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SUMMARY The cranial ultrasound features of two neonates with neuronal migration disorders are described. One infant had lissencephaly and the other polymicrogyria in conjunction with the Pena-Shokeir syndrome type 1. A third infant is described who was born extremely prematurely and with Down's syndrome, who had similar ultrasound features. By two weeks of age, however, the scan of this third infant had become normal, which illustrates the need for caution in diagnosing migrational disorders in very preterm babies and those with Down's syndrome. The disorders of neuronal migration are discussed. RESUME Troubles de la migration neuronique: caracteristiques echographiques L'article decrit les images echographiques de deux nouveau-nes presentant des troubles de la migration neuronique. Un nourrisson presentait une lissencephalie, un autre une polymicrogyrie associee a un syndrome de Pena-Shokeir de type 1. Un troisieme enfant ne tres prematurement avec un mongolisme presentait des images echographiques identiques. Cependant, a l'âge de deux semaines le scanner de ce troisieme enfant etait devenu normal, ce qui doit rendre prudent dans le diagnostic de troubles migratoires chez les tres grands prematures et les mongoliens. Les desordres de la migration neuronique sont discutes. ZUSAMMENFASSUNG Erkrankungen infolge neuronaler Migration: sonographische Merkmale Es werden die cranialen Ultraschallbefunde bei zwei Neugeborenen mit Erkrankungen infolge neuronaler Migration beschrieben. Ein Kind hatte eine Lissencephalie und das andere eine Polymikrogyrie mit dem Pena-Shokeir Syndrom Typ I. Ein drittes Kind wird beschrieben, das sehr viel zu fruh mit einem Down Syndrom geboren wurde und bei dem ahnliche Ultraschallergebnisse gefunden wurden. Nach zwei Wochen jedoch hatte sich das Ultraschallbild des dritten Kindes normalisiert; hierdurch wird deutlich, das man bei der Diagnosestellung von Erkrankungen infolge neuronaler Migration bei sehr unreifen Kindern und bei Kindern mit Down Syndrom vorsichtig sein mus. Die Krankheitsbilder infolge neuronaler Migration werden diskutiert. RESUMEN Desordenes en la emigracion neuronal: caracteristicas sonograficas Se describen las caracteristicas de los ultrasonidos craneales de dos recien nacidos con alteraciones en la emigracion de las neuronas. Un lactante tenia lisencefalia y el otro polimicrogiria junto con sindrome de Pena-Shokeir del tipo I. Se describe un tercer nino que habia nacido extremadamente prematura y con un sindrome de Down y que tenia una caracteristicas ultrasonicas similares. Sin embargo a las dos semanas de edad la TAC de este tercer nino se habia hecho normal, lo cual ilustra la necesidad de ser prudente en el diagnostico de las alteraciones de la emigracion en ninos muy a pretermino y en los sindromes de Down. Se discuten las alteraciones de la emigracion neuronal.

A severely mentally handicapped Caucasian male with cataracts, deafness, distal muscle wasting and skeletal abnormalities, including calcification of the pinnae, is described. The findings in this patient strongly resemble those in a male described in 1982 by Primrose, and it suggested that this unusual pattern of abnormalities constitutes a discrete entity, which we propose should be known as 'Primrose syndrome'.

A profoundly mentally handicapped patient is described with the karyotype 47,X, fra (X) (q27), + 21. Her phenotype demonstrates features of both Down's Syndrome and fragilc-X syndrome. The authors believe only one other similar case has been described.

A mother and son, each showing the characteristic features of the Weill-Marchesani syndrome, are described. It is suggested that this family provides further evidence for genetic heterogeneity in this condition.

A brother and sister with developmental delay, relative macrocephaly and agenesis of the corpus callosum are described. The brother also had unilateral cerebellar hypoplasia and malrotation of the large bowel. Published cases of familial agenesis of the corpus callosum are reviewed and the value of ultrasonography in demonstrating agenesis of the corpus callosum in the neonate is emphasised.

