PubMed Health⌕ Search

Biomedical subjects

H C Kinney

Publications and source records attributed to H C Kinney.

At least 55 records · Page 3Linked to original sources
PubMed1992

Insulin-like growth factor II expression in the developing human brain.

Insulin-like growth factor II (IGF-II) is a polypeptide hormone with insulin-like metabolic activity and neurotrophic activity in vitro that has been implicated in human brain development. In this study, we used northern blot analysis to examine the patterns of IGF-II mRNA expression in selected regions of 18 human brains from cases ranging in age from 20 gestational weeks to 2.5 years (median age 31 gestational weeks). The expression of IGF-II mRNA was widespread throughout the brain from midgestation through the perinatal period. Each region showed a distinct developmental pattern of expression and IGF-II mRNA levels varied considerably between regions. The highest levels of expression at all ages were in leptomeninges and choroid plexus. After two postnatal months, IGF-II mRNA virtually disappeared from parenchymal regions. Beyond the perinatal period, IGF-II expression persisted primarily in choroid plexus. Transcripts of both 6.0 and 4.8 kb were detected in most brain regions. A developmental change in the relative amounts of the two transcripts occurred in choroid plexus, leptomeninges and medulla. The expression of IGF-II mRNA in the brain parenchyma during the last half of gestation correlates with a period of major brain growth and supports the hypothesis that high levels of IGF-II stimulate the proliferation and differentiation of neural cells early in development.

Blotting, Northern↗
PubMed1991

Opioid receptors localize to the external granular cell layer of the developing human cerebellum.

The distribution of opioid receptors in the developing human cerebellum was determined by tissue autoradiography using [3H]naloxone. In infants, opioid receptors were heavily concentrated in the external granular layer, a matrix of germinal cells, and were substantially less concentrated in the internal granular layer, differentiating progeny of external granular cells. In the mature internal granular layer of the child and adult, opioid receptors were negligible. Thus, in the human cerebellum, opioid receptors localize to a population of germinal cells and are negligible in their mature progeny. These data support the idea that endogenous opioids play a role in human brain development and may function as receptor-mediated growth factors. The cerebellum provides a model site to examine abnormal opioid effects upon human brain development, particularly in infants exposed to narcotics in utero.

Cell Differentiation↗
PubMed1991

Delayed central nervous system myelination in the sudden infant death syndrome.

This study was designed to assess whether development of the central nervous system (CNS) is delayed in victims of the sudden infant death syndrome (SIDS). We selected the parameter of myelination because it is a continuously changing and readily accessible marker of CNS development in the SIDS age-range. We assessed myelination blindly in 61 SIDS and 89 autopsy controls. In 62 sites the degree of myelination was visually graded in myelin-stained histological sections on an ordinal scale of 0-4 using the inferior cerebellar peduncle as an internal standard of degree 3. Cases were stratified by postconceptional age at death and SIDS and controls were compared with respect to myelin degree at each site. Significantly delayed myelination (p less than 0.05) occurred in the SIDS group in 25 of the 62 sites examined. Hypomyelination affected fiber systems in which myelination is initiated before or after birth and which myelinate with different tempos and preferentially affect pyramidal and cerebellar (somatomotor) and prefrontal-temporal-limbic (visceromotor) systems. Hypomyelination was not associated with individual clinicopathologic variables in the SIDS group. Somatic growth and brain weight were significantly greater in SIDS than controls. Therefore, we suggest that SIDS is associated with a developmental CNS disorder. Although delayed CNS myelination most likely shares a common antecedent with sudden death and is not its cause, the role of somato- and viscero-motor systems in central cardiorespiratory control and arousal warrants further analysis in SIDS.

Birth Weight↗
PubMed1990

Candidate cell populations for respiratory chemosensitive fields in the human infant medulla.

