Fetal cervical hyperextension in arthrogryposis

Perhaps the most dramatic position of a newborn after delivery is when there is hyperextension of the neck and spine. It will have been presented in utero and today, almost always, such babies will have been delivered by C‐section. The associated anomalies are variable. The process(es) that can lead to cervical hyperextension is/are largely unknown. The outcome is variable from lethal to completely resolve. Individuals with arthrogryposis and in particular with Amyoplasia appear to have an increased frequency of neck, cervical, and spine hyperextension at birth. We present here 41 cases of arthrogryposis (mainly Amyoplasia) with fetal cervical hyperextension. The outlook is surprisingly good if spinal cord trauma does not occur. Ultrasound late in pregnancy when arthrogryposis is recognized prenatally should determine whether cervical hyperextension has developed, so that appropriate preventive measures can be taken.     

The major histocompatibility complex (CyLA) of the cynomolgus monkey. I. Serologic definition of 21 specificities

Thirty-seven lymphocytotoxic antisera, 27 of which were raised by immunization with skin grafts and blood from partially matched donors, were tested against cells obtained from 218 unrelated animals and 205 offspring from a colony of cynomolgus monkey (Macaca fascicularis). Evidence was obtained for the presence of at least 21 specificities defined by cluster analysis and segregation within families. Allelic relationships between 16 specificities was suggested by segregation patterns, the absence of triplets and statistical analysis of association in the unrelated population sample. The data support a two-locus model, with tentative assignment of seven specificities to the A locus and six to the B locus. That these lymphocyte alloantigens constitute the major histocompatibility complex (MHC) of the cynomolgus monkey is suggested by analogy with other known MHCs and by the increased survival times of skin grafts between paternally matched half sibs compared to haplodistinct full sibs.     

Characterization of a subtype of primary osteoclastoma: Extracellular calcium but not calcitonin inhibits aggressive HLA-DR-positive osteoclastoma possessing ‘functional’ calcitonin receptors

We report here a case of primary osteoclastoma that despite possessing HLA-DR-positive status and ‘functional’ calcitonin receptors, exhibited aggressive in vitro and in vivo bone resorptive activity. In the osteoclast bone slice assay employing scanning electron microscopy, the giant cell-mediated bone resorption was uninhibited by salmon calcitonin (10 nM) and significantly inhibited by raised extracellular calcium (20 mM). In Fura-2AM based microspectrofluorimetric assays, the presence of the ‘functional’ calcitonin receptors was ascertained by a rise in intracellular calcium induced by calcitonin and high extracellular calcium. These findings provide evidence for a hitherto unrecognized subtype of giant cells that have HLA-DR-positive status, exhibit avid bone resorptive activity, but remain insensitive to calcitonin despite possessing calcitonin receptors.     

Localization of class i histocompatibility molecule assembly by subfractionation of the early secretory pathway

Class I molecules of the major histocompatibility complex bind peptides derived from cytosolic proteins and display them on the cell surface. This function alerts cytotoxic T cells to the presence of intracellular pathogens. Class I molecule assembly requires the association of the heavy chain with β₂-microglobulin, accompanied by peptide loading via specific transporters. This study localizes where these assembly steps take place, using monoclonal antibodies recognizing class I molecules in different assembly states to analyze subcellular fractions of the early secretory pathway. The distribution of peptide-loaded class I molecules was more localized than the distribution of the total pool of class I molecules in the early secretory pathway. Loaded molecules colocalized with the peptide transporter, free heavy chains, and the chaperone calnexin in high density rough endoplasmic reticulum (RER) membranes. These data suggest that subunit assembly and peptide acquisition occur at the same intracellular site. Class I molecules also localized to less dense subfractions of the early secretory pathway, which contained comparatively less peptide-loaded molecules than the high density RER fractions, at steady state. Following a 15 °C temperature block, class I molecules accumulated in these less dense membrane fractions, indicating that these fractions represent the intermediate compartment where empty class I molecules are trapped in mutant cells. In the presence of cycloheximide, a pool of class I molecules recycling to the RER was detected, suggesting empty molecules recycle to acquire peptide.     

Marden-Walker syndrome: case report, literature review and nosologic discussion

Schrander-Stumpel C, de Die-Smulders C, de Krom M, Schyns-Fleuren S, Hamel B, Jaeken D, Fryns J-P. Marden-Walker syndrome: case report, literature review and nosologic discussion.
Clin Genet 1993: 43: 303–308. © Munksgaard, 1993
The Marden-Walker syndrome is characterized by psychomotor retardation, a mask-like face with blepharophimosis, micrognathia and a high-arched or cleft palate, low-set ears, kyphoscoliosis and joint contractures. We report on a male patient with the clinical features of the syndrome. In addition, he had a Dandy-Walker malformation with hydrocephalus and vertebral abnormalities. During pregnancy, there were feeble fetal movements and polyhydramnios. We propose that Marden-Walker syndrome is one of the etiologic possibilities in children with the heterogeneous fetal a(hypo)kinesia deformation sequence (FADS). Differential diagnosis is discussed. The etiology is probably heterogeneous.     

