Biomedical subjects

M Li

Publications and source records attributed to M Li.

At least 721 records · Page 40Linked to original sources

PubMed1997

The lateral corticospinal tract and spinal ventral horn in X-linked recessive spinal and bulbar muscular atrophy: a quantitative study.

A quantitative study was performed on spinal cord lesions in seven patients with X-linked recessive spinal and bulbar muscular atrophy. The myelinated fiber density of the lateral corticospinal tracts at the T7 cord level was well preserved for both large and small myelinated fibers. On the other hand, neurons in the L4 ventral horn were markedly depleted; marked loss was noted of the large alpha and medium-sized gamma motor neurons located in the lateral and medial nuclei as well as the small neurons in the intermediate zones of the ventral horn. These results suggest that myelinated fiber density and fiber-size distribution in the corticospinal tract are well preserved and that neuronal loss in the ventral horns is not restricted to alpha and gamma motoneurons but also involves small interneurons.

Aged↗

PubMed1997

Blockade of neuromuscular transmission by huwentoxin-I, purified from the venom of the Chinese bird spider Selenocosmia huwena.

Huwentoxin-I (HWTX-I) is a neurotoxic peptide purified from the venom of the Chinese bird spider Selenocosmia huwena. The effects of HWTX-I on neuromuscular transmission of vertebrate skeletal muscle have been investigated by means of twitch tension and electrophysiological techniques. On isolated mouse phrenic nerve-hemidiaphragm preparations, HWTX-I blocked the twitch responses to indirect, but not to direct, muscle stimulation. The time needed for complete block of the neuromuscular transmission was dose dependent. The transmission could be mostly restored by prolonged repeated washing with Tyrode's solution. If the preparation was pretreated with D-tubocurarine and then immersed in a mixed solution of D-tubocurarine and HWTX-I, the washout time necessary to restore the neuromuscular transmission was significantly decreased. Intracellular recording at the end-plate region of frog sartorius muscle revealed that HWTX-I could synchronously reduce the amplitude of the acetylcholine potential induced by ionophoretic application of acetylcholine as well as the amplitude of the end-plate potential evoked by nerve stimulation. Both of these effects eventually disappeared; however, both could be restored by prolonged washing. Experiments on Xenopus embryonic myocytes indicated that HWTX-I reduced the open probability of acetylcholine-induced channel activity, and finally blocked the channel. All of these results demonstrated that HWTX-I was a peptide neurotoxin and the postsynaptic nicotinic acetylcholine receptor was its site of action.

Acetylcholine↗

PubMed1997

Abnormal intracellular and extracellular distribution of basement membrane material in papillary carcinoma and hyalinizing trabecular tumors of the thyroid: implication for deregulation of secretory pathways.

Papillary carcinoma (PC) and hyalinizing trabecular tumors (HTT) of the thyroid share several morphological features, including the presence of nuclear pseudoinclusions (NPI). One of the distinct characteristics of HTT is its hyalinizing stroma, which contains abundant basement membrane (BM) material. We investigated the distribution of BM material in PC and HTT. Fifteen cases of PC and nine cases of HTT were analyzed immunohistochemically with monoclonal antibodies for type IV collagen and laminin. Three stromal staining patterns were observed: (1) linear staining along the epithelium lining papillae, between trabeculae, and around follicles; (2) focal absence of staining; (3) lumpy or diffuse stromal staining. Although the latter was more commonly seen in HTT, all three patterns were present in both tumor types. More interestingly, we observed two hitherto undescribed intracellular staining patterns in both tumor types: intracytoplasmic dotlike staining and staining of NPI. Electron microscopy was performed in three cases of PC. Dilated cisternae of endoplasmic reticulum containing dense amorphous material resembling BM were observed in the cytoplasm in one case and in the NPI in another. These findings suggest the presence of a common pathway for the abnormal production of BM in both PC and HTT. Two mechanisms that may account for the abnormal intracellular detection of BM materials are proposed: (1) intracellular invagination/phagocytosis of extracellular matrix by the tumor cells; (2) abnormal production or alteration in secretory pathway in tumor cells resulting in intracellular accumulation and intranuclear invagination. The combination of immunohistochemical and electron microscopic findings favors the latter. The similar patterns of BM deposition shared by PC and HTT further support the hypothesis that PC and HTT are related to each other.

