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Biomedical subjects

P Kim

Publications and source records attributed to P Kim.

At least 55 records · Page 3Linked to original sources

Increased sarcolemmal permeability in the cerebral artery during chronic spasm: an assessment using DNA-binding dyes and detection of apoptosis.

Alteration of sarcolemmal permeability was evaluated in the cerebral artery after subarachnoid hemorrhage. Significance of membrane dysfunction in the pathogenesis of chronic spasm and contribution of apoptosis were investigated in a canine model. Permeability of the smooth muscle cell (SMC) membrane was assessed by double staining with a hydrophilic (ethidium bromide [EB]) and a lipophilic (Hoechst 33342) DNA-binding dye. Quantitative observations were made with a ultraviolet-fluorescence microscope and a ultraviolet-laser confocal microscope. Occurrence of apoptosis was studied using electrophoresis and TUNEL method. In the normal arteries, nuclei of SMC were stained with Hoechst 33342 but not with EB. In the spastic arteries, SMC in the inner layer of the tunica media were stained with EB. The incidence of EB-positive cells reached maximum on day 7 (45 +/- 19%) and decreased in 2 to 4 weeks (13 +/- 5.2% and 5.0 +/- 2.1%, respectively), in parallel with amelioration of spasm. Electron and light microscopic observations revealed increased density of SMC cytoplasm with widening of the extracellular space. Necrosis was not evident. Apoptosis was not detected by the two methods. These results demonstrate that an augmentation in sarcolemmal permeability takes place during the course of chronic vasospasm and suggest its close correlation to pathogenesis.

Animals↗

Absence of gonadotropin surges and gonadotropin-releasing hormone self-priming in ovariectomized (OVX), estrogen (E2)-treated, progesterone receptor knockout (PRKO) mice.

It is well known that estrogen (E2) stimulates expression of progesterone receptors (PRs), thereby inducing responsiveness of several tissues to the actions of progesterone (P). Recent studies have also suggested, however, that biological actions previously ascribed to E2 alone may also be mediated by activation of E2-induced PRs, even independently of signal changes in P concentrations. In the present experiments, the progesterone receptor knockout (PRKO) mice were used to assess the role of PR activation in the positive feedback actions of E2 on gonadotropin release. Ovariectomized (OVX) PRKO mice were tested for their capacity to mount primary gonadotropin surges in response to exogenous E2, and to exhibit a GnRH self-priming effect in response to sequential injections of the decapeptide. Wild-type (WT) and PRKO mice were OVX, treated with both 17beta-estradiol and estradiol benzoate (EB), and then killed at 1900 h on day 7 postOVX. Plasma LH RIA revealed that WT mice exhibited surges in response to the E2 treatment; the PRKO mice, however, showed no elevation in plasma LH above untreated controls. Instead, plasma LH levels in E2-treated, OVX PRKO mice decreased significantly in comparison to untreated OVX PRKO mice, suggesting that E2 can exert a negative feedback influence on LH release in PRKO mice, despite the absence of positive feedback effects. A slight but significant rise in plasma FSH was observed in E2-treated OVX WT mice in comparison to untreated controls: an effect not seen in E2-treated OVX PRKO mice, reinforcing the observation that estrogen's positive feedback effects are compromised in PRKO mice. In a second experiment, E2-treated OVX WT and PRKO mice were given either one or two pulses of GnRH 60 min apart, and killed 10 min later. The WT mice were found to exhibit a robust GnRH self-priming effect, as WT mice receiving two GnRH pulses displayed LH responses approximately 2-fold greater than those receiving only one pulse. By contrast, PRKO mice receiving two GnRH pulses exhibited no additional increase in plasma LH levels. We conclude that PR activation is obligatory for expression of the GnRH self-priming effect as well as for generation of E2-induced LH and FSH surges. The extent to which failure of LH surge secretion in PRKO mice is due to the absence of GnRH self-priming, lack of hypothalamic GnRH surges, and/or defects in other processes remains to be determined. These observations clearly demonstrate, however, that the presence of PR is an absolute requirement for the transmission of E2-induced signals leading to gonadotropin surges.

