Transient cytochrome oxidase deficiency with Ohtahara syndrome.
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Biopsy↗
Biomedical subjects
P Ramani
Publications and source records attributed to P Ramani.
Detection of MYCN amplification in neuroblastoma using competitive PCR quantitation.
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Base Sequence↗
An established case of dentatorubral pallidoluysian atrophy (DRPLA) with unusual features on muscle biopsy.
Dentatorubral pallidoluysian atrophy (DRPLA) belongs to the group of autosomal dominant ataxias. Central nervous system pathology and inheritance are both well characterized, although the illness is rare. The presentation of a European child affected by this illness is described. He presented at 9 years of age with intractable progressive myoclonus epilepsy against a background of learning difficulties and developed progressive hypertonicity and dementia before his death at 15 years of age. Significant histological changes in a muscle biopsy were found. There was an absence of type IIB fibres and a predominance of type I fibres. Mean fibre diameter of all the fibre types was markedly reduced. All type I fibres showed an increase in lipid droplets. No previous descriptions exist of muscle histology in DRPLA. Although at least five adult family members have symptoms consistent with a diagnosis of DRPLA, their condition had not been recognized. We therefore describe the clinical picture and histological findings.
Adolescent↗
Expression of the stem cell factor receptor c-kit in normal and diseased pediatric liver: identification of a human hepatic progenitor cell?
The stem cell factor (SCF)/c-kit ligand/receptor system has been implicated in stem (oval) cell activation following liver injury in the rat. The aim of this study was to determine the role of the SCF/c-kit system in pediatric human liver during acute and chronic liver injury. Tissue was obtained from hepatectomy specimens of patients undergoing liver transplantation for extrahepatic biliary atresia (EHBA) and fulminant hepatic failure (FHF). Specific expression of mRNA for c-kit and beta-actin was measured by ribonuclease protection and by immunohistochemistry to localize c-kit in tissue sections. Expression of c-kit was detected at relatively consistent levels in normal and cirrhotic (EHBA) livers. However, in FHF, c-kit mRNA levels were elevated in 3 of 6 specimens. Immunolocalization highlighted the presence of small numbers of c-kit-positive cells in the portal tracts of normal livers with increased numbers in cirrhotic livers. The highest c-kit staining, however, was observed in FHF, in which, in addition to the cells in the portal tracts, discrete c-kit-positive cells were also found integrated into bile ducts. Colocalization studies demonstrated some of the c-kit-positive cells to be of mast cell, leukocyte, and hematopoietic cell origin. However, there remained a subset that was also negative for these markers. The up-regulation of c-kit receptor expression in diseased livers suggests an involvement of this receptor/ligand system in hepatic repair mechanisms, and we speculate that c-kit-positive cells may represent a hepatic progenitor cell population. The origin and growth/differentiation potential of these c-kit-positive cells is under investigation.
Adolescent↗
A case of Ohtahara syndrome with cytochrome oxidase deficiency.
Ohtahara syndrome is a rare cause of epileptic seizures during the neonatal period. This is believed to be the first report of this syndrome with a specific metabolic defect. Defects in respiratory chain function may be more common than previously assumed in patients with this epilepsy syndrome.
Cytochrome-c Oxidase Deficiency↗
The use of SCID mice for the growth of retinoblastoma cell lines and for the establishment of xenografts from primary tumours.
We investigated the possibility of growing primary retinoblastoma tumour tissue in SCID mice. In preliminary experiments with the WERI retinoblastoma cell line injected subcutaneously in SCID mice, tumours arose at only 25% of the inoculation sites. After mixing these cells with a reconstituted basement membrane extracellular matrix (Matrigel) prior to inoculation, tumours arose at 100% of inoculated sites. When primary retinoblastoma cells were injected subcutaneously into SCID mice in the presence of Matrigel, tumours arose in 5/8 cases. On average, the latency period was 4 months before the tumours were palpable. Histopathological examination of the tumours showed that they resembled surgically resected human retinoblastomas and one of the tumours formed pseudo-rosettes which is a characteristic of these tumours. Unfortunately, when these xenografted tumours were introduced into tissue culture, it was not possible to establish cell lines directly and the cultures were soon overgrown by mouse cells which could clearly be shown to be infiltrating the tumour. The ability to grow retinoblastoma cell lines and primary tissue subcutaneously in SCID mice offers a convenient model system to study the genetics of tumorigenesis in this tumour type and possibly an opportunity to study the role of chemotherapy in the treatment and progression of the disease.
Animals↗
The expression pattern of Wilms' tumour gene (WT1) product in normal tissues and paediatric renal tumours.