Basement Membrane↗

PubMed1997

Discriminative stimulus effects and antipunishment effects of drugs measured during the same session.

The effects of pentobarbital, diazepam, phencyclidine, buspirone and methamphetamine on drug discrimination and on responding under a variable-interval variable-interval with punishment schedule were studied in pigeons trained to discriminate 5.0 mg/kg pentobarbital from saline. Pentobarbital produced dose-dependent increases in the proportion of responses on the drug key and on rates of punished responding. Diazepam had very similar effects except that the dose-effect curve for punished responding turned over at the highest dose level. Phencyclidine produced only partial responding on the drug key and weakly increased punished responding. Buspirone produced small increases in punished responding, but in the drug discrimination experiments buspirone did not cause responding on the drug key. Methamphetamine did not produce responding on the drug key, nor did it increase rates of punished responding. These experiments are among the first to demonstrate that drug discrimination and other behaviors can be studied within single test sessions in the same animals and they suggest that there is a close correspondence between the discriminative stimulus effects of some drugs and their anti-punishment activity.

Animals↗

PubMed1997

Hemodynamic effects of the Fab fragment of digoxin antibody (digibind) in corticotropin (ACTH)-induced hypertension.

To determine whether the immune Fab fragment of digoxin antibody (digibind) attenuates established corticotropin (ACTH) hypertension, rats were given ACTH sham control (0.1 mL normal saline, twice daily, subcutaneously, n = 18) or ACTH treatment (2.5 microg/kg in 0.1 mL normal saline, twice daily, subcutaneously; n = 27) for 10 days. Acute hemodynamic effects of digibind (30 mg/kg, intravenous bolus injection) were examined after 10 days of sham control or ACTH treatment. Rats were divided into 7 groups: digibind (30 mg/kg, in 1 mL 0.9% NaCl intravenous bolus injection) plus sham (n = 6) or ACTH (n = 8), sham digibind (1 mL 0.9% NaCl intravenous bolus) plus ACTH (n = 7), digibind vehicle (sorbitol 1.8 mg in 1 mL 0.9% NaCl, intravenous bolus) plus sham (n = 6), preimmune sheep IgG (30 mg/kg in 1 mL 0.9% NaCl intravenous bolus) plus sham (n = 6) or ACTH (n = 6) and preimmune sheep IgG (Fab)2 fragment (30 mg/kg in 1 mL 0.9% NaCl intravenous bolus) plus ACTH (n = 6). ACTH increased systolic blood pressure (SBP) from 118 +/- 2 to 132 +/- 3 mm Hg on treatment day 10. BP was unchanged in sham treated rats. The acute administration of digibind decreased MAP (-14 +/- 3 mm Hg, P <.001) in ACTH hypertensive rats, but not in ACTH sham control normotensive rats (+2 +/- 3 mm Hg). Blood pressure reached a minimum after 14 +/- 3 min and the effect lasted more than 30 min. No significant change of blood pressure was found in ACTH treated rats receiving sham (0.9% NaCl) digibind injection (+2 +/- 2 mm Hg). However, both preimmune sheep IgG and IgG (Fab)2 fragment caused a decrease of blood pressure in both sham or ACTH treated rats. Although these data that digibind decreases BP in ACTH but not sham treated rats are consistent with the notion that digitalis-like substances may play a role in ACTH induced hypertension, the evidence that both preimmune sheep IgG and IgG (Fab)2 fragments also decreased blood pressure in rats suggests caution in interpretation of studies that employ digibind preparations.

Adrenocorticotropic Hormone↗

PubMed1997

Time course of femoral neck osteopenia in ovariectomized rats.