Animals↗

Gliomas in rodent whisker barrel cortex: a new tumor model.

OBJECT: Surgical treatment of gliomas is difficult because they are invasive. Invasion of essential cortex often limits or precludes surgical resection. A tumor model was developed in which the rodent whisker barrel cortex was used to examine how gliomas affect cortical function and structure. METHODS: Both DBT (mouse) and C6 (rat) glioma cell lines were grown in culture and labeled with the fluorescent marker Dil in vitro. Labeled tumor cells were then injected into the whisker barrel cortex of adult mice and rats. Neurological assessments were made daily and magnetic resonance (MR) images were obtained. Animals were killed by perfusion 6 to 14 days after injection, and histological sections were prepared and studied. Tumors were found in all 20 rats and 10 mice that had been injected with the C6 and DBT cell lines, respectively. The animal cells had been labeled with Dil in vitro, and all in vivo tumors proved to be Dil positive. The MR images revealed the tumor locations and serial MR images demonstrated tumor growth. Histological evaluation confirmed the location of the tumor and the disruption of barrel cortex architecture. CONCLUSIONS: Both DBT and C6 glioma cell lines can be used to generate malignant glial tumors reproducibly in the whisker barrel cortex. Fluorescent labeling and cytochrome oxidase staining permit visualization of tumor growth patterns, which disrupt the barrel cortex by microscopic invasion and by gross tissue deformation. Magnetic resonance imaging demonstrates the anatomical extension of these tumors in live rodents. Using this model for further studies on the effects of malignant glioma growth on functional cerebral cortex should advance our understanding of the neurological issues and management of patients with these tumors.

Animals↗

Patterns of recurrence of intussusception in children: a 17-year review.

PURPOSE: Patterns of recurrence of intussusception (INT) were reviewed to determine whether changes in management have affected the rate and patterns of recurrence as well as long-term outcome in children with multiple (i. e., 2 or more) recurrences. MATERIALS AND METHODS: Review was done of 763 children with 876 intussusceptions, including (1) recurrence rate, (2) patterns of recurrence (number of and interval between recurrences), (3) reducibility, (4) pathologic lead points (PLP), (5) operative findings and (6) long-term follow-up in those with multiple recurrences. RESULTS: Above features (1)-(6) were the same in those managed with barium enema (1979-1985) and those managed with air enema (1985-1996). Overall recurrence rate was 9 %; 11 % with barium enema and 8 % with air enema. Sixty-nine patients had 113 recurrences: 47/69 (68 %) and 1 recurrence and 22/69 (32 %) had multiple recurrences. Multiple recurrences presented as isolated episodes or in clusters up to 8 years. Reducibility was 100 % for initial INT and 95 % for recurrent episodes; there were no perforations. Surgery, in 4 with irreducible recurrence, revealed no PLP. PLP were present in 5 (8 %): 2 (4 %) with 1 recurrence and 3 (14 %) with multiple recurrences. No pattern of recurrence was predictive for PLP. Long-term follow-up (up to 15 years) available in 11 with multiple recurrences revealed a favourable outcome. CONCLUSIONS: Rates and patterns of recurrence did not change with altered management. Because of the high reduction rate of recurrences, lack of perforation and favourable long-term follow-up, we recommend radiological reduction for recurrent INT. Multiple recurrences are not a contraindication. A careful search for PLP is mandatory. Surgery should be reserved for irreducible recurrences or for demonstrated PLP.

Adolescent↗

Expression of p210 and p190 BCR-ABL due to alternative splicing in chronic myelogenous leukaemia.

