Search PubMed⌕ Search

Biomedical subjects

J McConnell

Publications and source records attributed to J McConnell.

At least 73 records · Page 4Linked to original sources
PubMed1990

Changes in protein phosphorylation associated with compaction of the mouse preimplantation embryo.

In order to investigate the role of protein phosphorylation in the early differentiative events of mouse preimplantation development, timed groups of embryos of various stages were incubated in medium containing [32P]orthophosphate and harvested immediately after labelling or following a chase period. The phosphoproteins obtained were separated by electrophoresis in one and two dimensions. While some of the phosphoproteins found were common to all the stages examined, the detection of many depended on both the combination of pulse-labelling and chase periods used and on the developmental stage examined. Some phosphoproteins were only found in compacted 8-cell embryos, a correlation which suggests a possible link with the post-translational mechanisms which underlie compaction.

Animals↗
PubMed1990

Cocaine and lidocaine interfere with epinephrine-induced changes in intracellular calcium concentration and glucose efflux from rat hepatocytes.

The mechanism of cocaine-induced hepatotoxicity is not clearly understood. Recent studies show that fluctuations in intracellular Ca2+ ([Ca2+]i) and/or cyclic-AMP ([cAMP]) concentration play a major role in hormone action, and sustained elevations in [Ca2+]i may be involved in the initiation of hepatocellular damage. To evaluate the possible involvement of intracellular Ca2+ and/or cAMP, we investigated effects of cocaine and lidocaine on basal, epinephrine and dibutyryl cyclic-AMP (DBcAMP)-induced changes in [Ca2+]i and glucose efflux from isolated rat hepatocytes. [Ca2+]i was monitored continuously using a Ca2(+)-selective fluorescence indicator, Quin-2, and was calculated after correcting for autofluorescence. Neither cocaine nor lidocaine (0.1-5 mmol/l) affected basal [Ca2+]i, yet both agents decreased epinephrine (10 mumol/l) and DBcAMP (100 mumol/l)-induced increases in [Ca2+]i in a dose-dependent fashion. Half-maximal inhibition occurred at 0.75 mmol/l cocaine and 1.7 mmol/l lidocaine. Cocaine and lidocaine also decreased epinephrine and DBcAMP-induced glucose efflux. The dose-dependent effect on epinephrine-induced glucose efflux was similar to that of both anesthetics on epinephrine-induced increases in [Ca2+]i. However, 5 mmol/l cocaine or lidocaine decreased DBcAMP-induced glucose efflux by less than 50%, and [Ca2+]i by more than 80%. Taken together, these results indicate that cocaine and lidocaine decrease the ability of epinephrine to stimulate glucose efflux by interfering with the Ca2(+)-mediated, and not the cAMP-mediated intracellular pathway. It is therefore speculated that alterations in metabolic endocrine regulation may contribute to cocaine's hepatotoxic effect.

Animals↗
PubMed1990

Cell cycle control in early mouse development.

Recent advances in the understanding of the molecular basis of cell cycle control, particularly that of mitotic control, are reviewed with respect to what is known about cell cycle control in early mouse embryos. The behaviour of the murine homologue of cdc2+, a component of Maturation Promotion Factor (MPF), is described at these early stages.

Animals↗
PubMed1990

Intraventricular neurocytoma: a report of two cases.

Intraventricular neurocytoma is a rare clinicopathological entity that has been recently recognized. Previous reports have not described the magnetic resonance imaging findings of this tumor. This paper describes two patients with neurocytoma in which serpiginous flow voids and isointensity with cortex were distinctive features on the magnetic resonance imaging scan. Immunohistochemical studies showed reactivity for neuron-specific enolase, Leu-7, and S-100 protein.

Adult↗
PubMed1989

Computed tomography in intracranial, supratentorial metastases in children.

This study compares the CT characteristics in a consecutive sample of supratentorial metastases (n = 31) with primary tumors of the same location (n = 49) in childhood. Postcontrast CT was performed in all but one of the metastases cases. In all but one of these children the location and type of primary tumor was known at time of occurrence of cerebral metastasis. Primary CNS tumors (n = 12) had a higher incidense of supratentorial metastatic spread than tumor originating elsewhere. Three children had diffuse subarachnoid seeding, while 28 had solid tumors (21 solitary, 7 multiple). The predilection location for the solid metastases was the gray-white matter junction (n = 12). The following CT findings were significantly less frequent in metastases than in primary tumors (P less than 0.05): Midline location, calcification and cyst formation. On the other hand bleeding, pronounced contrast enhancement and location in the gray-white matter junction were more frequent in the metastatic group (P less than 0.05).

Brain Neoplasms↗
PubMed1989

Development of tight junctions de novo in the mouse early embryo: control of assembly of the tight junction-specific protein, ZO-1.

