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J F Bonadio

Publications and source records attributed to J F Bonadio.

13 recordsLinked to original sources
PubMed1996

Local expression of human growth hormone in bone results in impaired mechanical integrity in the skeletal tissue of transgenic mice.

The effect of local production of human growth hormone on murine cortical bone was investigated using a transgenic mouse model. Femora and humeri from human growth hormone transgenic mice and littermate control mice were obtained, and the geometrical, biomechanical, compositional, and histomorphometric properties of all specimens were determined. The goals were to investigate the effects of local expression of human growth hormone on skeletal integrity, including the functional geometry of long bone and its related structural and mechanical behavior, as well as tissue composition and integrity. As expected, local production of human growth hormone by osteoblasts indeed resulted in longer femora with significantly greater mid-diaphyseal cross-sectional geometry in the transgenic mice (16% increase in cross-sectional area and 29% increase in bending moments of inertia). However, the significant increase in geometry was not associated with a proportional increase in bending stiffness and other structural properties, which suggested that the mechanical properties of the cortical bone tissue may have been inferior. Microspecimen bending tests verified this prediction, given that transgenic cortical bone tissue had significantly lower apparent elastic modulus and ultimate strength (52 and 68%, respectively, of control values). These defects in the whole bone structural and tissue mechanical properties of transgenic specimens were associated with a smaller fraction of ash, larger fractions of woven bone and cartilage islands, and greater porosity in the mid-diaphyseal cortices. These results suggest that local production of human growth hormone by osteoblasts is indeed anabolic for bone, but at the expense of bone tissue integrity.

Adaptation, Physiological↗
PubMed1990

Nephrogenic rests, nephroblastomatosis, and the pathogenesis of Wilms' tumor.

A new classification and terminology is proposed for precursor lesions of Wilms' tumor (WT), based upon morphology and natural history. The generic term nephrogenic rest (NR) is used for all WT precursors. Two major categories of NR are recognized: perilobar (PLNR) and intralobar (ILNR). Nephroblastomatosis signifies the presence of multiple or diffuse NRs. Nephroblastomatosis can be classified into four categories: (a) perilobar (PLNR only); (b) intralobar (ILNR only; (c) combined (PLNR and ILNR); and (d) universal. The individual rests can be subdivided into (a) nascent or dormant NRs; (b) maturing or sclerosing NRs; (c) hyperplastic NRs; and (d) neoplastic NRs. Of 282 evaluable unilateral WT specimens, 28.4% were definitely rest-positive, and an additional 12.4% were probably positive, with equal prevalence of PLNRs and ILNRs. Median age at diagnosis of WT was 36 months with PLNRs, 16 months with ILNRs, and 12 months if both types were present. PLNRs were strongly associated with synchronous bilateral WTs, and ILNRs with metachronous contralateral WTs. ILNRs were associated with aniridia and Drash syndrome, whereas PLNRs were more commonly found with hemihypertrophy and/or Beckwith-Wiedemann syndrome. The delineation of two distinct categories of WT precursors suggests pathogenetic heterogeneity for WTs. The biological and clinical implications of NRs are considered in the context of this classification.

Antineoplastic Agents↗
PubMed1988

Significance of polymorphonuclear leukocytes in CSF of bacteremic children.

A retrospective study was performed of 32 bacteremic children not receiving preadmission antibiotic therapy who had a diagnostic lumbar puncture for analysis of cerebrospinal fluid at the time of initial evaluation for an acute illness. In each instance, the CSF contained polymorphonuclear leukocytes without pleocytosis. Of these 32 bacteremic patients, 88% had a CSF differential cell count with 20% or fewer polymorphonuclear cells, and greater than 90% had glucose and protein concentration within the range of normal limits. All patients had a Gram-stained smear of CSF which revealed no organisms. In no instance was a CSF culture positive for a bacterial pathogen. In the bacteremic child not pretreated with antibiotics, cerebrospinal fluid which contains total white blood cell, glucose, and protein concentrations within limits of normal, a differential cell count with 20% or fewer polymorphonuclear leukocytes, and Gram-stained smear which reveals no organisms is not indicative of risk for bacterial meningitis.

Cerebrospinal Fluid↗
PubMed1988

Perinatal lethal osteogenesis imperfecta (OI type II): a biochemically heterogeneous disorder usually due to new mutations in the genes for type I collagen.