The hallmark of chronic myelogenous leukaemia (CML) is the presence of the Philadelphia chromosome and its resultant fusion message, BCR-ABL, and fusion protein, p210. Patients with CML in blast crisis, or with Philadelphia positive acute lymphoblastic leukaemia (ALL), can have a smaller BCR-ABL fusion transcript possessing only the first exon of BCR fused to ABL. This smaller transcript encodes a 190 kD protein which is more strongly transforming than the p210 protein derived from the larger CML-associated transcript. We performed RT-PCR on samples from CML patients in chronic phase to determine the frequency and mechanism of p190 and p210 co-expression and to see if this correlated with clinical indices. We examined the peripheral blood or marrow of 67 patients with CML and found that 35 of them expressed both transcripts whereas the remainder expressed the p210-encoding transcript exclusively. Additional PCR products of an intermediate size were also frequently detected and have been isolated and sequenced. Data from two of these products indicate that they are the result of alternative splicing and include variable combinations of BCR exons. We believe that the expression of the p190-encoding transcript in the chronic phase of CML is also due to alternative splicing. A comparison of patients co-expressing the p190- and p210-encoding transcripts with those patients who expressed only the p210-encoding transcript detected significantly higher white blood cell (WBC) counts and blast cell counts at time of testing as well as significantly higher white blood cell counts at diagnosis.

Adolescent↗

Bisegmental cervical interbody fusion using hydroxyapatite implants: surgical results and long-term observation in 70 cases.

UNLABELLED: Hydroxyapatite (HA) is the main constituent of bone mineral, and synthetic HA serves as a biocompatible and bioactive material. It permits bone growth on its surface and forms a union with the adjacent bone. OBJECT: The authors have developed implants made of porous HA, which they have used in more than 90 cases in the past 6 years to achieve cervical interbody fusion. The implants were designed to provide maximum durability, biomechanical stability, and alignment preservation and to be technically easy to use. The authors summarize their experience and results with the use of these implants. METHODS: The results of postoperative follow-up observation of 12 months or longer (mean 37.1 +/- 2.4 months) are available in 70 patients with underlying disease including: spondylosis, disc extrusion, ossification of the posterior longitudinal ligament (PLL), hypertrophy of the PLL, and trauma. The patients' ages at the time of surgery ranged from 22 to 83 years (mean 50.6 +/- 1.3 years). Flexion-extension radiographs and tomograms, obtained 6 and 12 months after surgery and every year thereafter, were used to demonstrate solid fusion in all cases. Dislocation of the implant occurred in three patients who were treated during the early portion of the series. At 6 to 12 months after surgery, encasement of the implant and formation of union were observed. Normal lordosis, if present prior to surgery, was maintained postsurgery. No neurological deterioration related to the site of fusion occurred during the period of observation. CONCLUSIONS: The authors conclude that satisfactory interbody fusion can be achieved by using HA implants, provided their design is appropriate and adequate surgical techniques are used.

Adult↗

Terrorism. Part 1: Calibrating your risks and response.

Emergency service organizations are "in combat" every day. Yet with the experience and education we have amassed over the years, we remain ill-prepared to deal with the full effects of a terrorist attack. Terrorism has many definitions. For this article we choose this one: Terrorism: The use of violence, threats, intimidation or information manipulation for revenge, politics, support of a cause or the furthering of a criminal enterprise.

Biological Warfare↗

XATH-1, a vertebrate homolog of Drosophila atonal, induces a neuronal differentiation within ectodermal progenitors.

XATH-1, a basic/helix-loop-helix transcription factor and a homolog of Drosophila atonal and mammalian MATH-1, is expressed specifically in the dorsal hindbrain during Xenopus neural development. In order to investigate the role of XATH-1 in the neuronal differentiation process, we have examined the effects of XATH-1 overexpression during Xenopus development. XATH-1 induces the expression of neuronal differentiation markers, such as N-tubulin, within the neural plate as well as within nonneural ectodermal progenitor populations, resulting in the appearance of process-bearing neurons within the epidermis. The related basic/helix-loop-helix genes neurogenin-related-1 and neuroD are not induced in response to XATH-1 overexpression within the embryo, suggesting that XATH-1 may activate an alternate pathway of neuronal differentiation. In further contrast to neurogenin-related-1 and neuroD, high-level expression of general neural markers expressed earlier in development, such as N-CAM, is not induced by XATH-1 overexpression. Competent ectodermal progenitors therefore respond to ectopic XATH-1 expression by initiating a distinct program of neuronal differentiation.