The histology and location of human respiratory chemosensitive fields are not known. In contrast, the physiology of respiratory chemosensory areas in the ventral medulla of cats has been studied extensively, and their anatomy has been partially described. Using basic principles of comparative cytoarchitecture and computer-aided reconstructions of serial-sectioned medullae, we describe the histology and three-dimensional distribution of putative respiratory chemosensors in the feline and human infant medulla. We found that ventrolateral neurons of the human nucleus conterminalis are homologous to neurons identified in the feline L chemosensitive field by Trouth and others, and that ventrolaterally situated neurons in the human arcuate nucleus correspond to neurons predominating in the feline S and M fields. In addition, there are foci of thickened marginal glia along the feline ventral medullary surface that colocalize with chemosensitive fields identified by physiologic studies reported by others; we identify similar foci in the infant medulla. Thickened marginal glia are intermixed with neuronal fibers, often adjacent to neurons of the feline chemosensitive fields and their human counterparts, suggesting that they constitute a chemosensory neuropil at the medullary surface. Computer-aided reconstructions provide insight into the three-dimensional topography of putative respiratory chemosensors and their relationships to other brainstem structures in ways not obvious in single or even multiple sections. This delineation of candidate human respiratory chemosensors is a first step toward their postmortem analysis in patients with central ventilatory control disorders where finding histological abnormalities in these sites would support their role in human ventilation.

Animals↗
PubMed1990

Three-dimensional distribution of 3H-naloxone binding to opiate receptors in the human fetal and infant brainstem.

Despite the putative role of opioids in disorders of the developing human brainstem, little is known about the distribution and ontogeny of opioid-specific perikarya, fibers, terminals, and/or receptors in human fetuses and infants. This study provides baseline information about the quantitative distribution of opiate receptors in the human fetal and infant brainstem. Brainstem sections were analyzed from three fetuses, 19-21 weeks gestation, and seven infants, 45-68 postconceptional weeks, in whom the postmortem interval was less than or equal to 12 hours. Opiate receptors were localized by autoradiographic methods with the radiolabelled antagonist 3H-naloxone. Computer-based methods permitted quantitation of 3H-naloxone binding in specific nuclei, as well as three-dimensional reconstructions of binding patterns. High 3H-naloxone binding corresponds primarily to sensory and limbic nuclei, and to nuclei whose functions are known to be influenced by opioids, e.g., trigeminal nucleus (pain), nucleus tractus solitarii and nucleus parabrachialis medialis (cardio-respiration), and locus coeruleus (arousal). The regional distribution of opiate receptors as determined by 3H-naloxone binding is similar in human infants to that reported in human adults and animals and corresponds most closely to that of mu receptors. We found, however, that opiate receptor binding is high in the fetal and infant inferior olive, in comparison to low binding reported in this site in adult humans, primates, and rodents. In addition, opiate receptors are sparse in the fetal and infant substantia nigra, as in reports of the adult human substantia nigra, compared to moderate densities reported in primates and rodents. By midgestation, the regional distribution of 3H-naloxone binding in human fetuses is similar, but not identical, to that in infants. Highest 3H-naloxone binding occurs in the inferior olive in fetuses at midgestation, compared to the interpeduncular nucleus in infants. Tritiated naloxone binding quantitatively decreases in virtually all nuclei sampled over the last trimester, but not to the same degree. The most substantial binding decrease (two- to fourfold) occurs in the inferior olive and may reflect programmed regressive events, e.g., neuronal loss, during its development. Definitive developmental trends in 3H-naloxone binding are not observed in the postnatal period studied. The heterogeneous distribution of opiate binding in individual brainstem nuclei underscores the need for volumetric sampling in quantitative studies.

Brain Stem↗
PubMed1989

Volumetric sampling strategies for heterogeneous brainstem nuclei.

Many brainstem nuclei are heterogeneous structures in which neuronal and glial populations are unevenly distributed, and focal normal or pathologic deviations in cell density, so-called "features," are found. Examples of features include subnuclei, focal neuronal loss, and focal gliosis. We present a statistical test that justifies an investigator's claim that a feature is present in a nucleus at a selected level of confidence after completion of a cell counting experiment. The computer program developed for the test also indicates the most probable location of the feature within the nucleus, and its most probable density and length, and potentially allows one to make comparisons of feature characteristics among cases. We also present quantitative guidelines for the selection of a sampling periodicity in a heterogeneous nucleus before a cell counting experiment. Sampling periodicity is based upon analysis of computer-generated simulations of the nucleus with features of different sizes; for each feature the probability of Type I (false positives) and Type II (false negatives) errors are examined against one another. Type II error rate is dependent upon feature length and density, acceptable Type I error rate, and sampling periodicity. Feature detection is important for devising sampling strategies in brainstem nuclei.

