the progressive beta-cell deterioration. The aim of the present study is to assess whether or not disease duration is influential in remodelling the secretion pattern of insulin-like molecules and in glucose control of SU-treated type 2 diabetes. A research model is used to investigate proinsulin secreting capacity over time, using two groups of patients: i) disease duration <5 years (n=62), comprising SU responders (SUr; n=48) and SU failures (SUf; n=14); and ii) disease duration > or = 5 years (n= 37), comprising an SUr group (n=17) and an SUf group (n=20). Blood samples are taken at 0 h, 0.5 h 1 h, 2 h and 3 h during a standard oral glucose tolerance test and measured for glucose, total proinsulin (TPI), intact proinsulin (IPI) and specific insulin (SI) concentrations. Pairwise comparison of estimated marginal means of blood glucose, SI, IPI and TPI levels at each time point are carried out between groups and subgroups. (SUr vs. SUf). Homa insulin resistance index (IR index) is applied to analyse IR between the groups. It was found that patients with shorter disease duration had higher proinsulin (TPI and IPI) levels at all time points (P<0.05), together with a lower glucose level at 2 h and 3 h (P<0.05). Homa insulin index analysis showed no difference between the two groups (P=0.26). Results also showed that the SUr group had a significantly lower glucose level at Oh and 3h (P<0.05), although no significant difference in insulin and proinsulin levels was found between the SUr and SUf groups. In conclusion, proinsulin may play an important role in glucose control in SU-treated type 2 diabetes, but the effect is reduced in SUf patients.     

Identification of a new locus for autosomal dominant non-syndromic hearing impairment (DFNA7) in a large Norwegian family

Hereditary hearing impairment affects about 1 in 1000 newborns. In most cases hearing loss is non-syndromic with no other clinical features, while in other families deafness is associated with specific clinical abnormalities. Analysis of large families with non-syndromic and syndromic deafness have been used to identify genes or gene locations that cause hearing impairment. The present report describes a large Norwegian family with autosomal dominant non-syndromic, progressive high tone hearing loss with linkage to 1q21-q23. A maximum LOD score of 7.65 (theta = 0.00) was obtained with the microsatellite marker D1S196. Analysis of recombinant individuals maps the deafness gene (DFNA7) to a 22 cM region between D1S104 and D1S466. The region contains several attractive candidate genes. This report supports the idea of extensive genetic heterogeneity in hereditary hearing impairment and represents the first localization of a deafness gene in a Norwegian family.      

Deletion of stem-loop 3 is compensated by second-site mutations within the Gag protein of human immunodeficiency virus type 1

Encapsidation of human immunodeficiency virus type 1 (HIV-1) RNA involves specific interactions between viral Gag proteins and viral RNA elements located at the 5' untranslated region (UTR). These RNA elements are termed packaging (psi) or encapsidation (E) signals and mainly comprise the stem-loop 1 (SL1) and SL3 RNA structures. We have previously shown that deletion of the SL1 sequences is compensated by second-site mutations within Gag. Similar studies are now extended to SL3 and the results demonstrate that deletion of this RNA structure is rescued by two point mutations, i.e., A11V in p2 and I12V in nucleocapsid (NC). These two compensatory mutations are different from those associated with the rescue of SL1 deletion, suggesting that SL1 and SL3 may bind to different residues of Gag during viral RNA packaging. Analysis of virion-derived RNA in native agarose gels shows that deletion of SL3 leads to decreases in both viral RNA packaging and dimerization. These defects are corrected by the compensatory mutations A11V and I12V. Yet, defects in viral RNA dimerization at an early stage that were caused by the SL3 deletion in the context of a viral protease-negative mutation cannot be overcome by these two suppressor mutations. Therefore, the positive effects of A11V and I12V on dimerization of the SL3-deleted RNA must have taken place at the maturation stage.     

Criteria for the administration of KI for thyroid blocking of radioiodine

Scientific data are reviewed to evaluate the risks of radioiodine uptake and to compare those risks with the benefits and risks of low milligram doses of stable potassium iodide (KI). The limit of 25 rad to the thyroid due to radioiodine uptake is adopted as the "break-even" point above which 130-mg KI doses should be administered. The biological and radiological kinetics of radioiodine for protracted uptakes were derived from the Medical Internal Radiation Dose Committee (MIRD) model (MIRD75). Resulting calculations yielded estimates of dose commitment rates to the thyroid as a function of thyroidal uptake. The extrapolated value of the 1-hr inhalation curve for 131I with 30% uptake compares well with the established MPCa value and intercepts the origin. The calculated KI-blocking efficiency as a function of time after radioiodine uptake agrees well with previously reported experimental data. The prevention or "blocking" of 25 rad to the thyroid was the criterion used to define critical values of radioiodine in the thyroid. Critical values are functions of isotope, the duration of uptake and the elapsed time between inhalation and assay of thyroid content. The presence of radioiodine in the thyroid in amounts greater than the critical value indicates that more than 25 rad to the thyroid can be averted, and KI should be administered in the absence of contraindications. Critical average concentrations are implicitly defined by the method of calculation used in the derivation. Critical average concentrations are presented as criteria for KI administration when assays of the radioiodine content of the thyroid are unavailable. Illustrative applications of critical values and critical average concentrations are presented in the Appendix.     

Histiocytoid hemangioma of the heart with peripheral eosinophilia

A histiocytoid hemangioma of the heart is reported, which was found incidentally in a man with unusually high eosinophilia. The eosinophilia subsided dramatically following removal of the tumor. The "histiocytoid" or the "epithelioid" appearance of the tumor cells and the presence of vacuolated cells were the characteristic microscopic features. The endothelial origin of this tumor was verified by positive immunostaining for factor VIII-related antigen and ultrastructural demonstration of intracytoplasmic lumen formation, abundant cytoplasmic filaments, pinocytotic vesicles, and prominent basal lamina. The presence of mitotic activity, cellular pleomorphism, and tumor necrosis raised the possibility of its malignant potential. The occurrence of this tumor in the heart may be mistaken for a myxoma clinically and a metastatic carcinoma pathologically.