Amino Acid Sequence↗

Gene transfection-mediated overexpression of beta1,4-N-acetylglucosamine bisecting oligosaccharides in glioma cell line U373 MG inhibits epidermal growth factor receptor function.

N-linked oligosaccharides appear to be important for the function of the epidermal growth factor (EGF) receptor. In a previous study (Rebbaa, A., Yamamoto, H., Moskal, J. R., and Bremer, E. G. (1996) J. Neurochem. 67, 2265-2272), we showed that binding of the erythroagglutinating phytohemagglutin lectin from Phaseolus vulgaris to the bisecting structures on the EGF receptor from U373 MG glioma cells blocked EGF binding and receptor autophosphorylation. In this study we examined the consequences of overexpression of the bisecting structure on the EGF receptor by gene transfection of U373 MG cells with the N-acetylglucosaminyltransferase III (GnT-III). This modification leads to a significant decrease in EGF binding and EGF receptor autophosphorylation. In addition, the cellular response to EGF was found to be altered. Proliferation of U373 MG cells in serum-free medium is inhibited by EGF. In contrast, proliferation of the GnT-III-transfected cells was stimulated by EGF. These data demonstrate that changes in EGF receptor glycosylation by GnT-III transfection reduces the number of the active receptors in U373 MG cells and that this change results in change in the cellular response to EGF.

Acetylglucosamine↗

Plasmid replication and partition in Escherichia coli: is the cell membrane the key?

The DNA-membrane complex has been the subject of intensive investigation for over 35 years as the possible site for DNA replication in the prokaryotic cell and the site through which newly synthesized chromosomes are segregated into daughter cells. However, the molecular mechanisms which control these phenomena are, for the most part, poorly understood despite genetic, biochemical, and morphologic evidence in favour of their existence. This is probably due to the transient nature and non-covalent interactions that occur between DNA and the membrane. In addition, there is a paucity of knowledge concerning the nature of the membrane receptors for DNA and whether the membrane plays simply a structural or metabolic role in the two processes. Plasmids can provide important insights into the role of the membrane in replication and partitioning because the plasmid life cycle is relatively simple, with replication occurring during the cell cycle and partitioning during cell division. The replicon model of Jacob et al. (1963, Cold Spring Harbor Symp Quant Biol 28: 329-348) still represents a good conceptual framework (with modifications) to explain how plasmid replication and partitioning are linked by the membrane. In its simplest form, the model focuses on specific membrane binding sites (possibly along the equator of the cell) for plasmid (or bacterial) replication, with the membrane acting as a motive force to separate the newly synthesized replicons and their attached sites into daughter cells. Indeed, proteins involved in both plasmid replication and partitioning have been found in membrane fractions and some plasmids require membrane binding for initiation and an active partitioning. We propose that several factors are critical for both plasmid DNA replication and partitioning. One factor is the extent of negative supercoiling (brought about by an interplay of various topoisomerases, but most importantly by DNA gyrase). Supercoiling is known to be critical for initiation of DNA replication but may also be important for the formation of a partition complex in contact with the cell membrane. Another factor is the presence of specific subdomains of the membrane which can interact specifically with origin DNA and possibly other regions involved in partitioning. Such domains may be induced transiently or be present at all times during the cell cycle.

Cell Membrane↗

Inflammatory bowel disease and immune thrombocytopenic purpura: is there a correlation?

Different hematologic abnormalities are often encountered in patients with inflammatory bowel disease. Among them anemia, leukocytosis, and thrombocytosis are commonly seen. Leukopenia and thrombocytopenia are observed mostly as a side effect of therapy, particularly with use of immunosuppressive drugs. Immune thrombocytopenic purpura is rarely reported in association with inflammatory bowel disease. We present two cases with combination of these entities along with a literature review and treatment options. Immune thrombocytopenic purpura in these patients presented as an extraintestinal manifestation of inflammatory bowel disease mediated by a disturbance of the immune system.

