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Biomedical subjects

S M Lu

Publications and source records attributed to S M Lu.

At least 19 recordsLinked to original sources

Human papillomavirus type 18 DNA in gestational trophoblastic tissues and choriocarcinomas.

The objectives of our study were to better understand carcinogenesis of gestational trophoblastic tumors and to investigate the possible presence of human papillomavirus types 16 and 18 DNA sequences in these tumors. Amplification-based DNA methodology was used on 11 hydatidiform moles, 5 invasive moles, 8 choriocarcinomas and 9 normal early placental tissues. Human papillomavirus type 16 DNA was not found in any of these tissues. Although human papillomavirus type 18 DNA was also not found in the 9 normal placentas and 5 invasive moles, it was present in 2 of the 11 (18%) hydatidiform moles and in 4 of the 8 (50%) choriocarcinomas.

Base Sequence

Latency variability of responses to visual stimuli in cells of the cat's lateral geniculate nucleus.

We constructed average histograms from responses evoked by flashing stimuli and noted previously described variations in the shape of the response profile, particularly with respect to sharpness of the peak. To express this variable, we measured the half-rise latency, which is the latency from stimulus onset required to reach half the maximum response. A short half-rise latency, which is characteristic of nonlagged cells, is associated with a brisk response and sharp peak; a long half-rise latency, characteristic of lagged cells, is associated with a sluggish response and broad peak. Nonlagged cells were readily seen; we attempted to identify cells with long latencies as lagged, but we were unable to do so unambiguously due to failure to observe lagged properties other than latency. We thus refer to these latter cells as having "lagged-like" responses to indicate that we are not certain whether these are indeed lagged cells. In addition to the histograms, we analyzed the individual response trials that were summed to create each histogram, and we used spike density analysis to estimate the initial response latency to the flashing spot for each trial. We found that lagged-like responses were associated with more variability in initial response latency than were nonlagged responses. We then employed an alignment procedure to eliminate latency variation from individual trials; that is, responses during individual trials were shifted in time as needed so that each had a latency equal to the average latency of all trials. We used these "aligned" trials to create a second, "aligned" response histogram for each cell. The alignment procedure had little effect on nonlagged responses, because these were already well aligned due to consistent response latencies amongst trials. For lagged-like responses, however, the alignment made a dramatic difference. The aligned histograms looked very much like those for nonlagged responses: the responses appeared brisk, with a sharply rising peak that was fairly high in amplitude. We thus conclude that the slow build up to a relatively low peak of firing of the lagged-like response histogram is not an accurate reflection of responses on single trials. Instead, the sluggishness of lagged-like responses inferred from average response histograms results from temporal smearing due to latency variability amongst trials. We thus conclude that there is relatively little difference in briskness between nonlagged and lagged-like responses to single stimuli.

Animals

Cellular bases for the control of retinogeniculate signal transmission.

The dorsal lateral geniculate nucleus (LGN) is the major thalamic relay for retinal signals en route to cortex. However, LGN cells operate as more than just a simple relay of their retinal inputs. Rather, they function as a variable gate, determining what, when, and how much retinal information gets passed to visual cortex. Two factors that are key to this control are the innervation patterns and electrophysiological membrane properties of geniculate cells. This paper discusses three active membrane properties and the manner in which they modulate the transfer of retinal signals to cortex. They are the low threshold calcium (Ca2+) conductance, a transient potassium (K+) conductance, and NMDA receptor-mediated excitatory postsynaptic potentials (EPSPs). The low-threshold Ca2+ conductance transforms a geniculate cell from a state of single spike activity to one of bursting discharge, the potassium current leads to a delay in membrane depolarization to reach spike threshold, and NMDA receptor activity modulates EPSP amplitude and duration near spike threshold. Additionally, we consider how nonretinal inputs, such as the ascending cholinergic pathway from the brainstem parabrachial region and the descending pathway from layer VI of visual cortex, influence the expression of these membrane properties through their control of membrane potential.