This report describes the clinical and investigative findings in a 31-year-old man with Hunter's syndrome, showing evidence of severe multisystem involvement. Papilloedema has been present for at least 8 years with no evidence of progressive visual impairment. His most serious and life-threatening complications are laryngeal oedema and tracheal narrowing, which both compromise his respiratory function and constitute a major anaesthetic risk.

The objective of the study was to investigate childhood hearing impairment in a population-based sample from a genetic perspective. Participants included 82 families with hearing-impaired children (aged 4-13) previously ascertained in the Trent Health Region. A questionnaire was mailed to all families, followed by a home visit and Connexin-26 35delG mutation screen. The Connexin-26 35delG mutation was identified in seven families (approximately 10 per cent of non-syndromal hearing impairment). Children of these families were significantly more likely than children with other modes of inheritance to have a profound hearing loss with a flat audiogram profile. The families of children with a significant admission to a neonatal intensive care unit were significantly less likely to have had genetic counselling. Eight families visited were found to have features suggestive of a genetic syndrome that had not been previously assigned a specific diagnosis. The study concluded that hearing-impaired children should ...

All major JET systems have been fully commissioned for D-T and the DTE1 series of experiments has started with the D-T fuel mixture and operating conditions foreseen for ITER. In the area of ITER physics, significant results have been produced in both D-D and D-T. In D-D, the LH threshold power database has been extended, the bounds on edge-electron temperature and density in ELMy H-modes have been defined and the advantages of Types I and III ELMy discharges have been compared. In D-T plasmas, the isotope effect on H-mode threshold power and transport has been determined so that a more accurate assessment can be made of the ignition margin and heating requirements for ITER. Trace tritium experiments have provided first particle transport measurements and an assessment of the ITER reference ion-cyclotron resonance-frequency heating scenarios has been started, In the area of fusion performance, record D-D neutron yields have been obtained by controlling the plasma and current profiles in hot ion ELM-free H-modes and optimized shear modes. In D-T, internal transport barriers have been readily established in optimized shear discharges and Alfven eigenmodes have been observed.

International audience; We report a deletion of 1p36.3 in a child with microcephaly, mental retardation, broad forehead, deep set eyes, depressed nasal bridge, flat midface, relative prognathism, and abnormal ears. The phenotype is consistent with that described for partial monosomy for 1p36.3. Reverse chromosome painting and microsatellite and Southern blot analyses were used to map the extent of the deletion. Fluorescence in situ hybridisation (FISH) analysis using probes from every telomere indicates that the rearrangement is likely to be a chromosomal truncation or rearrangement involving subtelomeric repetitive DNA. The deletion was identified by screening a sample of children and adults with idiopathic mental retardation. In conjunction with previous work on this sample, we estimate that 7.4% of the group have subtelomeric rearrangements.

A clinical and genetic study of the Holt-Oram syndrome (HOS) has been carried out in the United Kingdom involving 55 cases designated Holt-Oram syndrome, together with their parents and sibs. Data from the clinical assessment of both familial and isolated cases were used to define the HOS phenotype and to outline the spectrum of abnormalities, especially factors affecting severity. Skeletal defects affected the upper limbs exclusively and were bilateral and asymmetrical. They ranged from minor signs such as clinodactyly, limited supination, and sloping shoulders to severe reduction deformities of the upper arm (4.5%). The radial ray was predominantly affected than the right. All affected cases showed evidence of upper limb involvement. Cardiac defects were seen in 95% of familial cases and included both atrial septal defect (ASD, 34%) and ventricular septal defect (VSD, 25%); 39% had only ECG changes. Cardiac involvement ranged from asymptomatic conduction disturbances to multiple structural defects requiring surgery in infancy. Sudden death could be caused by heart block. Inheritance was autosomal dominant with 100% penetrance and no evidence of reduced fitness. Increasing severity occurred in succeeding generations consistent with anticipation.

The clinical features of Wolf-Hirschhorn syndrome are described in a 29-year-old woman who shows severe retardation of growth and development. It is important for health care professionals involved with families in which this condition is present to realize that long-term survival may occur.

