PubMed Health⌕ Search

Biomedical subjects

E A Zimmerman

Publications and source records attributed to E A Zimmerman.

At least 19 recordsLinked to original sources
PubMed2004

Predicting the rate of cognitive decline in aging and early Alzheimer disease.

OBJECTIVES: To determine prognostic factors affecting the course of Alzheimer disease (AD) and to determine the role of region-specific brain volumes as predictors of cognitive decline. METHODS: Longitudinal data from 166 normal elderly individuals and 59 early AD patients were analyzed. Brain volumes were extracted from MRI scans using semiautomated recursive segmentation methods. Prognostic factors were considered significant if they had a significant effect on the rate of cognitive decline. RESULTS: In multivariate analysis, higher Clinical Dementia Rating Scale (CDR) score at entry was a significant prognostic factor for an increased rate of cognitive decline. Significant prognostic factors within the baseline CDR = 0 group were base rate of progression and percent total high signal intensity (HSI), percent ventricular, and percent CSF volumes. Base rate of progression, family history, and percent ventricular volume were significant prognostic factors within the CDR = 0.5 group and APOE had a marginally significant effect on the rate of cognitive decline in the CDR = 1 group. CONCLUSIONS: Percent total HSI, ventricular, and total CSF volume measures can independently predict the rate of cognitive decline and improve the predictive power of statistical models that use only clinical data. Brain volumetric measures from MRI can be used to estimate the rate of cognitive decline even among normal elderly individuals and thus may aid in the prediction of time of onset of disease.

Age of Onset↗
PubMed2003

Remarkable improvement in adult Leigh syndrome with partial cytochrome c oxidase deficiency.

Leigh syndrome (LS) is a heterogeneous disorder, usually due to a defect in oxidative metabolism. Typically, signs and symptoms commence in infancy or childhood, although rare cases of adult onset have been described. Progressive deterioration is the norm. The authors describe a 22-year-old woman with partial cytochrome c oxidase deficiency who developed fulminant LS following an acute febrile illness and who subsequently showed dramatic clinical and neuroradiologic improvement.

Adult↗
PubMed1990

Immunological studies with a monoclonal antibody suggest a different conformation of neurophysin in parvicellular neurons of rat hypothalamus.

A monoclonal antibody (mAb L6) to a carcinoma surface antigen has previously been shown to recognize neurophysins (NP), proteins associated with oxytocin and vasopressin. L6-reactivity in rat hypothalamus was confined to magnocellular neuronal systems. No staining was detected in parvicellular suprachiasmatic or paraventricular systems. mAb L6 immunoprecipitated vasopressin-neurophysin only under reducing conditions, and detected it in Western blots only after gel-renaturation and electroblotting in basic buffer. These findings suggest L6-reactivity to NP is conformation-sensitive, and imply NP expression in a unique configurational form in hypothalamic parvicellular systems.

Animals↗
PubMed1990

The effect of borderline personality disorder on the hospital course of affective illness.

Two groups of patients with affective disorders, one group with a coexistent axis II diagnosis of borderline personality disorder and one group without, were compared to determine if the presence of borderline personality disorder affects the hospital course of patients with affective illness. Response to hospital treatment was assessed using standard psychiatric rating scales administered at admission, after one week of hospitalization, and before discharge. Although the patients with borderline personality disorder were more severely impaired than the comparison group, they were as likely as patients without the disorder to improve over the course of hospitalization.

Adult↗
PubMed1989

Comparative distribution of three opioid systems in the lower brainstem of the monkey (Macaca fuscata).