Acetylcholine

[The effects of the estradiol control delivery patch in the treatment of 176 cases of ovarian failure].

The effects of the estradiol control delivery patch made in China on the main manifestation in the 176 cases of ovarian failure patient were evaluated with the improvement of their symptoms, the changes of serum levels of LH, FSH, E2, the vaginal exfoliated cytologic maturation index (MI) and the histological alteration of endometrium. The results indicated that the six main symptoms including hectic fever, sweating, vaginal dry and hard-going, dizziness, emotioned lability and insomnia were improved significantly and progressively with prolongation of the treatment. The effective rates were 97.9%, 97.5%, 93.7%, 77.0%, 76.2%, 75.0% respectively form hectic fever to insomnia. The inhibitory effects on serum LH, FSH levels occurred on the 10th day of the treatment. The MI increased within whole course and the serum estradiol level elevated slightly and stably. There were no significant endometrial proliferation caused by the patch.

Adult

Immunoreactivity for GAD and three peptides in somatosensory cortex and thalamus of the raccoon.

Immunocytochemical methods were used to determine the distributions of glutamic acid decarboxylase (GAD), vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK), and somatostatin (SOM) in the primary somatosensory cortex and somatosensory thalamus of adult raccoons. The cortex showed extensive immunoreactivity for GAD, revealing a large population of GABAergic neurons. GAD-labeled cells were numerous in all cortical layers, but were most concentrated in laminae II-IV. The cells were nonpyramidal and of varying morphology, typically with somata of small or medium size. GAD-immunoreactive puncta, presumably synaptic terminals, were widespread and often appeared to end on both GAD-negative and GAD-positive neurons. Immunoreactivity for the peptides was much less extensive than that for GAD, with the number of labeled neurons for VIP > CCK > SOM. Peptidergic cells were preferentially located in the upper and middle cortical layers, especially laminae II and III. The cells were nonpyramidal, often bitufted or bipolar in morphology, and small to medium in size. Their processes formed diffuse plexuses of fibers with terminal-like varicosities that occasionally surrounded nonpeptidergic neurons. The thalamus showed a clearly differentiated pattern of immunoreactivity for GAD, but little or no labeling for the three peptides. Nuclei adjoining the ventral posterior lateral (VPL)/ventral posterior medial (VPM) complex--including the reticular nucleus--contained many GAD-positive neurons and fibers. In contrast, the VPL and VPM nuclei displayed considerably less GAD immunoreactivity, somewhat surprising given the raccoon's highly developed somatosensory system. However, the ventral posterior inferior (VPI) nucleus revealed rather dense GAD labeling, perhaps related to a specialized role in sensory information processing. Thus, the primary somatosensory cortex of the raccoon showed patterns of immunoreactivity for GAD and peptides that were similar to those of other species; the somatosensory thalamus revealed a distinctive profile of GAD immunoreactivity, with labeling that was light to moderate in the VPL/VPM complex and relatively extensive in VPL.

Animals

Effects of membrane voltage on receptive field properties of lateral geniculate neurons in the cat: contributions of the low-threshold Ca2+ conductance.