To resolve uncertainty concerning the inheritance of the perinatal lethal form of osteogenesis imperfecta (OI type II), we collected family data and radiographs for 71 probands and analyzed the collagens synthesized by dermal fibroblastic cells cultured from 43 of the probands, 19 parental pairs, and single parents of each of four additional probands. In 65 families for which there were complete data on sibship size, there was recurrence of the OI type II phenotype in five families such that six (8.6%) of 70 sibs were affected. In two families with recurrence, the radiographic phenotype was milder than that for the remainder; and one of those families was consanguinous, suggesting autosomal recessive inheritance. In the remaining three families there was no evidence of consanguinity, but in one of them the structure was compatible with gonadal mosaicism in the mother. In studies of collagens synthesized by cells from 43 infants, we identified two probands with separate rearrangements in an allele of one of the genes of type I collagen; but in the rest there were subtle mutations that disrupted the normal triple-helix structure of type I collagen molecules. In two probands we identified de novo mutations; in 16 additional families cells from the parents made only normal collagens, compatible with new mutations in their offsprings. These findings indicate that the OI type II phenotype is biochemically heterogeneous, that the majority result from new dominant mutations in the genes encoding type I collagen, and that some recurrences can be accounted for by gonadal mosaicism in one of the parents.

Cells, Cultured↗
PubMed1985

Anaplastic Wilms' tumor: clinical and pathologic studies.

A review of almost 1,200 children participating in the first and second National Wilms' Tumor Study (NWTS-1 and -2) has demonstrated a number of significant differences in the clinical presentation and response to therapy of anaplastic and nonanaplastic Wilms' tumor. Compared to their counterparts, children with anaplastic Wilms' tumor were generally one to two years older at diagnosis, more were non-white, and more had lymph node metastases at diagnosis. Consistent with previous studies, children with anaplastic Wilms' tumor survived for a significantly shorter time than those with non-anaplastic Wilms' tumor. A hopeful outlook, however, was suggested by the NWTS-2 experience since the more aggressive chemotherapies used in this study appear to have substantially improved the survival of patients with diffusely anaplastic tumors. Also, the survival of NWTS-2 patients with anaplastic Wilms' tumor was determined in part by clinicopathologic stage. It may be possible therefore to refine therapy according to stage so as to provide children with localized disease a chance for cure with fewer untoward treatment-related sequelae.

Anaplasia↗
PubMed1984

Clear cell sarcoma of the kidney with emphasis on ultrastructural studies.

Clear cell sarcoma of the kidney (CCSK) is a malignant childhood tumor distinguished from Wilms' tumor by its gross, microscopic, and ultrastructural morphologic features and its propensity to metastasize to bone. Some clinical features of 75 cases of CCSK registered in the National Wilms' Tumor Studies I-III are presented along with the results of electron microscopic study of 12 tumors. Ultrastructural features of the tumor are compared to those of tumors of pericytes, Schwann's cells, renomedullary interstitial cells, fibroblasts, other renal tumors, and other clear cell tumors. Fine structural properties of primitive cells with variable numbers of organelles do not strongly suggest a histogenetic origin. The effect of formalin fixation on perinuclear cytoplasmic filaments and the tendency of tumor cell extensions to enfold the pale extracellular matrix explain the vacuolated appearance of some tumor cells.

Adolescent↗
PubMed1984

Localization of collagen types IV and V, laminin, and heparan sulfate proteoglycan to the basal lamina of kidney epithelial cells in transfilter metanephric culture.

Mouse metanephric mesenchyme and embryonic spinal cord were cultured on opposite sides of a filter membrane. This resulted in formation of prenephronic vesicles after 36 hours in culture, S-shaped bodies after 2-3 days, and glomeruli and tubules after 4-7 days. The glomeruli consisted of an arborizing tuft of podocytes lying on a basement membrane without vascularization or a mesangial ingrowth. We have used antibodies to study the molecular composition of the nephron basement membrane at each stage of development. By immunofluorescence light microscopy, collagen Types IV and V, laminin, and heparin sulfate proteoglycan were expressed within the pericellular/intercellular matrix at the onset of morphologic differentiation. The molecules were organized into a linear basement membrane associated with epithelial cells during the prenephronic vesicle, S-shaped body, and glomerulus and tubule stages of development.

Animals↗