Successful in-vitro fertilization pregnancy with spermatozoa from a patient with Kartagener's syndrome: case report

This paper reports on the successful treatment by in-vitro fertilization (IVF) of a couple in whom the male partner had Kartagener's syndrome. His spermatozoa were severely asthenozoospermic with deficient dynein arms and disordered microtubular configuration. On computer-assisted sperm analysis (CASA) motile spermatozoa displayed straight non-progressive motility with minimal amplitude of lateral head displacement and none were hyperactivated. This is the first case report in which spermatozoa with axonemal disruption in a man with immotile cilia syndrome (ICS) have been shown to be able to penetrate the zona pellucida and fertilize oocytes. IVF may be a suitable treatment for certain variants of ICS.     

Specifically associated PCR products probed by coincident detection of two-color cross-correlated fluorescence intensities in human gene polymorphisms of methylene tetrahydrofolate reductase at site C677T: a novel measurement approach without follow-up mathematical analysis

Whole blood samples of known methylene tetrahydrofolate reductase (MTHFR) genotypes from 24 individuals were examined at site C677T. Their amplified DNA products were assessed by two-color fluorescence cross-correlation measurements and agarose gel electrophoresis/capillary gel electrophoresis. DNA subpopulations were identified which were not associated with the proper genotype by primer combinations and cycling conditions called multiplexes. We confirmed that DNA analysis by two-color fluorescence cross-correlation measurements allowed the detection of fluorescence signals specifically associated with the proper genotypes in a mixture of amplified nontarget DNA molecules without DNA sizing. The measurement approach does not require complex, follow-up mathematical analysis and is applicable to any single nucleotide polymorphisms. The simple immunogenetic model showed how the approach works to reveal specific DNA target by preventing detection of nontarget DNA. Under those experimental conditions, a new ultrasensitive, and specific method for clinical immunologists is born.     

新生儿G6PD缺陷病和晚发性维生素K缺乏症的特点与预防

目的 探讨新生儿C6PD缺陷病和晚发性维生素K缺乏症的危害与预防措施。方法 回顾分析1995-2000年儿内科住院的1周-2月(不含2月)的婴儿3104例次，其中病死56例。结果 1周-2月的小婴儿占住院患儿的19．34％，其中新生儿G6PD缺陷病239例，占7．70％；晚发性维生素K缺乏症92例，占2．96％。死因的第2、3位分别是晚发性维生素K缺乏症(13例，占23．21％)和新生儿C6PD缺陷病(12例，占21．43％)，两者的病死率分别为14．13％和5．02％，极显著高于(x^2＝17．59，P＜0．01)或相近于(x^2＝0．88，P＞0．05)肺炎的3．57％。新生儿G6PD缺陷病合并感染占38．49％、低氧血症占23．35％、低血糖占19．25％、酸中毒占15．90％，继发胆红素脑病占13．81％。晚发性维生素K缺乏症出现抽搐占90．22％、胃肠、注射部位出血占60．89％；CT证实颅内出血占98．91％。结论 1周-2月的小婴儿约占住院患儿的两成，新生儿G6PD缺陷病和晚发性维生素K缺乏症的病死率均很高，两者是除肺炎外最主要的死因。提议制定并推广预防这2种疾病的常规措施，并参照国内外相应的现状拟出其具体内容。     

IL-10-driven immunoglobulin production by B lymphocytes from IgA-deficient individuals correlates to infection proneness

In search for a possible explanation of the phenotypic heterogeneity in IgA deficiency, we studied the function of B cells from IgA-deficient (IgAd) individuals. Two groups of IgAd individuals, one frequently infected and one clinically apparently healthy, as well as normal controls, were studied. Peripheral blood mononuclear cells (PBMC) and B cells from IgAd individuals and controls were cultured with Staphylococcus aureus Cowan I strain and with anti-CD40 MoAb presented on the CD32-transfected fibroblast cell line in the presence of IL-10. In this experimental system PBMC and B cells from the infection-prone IgAd individuals produced only minute amounts of IgA. In contrast, PBMC and B cells from healthy IgAd subjects secreted significantly more IgA1 and IgA2 in comparison with infection-prone IgAd patients (P < 0.05). These data suggest that the abnormalities of B cell differentiation in IgAd could be of heterogeneous origin. Thus, whereas in healthy IgAd subjects IgA production may be efficiently up-regulated in vitro by addition of IL-10 to CD40-activated B cell culture, the corresponding B cell differentiation does not occur in infection-prone IgAd patients. These observations provide a conceptual framework for phenotypic heterogeneity in IgAd subjects.     