1. Thalamic relay cells, including those of the lateral geniculate nucleus, display a low-threshold spike (LT spike), which is a large depolarization due to an increased Ca2+ conductance. Typically riding the crest of each LT spike is a burst of from two to seven action potentials, which we refer to as the LT burst. The LT spike is voltage dependent, because if the cell's resting membrane potential is more depolarized than roughly -60 mV, the LT spike is inactivated, but if more hyperpolarized, the spike is deinactivated and can be activated by a depolarization, such as from an afferent excitatory postsynaptic potential (EPSP). Thalamic relay cells thus display two response modes: a relay or tonic mode, when the cell is depolarized and LT spikes are inactivated, leading to tonic firing of action potentials; and a burst mode, when the cell is hyperpolarized and tends to respond with LT spikes and their associated bursts of action potentials. 2. We were interested in the contribution of the LT spike on the transmission of visually evoked signals through geniculate relay cells to visual cortex. We recorded intracellularly from geniculate cells in an anesthetized, paralyzed, in vivo cat preparation to study the effects of membrane voltage, and thus the presence or absence of LT spikes, on responses to drifting sine-wave gratings. We monitored the visually evoked responses of 14 geniculate neurons (6 X, 7 Y, and 1 unclassified) at different membrane potentials at which LT spikes were inactivated or deinactivated. 3. Changing membrane voltage during visual stimulation switched the response mode of every cell between the relay and burst modes. In the burst mode, LT spikes occurred in phase with the visual stimulus and not at rhythmic intervals uncorrelated to visual stimuli. To any given stimulus cycle, the cell responded usually with an LT burst or a tonic response, and rarely was more than one LT burst evoked by a stimulus cycle. Occasionally a single cycle evoked both an LT burst and tonic response, but always the LT burst occurred first. 4. The spatial tuning characteristics of the cells did not differ dramatically as a function of membrane potential, because the tuning of the LT bursts was quite similar to that of the tonic response component. Although we did not obtain complete temporal tuning properties, we did note that hyperpolarized cells responded reliably with LT bursts at several temporal frequencies. 5. A consistent difference was seen between the LT burst and tonic response components in terms of response linearity.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials

Relative contributions of burst and tonic responses to the receptive field properties of lateral geniculate neurons in the cat.

1. In an anesthetized, paralyzed in vivo preparation, we recorded extracellular responses of 61 geniculate neurons (2 W, 25 X, 33 Y, and 1 mixed) to drifting sine-wave gratings of various spatial frequency, temporal frequency, and contrast. Our goal was to study the differential contributions to these visual responses of bursting caused by voltage dependent, low-threshold (LT) Ca2+ spikes and of purely tonic responses unrelated to LT spikes. Cells responding with LT spikes are said to be in the burst firing mode and those responding in a purely tonic fashion to be in the relay or tonic firing mode. We separated the total visual response into LT burst and tonic components by use of the empirical criteria set forth in our intracellular study described in the previous paper (Lu et al. 1992). A response component was considered to be an LT burst if its action potentials displayed interspike intervals < or = 4 ms and if the first spike in the burst episode occurred after a silent period of > or = 100 ms (or > or = 50 ms when the neuron responds to visual stimuli at temporal rates > or = 8 Hz). All other activity is considered to be part of the tonic response. 2. In addition to LT bursts, we recognized another type of burst response, the high-threshold (HT) burst. These also have clusters of action potentials with interspike intervals < or = 4 ms. However, HT bursts, unlike LT bursts, lack a preburst silent period. HT bursts are part of the tonic response component and merely reflect the gradual decrease in interspike intervals that occurs as the cell becomes more depolarized and thus more responsive. Thus interspike interval is a necessary but insufficient criterion to identify LT bursts. 3. Visually evoked LT bursts were recorded among W, X, and Y cells. When evoked, LT bursts occurred in phase with drifting sine-wave grating stimuli at a rate never exceeding one per stimulus cycle. In response to individual cycles of the visual stimulus, LT bursts could comprise the total response, a tonic component could comprise the total response, or an LT burst and tonic component could be mixed. When a stimulus evoked a mixture of LT bursts and tonic response components, LT bursts were always the first response. 4. Of the 61 cells tested with grating stimuli, 47 exhibited LT bursts and 14 did not. Those that did exhibited varying amounts of burstiness.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials

[Effects of combination chemotherapy of ovarian cancer in vitro].

To investigate the effects of combination chemotherapy on ovarian cancer in vitro, we observed the sensitivity of tumors to different drugs by incorporation assay of tritium thymidine (3H-TdR). The results revealed that the drugs and their sensitive degrees varied from tumor to tumor. Whether the combination of the drugs is synergism or sometimes only enhances toxicity depends on the difference of individuals. We suggest that in vitro anti-cancer drug sensitivity test could be applied in selection or determination of chemotherapy protocol.