The JET neutral beam injection system has proved to be both effective and reliable as a plasma heating device. The ion heating and plasma fuelling characteristics of the system are ideally suited to the production of high fusion performance plasmas while the flexibility in the choice of beam species (H, D, T, 3 He or 4 He) and the ability to inject into almost any JET plasma configuration allows a wide variety of related physics experiments to be carried out. The capability to inject (for the first time) tritium beams was essential to the successful execution of the first tritium experiments in which 1.7 MW of power from DT fusion reactions was generated.

An account is given of the high performance plasmas established by development of the H-mode regime in JET in the experimental campaigns up to 1992. High performance in this case is measured in terms of the confinement enhancement achieved over the L-mode scaling as measured using the plasma diamagnetism. Three JET H-mode regimes have achieved enhancement factors (H G DIA ) over Goldston L-mode scaling of 2.5 < H G DIA < 4.0. These are the Pellet Enhanced Performance (PEP) H-MODE, the high bootstrap fraction (high β POL ) H-mode and the Hot Ion (HI) H-mode. The phenomenology of these three regimes is reviewed and contrasts and common threads are elucidated

Epstein-Barr virus (EBV) DNA in renal tissue in acute interstitial nephritis (IN) has not been previously reported. An 18-year-old male presented with a sore throat, fever, cervical lymphadenopathy, and oliguric renal failure. The rapid slide test for heterophile antibodies associated with infectious mononucleosis was positive, and a renal biopsy showed an acute interstitial nephritis. A polymerase chain reaction (PCR) assay identified EBV DNA in the renal biopsy. In situ hybridization (ISH) for EBV RNA and immunohistochemistry for latent membrane protein 1 of EBV were negative. Hemodialysis and prednisone 60 mg PO OD were administered and the s-creatinine dropped from 1,224 to 75 µmol/l over 9 days. The identification of EBV DNA in the kidney raises the possibility that direct infection plays a role in acute IN associated with EBV.

Three patients with short stature, joint laxity, and peculiar pelvic radiology are described. The first case is similar to those described by Desbuquois et al. [3], with deviation of digitis and supernumerary metacarpal bones. The other two children are less severely affected and are compared with others reported in literature. The authors suggest the homogeneity of the Desbuquois syndrome in spite of the variability of expression.

A de novo case of 'pure' trisomy 14q21----qter is described which was detected at amniocentesis following an abnormal ultrasound scan of a 25-year-old woman. This is apparently the largest distal 14q duplication reported in a case surviving beyond the first trimester. The infant appeared to have an association of clinical abnormalities previously observed in distal 14q trisomy and proximal 14q trisomy/mosaic trisomy 14.

Patients with Angelman's syndrome have been reported to have ocular hypopigmentation and a number are now known to have a microdeletion of chromosome 15q 11----13. Detailed ocular examination of eight new cases revealed normal visual acuity and foveal reflexes, but a pigmentary deficiency which is limited to the choroid and iris stroma--both of neural crest origin. Patients with Prader-Willi syndrome have similar ocular features and many have a microdeletion of chromosome 15q 11----13. It is therefore possible that this region may influence neural crest development.

We report two pairs of siblings with the syndrome cranioectodermal dysplasia who have subsequently developed chronic renal failure secondary to tubulo-interstitial nephropathy. Renal disease has not been described before in this rare syndrome but has now occurred in four of the seven reported cases. Children with cranioectodermal dysplasia appear to be at significant risk of developing chronic renal failure. This is important information for clinicians looking after such children, and their families, when considering the long-term prognosis and management.

Deafness is the most frequent sensory impairment in humans, with significant social and psychological implications. Early-onset hearing loss can have major adverse effects on the development of a child’s speech and language with important potential long-term consequences for cognitive development (Davis and Hind, 1999).These problems may be exacerbated in developing countries where poor nutrition and/or limited access to educational and medical facilities, coupled with increased reliance on verbal communication skills, can result in social isolation and reduced occupational opportunities (Kumar, 1997; Elahi et al., 1998).