Tight junction development during trophectoderm biogenesis in the mouse preimplantation embryo has been examined using monoclonal antibodies recognizing the tight junction-specific peripheral membrane protein, ZO-1. In immunoblots, mouse embryo ZO-1 had a molecular mass (225 kD) equivalent to that in mouse liver, was barely detectable in four-cell embryos although later stages exhibited increasing levels. ZO-1 was first detected immunocytochemically at the compacting eight-cell stage, coincident with or just after the expression of basolateral cell adhesion and apical microvillous polarity. Initially, ZO-1 was present as a series of spots along the boundary between free and apposed cell surfaces in intact embryos or cell couplets, but subsequently staining became more linear with blastocyst trophectoderm cells being bordered by a continuous ZO-1 belt. Inhibition of cell adhesion at the 8-cell stage delayed ZO-1 appearance and randomized its surface distribution in a reversible manner. Microfilament disruption, but not microtubule depolymerization, produced major disturbances in ZO-1 distribution. ZO-1 assembly de novo appeared to be independent of proximate DNA and RNA synthesis but was inhibited substantially in the absence of protein synthesis during the eight-cell stage, a treatment that did not prevent intercellular adhesion and polarization. ZO-1 surface assembly, but not adhesion and polarization, was also perturbed when single eight-cells were combined with single four-cells. The results suggest that tight junction development in mouse embryos is a secondary event in epithelial biogenesis, being dependent upon cell adhesion and cytoskeletal activity for normal expression, and can be disrupted without disturbing the generation of a stably polarized phenotype.

Animals↗
PubMed1989

Neurosonographic findings in infants treated by extracorporeal membrane oxygenation (ECMO).

Extracorporeal membrane oxygenation (ECMO) is an approved therapy for some neonates who have respiratory failure that is due to hyaline membrane disease, meconium aspiration, persistent pulmonary hypertension, congenital diaphragmatic hernia, or sepsis. The major complication of this therapy is hemorrhage, with intracranial hemorrhage having the highest morbidity and mortality. Seizures, incisional bleeding and bleeding in the pleural space, hypoxic-ischemic encephalopathy, renal failure, and cardiovascular complications account for most of the other complications. Cranial sonography provides an ideal imaging modality for baseline evaluation and daily follow-up; however, computed tomography and magnetic resonance imaging, because of better sensitivity, are important for assessment after ECMO. The changes in intracranial blood flow related to ECMO can be noninvasively evaluated by Doppler ultrasound modalities.

Cerebral Hemorrhage↗
PubMed1989

Presence of cdc2(+)-like proteins in the preimplantation mouse embryo.

An antibody raised against a portion of the human equivalent of the yeast cdc2+ protein reacts with a 34K protein in mouse cell lines and early embryonic cells. Western blot analysis coupled with phosphatase treatment of material collected from the early preimplantation embryo has shown that the murine cdc2+ homologue does not correspond to the previously described newly synthesised proteins that are phosphorylated in a cell-cycle-dependent fashion [Howlett, 1986]. The cdc2(+)-like protein is converted into a slower migrating form on entry into S-phase and is further modified during G2 prior to mitosis. Studies of embryos that are held in extended periods of M-phase, i.e. unfertilised eggs or 1-cell embryos treated with nocodazole, demonstrate that the cdc2(+)-like protein becomes demodified in these cells.

Amino Acid Sequence↗
PubMed1988

Use of hemopexin domains and monoclonal antibodies to hemopexin to probe the molecular determinants of hemopexin-mediated heme transport.

Plasmin cleaves rabbit serum apohemopexin (Mr = 60,000) at a single site producing a heme-binding domain (I, Mr = 35,000) and a second domain (II, Mr = 25,000) (W. T. Morgan and A. Smith (1984) J. Biol. Chem. 259, 12001-12005). The absorbance spectra of heme-domain I are indicative of a bis-histidyl coordination complex with the central heme iron atom. Chemical modification of the 5 histidine residues of apo-domain I with diethylpyrocarbonate abolished heme binding, supporting this assignment. Upon binding heme, domain I migrates more rapidly in sucrose gradients, and, in sedimentation velocity experiments, the s value of domain I increases from 3.17 +/- 0.04 to 3.71 +/- 0.09, a notably large increase which indicates that the domain becomes much more compact. This conformational change which plays a pivotal role in hemopexin function requires the bis-histidyl coordination with heme iron and leads to a tighter association between domain I and domain II shown by the co-migration of heme-domain I and domain II in sucrose gradients. In turn, the association of heme-domain I with domain II increases the thermal stability of the heme-domain I chromophore. Results of binding studies using mouse hepatoma cells and isolated domains indicate that domain I not only binds heme but also plays a vital part in the hemopexin-receptor interaction. The change in conformation of domain I upon heme binding and the association between domains I and II induced by heme are both notable determinants of the strength of the hemopexin-receptor interaction, but an intact "hinge region" between the domains is not necessary for receptor binding. The importance of both domains in bringing about the transport function of hemopexin is confirmed by the ability of three (two specific for domain I and one for domain II) of seven monoclonal antibodies raised against hemopexin to inhibit the hemopexin-receptor interaction.