The regional distribution of the three opioid peptide neuronal systems--proopiomelanocortin (POMC), proenkephalin A, and proenkephalin B--was investigated in the lower brainstem of Japanese monkeys (Macaca fuscata) by immunocytochemical techniques. Antiserum to beta-endorphin/beta-lipotropin, [Met]-enkephalin-Arg6-Gly7-Leu8, and human leumorphin were used to identify the POMC and the proenkephalin A and B systems, respectively. POMC-related immunoreactive material was not found in the neuronal perikarya in the lower brainstem; reactive fibers and apparent terminals were distributed in the substantia nigra, lemniscus lateralis, midbrain central gray, the nucleus raphes, nucleus parabrachialis lateralis, ventral area of the spinal trigeminal nerve, nucleus tractus solitarii, and in the reticular formation throughout the lower brainstem. Proenkephalin A-related immunoreactive neuronal perikarya were detected in the central gray, reticular formation, nucleus raphes, trapezoid body, nucleus parabrachialis lateralis and medialis, nucleus spinalis nervi trigemini, nucleus dorsalis nervi vagi, and in the nucleus tractus solitarii. Densely packed immunoreactive fibers were widely distributed in the substantia nigra, nucleus interpeduncularis, nucleus raphes, superior colliculus, periaqueductal central gray, nucleus parabrachialis lateralis and medialis, locus coeruleus, trapezoid body, nuclei cochleares, nucleus spinalis nervi trigemini, tractus spinalis nervi trigemini, nucleus tractus solitarii, nucleus dorsalis nervi vagi, nucleus gracilis, nucleus cuneatus, nucleus cuneatus accessorius, and in the reticular formation throughout the lower brainstem. Neuronal perikarya containing immunoreactive material related to proenkephalin B were found in the periaqueductal central gray, nucleus parabrachialis lateralis and medialis, nucleus tractus solitarii, and nucleus spinalis nervi trigemini. In addition, immunoreactive fibers were detected in the ventral tegmental area, substantia nigra, nucleus parabrachialis lateralis and medialis, nucleus vestibularis lateralis and medialis, and in some areas of the reticular formation. These anatomical findings demonstrate that these three opioid peptide neuronal systems are widely but uniquely distributed in the lower brainstem of the monkey.

Animals↗
PubMed1988

Infants of depressed mothers show "depressed" behavior even with nondepressed adults.

To determine whether the "depressed" behavior (e.g., less positive affect and lower activity level) of infants noted during interactions with their "depressed" mothers generalizes to their interactions with nondepressed adults, 74 3-6-month-old infants of "depressed" and nondepressed mothers were videotaped in face-to-face interactions with their mothers and with nondepressed female strangers. "Depressed" mothers and their infants received lower ratings on all behaviors than nondepressed mothers and infants. Although the infants of "depressed" versus nondepressed mothers also received lower ratings with the stranger adult, very few differences were noted between those infants' ratings when interacting with their mother versus the stranger, suggesting that their "depressed" style of interacting is not specific to their interactions with depressed mothers but generalizes to their interactions with nondepressed adults as early as 3 months of age.

Adolescent↗
PubMed1988

Characterization of complementary deoxyribonucleic acid for precursor of porcine motilin.

Cloned cDNAs encoding the precursor protein for motilin and a novel peptide, motilin-associated peptide, were isolated from a library derived from porcine intestinal mucosa mRNA. Nucleotide sequence analysis predicts a precursor protein of 119 amino acids including a signal peptide in direct linkage with the 22 amino acid sequence for motilin, and a 70 amino acid peptide of unknown function. The putative bioactive moieties are separated by Lys-Lys, dibasic residues that serve as substrates for cleavage by proteolytic maturation enzymes in many polyprotein precursors. While there is an abundant literature detailing a spectrum of tissues and cell types which express motilin like immunoreactivity, analysis of mRNA derived from many of these tissues suggests that the mRNA for the mucosal motilin precursor is only transcribed in this tissue. The nature of the immunoreactive material in the central nervous system and other peripheral tissues remains to be determined.

Animals↗
PubMed1987

Accessory olfactory bulb transplants correct hypogonadism in mutant mice.

Transplantation of normal fetal gonadotropin-releasing hormone (GnRH) neurons from the accessory olfactory bulb (AOB) to the third ventricle of GnRH-deficient adult mutant mice reverses the genetically determined reduction in pituitary hormones and poorly developed gonads. The transplanted heterotopic AOB neurons adapt their morphology and secretory functions to what is observed with preoptic GnRH neurons when transplanted into deficient mice and in the normal intact mature animal. This suggests the presence of median eminence trophic factors affecting the growth, terminal sprouting, and functional behavior of the transplanted neurons.

Animals↗
PubMed1987

Implantation of fetal preoptic area into the lateral ventricle of adult hypogonadal mutant mice: the pattern of gonadotropin-releasing hormone axonal outgrowth into the host brain.