Objectives To establish precise incidence figures for trisomy 13 and trisomy 18 in the former Trent region, to identify current prenatal diagnostic practice, and to assess the potential impact of the introduction of recently devised prenatal diagnostic practices. Methods An audit of all cases of trisomy 13 and trisomy 18 ascertained through the records of the Trent Congenital Anomalies Register and the Trent Regional Cytogenetic Laboratories. Results Forty-four cases of trisomy 13 and 88 cases of trisomy 18 were ascertained. Advanced maternal age effects were observed. Of all cases, 64% were first detected through chromosomal analysis initiated because of abnormalities noted on fetal anomaly scanning in the second trimester, whereas only 3% of cases were detected through the serum-screening programme currently offered for Down syndrome. In 11% of cases, the diagnosis was first suspected after birth. Twelve percent of couples chose to continue pregnancy following chromosomal confirmation of a suspected diagnosis. Conclusion The introduction of a highly sensitive prenatal diagnostic screening programme would have a major impact on the timing and proportions of all trisomy 13 and 18 cases diagnosed in pregnancy as gauged by current practice. It is important that health professionals involved in prenatal counselling be aware that, as with Down syndrome and anencephaly, around 12% of prospective parents of a child with trisomy 13 or 18 choose to continue rather than terminate the pregnancy. Copyright © 2003 John Wiley & Sons, Ltd.

Holoprosencephaly (HPE) is a clinically variable and genetically heterogeneous central nervous system (CNS) malformation. Alobar HPE, which is its most severe form, is associated with a poor prognosis. At the milder end of the HPE spectrum microcephaly, hypotelorism, and single central maxillary incisor may be recognised. Currently, four genes have been identified for this condition. These include Sonic Hedgehog (SHH) on chromosome 7q36, which is thought to be responsible for a significant proportion of autosomal dominant HPE. We report an index case with alobar holoprosencephaly caused by an SHH mutation and six members of his family over two generations with this mutation, with a broad range of clinical presentation, including attention deficit hyperactivity disorder (ADHD). The combination of microcephaly, hypotelorism, subtle midline facial anomalies, and ADHD within a sibship should alert the physician to the possible diagnosis of HPE.

BACKGROUND—Submicroscopic subtelomeric chromosome defects have been found in 7.4% of children with moderate to severe mental retardation and in 0.5% of children with mild retardation. Effective clinical preselection is essential because of the technical complexities and cost of screening for subtelomere deletions. METHODS—We studied 29 patients with a known subtelomeric defect and assessed clinical variables concerning birth history, facial dysmorphism, congenital malformations, and family history. Controls were 110 children with mental retardation of unknown aetiology with normal G banded karyotype and no detectable submicroscopic subtelomeric abnormalities. RESULTS—Prenatal onset of growth retardation was found in 37% compared to 9% of the controls (p30%) among subtelomeric deletion cases were microcephaly, short stature, hypertelorism, nasal and ear anomalies, hand anomalies, and cryptorchidism. Two or more facial dysmorphic features were observed in 83% of the subtelomere patients. None of these features was significantly different from the controls. Using the results, a five item checklist was developed which allowed exclusion from further testing in 20% of the mentally retarded children (95% CI 13-28%) in our study without missing any subtelomere cases. As our control group was selected for the "chromosomal phenotype", the specificity of the checklist is likely to be higher in an unselected group of mentally retarded subjects. CONCLUSIONS—Our results suggest that good indicators for subtelomeric defects are prenatal onset of growth retardation and a positive family history for mental retardation. These clinical criteria, in addition to features suggestive of a chromosomal phenotype, resulted in the development of a five item checklist which will improve the diagnostic pick up rate of subtelomeric defects among mentally retarded subjects. Keywords: submicroscopic subtelomeric rearrangements; clinical preselection; checklist; chromosome deletion.

A male infant with lethal short limbed dwarfism is described. His father had spondyloepiphyseal dysplasia congenita and his mother had achondroplasia. It is believed that the infant inherited both of these disorders and that their combined effects resulted in early death owing primarily to severe pulmonary hypoplasia.