WT1, the Wilms' tumour suppressor gene located at chromosome 11p13, plays an important role in the development of the kidney. It is mutated in 10 per cent of Wilms' tumours (WTs) and their putative precursors called nephrogenic rests (NRs). A sensitive immunohistochemical technique was established to localize the WT1 gene product in archival normal tissues and paediatric renal tumour samples. Strong nuclear signal was seen in the various sites such as the kidneys, gonads, and decidua. Nuclear immunoreactivity of variable intensity was also seen in the skeletal muscle, smooth muscle of urinary bladder, ureter, and arteries. All 28 WTs (including the anaplastic variant) showed the WT1 gene product in a varying proportion of the blastema, epithelium, and stroma. The anaplastic nuclei in six WTs showed an intensity of staining comparable to their adjacent favourable histology counterparts. All the intralobar and perilobar types of NR demonstrated the WT1 gene product. All three malignant rhabdoid tumours were positive, while three of four mesoblastic nephromas and a clear cell sarcoma were negative. These findings provide an insight into the interrelationships of these renal tumours.
Child↗
Gorham's disease of the spine.
Massive osteolysis is a rare condition and is very uncommon in the spine. The MRI appearance of Gorham's disease of the spine has not previously been reported. We present here a case of this condition with imaging details.
Child, Preschool↗
Recent advances in the diagnosis, prognosis and classification of childhood solid tumours.
The diagnosis of paediatric tumours including the small round cell tumours (neuroblastoma, rhabdomyosarcoma and the Ewing family of tumours), brain tumours, germ cell tumours and anaplastic large cell lymphoma can pose particular diagnostic dilemmas, especially in cases with undifferentiated morphology. Substantial improvements have been made in the treatment and long term survival of paediatric patients with these tumours, however, these are based on disease and even stage specific treatments. Accurate diagnosis and prognosis can now be aided by identifying specific genotypic and phenotypic criteria using cytogenetics, interphase fluorescence in situ hybridisation, reverse transcription PCR and novel immunophenotypic markers. Some of these analyses should form an integral part of the management of patients with paediatric solid tumours.
Biomarkers, Tumor↗
Pediatric myelodysplasia: a study of 68 children and a new prognostic scoring system.
Clinical, morphologic, and cytogenetic features were examined in a group of 68 children with myelodysplasia (MDS) referred to a single institution between 1971-1991. The morphologic French-American-British (FAB) system of classification proved of limited value in this group of patients because 50% of the cases were categorized as chronic myelomonocytic leukemia and three patients with eosinophilia and MDS were unclassifiable. Cytogenetic analysis was performed in 63 cases and clonal abnormalities were detected in 55%; the most common chromosome involved was number 7. Modification of the FAB system to incorporate additional diagnostic features such as pretreatment fetal hemoglobin (Hb F) and cytogenetics allowed incorporation of the categories of juvenile chronic myeloid leukemia (JCML) and infantile monosomy 7 syndrome (IMo7). The resulting groups of patients had highly significant differences in survival (P = .00009). The overall 5-year survival for the patients was 31.9% (95% CI 21.7 to 44.1) and factors influencing prognosis included: modified FAB type, platelet count, Hb F level, and cytogenetic complexity. We developed a scoring system ("FPC") where each of the following findings at diagnosis scored one point: HbF greater than 10%, platelets < or = 40 x 10(9)/L, and complex karyotypic changes (two or more clonal structural/numerical abnormalities), which produced groups with highly significant differences, patients with a score of 0 having a 5-year survival of 61.6% (CI 33% to 84%), whereas those with a score of two or three all died within 4 years of diagnosis. The revised classification and scoring system may prove helpful in making treatment choices in pediatric MDS and now needs to be tested prospectively in large scale population-based studies.
Abnormalities, Multiple↗
Expression of mdr1/P-glycoprotein and p110 in neuroblastoma.
Overexpression of the multidrug resistance gene, mdr1, and its product, P-glycoprotein (Pgp), has been associated with cross-resistance to structurally unrelated compounds in cell lines and tumours. Recently, a non-Pgp-mediated form of drug resistance has been described, due to the overexpression of p110, a transport protein. Thirty formalin-fixed, paraffin-embedded neuroblastoma samples from 21 cases were examined for overexpression of mdr1 and Pgp using newly established non-radioactive in situ hybridization and sensitive immunocytochemical techniques. Tumours were examined from patients with all the stages of disease and from primary and metastatic sites. Paired tumour samples (pre-chemotherapy and post-chemotherapy) were available from cases with stage 2 (n = 1) and stage 4 disease (n = 8). Immunoreactivity to p110 was also tested on all the samples. Mdr1 mRNA was expressed in 16/21 cases and in all the stages. Pgp immunoreactivity was detected in all the cases. Weak cytoplasmic immunoreactivity to p110 was seen in the ganglion cells in 12/21 cases. The expression of mdr1, Pgp, and p110 showed a statistically significant (two-sided Fisher exact test, P = 0.04, 0.03, 0.04, respectively) correlation with differentiation (Beckwith and Martin grading) but there was no correlation with survival. Pgp immunoreactivity also showed a significant correlation with favourable clinical variables: age less than 1 year at diagnosis and stages 1, 2, and 4 s (two-sided Fisher exact test, P = 0.01, 0.005, respectively).
ATP Binding Cassette Transporter, Subfamily B, Mem↗
The familial syndrome of proliferative vasculopathy and hydranencephaly-hydrocephaly: immunocytochemical and ultrastructural evidence for endothelial proliferation.