Antibiotics, Antineoplastic

Intracellular and extracellular in vivo recording of different response modes for relay cells of the cat's lateral geniculate nucleus.

Prior studies of thalamic neurons have demonstrated that they exhibit at least two response modes: a relay mode and a burst mode. During the relay mode, sensory information is faithfully relayed to cortex; during the burst mode, which is caused by a voltage-dependent Ca2+ conductance, this relay of sensory information is interrupted. We began in vivo studies of these response modes in neurons from the lateral geniculate nucleus of anesthetized, paralyzed cats. Each of the 9 X and 10 Y cells we recorded intracellularly displayed voltage-dependent, low threshold spikes that were presumably the Ca2+ spikes described from in vitro recording. These spikes were triangular in waveform and typically had 2-7 fast action potentials (interspike intervals of 1.2-4 ms) riding its crest. Furthermore, the cell's membrane had to be hyperpolarized to de-inactivate the low threshold spike before a depolarization could then activate it. We could activate these low threshold spikes in Y cells from EPSPs, whether spontaneous or evoked from activation of the optic chiasm. However, in only one of the X cells could we activate low threshold spikes from chiasm shock; in the remainder, we could activate low threshold spikes only via depolarizing current pulses, possibly because the EPSPs of these X cells were too small to activate these spikes. We also used extracellular recording to study spontaneous activity and responses to chiasm shock from 114 geniculate neurons and, as a control, 57 optic tract axons. We concentrated on periods of bursty responsiveness signifying the burst mode. We define a burst as 2-7 action potentials with interspike intervals less than or equal to 4 ms, and the bursts are separated by greater than 100 ms; from our intracellular recording, we know that such bursts signify low threshold spikes. We found that, during extracellular recording, 20 of the 39 X cells and each of the 75 Y cells displayed evidence of the burst response mode, although burst periods were rare in X cells. Electrical activation of the optic chiasm greatly enhanced the burstiness of Y cells for periods of 500 ms or more. We also electrically stimulated the parabrachial region of the midbrain, which provides a mostly cholinergic innervation to the lateral geniculate nucleus. Although parabrachial activation by itself had no detectable effect on Y cell response modes, prior parabrachial activation prevented the enhanced burstiness caused by chiasm stimulation. This parabrachial effect lasted for roughly 500 ms after stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials

[Effect of levonorgestrel intrauterine device on human endometrial estrogen and progesterone receptors].

Estrogen and progesterone cytoplasmic receptors (ER, PgR) were determined by radiochemical DCC technique in the endometria of 16 normal women at before child bearing age and 6 to 9 months after LNG IUD insertion. The study showed that both ER and PgR were reduced significantly after LNG IUD insertion (P less than 0.01). The decrease of ER and PgR might play an important role in gland reduction and endometrial atrophy. It may be one mechanism of the contraceptive effect and the cause of anemia or spotting between menstruation during the course of LNG IUD insertion.

Adult

N-methyl-D-aspartate receptors contribute to excitatory postsynaptic potentials of cat lateral geniculate neurons recorded in thalamic slices.

Neurons of the cat's dorsal lateral geniculate nucleus were recorded intracellularly to study the contribution of N-methyl-D-aspartate (NMDA) receptors to excitatory postsynaptic potentials (EPSPs) and low-threshold calcium spikes. EPSPs were evoked by stimulation of retinogeniculate axons in the optic tract and/or corticogeniculate axons in the optic radiations; EPSPs from both sources were similar. These EPSPs had one or two components, and the second component had several characteristics of NMDA receptor-mediated events. For example, EPSP amplitude decreased when neurons were hyperpolarized and increased when stimulus frequency was increased; these EPSPs could also be blocked reversibly by application of the selective NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV). We also studied the influence of NMDA receptors on low-threshold calcium spikes, which are large, voltage- and calcium-dependent depolarizations that are often accompanied by high-frequency action potential discharge. APV blocked synaptically activated low-threshold calcium spikes, but APV had no effect on low-threshold calcium spikes that were elicited by current injection. Therefore, APV does not appear to have a direct effect on the T-type calcium channel that is involved in generation of low-threshold calcium spikes. The voltage and frequency dependence of the NMDA receptor-mediated component of the EPSPs, as well as its ability to trigger low-threshold calcium spikes, provide for complex signal processing in the lateral geniculate nucleus.