We describe a family with non-syndromic sensorineural hearing impairment inherited in a manner consistent with maternal transmission. Affected members were found to have a novel heteroplasmic mtDNA mutation, T7510C, in the tRNASer(UCN) gene. This mutation was not found in 661 controls, is well conserved between species, and disrupts base pairing in the acceptor stem of the tRNA, making it the probable cause of hearing impairment in this family. Sequencing of the other mitochondrial tRNA genes did not show any other pathogenic mutations. Four other mutations causing hearing impairment have been reported in the tRNASer(UCN) gene, two having been shown to affect tRNASer(UCN) levels. With increasing numbers of reports of mtDNA mutations causing hearing impairment, screening for such mutations should be considered in all cases unless mitochondrial inheritance can be excluded for certain. Keywords: hearing impairment; mtDNA mutation; tRNASer(UCN)

We report on 3 male and 2 female infants with acromelic frontonasal dysostosis. All 5 had a frontonasal malformation of the face and nasal clefting associated with striking symmetrical preaxial polysyndactyly of the feet and variable tibial hypoplasia. In contrast, the upper limbs were normal. This rare variant of frontonasal dysplasia may represent a distinct autosomal-recessive disorder. We suggest that the molecular basis of this condition may be a perturbation of the Sonic Hedgehog (SHH) signalling pathway, which plays an important part in the development of the midline central nervous system/craniofacial region and the limbs.

The clinical features in a 10-year-old girl with distal arthrogryposis, ectodermal dysplasia and a dilated cardiomyopathy are presented. Review of the relevant literature has not revealed any other similar report. Parental consanguinity points to autosomal recessive inheritance.

We report on a 3-year-old-girl with mosaic partial trisomy 17 due to an additional ring chromosome 17 in 13% of cells analysed. This was identified by fluorescence in situ hybridisation (FISH) using a whole chromosome 17 specific paint as well as probes specific for the Smith-Magenis and Miller-Dieker regions of chromosome 17p. This girl showed mild developmental delay with subtle facial and other minor abnormalities including single palmar creases, generalised joint laxity, and a scoliosis.

The clinical and radiological features are described in male and female siblings with a unique form of spondyloepimetaphyseal dysplasia. In addition to generalized platyspondyly with epiphyseal and metaphyseal involvement, these children also have thin tapering fingers with accentuated palmar creases and abnormal dentition with oligodontia and pointed incisors. Parental consanguinity suggests that this is an autosomal recessive disorder.

A 26-year-old female is described with multiple facial syringomas, neonatal teeth and oligodontia. Her father has similar dental findings but no reliable evidence of syringomas. This combination of findings probably represents a new autosomal dominant ectodermal dysplasia with variable expression between the sexes.

Hereditary multiple exostoses (EXT) is an autosomal dominant disorder characterized by the formation of cartilage capped prominences that develop from the epiphyses of the long bones. EXT is heterogeneous with three different locations currently identified on chromosomes 8, 11, and 19. Recently, we identified and studied 12 large multigenerational EXT families. Linkage analyses demonstrates that 6 of these families map to 8q24 and 6 to 11p. None of the families map to the chromosome 19 locus. The results suggest that there are two major loci, on chromosomes 8 and 11, involved in the cause of EXT. The locus on chromosome 19 remains to be confirmed.

Campomelic dysplasia (CMD) is a rare skeletal disorder that is usually lethal. It is characterised by bowing of the lower limbs, severe respiratory distress, and many of the chromosomal (XY) males show sex reversal. Because of a number of reports of familial campomelic dysplasia it is considered to be inherited in an autosomal recessive manner. In this study, details of 36 patients with campomelic dysplasia were collected from genetic centres, radiologists, and pathologists in the United Kingdom. The chromosomal sex ratio was approximately 1:1. There was a preponderance of phenotypic females owing to sex reversal. Three quarters of the chromosomal males were sex reversed or had ambiguous genitalia. Three cases are still alive, two with chromosomal rearrangements involving chromosome 17q. The majority of the others died in the neonatal period. The 36 index cases had 41 sibs of whom only two were affected. Formal segregation analysis gave a segregation ratio of 0.05 (95% CI approximately 0.00 to 0.11). This excludes an autosomal recessive mode of inheritance. The data suggest a sporadic, autosomal dominant mode of inheritance. Patients with a chromosomal rearrangement involving 17q (q23.3-q25.1) show a milder phenotype. The molecular mechanism for the difference is still unknown.