This is the fourth report of Fowler-type hydranencephaly, or proliferative vasculopathy and hydranencephaly-hydrocephaly (PVHH), and is both the first case in Europe and the first case reported in an Asian family. A 17-week fetus showed severe arthrogryposis, pterygia and muscular hypoplasia. Massive cystic dilatation of the cerebral ventricles with thin disorganized pallium was associated with calcifications and characteristic glomeruloid vasculopathy throughout the CNS. Hydranencephaly in a previous pregnancy was demonstrated ultrasonographically at 13 weeks gestation. The glomeruloid vasculopathy, unique to this disorder, has ill-defined vascular channels, prominent reticulin network and inclusion-bearing cells which our immunocytological and ultrastructural studies suggest are endothelial cells. Aetiopathogenesis remains uncertain; previous hypothesis include congenital infection or primary neuro-ectodermal failure. Our present clinical and morphological findings suggest a primary role for the glomeruloid vasculopathy at the time of vascular invasion of the cerebral mantle during the first trimester. Previous and present case data support autosomal recessive inheritance, in contradistinction to sporadic, encephaloclastic, hydranencephaly from which PVHH can be readily differentiated by microscopic examination.
Adult↗
Epstein-Barr virus associated lymphoproliferative disorder with fatal involvement of the gastrointestinal tract in an infant.
A case of fatal Epstein-Barr virus (EBV) associated lymphoproliferative disorder is reported in an 11 month old female. Heavy infiltrates of CD20 + and EBV EBER mRNA expressing lymphoid blasts were found to cause a series of ulcers along the entire length of the gastrointestinal tract and there was an ileal perforation. Similar infiltrates were also found in lymph nodes, spleen, and liver. Although blood phenotypic analysis performed shortly before her death revealed a severe decrease in T lymphocytes, neither the patient nor other members of her family had a history of primary or secondary immunodeficiency. EBV infection is common in children. However, such a fatal infection of the virus has not apparently been described previously in infants without pre-established immunodeficiency.
Fatal Outcome↗
Expression of bcl-2 gene product in neuroblastoma.
The expression of bcl-2 is associated with inhibition of apoptosis and prolonged cell survival. The purpose of this study was to examine the immunoreactivity of neuroblastoma and ganglioneuroblastoma tissue samples to the bcl-2 gene product in order to see if it was related to prognosis. BCL-2 protein was detected in all the 46 formalin-fixed, paraffin-embedded samples from 34 patients representing all clinical stages and sites of involvement. Immunopositivity was observed in tumours from the primary and metastatic sites. Moreover, it was demonstrated in the pre-chemotherapy and the post-chemotherapy samples from six cases with stage 4 disease. It was observed in neuroblasts in various stages of differentiation. A small proportion of undifferentiated neuroblasts were negative. As BCL-2 oncoprotein was present in all the cases irrespective of the clinical outcome, it does not appear to be one of the factors influencing prognosis.
Cell Differentiation↗
Infections in bone marrow transplant recipients in south India--a post-mortem study.
A study of post-mortem material obtained from ten patients who had undergone bone marrow transplantation is presented. The cause of death in all patients was infection. Six patients had fungal infection, two had bacterial infection and three had cytomegalovirus infection. Pneumocystis carinii and tuberculous infections were not detected.
Abscess↗
Massive oedema and fibromatosis ovary--a report of three cases.
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Adult↗
Testicular intratubular germ cell neoplasia in children and adolescents with intersex.
In a review of 102 cases with various intersex states, the frequency of intratubular germ cell neoplasia (IGCN) unclassified in testes of children and adolescents was 6%. It was seen in 2 of 87 cases in the prepubertal age group and 4 of 23 cases in the pubertal age group. The frequency of IGCN was 0 of 23 in androgen insensitivity syndrome (testicular feminization), 3 of 38 in gonadal dysgenesis, 1 of 12 in true hermaphroditism, 1 of 22 in male pseudohermaphroditism, and 1 of 7 in the group with multiple congenital anomalies and ambiguous genitalia. Five cases showed unilateral and one showed bilateral IGCN. Three pubertal cases had unilateral gonadoblastoma associated with IGCN. Invasive germ cell tumor was absent in all six cases. The atypical germ cells in all testes with IGCN showed immunoreactivity with placental alkaline phosphatase. Review of the literature revealed 30 prepubertal and pubertal cases with IGCN. The median age of the combined series of 36 cases with IGCN was 13 years (range 1 month to 19 years). Concomitant invasive tumor was present in 3 of 14 cases with gonadal dysgenesis and IGCN and 2 of 18 cases with androgen insensitivity and IGCN.
Adolescent↗
Myxoma of the maxillary antrum in children.
Myxomas of the maxillary antrum are rare tumours, particularly in childhood. Although circumscribed, they are often more extensive than apparent and so tend to recur despite their benign nature. Myxomas are gelatinous and are composed of stellate and spindle cells embedded in an abundant alcian blue-positive, mucoid stroma in which blood vessels are often scattered throughout the tumour. Three patients with maxillary myxomas, all presenting in infancy or early childhood, are described.
Age Factors↗