bluuebunny/crossref_metadata_2025 huggingface dataset:
Topology-driven protein-protein interaction network analysis detects genetic sub-networks regulating reproductive capacity
Authors: Kumar Tarun , Blondel Leo , Extavour Cassandra G
Published: September 2020

Understanding the genetic regulation of organ structure is a fundamental problem in developmental biology. Here, we use egg-producing structures of insect ovaries, called ovarioles, to deduce systems-level gene regulatory relationships from quantitative functional genetic analysis. We previously showed that Hippo signalling, a conserved regulator of animal organ size, regulates ovariole number inDrosophila melanogaster. To comprehensively determine how Hippo signalling interacts with other pathways in this regulation, we screened all known signalling pathway genes, and identified Hpo-dependent and Hpo-independent signalling requirements. Network analysis of known protein-protein interactions among screen results identified independent gene regulatory sub-networks regulating one or both of ovariole number and egg laying. These sub-networks predict involvement of previously uncharacterised genes with higher accuracy than the original candidate screen. This shows that network analysis combining functional genetic and large-scale interaction data can predict function of novel genes regulating development.
Effects of Leaf Extract of Cnidoscolus aconitifolius on Serum Lipids and Oxidative Stress Markers of Male Wistar Rats
Authors: Ezebuiro Ijeoma , Obiandu Chibuike , Saronee Friday , Obiandu Adesua C.
Published: September 2020

Introduction: Cnidoscolus aconitifolius is considered to be an important and effective medicinal plant in folklore remedies where it has been applied as an alternative therapy for the treatment of various ailments.

Aim: The present study aims to determine the effects of Cnidoscolus aconitifolius on lipid profile and some oxidative stress markers of male Wistar rats.

Methodology: A total of 15 male wistar rats were procured for the study and randomly assigned into three groups of 5 rats each. Group 1 served as control and received distilled water only. Group 2 received 200 mg/kg and group 3 received 400mg/kg of the hydromethanolic (1:4) extract of Cnidoscolus aconitifolius which was administered as single daily dose using oral cannula. On completion of treatment, blood samples were collected by cardiac puncture for determination of some serum lipid parameters and oxidative stress markers.

Results: Results showed that there were no significant difference in the serum level of total cholesterol, triglyceride, low density lipoprotein cholesterol and high density lipoprotein cholesterol at both doses of the extract, compared to control. However, compared to control, there was a significant (p<0.05) increase in the activity of superoxide dismutase and glutathione reductase but significant reduction in malondialdehyde level. The catalase enzyme activity was not significant.

Conclusion: The result obtained suggest that the extract may be useful in reducing oxidative stress by improving some antioxidant enzyme activities and may also prevent cell death due to lipid peroxidation.
Determination of LD50, Fecundity and Locomotor Effects of Methanol Root Extract of Ximenia americana Linn, in Drosophila melanogaster
Authors: Bagu Great David , Omale Simeon , Iorjiim Walter Mdekera , Uguru Mary O. , Gyang Steven Samuel
Published: September 2020

Aim: The study aimed at assessing the LD50, fecundity and locomotor effects of Ximenia americana L in Drosophila melanogaster.

Study Design: The study was an experimental design.

Place and Duration of Study: The study was done in the drosophila laboratory, Africa Centre of Excellence in Phytomedicine Research and Development (ACEPRD), University of Jos, Nigeria between November 2019 and Match, 2020.

Methods: The experimental animals (1-3 days old) of both sexes were exposed to different concentrations (1 mg 10 mg 50 mg, 100 mg, 200 mg, 250 mg 300 mg, 350 mg, 400 mg, 450 mg) of the plant extract per oral for seven days to determine the lethal dose, LD50. Thereafter, five days treatment was done using 50 mg, 100 mg 200 mg and 300 mg concentrations of the extract to assay for fecundity and locomotor effect in the fruit fly.

Results: The LD50 of the methanol extract of Ximenia americana in D. melanogaster was found to be 327.7 mg, this showed that the plant extract is relatively safe. Also, the result showed that both fecundity and locomotor behaviour of the treated and untreated flies was not significantly (P > 0.05) different. Thus, the extract at the used concentrations does not affects significantly both the reproductive capacity and the motor functions in the fruit fly.

Conclusion: All the tested concentrations used in this research are relatively safe (because of high LD50 327.7 mg) in the fruit fly and slightly increase the emergence of new fly with no noticeable negative effect in locomotor activity.
Effect of Nitrogen, Phosphorus, Potassium, Sulphur and Zinc on Yield and their Attributing Characterstics of Mustard Crop
Authors: Gautam Susheel , Pandey Hanuman Prasad , Pathak R. K. , Sharma Sanjeev , Pandey Shivam
Published: September 2020

A field experiment was conducted on Pot culture house of Department of Soil Science and Agricultural Chemistry at Chandra Shekhar Azad University of Agriculture and Technology, Kanpur during the rabi season 2016-17, In the present experiment 8 treatments  T1 (Control), T2 (100% RDF Recommended dose of fertilizer) , T3 (100% RDF+S30), T4 (100% RDF+Zn5), T5 (125% RDF), T6(125% RDF+S30 ), T7 (125% RDF+Zn5), T8 (150% RDF), were laid out in Randomized Block Design(RBD) with four replications. Mustard variety Pusa Bold was taken for study. The results revealed that the Yield (grain and stover yield) and their attributing characterstics of mustard respond significantly with the different treatment combination. The highest grain (20.11 q/ha) and stover yield (43.13 q/ha) was obtained in T7 (125% RDF+Zn5) . The treatment T7 cause 32.72 % increase in mustard grain yield and 14.22% increase in stover yield over control.. The treatment combination T7 (125% RDF+Zn5) gave the best result in terms of yield and their attributing characterstics.
Inoculation Methods and Doses and Relationship with the Vegetative and Reproductive Development of Soybeans
Authors: Rosa David Peres da , Verardi Junior , Girardi Junior Santana , Conte Paulo Henrique , Spagnolo Roger Toscan
Published: September 2020