Astrocytes↗
PubMed1988

Sequence of central nervous system myelination in human infancy. II. Patterns of myelination in autopsied infants.

The timing and synchronization of postnatal myelination in the human central nervous system (CNS) are complex. We found eight time-related patterns of CNS myelination during the first two postnatal years in autopsied infants. The intensity of myelination was graded in 162 infants with diverse diseases on an ordinal scale of degrees 0-4. The Ayer method for maximum likelihood estimates for censored data was utilized to generate curves of the temporal changes in the percent of infants with degrees 0 through 4 of myelin in 62 white matter sites. These sites fall into eight subgroups determined by the presence or absence of microscopic myelin (degree 1) at birth and the median age at which mature myelin (degree 3) is reached. There is variability in the timing of myelination within and across axonal systems, and early onset of myelination is not always followed by early myelin maturation. We reexamined general rules governing the timing of myelination proposed by previous investigators, and found that those rules are neither complete nor inviolate, and that there is a complex interplay among them. This study specifies distinct periods of maturation in which myelinating pathways are potentially vulnerable to insult during the first two postnatal years.

Brain↗
PubMed1988

Brainstem research in sudden infant death syndrome.

One of the leading hypotheses in SIDS research is that SIDS is due to a subtle defect in brainstem neural circuits which control respiration and/or cardiac stability during sleep. We review the rationale for the brainstem hypothesis and possible mechanisms of sleep-related sudden death. We also summarize the neuropathological studies in SIDS in the context of the neuroanatomy and neurochemistry of cardiorespiration and arousal. Quantitative abnormalities in brainstem reactive astrocytes (scar cells), dendritic spines, and neurotransmitter levels, and number of small myelinated vagal fibers have been reported in SIDS. The cause of these abnormalities is not known, nor is their relationship to each other or sudden death clear. Their complete elucidation, however, is perhaps the most compelling reason for continued SIDS brainstem research, since such abnormalities could be the critical clues necessary for solving SIDS.

Brain Stem↗
PubMed1987

Sequence of central nervous system myelination in human infancy. I. An autopsy study of myelination.

This study establishes the sequence of myelination in a population of autopsied infants from birth through the second postnatal year. Myelination was assessed in 62 precisely defined central nervous system (CNS) sites of 162 infants with diverse diseases who were autopsied from 1972 to 1984 at Children's Hospital, Boston. The degree of myelination was graded on an ordinal scale of 0-4 using the inferior cerebellar peduncle as an internal standard. This grading system is a modification of that used for fetal myelination in the National Collaborative Perinatal Project (NCPP). The data are summarized by, median degree of myelination for each age group and site; and Ayer estimates for the age at which at least 10, 50, and 90% of infants reach a particular myelin degree in each site. "Marker" sites in the cerebrum are provided for the pathologist to compare myelination between an individual infant brain and the brains from our autopsy population. These data should be useful in identifying diverse peri- and postnatal conditions affecting myelination in human infancy. They also provide guidelines for the assessment of CNS myelination by sophisticated imaging techniques in living infants.

Autopsy↗
PubMed1986

Pathology of the spongiform encephalopathy in the Gray tremor mutant mouse.