To characterize osteopenic changes in the femoral neck of ovariectomized (ovx) rats, female Sprague-Dawley rats were ovx or sham operated upon at 3 months of age and killed at various times from 0 to 360 days postsurgery. Quantitative bone histomorphometry was performed on undecalcified longitudinal sections of the proximal femur from each rat. This skeletal site was found to be slowly growing, as its rate of longitudinal bone growth in 3-month-old baseline control rats (5 microns/day) was nearly a factor of 10 less than that of a more commonly used sample site, the proximal tibia. In control rats, cancellous bone volume and cortical bone width of the femoral neck remained relatively constant, but cancellous mineral apposition rate declined with age during the course of the study. In contrast, cancellous bone volume in ovx rats was significantly decreased to 75%-82% of control level at 30-90 days and further decreased to 50%-56% of control level at later times postovariectomy. Indices of cancellous bone turnover such as osteoclast and osteoblast surfaces and bone formation rate were markedly increased in ovx rats at 30 days, declined toward control levels by 90 days, then increased moderately at 180-360 days. In comparison to control rats, a slight decrease in cortical width of the femoral neck was observed in ovx rats at 180 days and reached statistical significance at 360 days postovariectomy. Endocortical bone formation rate was increased significantly in ovx rats compared with control rats at most time points. The results indicate that both cancellous and cortical osteopenia associated with high bone turnover occur in the femoral neck of ovx rats. Cancellous bone loss at this skeletal site is statistically significant as early as 30 days postovariectomy, but remains relatively moderate for the first 90 days before becoming more pronounced at later times after ovariectomy. In contrast, cortical osteopenia was not observed in the femoral neck of ovx rats until 1 year postovariectomy. This histomorphometric characterization of osteopenic changes in the femoral neck of ovx rats may serve as a basis for use of this slowly growing sample site in preclinical studies of the prevention and treatment of bone loss in the estrogen-depleted skeleton.

Animals↗

PubMed1997

Apoptosis and mammary gland involution: reviewing the process.

Apoptosis is a process of programmed cell death. Mammary gland involution is a tissue remodelling process. Mammary epithelial cell apoptosis is an integral component of tissue remodelling but it is only one element. Equally important are the factors which degrade basement membrane and extracellular matrix. Both operations are required for completion of mammary gland involution. The primary apoptotic process occurs first and is temporally distinct from the second stage of involution typified by lobular-alveolar collapse. Local factors related to milk accumulation trigger the first stage, but loss of systemic hormonal stimulation governs the second stage. Changes in the expression patterns of cell cycle control genes and bcl-2 family member genes are found in the first stage. Proteinase gene activation dominates the second stage. These findings support a two stage model of mammary gland involution. Both mammary epithelial cell apoptosis and mammary gland remodelling advance through a process which includes both loss of survival factors and gain of death factors. This review focuses on signalling pathways and genetic controls which are activated and repressed during mammary gland involution.

Journal Article↗

PubMed1997

PDZ domain of neuronal nitric oxide synthase recognizes novel C-terminal peptide sequences.

PDZ domains are multifunctional protein-interaction motifs that often bind to the C-terminus of protein targets. Nitric oxide (NO), an endogenous signaling molecule, plays critical roles in nervous, immune, and cardiovascular function. Although there are numerous physiological functions for neuron-derived NO, produced primarily by the neuronal NO synthase (nNOS), excess nNOS activity mediates brain injury in cerebral ischemia and in animal models of Parkinson's disease. Subcellular localization of nNOS activity must therefore be tightly regulated. To determine ligands for the PDZ domain of nNOS, we screened 13 billion distinct peptides and found that the nNOS-PDZ domain binds tightly to peptides ending Asp-X-Val. This differs from the only known (Thr/Ser)-X-Val consensus that interacts with PDZ domains from PSD-95. Preference for Asp at the -2 peptide position is mediated by Tyr-77 of nNOS. A Y77D78 to H77E78 substitution changes the binding specificity from Asp-X-Val to Thr-X-Val. Guided by the Asp-X-Val consensus, candidate nNOS interacting proteins have been identified including glutamate and melatonin receptors. Our results demonstrate that PDZ domains have distinct peptide binding specificity.