This study aimed to evaluate and compare the method of in-furrow inoculant application with the other existing methods, as well as, in different doses in the development of soybean culture. The experimental design was randomized blocks in a two-factorial scheme (4 x 3), with four inoculation methods, without inoculation (control), by seed, in-furrow and leaf spray, with three doses, 100, 200 and 400%. Leaf and root dry mass, number of nodules, pods per plant, number of seeds per vegetables, height, knots per plant, productivity, root resistance and average chlorophyll content were measured. The combination of factors did not affect plant height, leaf dry matter, root resistance, grains and pods per plant, plant per knot and weight of 100 seeds, affecting only other parameters, in which the largest root dry matter occurred in in-furrow inoculation in the dose of 400%, with 3.82 g plant-1, against 3.43 g plant-1 in the by seed method in the same dose. In the in-furrow application at the 100% dose, the highest number of grains pod-1 occurred, with 3.42 grains pod-1, combined with an increase in pods plants-1, and a 19% increase in productivity relative to the control, and 9.5% at the third increase, in the spray. Co-inoculation methods affect the development of soybeans, and the method that provided the greatest of soybean development was by in-furrow.
Antibacterial Activity of Datura metel Linn. (TALONG-PUNAY) Fruit Extract
Authors: Lim Karina Milagros C. , Dagalea Flyndon Mark S. , Vicencio Manuela Cecille G.
Published: September 2020

Aim: The objective of this study is to determine the phytochemical constituent and antibacterial effect of fruit extract of Datura metel against Staphylococcus aureus and Escherichia coli.

Methods: The extract of the sample underwent a phytochemical screening to identify the secondary metabolites present. Also, an antibacterial test was carried out to test its effectiveness, it was tested by impregnating the respective disc on Mueller-Hilton agar streaked with Staphylococcus aureus and Escherichia coli.

Results: Datura metel fruit extract was observed to have a good antibacterial activity on the two bacteria and this was due to the presence of the phytochemical compounds terpenoids, saponin, alkaloids, steroid, flavonoids, and tannins.

Conclusion: The sample Datura metel fruit extract could be used in the field of pharmaceutical because of its antimicrobial activity and present secondary metabolites.
Pattern of Preoperative Astigmatism in Patients in South East Nigeria as Determined by Biometry
Authors: Kalu A. , Otuka O.I , Eweputana L. , Nwachukwu K. U. , Ume J. K.
Published: September 2020

Background: Astigmatism is an error of refraction that can affect visual outcome after cataract surgery. The degree of astigmatism is usually estimated pre-operatively by keratometry readings. These readings can help in the plan of surgical technique and choice of intraocular lenses during cataract surgery in order to improve visual outcome. This study was done to provide data on the pattern of preoperative astigmatism in cataract patients in South East Nigeria. It is hoped that this knowledge will increase the awareness on pre-operative astigmatism among ophthalmologist so that they can improve their surgical skills on ways of reducing this astigmatism or avoid worsening it.

Methods: A retrospective review of keratometry readings of 533 patients were taken from June 2018 to December 2019, with emphasis on the cylinders.

Results: The most common degree of astigmatism was -0.75DC. The proportion of patients with preoperative astigmatism ≤ -1.00DC was 60% while 40% had values higher than -1.00DC.

Conclusion: There may usually be significant pre-operative astigmatism in patients scheduled for cataract surgery. This calls for an improvement in surgical skills in minimizing astigmatism and avoiding worsening preoperative astigmatism. There should be increase availability and use of toric lenses for correction of preoperative astigmatism. Finally accurate postoperative refraction will have a positive impact in the management of astigmatism, whether preoperative or surgically induced.
Embryonic and Early Fetal Development of Human Lung Vasculature and Its Functional Implications
Authors: deMello Daphne E. , Reid Lynne M.
Published: July 2002

Recently, we have identified in the mouse three processes involved in the early development of pulmonary vasculature: angiogenesis for branching of central vessels, vasculogenesis (lakes in the mesenchyme) for peripheral vessels, and a lytic process to establish luminal connection between the two. We have established that these three processes also operate in the human by studying serial sections of human embryos and early fetuses. Vascular lakes of hematopoietic cells appear at stage 13, i.e., 4+ weeks gestational age (GA), the first intrapulmonary vascular structure to appear. At stage 20 (50.5 days GA), a venous network with luminal connections to central pulmonary veins (PV) is present. Airways have not yet reached these regions of lung.

At its first intrapulmonary appearance, the pulmonary artery (PA) is small and thick walled: it runs with the airway but its branching is slower, so many peripheral airways are not accompanied by a PA branch. By contrast, the PV has a peripheral patent network well before the PA.

In the pseudoglandular phase, airway branching continues, and the PA catches up so that small PA branches are found with all airways. Later in this phase small nonmuscular vessels lie in the mesenchyme close to airway epithelium.