TCR repertoire in early fetal mouse thymus

We investigated the rearrangement and expression of TCR genesin mouse fetal thymus organ culture, a system that avoids subsequententry of hematopoietic precursor cells. The first observablerearranged TCR gene was homogeneous V2-J2, detectable as earlyas fetal day 11 (d11) in the thymic primordla. The productiveTCR was homogeneous V5-J1, first detectable in d13 thymocytes,followed by adult-type TCR (V4 and V7). Sequence analysis ofTCR revealed five types of V-J junctional sequences. In thevery early stage, a homogeneous V-J junction is generated viaa short homology sequence in the coding region (Type I), whilea short homology sequence in the P-nucleotlde rather than thecoding region is used in the following stage (Type II). In thelater embryonic stages, diverse V-J junctions are generatedby well-known mechanisms, such as P-nucleotide (Type III), N-regioninsertion (Type IV) or trimming of the coding ends (Type V).These findings suggest that the generation of homogeneous TCR (V2 and V5) in the early fetal stages is due to the intrinsicrearrangement mechanisms and is in stage specific manner.     

Prenatal presentation and diagnosis of Baraitser‐Winter syndrome using exome sequencing

Baraitser‐Winter cerebrofrontofacial syndrome (BWCFF) is a rare autosomal dominant developmental disorder associated with missense mutations in the genes ACTB or ACTG1. The classic presentation of BWCFF is discerned by the combination of unique craniofacial characteristics including ocular coloboma, intellectual disability, and hypertelorism. Congenital contractures and organ malformations are often present, including structural defects in the brain, heart, renal, and musculoskeletal system. However, there is limited documentation regarding its prenatal presentation that may encourage healthcare providers to be aware of this disorder when presented throughout pregnancy. Herein we describe a case of a pregnancy with large cystic hygroma and omphalocele. Whole exome sequencing (WES) was performed and a de novo, heterozygous, likely pathogenic mutation in ACTB was detected, c.1004G>A (p.Arg335His), conferring a diagnosis of BWCFF.     

A monoclonal antibody (RH1-38) which inhibits multiple systems of cell-mediated cytotoxicity--II. Evidence that the epitope recognized is involved in a late step in the cytolytic mechanism

A monoclonal antibody (RH1-38) which blocks multiple systems of cell-mediated cytotoxicity was functionally characterized. RH1-38 specifically blocks, in the absence of complement, natural killer (NK) activity (K562 targets) without any effect on NK-K562 conjugate formation. Kinetic studies suggested that the antibody blocks a step that occurs 30-120 min after effector populations are mixed with target cells. Single-cell cytotoxicity assays in agarose, combined with standard 51Cr release assays and Michaelis-Menten analysis revealed that RH1-38 markedly decreases Vmax and the number of active NK cells, again without any effect on the number of target-binding cells. The maximum recycling capacity was usually decreased, but in some experiments unchanged, in the presence of the monoclonal antibody. RH1-38 inhibited equally well whole peripheral blood mononuclear leukocytes (PBML), Percoll-fractionated lymphocytes enriched for NK activity, and interferon (IFN)-boosted NK activity. PBML exposed to RH1-38 and then washed mediated depressed NK activity which was partially reversed by subsequent treatment with IFN. These studies are most consistent with the hypothesis that RH1-38 inhibits a step late in the NK cytolytic mechanism rather than through an effect on conjugate formation. The primary effect is probably not on the IFN-generating or boosting mechanism, but a secondary effect on IFN-related mechanisms cannot be ruled out. Inhibition through an effect on a small lymphocyte modulator of NK activity is also unlikely but not rigorously excluded. Thus, RH1-38 appears to inhibit NK activity through a direct effect on NK effector cells, probably by interfering with a cell-surface molecule which is important in the expression of NK activity. The companion paper demonstrates that this monoclonal antibody immunoprecipitates a molecule which is very similar or identical to the LFA-1 antigen. Thus, RH1-38 recognizes either a novel epitope on the LFA-1 molecule or alternatively a distinct, functional killer cell surface molecule. The epitope appears to be involved in a late step in the cytolytic mechanism, possibly part of the effector cell lytic machinery.     

人胚胎大脑海马发育过程中凋亡神经元超微结构观察

本文借助电子显微镜技术对 4月胎龄组及 6月胎龄组水囊引产胎儿海马中段部位的凋亡神经元超微结构进行观察、拍照 ,并对结果进行了分析讨论。结果显示 :两组对象中均可见凋亡神经元 ,所见的凋亡神经元的超微结构变化基本相同 ,即细胞核内有明显的染色质边集和凝结成块的现象 ,并可见核膜皱缩和扭曲。另外 ,6月组凋亡细胞的结构变化较 4月组更为明显。在 6月组细胞质内和核内均有小体出现 ,其他细胞器无显著变化。从而更进一步说明在胚胎海马发育中存在着神经元不同性质的死亡现象 -即正常死亡和凋亡。而且提出 6月组显现出更为明显的凋亡神经元形态变化     

Threshold of seizure activity of the brain and higher nervous activity in the postresuscitation period for intracerebral allotransplantation of fetal neocortex tissue

The threshold of seizure activity of the brain, long-term memory, and learning ability are studied in Wistar rats for bilateral transplantation of fetal nervous tissue in area CA1 of the hippocampus. The grafts are performed on the 2nd, 7th, 14th and 30th days after clinical death caused by asphyxia. A neurotransplantation performed on the 2nd day of the postresuscitation period is found to prevent seizure activity, whereas that performed on the 7th–14th days results in a sharp decline or cessation of spontaneous and induced epileptiform convulsive seizures, prolonged preservation of the long-term memory trace, an improvement of learning ability, and a lessening of defensive and phobic behavior in a large proportion of the animals. Translated fromByulleten's Eksperimental'noi Biologii i Meditsiny, Vol. 121, N ^o 2, pp. 234–237, February, 1996 Presented by V. A. Negovskii, Member of the Russian Academy of Medical Sciences