Gray tremor (gt) is an autosomal recessive mutation mapped to chromosome 15 in the mouse. Its phenotypic feature most relevant to human disease is a noninflammatory spongiform encephalopathy which has been transmitted to genetically normal mice in a previously reported, preliminary inoculation experiment. The present study describes the histopathology, topography, developmental sequence, and ultrastructure of the inherited spongiform encephalopathy in the gray tremor homozygote (gt/gt). Vacuolation is present in the first postnatal week in spinal and cerebellar white matter, and spreads rapidly by the second postnatal month to involve gray and white matter throughout almost the entire neuraxis. Adjacent swollen and vacuolated neuronal processes, particularly dendrites, appear to coalesce to form membrane-bound vacuoles in the neuropil. Neuronal abnormalities include focal distension of intracellular membranes and distension, fragmentation, bleb formation, rupture, and disintegration of plasma membranes. White matter vacuoles result from splitting of the myelin sheath at the intraperiod line and from vesicle formation in oligodendroglial inner loop cytoplasm. These ultrastructural abnormalities targeted on subcellular and cellular membranes in neurons and oligodendrocytes implicate a membrane disorder as a fundamental component of the pathogenetic mechanism. A comparison of the pathology of gt to that caused by unconventional agents and neurotropic retroviruses suggests that gt may be valuable in conceptually unifying the whole class of noninflammatory spongiform lesions.

Animals↗
PubMed1985

Transmissible spongiform encephalopathy in the gray tremor mutant mouse.

Gray tremor (gt) is an autosomal recessive mutation in the mouse linked to caracul (Ca) on chromosome 15. The complex mutant phenotype includes pigmentation defects, tremor, seizures, hypo- and dysmyelination in central and peripheral nervous systems, spongiform encephalopathy, and early death. The heterozygote (+/gt) is phenotypically normal but develops a mild spongiform encephalopathy from 2 months of age onward. The pigmentation and myelination disorders indicate that the gt genetic locus is active neonatally and probably earlier. This report focuses mainly on the later-expressed vacuolating disorder, which most closely mimics in tissue distribution, histopathology, and ultrastructure the spongiform encephalopathies caused by unconventional transmissible agents. This lesion was produced in genetically normal mice in a transmission experiment: of 99 neonatal mice inoculated intracerebrally with gt/gt brain homogenate, all 7 mice of three strains (BALB/cBy, C3HeB/FeJ, and C57BL/6J) allowed to survive for the unusually long interval of 682-721 days after inoculation, developed spongiform changes distributed as in the mutant phenotype. The gray tremor mutant presents a naturally occurring spongiform encephalopathy whose expression is determined by the interaction of genetic factors and a transmissible agent.

Age Factors↗
PubMed1983

'Reactive gliosis' in the medulla oblongata of victims of the sudden infant death syndrome.

A current hypothesis that the sudden infant death syndrome (SIDS) is a sleep apnea syndrome precipitated by defective control of involuntary respiration prompted the present study in which "reactive gliosis" in sections of the medulla oblongata of 45 SIDS victims was quantitated and compared with that in 20 control infants. Six anatomic regions were studied; five are related and one is unrelated to neural control of involuntary respiration. Increased numbers of "reactive" astrocytes were found in the SIDS group when the counts for all regions were combined (P = .04). Counts were also significantly higher in the SIDS victims for each of three regions alone: (1) the hilum of the inferior olivary nucleus (P = .01); (2) a lateral region (P = .02); and (3) the nucleus of the tractus solitarius (P = .03). The region with the greatest statistical difference, the inferior olivary hilum, has no recognized role in the control of involuntary respiration. There were no consistent associations between reactive astrocyte counts and specific clinical, socioeconomic, and pathologic variables. Characterization of the SIDS group whose counts exceeded that of the highest control infant also did not uncover distinguishing features. This study reinforces previous observations that, at least statistically, an abnormality of the brainstem occurs in a group of SIDS victims in contrast to a group of control infants, but also discloses considerable overlap in the numbers of such cells between these two groups.

Astrocytes↗
PubMed1982

Congenital cystic microphthalmia and consequent anophthalmia in the rat: a study in abnormal ocular morphogenesis.