By the early canalicular phase and the age of viability, continuity between pulmonary artery and the peripheral capillary network must be established. In a 10-week fetus several structures suggesting a breakthrough site were seen. Air-blood barrier structure is first seen at 19 weeks. Thus in the lung, the PA and PV are dissociated in their timing and pattern of branching. Early veins are present diffusely through the mesenchyme and establish central luminal connection to the main pulmonary vein before airway or artery are present at this level.
Synchronous Wilms Tumor and Fibrolamellar Hepatocellular Carcinoma: Report of a Case
Authors: Maitra Anirban , Ramnani Dharamdas M. , Margraf Linda R. , Gazdar Adi F.
Published: July 2002

Fibrolamellar hepatocellular carcinoma (FHCC) is a unique histologic variant of HCC that occurs in a younger subset of patients than classical HCC, and is associated with a better prognosis. Wilms tumor (WT) is a malignant embryonal neoplasm of the kidney and is one of the most common solid tumors of childhood, occurring at an estimated frequency of 1 in 8000 to 10,000 births. Although second malignant neoplasms (SMNs) following therapy for WTs have been reported in the liver, the coexistence of HCC and WT is extremely rare. We present the first report of a synchronous ana-plastic WT and FHCC in a previously healthy 4-year-old girl. Despite the presence of focal immunohistochemical positivity for p53 in the WT, molecular analysis failed to reveal a germline or somatic p53 mutation, and was inconclusive in establishing a clonal relation between the two tumors.
Adenomyoma Arising in a Meckel Diverticulum: Case Report and Review of the Literature
Authors: Yao Jorge L. , Zhou Hong , Roche Kevin , Bangaru Babu S. , Ginsburg Howard , Greco M. Alba
Published: July 2002

We report a case of adenomyoma of the small intestine arising in a Meckel diverticulum. The patient was a 22-month-old boy who presented with signs and symptoms of intussusception. At surgery, a Meckel diverticulum was found and removed. On histologic examination, a tumor consisting of dilated cystic glands and smooth muscle bundles was identified. A diagnosis of adenomyoma arising in a Meckel diverticulum was made. A review of the literature showed that only six other pediatric cases of adenomyoma of the small intestine have been reported. The presence of an adenomyoma in a young patient within a Meckel diverticulum favors the view that adenomyomas are a variant of pancreatic heterotopia.
Investigation of Stillbirth
Authors: Magee J.F.
Published: July 2002

The pathologic investigation of stillbirth is often frustrating, and may be viewed as unrewarding, because the reason for death of the infant frequently is not identifiable. This outline attempts to identify an approach to the examination of the stillborn and accompanying placenta, with appropriate use of ancillary studies that may uncover the cause of death and/or identify factors that could prejudice future pregnancies.
Congenital Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins Associated with Hypoplastic Left Heart Syndrome
Authors: Rabah R. , Poulik J.M.
Published: July 2002

Three full-term infants died in the first month of life with hypoplastic left heart syndrome (HLH) and persistent pulmonary hypertension (PPH). At postmortem examination, they were found to have alveolar capillary dysplasia with misalignment of pulmonary veins (ACD with MPV). The association of HLH syndrome, and ACD with MPV with intestinal malrotation and/or obstruction, is unique. Decreased blood flow in the ascending aorta in fetuses with left outflow tract obstruction might cause vasoconstriction of pulmonary arterioles to maintain cerebral perfusion. Vasoconstriction early during embryo-genesis might lead to decreased growth and development of alveolar capillaries and pulmonary veins. This results in pulmonary hypertension, and the arterial blood is forced to bypass the deficient capillary bed and can drain only via the anomalous bronchial veins.
Accidental Modification of Attwood's Stain on Decalcified Preparations, Yielding Improved Differentiation between Woven and Lamellar Bone
Authors: Lee S. , Stocks R. , de Sa D.J.
Published: July 2002

In an earlier report, a modification of the Attwood's stain was used to study sections of decalcified bone and the procedure aided in the distinction between lamellar and woven bone. Lamellar bone showed preferential affinity for phloxine (red) yet resisted differentiation with tartrazine (yellow), while woven bone stained well with tartrazine. In addition, osteoid seams were identified by their affinity for tartrazine. Differential staining was abolished by pretreatment with periodic acid. Recently, accidental use of potassium permanganate in an acidified medium of pH 1.94, instead of pH 6.44, yielded unexpected results with a much sharper, consistent distinction between woven and lamellar bone. This probably reflects changes in the noncollagenous, interfibrillary matrix proteins of bone, but the exact reason(s) is not known. In our view, this serendipitous modification represents an advance over the previous method, and has allowed us to study the structure of bone in some of the systemic disorders, e.g., osteogenesis imperfecta, with greater ease than before. This method does, however, suffer the disadvantage of interfering with the intensity of the staining of any cartilaginous matrix, and the original application is still of value.
Malignant Melanoma in Children and Congenital Melanocytic Nevi: DNA Content and Cell Cycle Analysis by Flow Cytometry
Authors: Alvarez-Mendoza Antonio , Reyes-Esparza Jorge , Ruiz-Maldonado Ramon , Lopez-Corella Eduardo , Juarez-Herrera Norma C.
Published: July 2002

Malignant melanoma (MM) in children, although a rare neoplasm, can occur within a preexisting congenital melanocytic nevus (CMN). All the potential risk factors for this phenomenon are not well known, but increases in S phase and G2 + M phase of cell cycle, DNA aneuploidy, and cell cycle abnormalities in precursor lesions might be among the risk factors.

Using paraffin-embedded tissue, we performed a retrospective analysis of DNA content, aneuploidy, and cell cycle by flow cytometry. Two groups of patients were analyzed: 28 children with CMN who did not developed MM, and 6 patients who further developed MM. In this second group, three patients had four biopsies done before the appearance of MM and in two patients biopsies were done after the appearance of MM.