Amino Acid Sequence↗

PubMed1997

Use of a modified bacteriophage to probe the interactions between peptides and ion channel receptors in mammalian cells.

Besides natural peptide ligands, screening of random peptide libraries has yielded novel bioactive peptides for cell surface receptors. A method is described that uses a modified bacteriophage as a detection reagent to monitor the expression of receptor channels in mammalian cells and to probe the molecular interaction between phage-tethered peptides (phi T-peptides) and specific receptor targets. By taking advantage of a specific multivalent interaction between phi T-peptides and the receptor target, assays have been developed that use phi T-peptides specific for the N-methyl-D-aspartate glutamate receptor, an important ligand-gated ion channel in the nervous system, to monitor the receptor expression in cultured mammalian cells. Combining these phi T-peptide binding assays with fluorescence-activated cell sorting, 10(4) random glutamate receptor mutants were screened and candidate interaction residues were identified. This dual heterologous expression system offers a powerful approach to the molecular studies of protein-protein interactions.

Amino Acid Sequence↗

PubMed1997

Determination of lignocaine hydrochloride by ion-pairing flow injection with piezoelectric detection.

A rapid and simple method for the determination of lignocaine hydrochloride by ion-pairing flow injection analysis was developed. It is based on the formation of an ion pair between lignocaine hydrochloride and sodium dodecyl phenylsulfonate and piezoelectric detection. The calibration curve was linear between 0.01 and 2.00 mg ml-1, with a detection limit of 8 micrograms ml-1, an RSD of 0.29% (10 replicates) and a sampling frequency of 120 h-1. The proposed method was satisfactorily applied to the determination of lignocaine hydrochloride in pharmaceutical preparations.

Flow Injection Analysis↗

PubMed1997

Oxytocin and milk removal are required for post-partum mammary-gland development.

The oxytocin (OT)-neurophysin preprohormone is synthesized in the paraventricular and supraoptic nuclei of the hypothalamus. OT is cleaved from its precursor, transported from the magnocellular neurons to the posterior pituitary and secreted during labour and upon the suckling stimulus of pups. OT induces the contraction of myoepithelial cells surrounding the mammary alveoli, which leads to the ejection of milk. Mice deficient in OT are unable to nurse their young. Administration of OT enabled OT-deficient dams to nurse. We now show that OT and milk removal are also required for post-partum alveolar proliferation and mammary-gland function. Alveolar density and mammary epithelial-cell differentiation at parturition was similar in wild-type and OT-deficient dams. However, within 12 h after parturition approx. 2% of the alveolar cells in wild-type dams incorporated DNA and proliferated, but virtually no proliferation was detected in OT-deficient dams. Continuous suckling of pups led to the expansion of lobulo-alveolar units in wild-type but not in OT-deficient dams. Despite suckling and the presence of systemic lactogenic hormones, mammary tissue in OT-deficient dams partially involuted. Our studies demonstrate that post-partum alveolar proliferation requires not only systemic lactogenic hormones, such as prolactin, but also the presence of OT in conjunction with continued milk removal.

Animals↗

PubMed1997

Dose-response relationship for nicotine-induced up-regulation of rat brain nicotinic receptors.