Transplantation of fetal preoptic area tissue containing gonadotropin-releasing hormone neurons into the third ventricle of male hypogonadal mice resulted in an elevation of pituitary gonadotropin levels and correction of hypogonadism. This reversal of the neuroendocrine deficit was correlated with innervation of the median eminence by gonadotropin-releasing hormone axons. The specificity of fiber outgrowth suggested that local neuromodulatory factors might guide these axons to the nearby median eminence. To test this hypothesis, 14 adult hypogonadal males received unilateral fetal preoptic area grafts into the lateral ventricle, a site distant from the median eminence. After four months, healthy grafts containing numerous gonadotropin-releasing hormone neurons were seen in 9 hosts. However, none of these grafts corrected the hypogonadism of the host and there was no gonadotropin-releasing hormone innervation of the median eminence in any of these animals, thus demonstrating that the presence of gonadotropin-releasing hormone neurons in the ventricular space is itself not sufficient to stimulate the pituitary-gonadal axis. Instead, gonadotropin-releasing hormone axons coursed in the host fimbria, fornix, corpus callosum, and stria terminalis. These fibers could be traced into the anterior hippocampal area, medial and lateral septum, and the anterior hypothalamus. The distribution of these fibers included a number of regions which receive gonadotropin-releasing hormone fiber input in the normal mouse. These findings show that gonadotropin-releasing hormone neurons transplanted into the lateral ventricle can survive and extend processes into the host brain, often projecting to sites of normal gonadotropin-releasing hormone innervation. Their success in contacting these sites suggests that gonadotropin-releasing hormone fiber outgrowth may be influenced by regionally specified trophic and/or guidance factors.

Animals↗
PubMed1987

The effects of the age of intracerebroventricular grafts of normal preoptic area tissue upon pituitary and gonadal function in hypogonadal (HPG) mice.

Hypogonadal mice are deficient in the hypothalamic gonadotrophic hormone releasing hormone and as a consequence postnatal testicular development does not occur. Grafting preoptic area tissue from normal mice directly into the hypogonadal third ventricle dramatically reverses the hypogonadism; however, the age of the grafted preoptic area tissue is crucial to the survival and function of the graft. Grafting embryonic tissue (E16-18) resulted in 69% of the hypogonadal mice increasing testis weight some sevenfold within 30 days (5.6 to 35 mg). Postnatal day 1 (P1) tissue grafts elicited a similar rise in testis weight in 77% of recipients, whereas P5 tissue was only successful in 22% of cases. In this experimental group, however, testis weight also increased sevenfold compared with hypogonadal untreated mice. Stimulation of testicular growth in the E16-18 and P1 experimental groups was accompanied by an increase in pituitary gonadotrophic hormone content. P10 tissue did not stimulate testis growth nor was pituitary gonadotrophic hormone control elevated and the majority of grafts failed to survive over the 30 day period of the experiment. The present study has shown that the age of grafted tissue is critical in the restoration of physiological function in hypogonadal mice, and that gonadotrophic hormone releasing hormone neurons from E16-18, P1 and P5 preoptic area grafts that survive the 30 day period of the experiment and whose axons reach the median eminence portal vessels are equipotent in stimulating pituitary gonadotrophin synthesis and secretion.

Age Factors↗
PubMed1986

Immunocytochemical study of the development of vasotocin/mesotocin in the hypothalamo-hypophysial system of the chick embryo.

The hypothalamo-hypophysial system of the chick embryo has been studied with a monoclonal antibody which cross-reacts with arginine vasotocin and mesotocin, using thick (100 micron) sections in conjunction with a peroxidase-conjugated rabbit anti-mouse antibody. Although weakly stained perikarya occur occasionally in the tuberal region on embryonic days 6 and 7, the most consistent immunostaining of perikarya is found in the periventricular region of the caudal midhypothalamus at the level of the optic chiasm after embryonic day 8 1/2. Synthesis of peptides, therefore, takes place while the cells are close to their site of origin. Between embryonic days 9 and 10, beaded axons run along the anterior median eminence closely apposed to the adenohypophysis, thereby forming the anlage of the zona externa. The axons of the hypothalamo-neurohypophysial tract surround the neural lobe between embryonic days 11 and 12. The caudal to rostral wave of neuronal maturation that occurs during development appears to be due to a progressive differentiation of the periventricular zone, as well as the migration of perikarya. The early periventricular perikarya at embryonic day 8 1/2 send processes rostrally in a wing-shaped formation that extends both dorso- and ventrolaterally. From embryonic days 10 to 12, perikarya can be observed in the wing-like extensions, apparently migrating to rostral levels. The dorsolateral pathway gives rise at its midportion to the lateral cell group, whereas those perikarya migrating more laterally form the anlage of the external supraoptic nucleus. The ventrolateral wing-shaped extension of perikarya appears to be directed toward the ventral group and those lateral perikarya continuous with it. The location of mature neuronal cell groups is well established by embryonic day 17.

Animals↗
PubMed1986

Comparative distribution of vasopressin and oxytocin neurons in the rat brain using a double-label procedure.