All CMN not associated with MM exhibited diploid cells only, their S phase was 11.5% (± 3.8), and their G2 + M phase was 2.5% (± 2.2). Among those patients who developed MM, 3/6 had an S phase > 15.5 and a G2 + M phase > 2.3 prior to the appearance of MM. Two out of six patients had a tetraploid DNA when MM developed and died with a disseminated MM. They had an S phase > 15.5 and their G2 + M phase was > 2.5.

We propose that evaluation of DNA content and cell cycle by flow cytometry is a useful method to supplement biopsy findings in children with CMN who have lesions suspicious of developing a MM.
Hypercellular/Heterotopic Ganglia in Omphalomesenteric Duct Remnants
Authors: Wu Sandy S. , Coventry Susan , de Chadarevian Jean-Pierre , Collins Margaret H.
Published: July 2002

Omphalomesenteric duct remnants (ODR) including Meckel diverticula often present with symptoms of bowel obstruction. Their histologic features are varied and include heterotopic gastrointestinal mucosa and/or pancreatic tissue within the wall. Abnormalities of the submucosal plexus of Meissner, however, have not been documented in the literature. Thus, we have examined a number of ODR for evidence of ganglion abnormalities. Fifty-three cases of ODR were retrieved from our archives, along with 25 nonduodenal small bowel control specimens obtained from autopsies of patients without clinical or pathologic evidence of enteropathy. Histologic criteria for the diagnosis of abnormal hypercellular/heterotopic ganglia (HHG) in ODR were defined as a single submucosal ganglion/plexus containing >10 neurons, or >5 submucosal ganglions per high-power (X40) field, or heterotopic ganglion cells within the muscularis mucosa or the lamina propria. HHG, histologically indistinguishable from intestinal neuronal dysplasia type B, were found in more than half of the ODR (ODR: 51.9%, n = 50 vs. control: 4%, n = 25, P = 3.6 X 10−6), particularly those excised for obstructive complications (ODR with acute abdomen: 65.7%, n = 35, vs. ODR without acute abdomen: 33.3%, n = 15, P = 0.035). HHG were present in equal numbers of inflamed and noninflamed ODR (inflamed: 53.6%, n = 28, vs. noninflamed: 59.1%, n = 22, P = 0.70). A similar incidence was found in ODR with heterotopia and without (with heterotopia: 61.1%, n = 18, vs. without: 53.1%, n = 32, P = 0.59). ODR frequently contained HHG histomorphologically similar to those found in intestinal neuronal dysplasia, type B (IND-B). The overrepresentation of HHG in symptomatic ODR patients suggests an association with bowel obstruction. The data did not demonstrate a relationship with either inflammation or heterotopia.
Neck Extension and Rotation in Sudden Infant Death Syndrome and Other Natural Infant Deaths
Authors: Krous Henry F. , Nadeau Julie M. , Silva Patricia D. , Blackbourne Brian D.
Published: July 2002

It has been hypothesized that some cases of sudden infant death syndrome (SIDS) are a result of neck extension and/or rotation that causes vertebral artery (VA) compression and brain stem ischemia. There is a paucity of relevant literature on this topic. Therefore, our aim was to compare neck rotation and extension in SIDS and other natural infant deaths. Cases of SIDS and other natural infant deaths within the San Diego SIDS Research Project database were analyzed retrospectively with respect to neck and body position as reported by the trained, experienced scene investigators and/or the caretakers who discovered the infants. Information was used from 246 SIDS cases and 56 cases of other natural deaths. Simultaneous neck extension and rotation was not reported in either group. When data regarding neutral/flexed/extended position and rotation of the neck were combined, no significant differences were found between the two groups ( P = 0.94); 40% of the SIDS cases and 41% of the other natural death cases were found with the neck either extended or rotated (odds ratio [OR] 0.97, [reference group = neck either neutral or flexed, and not rotated], 95% confidence interval [CI] 0.45, 2.11). There were also no significant differences between the groups when neck rotation and neck extension were analyzed independent of one another. Neck rotation among cases found in the prone position was common and was not significantly different between the two groups (49% of 146 SIDS cases, 58% of 24 other natural death cases, P = 0.38, OR 0.68, 95% CI 0.28, 1.62). Neck rotation among infants found in the supine position occurred one-third as often in the SIDS group (9% of 33 cases) as in the other natural death group (29% of 14 cases); however, the difference was not significant ( P = 0.17; OR 0.25, 95% CI 0.05, 1.31). Although our analysis does not exclude VA compression and brain stem ischemia in some cases of SIDS, we found no evidence to affirm its importance. This study demonstrates the importance of meticulous scene descriptions, including neck position.
Distribution of α2-Adrenergic Receptor Binding in the Developing Human Brain Stem
Authors: Mansouri Jaleh , Panigrahy Ashok , Assmann Susan F. , Kinney Hannah C.
Published: July 2002