The effects of methylprednisolone and cyclophosphamide were examined in a murine model of lupus nephritis (MRL-1pr/1pr). Animals were assigned to four groups at 12 weeks of age. Mice in the control group received intraperitoneal saline solution either daily or weekly. Animals in the low-dose methylprednisolone (MPLD) group received 6 mg/kg/day intraperitoneal methylprednisolone; those in the high-dose methylprednisolone (MPHD) group received 12 mg/kg/day intraperitoneal methylprednisolone. Animals in the cyclophosphamide group received 50 mg/kg/wk intraperitoneal cyclophosphamide. Animals surviving to 24 weeks were examined. MPHD and cyclophosphamide treatments were associated with maintenance of normal glomerular filtration rates and the development of only minimal proteinuria. However, detailed morphometric evaluation of the glomerulus revealed glomerular enlargement and mesangial matrix expansion in both groups. Unlike MPHD-treated mice, cyclophosphamide-treated animals demonstrated a marked reduction in the number of osmophilic dense deposits along the glomerular capillary walls. MPLD had little effect on function, despite significant reductions in cell proliferation and anti-double-strand DNA antibodies. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels were dramatically increased in plasma of control animals. Treatment with methylprednisolone and cyclophosphamide dramatically reduced TNF-alpha but not IL-6. Treatment also reduced renal IL-1 beta, TNF-alpha and transforming growth factor-beta mRNA levels compared with untreated mice. Despite minimal serologic activity and preservation of renal function, neither cyclophosphamide nor methylprednisolone was able to completely suppress disease activity, as measured by increased cytokine production and glomerular structural injury. The inability of treatment to reduce IL-6 levels may explain the resistance to treatment in this model.

A 9-year-old boy with multiple abnormalities including severe bilateral microphthalmia, diaphragmatic hernia and Fallot's tetralogy is presented. He has also been shown to have an apparently balanced de novo reciprocal translocation, 46,XY,t(1;15)(q41;q21.2), which suggests that one of those breakpoints may be the locus for a gene which is important in morphogenesis.

The expression of the 72-kd type IV collagenase has been implicated as an important factor in determining the invasive potential of malignant tumors. Using immunohistochemistry and nonisotopic in situ hybridization, type IV collagenase expression was assessed in benign and malignant prostatic tissue obtained from 117 surgical and autopsy specimens. Diffuse strong staining for type IV collagenase mRNA and protein was identified in the malignant cells of more than 85% of prostatic adenocarcinomas and the dysplastic cells of high grade prostatic intraepithelial neoplasia. Benign hyperplastic epithelium showed moderate expression in basal cells and mild expression in secretory cells. The qualitative patterns of type IV collagenase expression in prostatic epithelium at the protein and mRNA levels in individual cases were identical. There was no correlation between the level of type IV collagenase expression and either tumor grade or stage. In 10% of adenocarcinomas, focal mild to moderate stromal cell immunoreactivity was present but mRNA was not detectable in the stromal compartment in any case. The enhanced expression of type IV collagenase in dysplastic epithelium and prostatic adenocarcinoma suggests it contributes to the development of the invasive phenotype. The vast majority of the enzyme present in these tumors is synthesized by malignant cells and its production by stromal cells is negligible.

JET was extensively modified in the 1992/93 shutdown. The new pumped divertor and many new systems were brought into operation early in 1994. Operations have progressed to 4MA plasma current and, with substantial additional heating, H-mode confinement results confirm the expected scaling. The high power handling capability of the pumped divertor with sweeping is estimated at 20MW for 20s. H-mode plasmas have large Type I ELMs. With lower hybrid heating alone, 2MA full current drive has been achieved with good efficiency, with ICRF power, effective heating and direct electron heating have been demonstrated.

An 18 month old girl with dysmorphic features, severe developmental delay, multiple strawberry naevi, and capillary naevi is described. No previous report of a similar association of features has been identified.