The distribution of vasopressin (VP) and oxytocin (OT) neurons in the rat supraoptic (SON), paraventricular (PVN), and accessory magnocellular (AMN) nuclei was studied by localizing both peptides on the same section with a double immunocytochemical staining procedure employing specific monoclonal antibodies (MAB). This procedure allows us to visualize the distribution of one cell type relative to the other. In the rostral SON, VP cells lie dorsal and medial to the OT cells. Near the mid-point of the nucleus along its rostral-caudal length, there is a transition zone in which the two cell types are mixed. Proceeding caudalward, the relative locations of OT and VP cells are exchanged so that most of VP cells are located in the ventral and medial sector of the nucleus, whereas the OT cells are situated dorsal and lateral. However, there is no absolute segregation of the two types of cells anywhere in the nucleus. In the anterior part of the PVN a rostral group (rPVN) of cells composed of a medial portion and a lateral wing can be recognized. Nearly all of the cells in the rPVN are oxytocin-containing. The rPVN is separated from the next group, the middle PVN (mPVN), by a cell poor zone of about 100-150 micron. The mPVN contains both OT and VP neurons. As one proceeds caudally, the OT cells extend in the rostrocaudal direction from an anterior and ventromedial location, forming a shell around a core of VP neurons. In the most caudal PVN (cPVN), a triangular cell group characterized by fusiform cells with long-beaded processes can be distinguished from the more rounded cells of the remaining PVN. Many fusiform cells in the cPVN appear to send their axons to the posterior perifornical nucleus and the nucleus of the medial forebrain bundle. Other fusiform cells of the cPVN are oriented in a rostral-caudal plane and are situated more medially in this subdivision. The dendrites of these cells project into the mPVN while their posterior processes, most of which also appear to be dendrites, project caudally along a medial route.

Animals↗
PubMed1986

Transthyretin: a choroid plexus-specific transport protein in human brain. The 1986 S. Weir Mitchell award.

Plasma transthyretin (TTR, formerly called prealbumin) is a 55-kd protein that participates in the plasma transport of both thyroxine and retinol (vitamin A). TTR concentrations are disproportionately high in human ventricular CSF, suggesting that TTR is either selectively transported across or synthesized de novo within the blood-CSF barrier. To address this question, we adopted a molecular genetic approach; after isolating a cDNA clone encoding human TTR, we previously demonstrated specific TTR messenger RNA (mRNA) synthesis in rat choroid plexus. We have now extended these investigations to the human brain. Northern analysis of postmortem brain homogenates revealed abundant TTR mRNA in choroid plexus, but not in cerebellum or cerebral cortex. Choroid plexus mRNA was readily translated into TTR preprotein in an in vitro translation system. An immunocytochemical survey of human postmortem brain sections revealed the presence of TTR protein specifically and uniquely in the cytoplasm of choroid plexus epithelial cells; these results were corroborated at the mRNA level by an extensive survey of whole rat-brain sections by in situ hybridization. Therefore, within the mammalian CNS, TTR is the first known protein synthesized solely by the choroid plexus, suggesting a special role for TTR in the brain or CSF. Whether this function differs from its established plasma transport functions is presently unknown.

Animals↗
PubMed1986

Ultrastructure of gonadotropin-releasing hormone neuronal structures derived from normal fetal preoptic area and transplanted into hypogonadal mutant (hpg) mice.

The hpg mutant mouse lacks the neurohormone gonadotropin-releasing hormone (GnRH) and hence has a reproductive deficit. This deficit can be corrected by placement of normal fetal preoptic area into the third ventricle (see Krieger et al., 1985). We have now used ultrastructural immunocytochemistry to investigate the morphology of GnRH neurons in such intraventricular grafts, the routes that their axons take as they exit into the host, and the neurosecretory terminations that they make in the host median eminence. The GnRH cells in the transplant were similar in morphology to that reported for such cells in the preoptic area of other rodents. There was a large central nucleus, frequently indented and containing 1 or 2 nucleoli. The thin rim of cytoplasm was filled with rough endoplasmic reticulum, Golgi stacks, and mitochondria. Both dendritic and axonal profiles were identified, and a modest synaptic input to the former was found. Between the host and the implant a complex multilayered ependymal zone developed, and it was through this region that GnRH axons exited into the host arcuate nucleus and median eminence, usually surrounded by ependymal or glial elements. Within the median eminence, GnRH terminals were in close association with fenestrated blood vessels forming a normal neurosecretory terminus.

Animals↗