Adolescent↗

Cerebral venous malformation complicated by spontaneous thrombosis.

A case of spontaneous thrombosis and infarction leading to death as complications of a cerebral venous malformation in a 13-year-old boy is reported. This is the first published report of this type of complication occurring in a case of venous angioma. While the biologic behavior of cerebral venous malformations has suggested that they are benign in nature, and the results of surgical management have encouraged a conservative approach, the present case illustrates a potential complication and argues against the assumption that these malformations are completely benign in nature.

Adolescent↗

Chronic nicotine working and reference memory effects in the 16-arm radial maze: interactions with D1 agonist and antagonist drugs.

Chronic nicotine infusion has been found in a series of studies in our laboratory to significantly improve choice accuracy of rats in the eight-arm radial maze. The current study was designed to compare the effects of chronic nicotine infusion on working and reference memory in a 16-arm radial maze. Nicotine was administered to female Sprague-Dawley rats at approximately 5 mg/kg per day SC via osmotic minipumps. Controls received saline infusions. Chronic nicotine infusion significantly lowered the number of working memory errors compared to controls, whereas the number of reference memory errors was not significantly affected. The modest nicotine-induced reduction in working memory errors was seen as a main effect over the 4 weeks of infusion, but the clearest effect was seen in weeks 3-4 of nicotine administration. For the 2 weeks after withdrawal, the nicotine effect was no longer evident. Acute D1 challenges were given with the D1 agonist dihydrexidine (0, 0.25, 0.5 and 1 mg/kg) and the D1 antagonist SCH 23390 (0, 0.005, 0.015 and 0.05 micrograms/kg) during weeks 3-4 of chronic nicotine administration and weeks 1-2 after withdrawal from nicotine. Dihydrexidine caused a modest dose-related increase in reference memory errors but not working memory errors in the nicotine-treated, but not the control rats. The D1 antagonist SCH 23390 caused a modest though significant decrease in reference memory errors but not working memory errors in the control, but not the nicotine-treated rats. The behavioral specificity of chronic nicotine infusion was demonstrated with selective improvement in working memory function. Pharmacological interactions were seen with chronic nicotine treatment increasing responsivity to D1 agonist and decreasing responsivity to a D1 antagonist with regard to reference memory. The mechanisms of this interaction are still undiscovered.

Animals↗

Cisternal talc injection in dog can induce delayed and prolonged arterial constriction resembling cerebral vasospasm morphologically and pharmacologically.

BACKGROUND: The possible role of inflammation in the pathogenesis of cerebral vasospasm has been noted in recent studies. In order to examine the role of inflammation, we examined the vasocontractile activity of talc, which is known to cause severe inflammation, using a canine cisternal talc injection model. METHODS: Under general anesthesia, a sterile talc powder suspended in saline was injected into the cisterna magna of the dog. Serial vertebral angiography and postmortem histologic changes of the harvested basilar artery were examined. The morphologic and pharmacologic features of talc-induced vessel spasm were compared with the usual autologous blood-induced artery spasm. RESULTS: Cisternal injection of sterile talc powder caused no early spasm, but induced definite basilar arterial constriction 2 days after injection. This vascular constriction was observed to continue up to 7 days after injection. Ultrastructural study of the constricted vessel revealed several morphologic changes, such as corrugation of the elastic lamina, subintimal proliferation, migration of smooth muscle cells, detachment of endothelial cells, etc.; findings that are compatible with the changes observed in vasospasm. Pharmacologic study showed a moderate decrease in the maximal contraction to KCl and UTP. Endothelium-dependent relaxation was markedly disturbed, while endothelium-independent relaxation was preserved. These pharmacologic properties were also similar to those reported in vasospasm. CONCLUSIONS: Our present study indicates that the several changes of vascular properties, which had been considered to be specific to cerebral vasospasm, can be regarded as a nonspecific biologic defense reaction against the foreign body. The analysis of the common pathway from talc and autologous blood to vasospasm may lead to the pathogenesis of cerebral vasospasm.

Animals↗