中国汉族雄激素过多症女性21-羟化酶缺陷症携带者基因检测

目的　初步了解中国汉族女性雄激素过多症患者中2 1-羟化酶缺陷症(2 1- hydroxylasedeficiency,2 1- OHD)携带者发生率,探讨促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)兴奋试验结果与基因突变检测结果的相关性。方法　82例汉族女性雄激素过多症患者及14名健康女性进行ACTH兴奋试验,并应用PCR扩增产生限制性酶切位点方法检测已知的9个2 1- OHD常见突变位点。结果　雄激素过多组(n=82 ) F0 显著高于正常对照组(P<0 .0 1) ;17- OHP0 及17- OHP6 0 也显著高于对照组(P<0 .0 1) ,而F6 0 差异没有统计学意义(P>0 .0 5 )。比较17- OHP净增值及17- OHP净增值/ F净增值,雄激素过多组也均显著高于正常对照组(P<0 .0 1)。正常对照组未检测出细胞色素P4 5 0 (cytochrome P4 5 02 1,CYP2 1)基因突变。发现雄激素过多组4例CYP2 1基因突变携带者(4/ 82 ,4 .9% ) ,分别携带V2 81L(2例) ,i2 g及Q318X(各1例) ,携带者的ACTH兴奋试验结果与正常对照及未检出突变的雄激素过多症患者的结果存在一定的交叉。结论　82例汉族雄激素过多症女性中2 1- OHD携带者为4例,占4 .9%。ACTH兴奋试验不能用以发现携带者,应进行基因检测确定。     

Muscle cell leakage due to long distance training

Summary Abnormal myoglobinemia (above 77 g/1) and free hemoglobin in plasma were found in 16 runners and in nine non runners immediately following distance running. The same abnormalities were found in six elite rowers following rowing. In parallel with the rise in myoglobin and free hemoglobin a rise was found in serum concentrations of cellular enzymes (LDH, CK, ASAT, alkaline phosphatase) and of various metabolites. We found no proteinuria nor casts in the urine. Non runners had a higher rise in serum myoglobin than runners. Competitive running caused a rise in the serum concentration of the heart specific fraction of creatine kinase in seven of the nine (healthy) elite runners. The abnormal findings are only explainable on the basis of leakage of proteins from muscle cells to the circulation in otherwise healthy, well trained persons. Myoglobinemia and a transient rhabdomyolysis is a common phenomenon in long distance running, but evidently also occurs in distance rowing. Three months of running training prevented most of the muscle damage from relaxed jogging in the nine previous non runners. Neither the observed myoglobinemia nor the hemoglobinemia resulted in any significant loss of iron in the urine.Supported by IdrÆttens Forskningsråd, Dansk IdrÆtsforbund     

Diagnosis of arylsulfatase A deficiency in intact cultured cells using a fluorescent derivative of cerebroside sulfate

A fluorescent derivative of cerebroside sulfate (12-(1-pyrene)dodecanoyl-sphingosylgalactosyl-0-3-sulfate (P12-sulfatide) has been synthesized as a potential substrate for the determination of cerebroside sulfatidase (or arylsulfatase A) activity. It was administered into cultured human skin fibroblasts and thereby utilized for the diagnosis of arylsulfatase A deficiency. Cultured skin fibroblasts from normal individuals and healthy persons suffering from a pseudoarylsulfatase A deficiency (PD) degraded the P12-sulfatide, while in cells derived from a metachromatic leukodystrophy (MLD) patient it remained essentially intact. This contrasts with in vitro determinations of enzymatic activity, where the MLD or PD-derived arylsulfatase A exhibit similar deficiency, in spite of a profoundly different clinical course. Administration of the fluorescent sulfatide into the intact cells permitted a sensitive and rapid diagnosis of MLD and its distinction from the PD-phenomenon. This might be of particular importance for cases in which a rapid diagnosis is required and for prenatal diagnosis of fetuses from families afflicted with both MLD and pseudo-deficiency mutant genes.     

Prevalence, geographical distribution and genealogical investigations of mutation 188 of lipoprotein lipase gene in the French Canadian population of Québec

Familial lipoprotein lipase deficiency (FLD) is of particular interest to the French Canadian population of Québec since the largest concentration of homozygotes and carriers of this genetic disease in the world resides in this area. We have previously described a missense mutation (M-188) in the lipoprotein lipase (LPL) gene which was present in FLD patients belonging to different ancestries, including a number of French Canadians (Monsalve MV et al. J Clin Invest 1990: 86: 728-734). In the present report, we show that this mutation, although found in largest absolute numbers among French Canadians as compared to other groups in the world, accounts for only a small proportion (24%) of all the LPL mutant alleles in this population. The M-188 occurs either in the homozygote state or as a compound heterozygote with another LPL mutation. Analysis of geographic distribution indicates that the M-188 is more prevalent in western Québec, with the highest carrier rate in the Mauricie region. Genealogical reconstruction leads to the recognition of four founders for M-188, all emigrants from France to Québec in the 17th century.     

Functional vulnerability of developing central nervous system to maternal thiamine deficiencies in the rat

Thiamine deficiency (B1 vitamin) was induced during three periods of rat central nervous system (CNS) ontogenesis. Females were fed a thiamine deficient diet such that developing offspring were exposed either to pre-, peri-, or postnatal thiamine deficiency. To control the effects of undernourishment generated by different thiamine deficiencies, every treatment group had its own pair-fed control pup from a non drug-treated but undernourished dam. Seven different developmental abilities (exploratory activity, emotional reaction, hind paws lifting reflex, wire grasping times, crawling and leap execution latencies, and nociception) were recorded in the offspring from the 10th to the 45th postnatal day. The vulnerability of developing brain to the specific lack of B1 vitamin increases from prenatal (28%) to perinatal (43%) and postnatal periods (57%).