Rapid and dramatic changes occur in cardiorespiratory function during early human life. Catecholamines within select brain stem nuclei are implicated in the control of autonomic and respiratory function, including in the nucleus of the solitary tract and the dorsal motor nucleus of X. Animal and adult human studies have shown high binding to α2-adrenergic receptors in these regions. To determine the developmental profile of brainstem α2-adrenergic binding across early human life, we studied brain stems from five fetuses at mid-gestation, three newborns (37–38 postconceptional weeks), and six infants (44–61 postconceptional weeks). We used quantitative tissue receptor autoradiography with [3H]para-aminoclonidine as the radioligand and phentolamine as the displacer. In the fetal group, binding was high (63–93 fmol/mg tissue) in the nucleus of the solitary tract, dorsal motor nucleus of X, locus coeruleus, and reticular formation; it was low (<32 fmol/mg tissue) in the principal inferior olive and basis pontis. Binding decreased in all regions with age: in infancy, the highest binding was in the intermediate range (32–62 fmol/mg tissue) and was localized to the nucleus of the solitary tract and dorsal motor nucleus of X. The most substantial decrease in binding (75%–85%) between the fetal and infant periods occurred in the pontine and medullary reticular formation and hypoglossal nucleus. Binding remained low in the principal inferior olive and basis pontis. The decreases in binding with age remained significant after quench correction. These data suggest that rapid and dramatic changes occur in early human life in the brain stem catecholaminergic system in regions related to cardiorespiratory control.
Extramedullary Hematopoiesis within a Frontoethmoidal Encephalocele in a Newborn with Holoprosencephaly
Authors: Elgin Virginia E. , Connolly E. Sander , Millar William S. , Feldstein Neil A. , Dwork Andrew J.
Published: July 2002

We present the first report of extramedullary hematopoiesis (EMH) in an encephalocele. The patient was a newborn with semilobar holoprosencephaly, a frontoethmoidal encephalocele, and a large subdural hematoma. The encephalocele appeared as a hemorrhagic mass, protruding from the forehead to cover the right eye, without involvement of the sinuses or nasopharynx. Computerized tomography and magnetic resonance imaging studies ruled out other forms of holoprosencephaly and confirmed the continuity of the brain with the extruded mass. Immunohistochemistry confirmed the presence of an atrophic epithelium covering the mass. Histologic examination of the encephalocele revealed EMH both within and adjacent to malformed cerebral cortex, with a tendency for the hematopoietic cells to line up in columns within malformed cerebral cortex. We propose that a single event during the fourth week of gestation could both interrupt closure of the neural tube, giving rise to the encephalocele, and impair migration of the neural crest, leading to holoprosencephaly secondary to failure of neural crest derivatives to induce basomedial telencephalic differentiation. EMH may have been induced from hematopoietic stem cells in the richly vascular meningeal component of the encephalocele, in response to anemia and hypoxia.
Cytoplasmic Inclusion Bodies and Minimal Hepatitis: Fibrinogen Storage without Hypofibrinogenemia
Authors: Abukawa Daiki , Tazawa Yusaku , Noro Tomoyo , Nakagawa Michiko , Iinuma Kazuie , Sugiyama Kohachiro , Knisely Alexander S.
Published: July 2002

A 12-year-old Japanese boy had chronic elevation and fluctuation of serum transaminase levels since infancy, with no signs or symptoms of liver failure. Usual infections or metabolic disorders were eliminated from consideration. No coagulopathy or abnormality in plasma concentrations of clotting factors was found. Light microscopy of liver biopsy specimens obtained at ages 2,5, and 7 years showed slight hepatocyte disarray and minimal mononuclear-leukocyte lobular inflammation, with eosinophilic inclusion bodies in the cytoplasm of hepatocytes throughout the lobule. These bodies stained with the periodic acid-Schiff (PAS) technique; the PAS-positive material was partly diastase digestible and on immunostaining marked for fibrinogen but not for α1-antitrypsin. On transmission electron microscopy, the bodies were represented by finely granular material contained within membranes and were interpreted as tentatively endoplasmic reticulum. Fibrinogen storage may be manifest as minimal hepatitis without coagulopathy.
Cell Proliferation in the Developing Human Kidney
Authors: Nadasdy T. , Lajoie G. , Laszik Z. , Blick K.E. , Molnar-Nadasdy G. , Silva F.G.
Published: July 2002

In a previous study, utilizing antibodies to proliferating cell nuclear antigen (PCNA), we determined the proliferation index (PI) (percentage of PCNA-positive cells) of intrinsic renal cell populations in the normal adult and pediatric kidney. We have found that the PI in both adult and pediatric kidneys was very low (below 0.5 in all examined cell populations). In our present study, we investigated cell proliferation in the developing human kidney with an antibody to PCNA. Histologically normal kidneys were collected from 25 fetuses (spontaneous abortions and stillborns) ranging from 10 wk of gestation to term. Immature mesenchyme (blastema), immature early tubules, ampulla of ureteric bud, proximal tubules, Tamm-Horsfall protein (THP)-positive tubules, distal tubules, collecting ducts, and glomeruli were evaluated separately. The PI for each cell population was calculated. The PI of immature early tubules remains high (33–43) throughout embryonic life. The PI of blastemal cells is initially similarly high, but gradually decreases starting from the second trimester. The PI of THP-positive tubules, distal tubules, collecting ducts, and glomeruli starts out relatively high (5.9, 8.6, 6.0, and 12.4, respectively) and decreases gradually as term approaches (1.8, 1.3, 1.2, and 1.4, respectively). Interestingly, as soon as proximal tubules become differentiated (appearance of light microscopic features of proximal tubular epithelium with TP lectin positive brush border), their PI becomes very low (below 1) irrespective of the age of the kidney. This is the first quantitative study to show changes of the PI in various renal cell populations during human nephrogenesis. These changes in the PI relate to the stage of differentiation of the developing nephron segments.
Pathological Evaluation of Renal Tumors in Children: International Society of Pediatric Oncology Approach
Authors: Boccon-Gibod Liliane A.
Published: July 2002