The chronic administration of nicotine to animals has been shown to result in an increase in brain nicotinic acetylcholine receptor (nAChR) density. It has been suggested that this agonist-induced receptor up-regulation is a consequence of long-term nAChR desensitization in vivo. In this study, the effects of different nicotine doses and administration schedules as well as the resulting blood and brain nicotine levels were determined to assess the effect of in vivo nicotine concentration on nAChR density in the brain. Rats with indwelling subcutaneous cannulas were infused for 10 days with 0.6-4.8 mg/kg/day nicotine either 2x, 4x, or 8x/day or by constant infusion. The nAChR density in cortical, striatal, and hippocampal tissue measured by [3H]cytisine binding as well as the corresponding plasma and brain nicotine levels measured by GC analysis were determined. The results showed a dose-dependent increase in nAChR density with significant increases achieved at 2.4 mg/kg/day in all three brain areas. It is surprising that at this dose there was little difference between the constant infusion of nicotine and twice-daily administration, whereas more frequent periodic injections were actually less effective at up-regulating nAChRs. An analysis of the blood and brain levels of nicotine compared with the concentrations that produce nAChR desensitization suggests that in vivo desensitization alone is not sufficient for nAChR up-regulation to occur.

Animals↗

PubMed1997

Use of medical care by African American and White older persons: comparative analysis of three national data sets.

Historically, there has been a large gap between African Americans and Whites in access to health care, but this gap was ostensibly lessened by the advent of Medicare and Medicaid for older adults in the mid 1960s. The extent to which older African Americans continue to receive less access to medical care as a result of economic inequalities, institutionalized forms of discrimination, and life-style factors remains a subject of policy debate. Empirical enquiry has produced inconsistent results. The purpose of this study is to test the same set of models of medical use using identically measured predictor variables in three nationally representative data sets of older Americans: 1984 Study of Aging (SOA); 1984 National Long-Term Care Survey (NLTC); and the 1987 National Medical Care Expenditure Survey (NMES). Multivariate logistic regression of use of physician and hospital services and Poisson regression of amount of service use identified inconsistent results in race differences across data sets, but consistent results in terms of the importance of health status and insurance as predictors of use and amount of use. The findings suggest that health status and financial resources may be more relevant areas for policy interventions than considerations related to race and ethnicity.

Black or African American↗

PubMed1997

A preliminary morphometric study on the endometrium from patients treated with indomethacin-releasing copper intrauterine device.

The intrauterine device (IUD) is an effective method of birth control. However, IUD-induced uterine bleeding is a major side-effect and always causes inconvenience, sometimes even anaemia. It has been reported that oral administration of indomethacin could can reduce IUD-induced uterine bleeding. In the present study, we investigated whether indomethacin-releasing copper IUD (IR-Cu-IUD) can prevent insertion-induced uterine bleeding and its mechanism. Nine healthy volunteers of reproductive age were selected for the study. Endometrial tissues were collected at same menstrual stage prior to and 3-6 months after IR-Cu-IUD insertion. Endometrial morphology, cell proliferation/differentiation, morphometry and activity of complement Factor VIII were examined. No significant difference was found in any of the parameters examined in the same patients, both prior to and after IR-Cu-IUD insertion. By comparison with data previously obtained from the patients who had Cu-IUD insertions, it is clear that IR-Cu-IUD markedly reduced IUD-induced uterine bleeding and this reduction is primarily contributed by the anti-inflammatory action of indomethacin.

Adult↗

PubMed1997

Regulation of cytosolic phospholipase A2 in hen granulosa cells by transforming growth factors at different stages of follicular development.