Animals↗
PubMed1986

Construction of a representative cDNA library from mRNA isolated from mouse oocytes.

A representative cDNA library has been constructed from the small quantities of poly(A)+ RNA present in unfertilised mouse oocytes. The construction of this library has been achieved by use of cow pea mosaic virus RNA as a carrier during isolation of polyadenylated message and during subsequent cloning procedures. This approach may be applicable to any system in which amounts of mRNA are limiting.

Animals↗
PubMed1984

Anatomical localization and some pharmacological effects of vasoactive intestinal polypeptide in human and monkey corpus cavernosum.

Vasoactive intestinal polypeptide is hypothesized to be a nonadrenergic, noncholinergic neurotransmitter important in the physiology of penile erection. To further explore this concept, anatomical localization of vasoactive intestinal polypeptide, in vitro muscle bath studies and in vivo injection experiments were undertaken in the monkey and man. Using immunohistochemical techniques vasoactive intestinal polypeptide was localized at the light microscopic level to nerves within the monkey and human penis. Ultrastructurally, a modified peroxidase-antiperoxidase technique was used to identify large vasoactive intestinal polypeptide-positive vesicles within peptidergic and cholinergic varicosities. In the in vitro muscle bath, the addition of 10(-7) M vasoactive intestinal polypeptide did not alter the baseline tension of strips of monkey and human corpus cavernosum. During contraction produced by norepinephrine stimulation, however, vasoactive intestinal polypeptide (10(-7) M) caused relaxation of the monkey (41 +/- 18 per cent, no. = 8) and human (23 +/- 8 per cent, no. = 5) corpus cavernosum. Intracorporal injection of vasoactive intestinal polypeptide (0.75 X 10(-9) to 3.75 X 10(-9) moles/kg.) had no effect on the monkey penis. Administration of vasoactive intestinal polypeptide (1.25 X 10(-9) to 2.5 X 10(-9) moles/kg.) into the internal iliac artery of the monkey, while having no effect on the flaccid penis, caused detumescence of the erect penis obtained by cavernous nerve stimulation (2-5 V, 40 Hz, 2 msec.). Although vasoactive intestinal polypeptide can be found within the nerves of the penis, its apparent in vitro and in vivo effects raise further questions concerning the role of this peptide in penile erection.

Adult↗
PubMed1984

Some pharmacologic effects of yohimbine on human and rabbit penis.

The pharmacologic effects of yohimbine on human and rabbit penile tissue were studied in 2 experimental systems. Yohimbine (10(-7) to 10(-4) M), in a dose-related manner, partially antagonized norepinephrine-induced contraction of human corpus cavernosum in an in vitro muscle bath. Yohimbine alone, however, did not alter the baseline tension of strips of human corpus cavernosum. The catecholamine content of the corpus cavernosum and corpus cavernosum urethrae of saline (control) and yohimbine-treated rabbits was determined by high pressure liquid chromatography. There was no statistically significant difference in mean norepinephrine content between control (0.38 +/- 0.29 microgram. per gm. wet wt.) and yohimbine-treated (0.25 +/- 0.21 microgram. per gm. wet wt. at 1 mg. per kg. body wt.; 0.50 +/- 0.10 microgram. per gm. wet wt. at 2 mg. per kg. body wt.) rabbit corpus cavernosum and control (0.53 +/- 0.34 microgram. per gm. wet wt.) and yohimbine-treated (0.86 +/- 32 microgram. per gm. wet wt. at 1 mg. per kg. body wt.; 0.53 microgram. per gm. wet wt. at 2 mg. per kg. body wt.) rabbit corpus cavernosum urethrae. It appears that, in the penis, yohimbine exhibits alpha adrenergic blocking properties and does not affect catecholamine levels in this tissue.

Animals↗
PubMed1983

Time of neuron origin in the amygdaloid complex of the mouse.

The time of origin of the amygdaloid complex was studied in mice injected once with tritiated thymidine during gestation or early neonatal development. Neurons for this nucleus and related nuclei arose during embryonic days 11-15. No mediolateral or dorsoventral gradients, but a distinct rostrocaudal gradient of proliferation was evident in comparisons of both rostral vs caudal nuclei and of anterior vs posterior regions of individual nuclei, such as the cortical nucleus. Since the pattern of development of this controversial nucleus was similar to that of nuclei in both centromedial and basolateral groups, time of origin data could not aid its assignment to one of these subdivisions.

Amygdala↗