In the majority of European countries, children with renal tumors now enter the SIOP-93-01 Trial and Study. The objective of this Study is to refine methods of treatment especialy in stage I patients. The role of institutional pathologists is important in this trial. There are new criteria for stages I and II, a new SIOP Working Classification of Renal Tumors of Childhood, and morphologic and prognostic similarities of pretreated and non-pretreated anaplastic cases. Specific problems encountered in assessing tumors treated with preoperative chemotherapy, administered to the majority of children over 6 months of age entering the SIOP Study, are discussed. The identification of a new low-risk group, the completely necrotic Wilms tumor, is outlined.
Detection of Mycobacterial Infections Using the Dieterle Stain
Authors: Brady John G. , Schutze Gordon E. , Seibert Robert , Horn Hazel V. , Marks Barbara , Parham David M.
Published: July 2002

Retrospective review comparing the modified Dieterle stain with standard acid-fast stains was performed on seven surgical pathology cases that contained culture-positive mycobacteria infections. Tissues examined comprised cervical and submandibular lymph nodes and soft tissues of the face and chest. Modified Dieterle staining was performed on paraffin-embedded tissue sections, and the results were compared with those of hematoxylineosin stains and auramine-rhodamines and carbol-fuchsin acid-fast stains. The acid-fast stain showed organisms in three of seven cases on initial review and five of seven cases on retrospective review; the auramine-rhodamine stain retrospectively revealed organisms in five cases. In contrast, the Dieterle stain showed organisms in all seven sections on retrospective examination. Dieterle stains revealed either beaded bacilli or nocardia-like filamentous organisms, sometimes with abundant granular debris possibly representing degenerative organisms. In three cases in which bacteria were readily apparent with the Dieterle stain, only rare organisms could be identified with the acid-fast stain. The modified Dieterle stain was more sensitive than the acid-fast stain in the identification of mycobacteria in pediatric specimens, and its use is recommended in cases with necrotizing granulomas. However, its specificity is limited by morphologic similarities of the organisms to those of nocardiosis and cat scratch disease.
Massive Myocardial Calcification in the Perinatal Period
Authors: Drut Ricardo , Drut Rosa Mónica , Greco M. Alba
Published: July 2002

Massive myocardial calcification (MMC) in the perinatal period is an unusual finding considered to be a unique tissue reaction. This report summarizes the clinical and pathologic findings of seven cases of perinatal MMC. All patients presented clinical evidence of myocardial damage. In two cases arrhythmia was detected in utero. Four cases presented with hydrops, one of which was associated with major heart malformation. One case was a trisomy 13. Three cases had polyhydramnios. Our results demonstrate that calcification follows progressive stages from patches of calcified myocardial cells (stage I), to coagulative and colliquative myocytolysis with clusters of interstitial mononucleated cells (stage II), to collapsing fibrosis with granulation tissue and multinucleated regenerative myocardial cells (stage III), and finally to fibrous scars containing entrapped remaining myocardial cells (stage IV). Literature review and our findings suggest that perinatal MMC results from different conditions inducing hypoxic–ischemic damage that later is followed by progressive scarring if the patient survives the acute stage. The lesion may represent the human counterpart of the so-called dystrophic cardiac calcinosis in mice. This disease is related to an abnormality at the Dyscalc locus of proximal chromosome 7 (syntenic with human chromosome 19q13 and 11p15).
Enzyme-linked Immunoassay for Respiratory Syncytial Virus is Not Predictive of Bronchiolitis in Sudden Infant Death Syndrome
Authors: Parham David M. , Cheng Richard , Schutze Gordon E. , Dilday Bradley , Nelson Rebecca , Erickson Stephen , Kokes Charles , Peretti Frank , Sturner William Q.
Published: July 2002

Although respiratory syncytial virus (RSV)-infected infants may present with apnea, the role that RSV plays in sudden infant death syndrome (SIDS) is speculative. To determine whether RSV is associated with bronchiolitis in these patients, we examined histologic sections of lungs from 41 apparent SIDS cases and compared the results with those of enzyme-linked immunofluorescent assay (EIA) from nasal washings. Bronchiolitis was defined by a bronchiolar inflammatory cell infiltrate plus epithelial necrosis. A positive EIA was associated with bronchiolitis in 8 instances, compared with 6 having a positive EIA and negative histology, 14 having a negative EIA and positive histology, and 13 having EIA and histology both negative. These results yield a predictive value of a positive test of 57% and a predictive value of a negative test of 48% ( P > .9 by chi square analysis). Although RSV of the upper respiratory tract may be related to SIDS, our results indicate that EIA of nasal washings is not predictive of bronchiolitis, and we recommend other means of verification of histologic results.
Third Report of t(19q)(13.4) in Mesenchymal Hamartoma of Liver with Comments on Link to Embryonal Sarcoma
Authors: Bove Kevin E. , Blough Ruth I. , Soukup Shirley
Published: July 2002

We report the third known case of mesenchymal hamartoma of the liver (MHL) with a balanced translocation involving a common breakpoint, 19q13.4. A common clonal chromosome abnormality appears to characterize an important subset of MHL, some of which may be low-grade neoplasms. We found no consistent karyotype abnormality in a post-treatment sample of embryonal sarcoma of the liver (ESL). Reports of coexistent MHL and ESL in two patients and detection of 19q abnormalities in two ESLs appear to support Stocker's hypothesis of a histogenetic link between these two rare liver lesions. More data are needed to clarify this relationship. It is possible that MHLs are etiologically heterogenous and may be developmental disorders, disruptions, or neoplasms.
Differences among Acute, Subacute, and Chronic Chorioamnionitis Based on Levels of Inflammation-Associated Proteins in Cord Blood
Authors: Miyano Akira , Miyamichi Toru , Nakayama Masahiro , Kitajima Hiroyuki , Shimizu Akira
Published: July 2002