Phospholipase A2 (PLA2) is a key enzyme involved in the release of arachidonic acid and subsequent production of prostaglandins (PGs), which play important roles in regulating ovarian function, including mitogenic signalling by transforming growth factor (TGF) alpha. Cytosolic PLA2 (cPLA2), a newly identified member of the PLA2 family, is distinct from the well-characterized, secreted 14-kDa group I and II PLA2 in that cPLA2 selectively cleaves arachidonic acid-containing phospholipids at the sn-2 position. Our previous studies have demonstrated that TGF alpha stimulates and TGF beta suppresses PG production in hen granulosa cells during ovarian follicular development. The present work extends these findings. A cPLA2 is present as a 100-kDa protein doublet and has a transcript size of 3.2 kilobases (kb) in hen granulosa cells from the largest (F1) and the fifth and sixth (F5-6) preovulatory follicles. Treatment of these cells with TGF alpha caused a shift from an electrophoretically fast-migrating to slow-migrating protein, a phenomenon sensitive to inhibitors of serine/threonine kinase as well as mitogen-activated protein (MAP) kinase pathways and indicative of phosphorylation and activation of cPLA2. In contrast, TGF beta suppressed cPLA2 expression, as evidenced by a marked decrease of cPLA2 mRNA abundance and protein content, but failed to prevent the mobility shift of cPLA2 induced by TGF alpha. Consistent with the influence of this growth factor on PG production observed previously and in contrast to the action of TGF alpha, the inhibition of cPLA2 by TGF beta is more pronounced in granulosa cells at the early stage of follicular development. Our results demonstrate, for the first time, the regulation of granulosa cell cPLA2 at the transcriptional and posttranscriptional levels at different stages of follicular development. We propose that the activation by TGF alpha and suppression by TGF beta of cPLA2 may be important regulatory mechanisms in the control of granulosa cell PG production and thereby the mitogenic response of the cells to the growth factors during ovarian follicular development.

Animals↗

PubMed1997

Molecular genetics of Beckwith-Wiedemann syndrome.

Beckwith-Wiedemann syndrome (BWS) is an overgrowth disorder characterized by developmental anomalies, tissue and organ hyperplasia, and an increased risk of embryonal tumors. BWS is a multigenic disorder with dysregulation of the expression of imprinted genes involved in growth and cell cycle control in the 11p15 chromosomal region. The molecular genetics appear to involve either mutations of imprinted genes or chromosomal alterations of a putative imprinting center that controls gene expression across a large chromosomal domain. As the molecular genetics underlying BWS are unraveled, our knowledge of this imprinting disorder and its relationship to neoplasia and developmental anomalies will be expanded. Currently available diagnostic testing and follow-up protocols will evolve as our understanding of the molecular basis of this disease progresses.

Beckwith-Wiedemann Syndrome↗

PubMed1997

Deletion in the genes encoding outer surface proteins OspA and OspB of Borrelia garinii isolated from patients in Japan.

We detected the expression of outer surface proteins OspA and OspB, and characterized the genes encoding the two Osps of eight Borrelia garinii isolates from patients in Japan. Six of the eight strains shared a common antigenic epitope in their OspA and/or OspB proteins to monoclonal antibody P3134 against OspB, and were identified to have a conserved carboxyl terminus on their ospA and ospB genes by Southern blot hybridization. One strain, JEM4, did not express OspB protein, which was due to lack of the ospB gene. Gene cloning and sequencing analysis revealed that it had only one osp open reading frame with 819 nucleotides, which was similar to the ospA gene. The deletion of the ospB gene could be explained by a homologous recombination based on the common C-terminal sequences on the ospAB operon.

Antigens, Bacterial↗

PubMed1997

Adherence of human oral spirochetes by collagen-binding proteins.

The ability of spirochetes to adhere to collagens was compared among three species of human oral treponemes. Immunoblot analysis demonstrated that type I-, IV-, and V-collagen-binding polypeptides (CBPs) were detected in the heated and unheated preparations from both Treponema denticola ATCC 33520 and T. socranskii subsp. buccale ATCC 35534. Few CBPs, however, were detected in the heated and unheated preparations from a recently characterized isolate, T. medium strain G7201. Immunoelectron microscopy using rabbit antisera against the CBPs from the unheated preparations demonstrated that four CBPs, a 27 kDa type V-CBP of T. denticola ATCC 33520, a 95 kDa type IV-CBP and a 110 kDa type I-CBP of T. socranskii subsp. buccale ATCC 35534, and a 95 kDa type IV-CBP of T. medium strain G7201, were located on the outer envelopes of the individual cells. The adherence of T. denticola to the collagen-coated surfaces was significantly greater than that of T. medium, suggesting that the CBPs on the oral spirochetal cells play an important role in their adherence to collagen-rich connective tissues of the host.

Bacterial Adhesion↗