2-Amino-5-phosphonovalerate

The acceptable load while marching at a speed of 5 km h-1 for young Chinese males.

Ninety-three young Chinese men selected at random were involved in the load carrying experiments. They marched at 5 km h-1 carrying loads of 0, 15, 20, 25 and 31 kg for 7 h per day. At this speed the acceptable load to be carried was 20 kg. Under this load 95% of the men had heart rates below 120 bt min-1 while marching and energy metabolism was in balance. Nevertheless, 10-15% of the men were fatigued and felt tired.

Adult

[In vitro drug-resistance decrease of ovarian cancer cells].

A chemosensitivity test for ovarian cancer using tritiated thymidine incorporation assay was carried out. A dose-response relationship was observed for cis-platinum and an 5-fold increase of concentration converted the drug resistant tumor into a drug-sensitive one. Verapamil was found to enhance the cytotoxic effect of vincristine against ovarian cancer cells. It is suggested that combination of vincristine with verapamil may be helpful in treating some vincristine-resistant cases.

Cisplatin

Immunoreactivity to calcitonin gene-related peptide in the superior olivary complex and cochlea of cat and rat.

In both cat and rat, the cells of origin, axons, and terminals of the lateral olivocochlear system exhibit immunoreactivity to antisera to calcitonin gene-related peptide (CGRP). In the cat, immunoreactive neurons in the brainstem are located in the hilus of the lateral superior olivary nucleus and around its margins. In the rat, immunoreactive neurons are located within the lateral superior olivary nucleus proper. In both species, immunoreactivity in the cochlear duct is limited to the region beneath the inner hair cells. Immunoreactive axons in the cochlear nucleus could not be traced to their source but may arise as collaterals of the lateral olivocochlear system. No other components of the brainstem auditory system react to any extent with the antisera.

Animals

Glutamic acid decarboxylase and somatostatin immunoreactivities in rat visual cortex.

Antibodies to glutamic acid decarboxylase (GAD) and somatostatin (SS) were used to determine the laminar distribution and morphology of GAD- and SS-immunoreactive neurons and terminals in rat visual cortex. The present study demonstrates that GAD-immunoreactive neurons constitute several morphologically distinct subclasses of neurons in rat visual cortex. These subclasses of neurons can be distinguished by differences in soma size, soma shape, dendritic branching patterns, axonal arborizations, and location in the neuropil. GAD-immunoreactive neurons are found throughout all layers of visual cortex. They have nonpyramidal morphology and constitute roughly 15% of the total neuronal population. The laminar pattern of GAD-immunoreactive puncta is uneven, with a prominent band of terminals in layer IV. Numerous large GAD-positive puncta surround the somata and proximal dendrites of pyramidal cells in layers II, III, and V. SS-immunoreactive neurons constitute a less numerous and more restricted population of nonpyramidal neurons. Their somata are located mainly in layers II, III, V, and VI. Very few, if any, SS-immunoreactive neurons are found in layers I and IV. SS-immunoreactive terminals are arranged along vertical and diagonal collateral branches that have a beaded appearance. Finally, many neurons in the supra- and infragranular layers and in the white matter are immunoreactive to both glutamic acid decarboxylase and somatostatin. This coexistence of immunoreactivity to both GAD and SS may characterize a broad subclass of cortical nonpyramidal neurons.

Animals