The serum concentration of inflammation-associated proteins and several complement components in the cord blood of 215 newborns with and without chorioamnionitis (CAM), who were delivered between 17 and 42 weeks of gestation, were measured. We investigated the relationship of levels of serum proteins to acute, subacute, and chronic CAM, and to subacute necrotizing funisitis (SNF). Complement components C3d, C3, and C4 levels increased in subacute CAM ( P = 0.0002, P = 0.0007, P = 0.0029, respectively), whereas factor B increased in each type of CAM ( P = 0.0001, P = 0.0009, P = 0.0004, respectively). Among the immunoglobulins, IgG levels were unrelated to the presence or type of CAM, IgM levels increased in subacute CAM ( P < 0.0001), and IgA levels increased in chronic CAM ( P < 0.0001). Among the acute phase reactants (APR), haptoglobin and C-reactive protein (CRP) levels increased in acute ( P < 0.0001, P = 0.0022, respectively) and chronic CAM ( P = 0.0035, P = 0.0345, respectively), whereas orosomucoid levels increased in chronic CAM ( P = 0.0003). IL-6 levels increased in acute ( P = 0.0011) and subacute ( P = 0.0475) CAM. C3d ( P = 0.0063), C3 ( P = 0.0289), C4 ( P = 0.0491), and IgM ( P < 0.0001) levels were increased in SNF. These findings suggest that the histologic distinction of acute, subacute, and chronic CAM is a useful indicator of the inflammatory mediator status of the infants. The infants with SNF may have ended their initial active inflammatory states, but they still have subacute immune activation.
Severity of Esophageal Eosinophilia Predicts Response to Conventional Gastroesophageal Reflux Therapy
Authors: Ruchelli Eduardo , Wenner William , Voytek Theresa , Brown Kurt , Liacouras Chris
Published: July 2002

Pediatric patients who present with symptoms of gastroesophageal reflux and severe eosinophilic esophagitis may be unresponsive to aggressive anti-reflux medical therapy. In order to determine whether the degree of eosinophilia predicts anti-reflux treatment response and possibly distinguishes different etiologies, we reviewed the initial biopsies of patients with esophageal eosinophilia and compared the number of eosinophils with the response to anti-reflux treatment. Over a 1-year period, 102 patients with a biopsy demonstrating at least 1 intraepithelial eosinophil were identified among patients undergoing initial endoscopy for symptoms of reflux. All patients were treated with H2 blockers and prokinetic agents. Treatment response was classified into three categories: improvement, relapse, and failure. There were significant differences between the group who improved (mean eosinophil count [MEC] 1.1 ± 0.3SEM) and those who failed (24.5 ±6.1 SEM, P < 0.0025) or relapsed 6.4 ± 2.4 SEM, P < 0.05). A threshold MEC value of ≥7 provided a sensitivity of 61.3%, a specificity of 95.7%, and a predictive value for treatment failure of 86.1. A MEC value of <7 provided an 85% predictive value of successful therapy. From these data we made the following conclusions: ( 1) The number of eosinophils has a predictive value of treatment response with ≥7 per high power field offering a valuable clinical threshold for predicting outcome of conventional therapy. ( 2) The variable response to conventional reflux treatment may reflect different etiologies. ( 3) Alternate medical treatment modalities may be appropriate in the presence of severe eosinophilia, before considering surgical intervention.
Renal Cell Carcinoma in Children with Diffuse Cystic Hyperplasia of the Kidneys
Authors: Henske Elizabeth Petri , Thorner Paul , Patterson Kathleen , Zhuang Zhengping , Bernstein Jay
Published: July 2002

We report the clinical, pathologic, and genetic features of renal malignancy in two children with diffuse cystic hyperplasia. Both presented with massive bilateral nephromegaly. Neither had a family history or clinical findings suggestive of tuberous sclerosis or von Hippel–Lindau disease. The kidneys of both children were extensively replaced by tubulocystic hyperplasia with large eosinophilic epithelial cells. The masses of hyper-plastic tissue were nodular, compressing remnants of uninvolved renal parenchyma. Tubulopapillary carcinoma was present in both children, one of whom had bilateral multicentric carcinoma. No loss of heterozygosity was detected in the tumors at the TSC1, TSC2, or VHL gene regions, and no alterations in the VHL gene were detected using single-strand conformation polymorphism analysis. These cases of bilateral renal enlargement with diffuse cystic hyperplasia appear to represent a new clinical syndrome that may warrant bilateral nephrectomy because of the risk of malignancy.
Isovaleric Acidemia with Promyelocytic Myeloproliferative Syndrome
Authors: Gilbert-Barness Enid , Barness Lewis A.
Published: July 2002

Isovaleric acidemia, an autosomal recessive disorder, is due to isovaleryl-coenzyme A dehydrogenase deficiency and is one of the branched-chain aminoacidopathies. Isovaleric acidemia may present in the neonatal period with an acute episode of severe metabolic acidosis, ketosis, and vomiting and may lead to coma and death in the first 2 months of life. This report concerns an infant who presented at 10 days of age because of lethargy, poor feeding, hypothermia, cholestasis, and thrombocytopenia, leukopenia, and profound pancytopenia. Death occurred at 19 days of age. Autopsy showed mild fatty change in the liver and extramedullary hematopoiesis, generalized Escherichia coli sepsis, and myelodysplasia of the bone marrow with arrest of the myeloid series at the promyelocytic stage. The appearance resembled promyelocytic leukemia, but the diagnostic 15:17 translocation was not present. The maturation arrest in granulopoiesis in isovaleric acidemia appears to be most likely due to a direct metabolic effect on granulocyte precursor cells.
Testicular Changes in Newborn Rats Exposed to Phototherapy
Authors: Koç H. , Altunhan H. , Dilsiz A. , Kaymakçi A. , Duman S. , Oran B. , Erkul I.
Published: July 2002

In this study we investigated the long-term effects of 72-h continuous phototherapy on the reproductive system of newborn rats. The animals' weight, fertilization rates, and number of newborn and histopathological changes in the gonads in a normal group not exposed to phototherapy and in the test animals were compared.