In a murine model of AA amyloidosis, it has been demonstrated that perlecan, the basement membrane heparan sulfate proteoglycan, is co-deposited with AA amyloid as it forms in various tissues. The objectives of this study were to determine whether the accumulation of perlecan during amyloidogenesis is associated with induction of perlecan gene expression and, if so, to define the temporal relationship of this induction to the onset of amyloid formation.Accelerated splenic AA amyloidosis was stimulated in mice by concomitant administration of subcutaneous silver nitrate as an inflammatory stimulus and amyloid-enhancing factor. A kinetic analysis of splenic perlecan mRNA levels during amyloid formation in the spleen was conducted using a reverse transcription-polymerase chain reaction assay. Amyloid deposits were detected histochemically with the Congo red stain and by immunohistochemistry using anti-AA antisera.Perlecan mRNA levels increased significantly during amyloidogenesis, increasing 4.1-fold within 72 hours of the amyloidogenic stimulus and subsequently falling to steady-state levels. A 2.0-fold induction of perlecan mRNA occurred by 24 hours post-stimulation, a time at which amyloid was not detectable by either histochemistry or immunohistochemistry. In contrast, control animals administered either the inflammatory stimulus or AEF alone showed no significant change in perlecan mRNA levels.Increased perlecan mRNA levels account, at least in part, for the accumulation of perlecan in murine splenic AA amyloid deposits. This induction of perlecan gene expression occurs before the onset of amyloid formation, supporting a role for perlecan in the earliest stages of amyloid fibrillogenesis.

A family is described in which three males have been affected by congenital valvular dysplasia of one or more heart valves, in one case leading to neonatal death. The pedigree is consistent with sex linked inheritance.

The clinical and radiological features in a baby thought to have Blomstrand chondrodysplasia are presented. The hallmarks of this rare lethal disorder are an increase in bone density and advanced skeletal maturation. A high incidence of parental consanguinity is consistent with autosomal recessive inheritance.

The 72-kDa Type IV collagenase (T4C) is a matrix metalloproteinase, the expression of which may be important in normal basement membrane metabolism. The production of T4C by malignant cells has been linked to their invasive and metastatic potential in several tumor systems. The pattern of T4C immunoreactivity was assessed in formalin-fixed, paraffin-embedded prostatic tissue using polyclonal, monospecific antibodies. Basal cells in normal and hyperplastic epithelium demonstrated slight to moderate cytoplasmic immunoreactivity, while secretory epithelial cells showed generally weaker immunostaining. In 35 of 35 cases of primary adenocarcinoma and five of five cases of metastatic adenocarcinoma in lymph nodes, the majority of malignant cells showed strong immunoreactivity. Similar strong immunostaining was also seen in foci of prostatic intraepithelial neoplasia. The high level of expression of T4C in prostatic adenocarcinoma and its metastases suggests this metalloproteinase may play a role in determining the invasive and metastatic properties of this tumor. The enhanced immunoreactivity in prostatic intraepithelial neoplasia suggests the induction of T4C may be an early event in the development of the invasive phenotype. The expression of T4C in benign epithelial cells may be a manifestation of its putative physiological role in basement membrane metabolism.

Amyloid in the islets of Langerhans is the uniform pathologic feature in the pancreata of patients with type II diabetes mellitus. Although the mechanisms of islet amyloid fibrillogenesis are unknown, the presence of heparan sulfate proteoglycan in many other forms of amyloid suggests a role for this proteoglycan in amyloidogenesis in general. In this study, islet amyloid was evaluated for the presence of the basement membrane heparan sulfate proteoglycan using histochemical and immunohistochemical techniques. Staining with sodium sulfate-alcian blue identified highly sulfated glycosaminoglycans within all islet amyloid deposits, and anti-basement membrane heparan sulfate proteoglycan antisera localized this specific proteoglycan within the islet amyloid. The presence of the basement membrane heparan sulfate proteoglycan links islet amyloid to other disparate forms of amyloid and further supports the hypothesis that it has a role in a common pathway of amyloid fibrillogenesis.