Vascular birthmarks of infancy: resolving nosologic confusion

The terminology describing congenital vascular birthmarks has been a source of confusion in the medical literature. Mulliken and Glowacki [1982: Plas. Recons. Surg. 69:412-422] published a biologic classification system which has become the most widely accepted framework for classifying vascular birthmarks and is accepted as the official classification schema by the International Society for the Study of Vascular Anomalies (ISSVA). In this study, we evaluate the current nosology of vascular birthmarks used in standard medical genetics reference texts compared with the accepted Mulliken ISSVA framework. In five sources examined, a variety of terms were used to describe congenital vascular anomalies. The degree of agreement with accepted ISSVA classification varied both within and among texts, with agreement as low as 22% and as high as 75%. In all texts, hemangioma was the most commonly used term, appearing 79 times. Use of the term "hemangioma" had the lowest rate of agreement with the ISSVA classification criteria, with agreement in 23% of citations. The terms "vascular malformation" and "port-wine stain" were used less frequently, but with a much higher degree of agreement with the ISSVA classification: 82% and 66%, respectively. These results establish that nosologic confusion is widespread even in standard genetic reference texts. In particular, the term "hemangioma" is used imprecisely. The ISSVA classification system provides an extremely useful framework for geneticists to classify vascular birthmarks in their evaluation of infants and children with vascular anomalies in order to provide more accurate evaluation, prognosis, and genetic counseling.     

The Plasmodium falciparum knob-associated PfEMP3 antigen is also expressed at pre-erythrocytic stages and induces antibodies which inhibit sporozoite invasion

The expression of the pfemp3 gene and the corresponding PfEMP3 knob-associated protein in the pre-erythrocytic stages of Plasmodium falciparum was demonstrated by RT-PCR, Western blots, IFAT and IEM. The antigen was found on the surface of the sporozoite and in the cytoplasm of mature hepatic stage parasites. Immunological cross-reactivity was observed with sporozoites from the rodent malaria parasites Plasmodium yoelii yoelii and Plasmodium berghei and was exploited to assess a potential role of this protein at the pre-erythrocytic stages. Specific antibodies from immune individuals were found to inhibit P. yoelii yoelii and P. berghei sporozoite invasion of primary hepatocyte cultures. PfEMP3 should now be added to the small list of proteins expressed at the pre-erythrocytic stages of P. falciparum, and its vaccine potential now deserves to be investigated.     

Spectrum of mutations in the Fanconi anaemia group G gene, FANCG/XRCC9

FANCG was the third Faconi anaemia gene identified and proved to be identical to the previously cloned XRCC9 gene. We present the pathogenic mutations and sequence variants we have so far identified in a panel of FA-G patients. Mutation screening was performed by PCR, single strand conformational polymorphism analysis and protein truncation tests. Altogether 18 mutations have been determined in 20 families - 97% of all expected mutant alleles. All mutation types have been found, with the exception of large deletions, the large majority is predicted to lead to shortened proteins. One stop codon mutation, E105X, has been found in several German patients and this founder mutation accounts for 44% of the mutant FANCG alleles in German FA-G patients. Comparison of clinical phenotypes shows that patients homozygous for this mutation have an earlier onset of the haematological disorder than most other FA-G patients. The mouse Fancg sequence was established in order to evaluate missense mutations. A putative missense mutation, L71P, in a possible leucine zipper motif may affect FANCG binding of FANCA and seems to be associated with a milder clinical phenotype.     

Erythropoietin and renin substrate in cerebellar haemangioblastoma

We examined eight cerebellar haemangioblastoma tumours from eight patients, aged 16-63 years, 5 females and 3 males. Preoperative haemoglobin values exceeded 180 g/l in four patients, and 150 g/l in four. All high Hb values were normalized upon surgical removal of the tumours. All tumours contained scattered cells which stained positively with antisera against pure human urinary erythropoietin and plasma renin substrate. We conclude that cerebellar haemangioblastomas produce immunoreactive erythropoietin, which shares common antigenic determinants with renin substrate.     

In vitro phosphorylation of SV40 large T antigen

Phosphorylation of simian virus 40 large T antigen (large T) was investigated in vitro. "Autophosphorylation" of large T resulted in the modification of Ser106, Ser112, Ser123, Thr124, either Ser676, Ser677, or Ser679, and Thr701. All of these residues were also found to be phosphorylated in vivo. Reaction of large T with purified casein kinase I resulted in phosphorylation of Ser123, possibly Thr124, and either Ser676, Ser677, or Ser679, while purified casein kinase II phosphorylated Ser106 and possibly Ser112. Submolar amounts of phosphate were transferred to large T indicating that only a fraction of large T served as substrate for the casein kinases. Removal of serine-bound phosphate did not affect the subsequent autophosphorylation or phosphorylation by casein kinase I and II. No phosphorylation at in vivo sites was observed with the cAMP-, cGMP-, or Ca2+/phospholipid-dependent protein kinases, or with the protease-activated kinase I and II.     

Hemispheric asymmetry of feedback-related potentials in a positioning task: comparison of right- and left-handed subjects

Previous research has demonstrated that delayed nonverbal information feedback (IF) about the correctness of a positioning movement is preceded by a contingent negative variation (CNV) which is larger over the right hemisphere independent of movement side. It was hypothesized that this asymmetry is a manifestation of functional hemispheric specialization, and that, therefore, the distribution of the differences between CNV amplitude measures of the two hemispheres should be different in right-handed and left-handed subjects. The latter group should show a mean asymmetry score closer to zero, and a larger between-subject variance of the asymmetry scores. The present investigation was intended to test these assumptions in samples of rigorously defined right-handers (n = 12) and left-handers (n = 8). The results revealed the expected group differences of the CNV asymmetry scores. In addition, the P1-N1 peak-to-peak amplitude of the IF-evoked potentials was similarly lateralized as the pre-IF CNV and showed the same group differences. In contrast, the handedness groups did not differ in the contralateral lateralization of the movement-related potential shift in the same task.     

Multiple endometrial stromal nodules with sparse cysts and glands in the lung--a nodular variation of endometriosis that may mimic metastases of sarcoma

We report an unusual case of a nodular variation of pulmonary endometriosis. To our knowledge, there is no previous report on a morphological investigation of this entity. The etiology of this rare condition is still a matter of discussion. The well-circumscribed nodular mass is composed of cells identical to, or closely resembling, those of endometrial stroma containing sparse cysts and glands. Immunohistochemically, the cells showed an extensive co-expression of cytokeratin AE1/AE3 and vimentin and were highly positive for progesterone receptor (PRICA) and estrogen receptor (ERICA). Cells lining the cysts and glands as a monolayer were reactive for Ber-Ep4, cytokeratin Pan and cytokeratin AE1/AE3 and negative to all other markers used including PRICA and ERICA. The differential diagnosis of this entity included fibrous tumor of the pleura and metastatic low-grade-endometrial-stromal-sarcoma. The morphological findings are correlated with immunohistochemical studies and results of cell image analysis. This study details the clinicopathological features of the nodular variation of pulmonary endometriosis.