At the age of 24 weeks there were no significant differences between the two groups, apart from the histology of the testicles of the male rats who were exposed to the phototherapy. The study group showed a significantly reduced diameter of the seminiferous tubules when compared to the controls ( P < 0.001). It can be postulated that phototherapy may cause histological degenerative changes in the structure of the rat's testes, even though there were no changes in fertilization rates. Further studies are necessary to reveal the effects of phototherapy on humans and to determine the effects, if any, on fertility.
Infantile Liver Giant Cells: Immunohistological Study of Their Proliferative State and Possible Mechanisms of Formation
Authors: Koukoulis George , Mieli-Vergani Giorgina , Portmann Bernard
Published: July 2002

The mechanism of liver giant cell formation is not clarified. Some authors consider the giant cells regenerative, others, degenerative. Paraffin sections of 10 archival cases of idiopathic neonatal hepatitis (INH), 8 of extrahepatic biliary atresia (EHBA), and 5 normal liver samples were immunostained with two well-characterized cell proliferation markers: anti-PCNA monoclonal antibody (MAb) (clone PC-10) and MAb MIB-1, which detects Ki-67, a nuclear proliferation-related antigen. In addition, polyclonal antibody to carcinoembryonic antigen (CEA) was used to identify remnants of canalicular, therefore hepatocytic, membranes in giant cells. Quantitative analysis of immunostaining was done by estimating PCNA and Ki-67 indices separately in giant cells and in nongiant hepatocytes. In normal samples, mean PCNA and Ki-67 indices were 1.22% and 0.74%, respectively. In the cases of INH and EHBA, only a small minority of giant cells showed PCNA or Ki-67 staining limited to occasional peripherally located nuclei. PCNA and Ki-67 indices were significantly higher in the non–giant cell compartment. CEA staining was seen only in rare giant cells as centrally located canalicular remnants bordered by polarized nuclei, suggesting that they had been formed from rosettes through dissolution of cell membranes. Other giant cells shared CEA-labeled canalicular membranes with mononuclear hepatocytes in rosettes. These findings indicate that the giant cells in INH and EHBA are not regenerative cells, they are not formed by amitotic division of nuclei in syncytia, and that fusion of rosette-forming hepatocytes is a possible mechanism of their formation.
Hemophagocytic Syndrome Presenting as Acute Hepatic Failure in Two Infants: Clinical Overlap with Neonatal Hemochromatosis
Authors: Parizhskaya Maria , Reyes Jorge , Jaffe Ronald
Published: July 2002

Two patients with hemophagocytic lymphohistiocytosis who presented with acute liver failure are reported. Both presented with fever, hepatosplenomegaly, markedly elevated liver function tests, abnormal coagulation profiles, and an increase in serum ferritin. Both infants were diagnosed with neonatal hemochromatosis based on a clinical picture of hepatic insufficiency with hyperferritinemia and were referred for liver transplantation. The first patient died of liver failure and septicemia before transplantation. Review of autopsy material revealed a hepatitis-like pattern and extensive infiltration of liver and other organs including bone marrow by histiocytes, some of which were hemophagocytic. The second patient underwent liver transplantation but died 44 days thereafter from progressive hemophagocytic lymphohistiocytosis. Examination of the resected liver demonstrated a hepatitis-like pattern, proliferation of histiocytes, and hemophagocytosis, and the bone marrow revealed hemophagocytic histiocytosis. Hemophagocytosis recurred in the allograft. Hepatic manifestations are common in hemophagocytic lymphohistiocytosis and overt hepatic failure may occur, but initial presentation as fulminant hepatic failure is not well recognized. Elevated serum ferritin can make the distinction from neonatal hemochromatosis and other forms of neonatal liver failure difficult. Hemophagocytic lymphohistiocytosis should be considered in the differential diagnosis of neonatal liver disease, especially when it is accompanied by cytopenias.
Hematogones as an Internal Control in Flow Cytometric Analysis of Suspected Acute Lymphoblastic Leukemia
Authors: Vargas Sara O. , Hasegawa Susan L. , Dorfman David M.
Published: July 2002

Hematogones are benign immature B cells that commonly populate the bone marrow of children. Their presence has been noted to interfere with the flowcytometric analysis of cases of suspected acute lymphoblastic leukemia (ALL) because their immunophenotype (positive for CD19, CD10, CD34, and terminal deoxynucleotidyl transferase) is similar to that of pre–B cell lymphoblasts. Here we report a case in which the presence of a discrete population of hematogones, characterized by low-intensity CD10 cell-surface staining compared with pre–B cell lymphoblasts, actually aided in the recognition of early relapsed ALL and disease progression over a 4-day period. We also review our experience with flow-cytometric immunophenotyping in pediatric cases of suspected leukemia to evaluate the frequency of this occurrence.