An otherwise normal adult Charles River rat (CD strain) was observed to have no recognizable eyes. Breeding and morphological studies were undertaken to determine the nature of the ocular defect, as well as its cause and pathogenesis. The anomaly was found to be inherited as an autosomal recessive trait with variable expressivity. It was characterized by unilateral or bilateral congenital microphthalmia with multiple associated ocular abnormalities including a neuroepithelial cyst, optic nerve aplasia, and cataract. In several elderly rats, no eye was found histologically in the orbit, suggesting reabsorption of malformed tissues as the basis of the anophthalmia. Study of the prenatal morphogenesis of the microphthalmia suggested that the primary disorder reflects a disturbance of the neuroepithelium of the retinal anlage and results in defective early formation of the optic cup. The abnormalities in other ocular structures, particularly in the lens, are considered secondary. This ocular malformation emphasizes the early interactions and interdependence of the lens and retina in normal morphogenesis and provides an animal model for study of lens-retinal relationships in abnormal morphogenesis. It is particularly relevant in understanding the pathogenesis of microphthalmia with cysts in the human eye.

Animals↗
PubMed1982

Degeneration of the central nervous system associated with celiac disease.

The following report describes a 57-year-old man with celiac disease who developed a progressive and fatal neurologic disorder despite intensive medical and nutritional care. The clinical and pathological CNS findings in this patient are compared with those of 9 previously reported patients with well documented celiac disease in whom a progressive CNS disorder was carefully studied both pre-and postmortem. An entity of CNS degeneration associated with celiac disease appears to emerge from the study of these 10 cases. This disorder affects predominantly the cerebellum, deep gray masses, certain brain stem nuclei, and spinal cord; its cause and pathogenesis are unknown.

Brain↗
PubMedDate not supplied

Distribution of alpha 2-adrenergic receptor binding in the developing human brain stem.

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 alpha 2-adrenergic receptors in these regions. To determine the developmental profile of brainstem alpha 2-adrenergic binding across early human life, we studied brain stems from five fetuses at midgestation, 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.

Adrenergic alpha-Agonists↗
PubMedDate not supplied

Congenital apnea with medullary and olivary hypoplasia: a pathologic study with computer reconstructions.

We report a three-month-old infant with congenital central apnea who was ventilator-dependent throughout his brief life. At autopsy the most significant findings were localized to the medulla and included severe tegmental necrosis involving respiratory-related sites and olivary hypoplasia. Golgi impregnations of the cerebellum demonstrated several Purkinje cells with changes consistent with experimental olivary ablation. The majority of Purkinje cells, however, were normal; this observation suggests that in an early and subtotal olivary lesion, the incomplete complement of olivary neurons maintains sufficient collateral axonal branches to compensate for decreased cell number. Computer graphics enabled us to dissect the components of the complex medullary pathology and examine them individually and in selected combinations in three dimensions. Computer reconstruction aided the identification and dating of a malformative lesion (first trimester) from a later (second/third trimester), superimposed destructive lesion. This report suggests that the synthesis of complex morphologic data in human neuropathology into meaningful three-dimensional visual displays by computer reconstruction facilitates their comprehension. Computer reconstruction is especially valuable in the elucidation of 3-D topographic relationships in functionally and architecturally complex regions such as the brain stem.

Apnea↗
PubMedDate not supplied

Arthrogryposis multiplex congenita with posterior column degeneration and peripheral neuropathy: a case report.

Congenital sensory neuropathies associated with arthrogryposis multiplex congenita (AMC) are rare. We report a unique case of a nine-week-old, full-term infant with AMC, congenital sensory neuropathy, and posterior column degeneration. The family history was negative for neuromuscular disease. At birth, the infant was small for gestational age, indicative of intrauterine growth retardation. He was hypotonic and hyporeflexic, and failed to sustain respiration. He remained ventilator-dependent throughout his life. Electrodiagnostic studies indicated widespread peripheral neuropathy. At two weeks of age, biopsied sural nerve was almost completely devoid of myelinated axons; quadriceps skeletal muscle contained only mild and nonspecific abnormalities. Autopsy showed pulmonary hypoplasia. The major nervous system findings were severe, bilateral posterior column degeneration, mild posterior horn gliosis, atrophy of posterior roots, and axonal degeneration of the peripheral nerves. Sensory and autonomic (vagal) nerves were preferentially involved, with relative sparing of motor nerves. This case suggests that interruption of kinesthetic pathways early in gestation may result in fixed joints.

Arthrogryposis↗