Unresponsive Period Research Articles

A rare case of gastric cancer with bilateral breast metastasis during pregnancy

Gastric cancer is rare during pregnancy and often diagnosed at a later stage due to overlapping symptoms of pregnancy. Breast metastasis of gastric cancer is another uncommon entity. We present a rare case of breast metastasis of gastric cancer during pregnancy. A 26-year-old female was diagnosed with gastric cancer at 14 weeks of gestation and underwent total gastrectomy. She rejected adjuvant chemotherapy and continued pregnancy without any follow-up. Cancer recurred in bilateral breasts at 34th week of gestation mimicking primary inflammatory breast cancer. It was difficult to diagnose breast metastasis during pregnancy because of overlapping pregnancy symptoms. Following an unresponsive period to antibiotherapy, a fine needle biopsy on breast was performed and signet cell adenocarcinoma metastasis was determined. We started chemotherapy after delivery. There was a near complete response after first line of chemotherapy. Unfortunately, cancer was relapsed within three months and we started second-line chemotherapy. To our knowledge, this is the fourth case reported in medical literature of gastric cancer presented with breast metastasis during pregnancy. We will try to draw attention to diagnosis, treatment and different presentation of gastric cancer during pregnancy with review of the literature.

Behavioral responses and mortality in German cockroaches (Blattodea: Blattellidae) after exposure to dishwashing liquid.

Behavioral responses and mortality of the German cockroach, Blattella germanica (L.), after exposure to solutions of common household dishwashing liquid diluted in tap water without other known insecticidal active ingredients are described. Soap solutions of 0.05, 0.1, 0.25, 0.5, 1.0, 2.0, 3.0, 4.0, and 5.0% were tested on first and second instars, fifth and sixth instars, and adults. Cockroaches were treated individually or in groups. Behavioral observations after treatment included an immediate knockdown period, an awakening and a struggle period, an unresponsive period, and either death or recovery between 30 min and 18 h after treatment. Probit analysis gave an excellent fit of unresponsive rates 18 h after treatment with the various soap concentrations, and LD50 and LD99 values were calculated to be 0.4 and 3.0% soap, respectively. Adult females were the most difficult to kill, but at soap concentrations of 1% or higher, 95% or greater unresponsiveness and death occurred. Soap concentrations of 3% or greater resulted in 100% unresponsiveness after 3 min, and eventually resulted in 100% mortality within 72 h for all adults and nymphs treated. Observations on the mode and site of action for soap are consistent with the blockage of spiracles and/or tracheae that results in asphyxiation and death. Future investigations into the efficacy of soaps against other arthropod groups are warranted and may be beneficial in certain situations.

Interleukin-2 inhibition of oligodendrocyte progenitor cell proliferation depends on expression of the TAC receptor.

Interleukin-2 (IL-2) has been shown to inhibit oligodendrocyte progenitor cell proliferation. Within the immune system, IL-2 biological action is dependent strictly on the expression of the IL-2 receptor. The antibody TAC, which specifically binds the lymphocyte IL-2 receptor, has been shown to also bind oligodendrocyte progenitor cells cultured in a serumless, chemically defined medium. The expression of the TAC antigen was found necessary for IL-2 inhibition of oligodendrocyte progenitor cell proliferation. After IL-2 induced down-regulation of the TAC antigen, the progenitor cell was unresponsive to IL-2, even 72 hr after IL-2 withdrawal. During this unresponsive period, the oligodendrocyte progenitor cell was immunocytochemically negative for the TAC antigen. Thus, in contrast to IL-2 receptors on T-cells, IL-2 does not up-regulate its receptor on oligodendrocyte progenitor cells. However, upon interleukin 1 (IL-1) addition both IL-2 responsiveness and TAC immunocytochemical staining reappeared. These data suggest that IL-2 inhibition of progenitor cell proliferation depends on the expression of the TAC antigen, which can be regulated by IL-1.

Cell mediated immunity to liver fluke antigens during experimental Fasciola hepatica infection of cattle.

Cell mediated immunity (CMI) to Fasciola hepatica antigens was detected by lymphocyte proliferation and interleukin-2 (IL-2) production tests in cattle during the first 4 weeks following liver fluke infection. From the fifth week of infection onwards peripheral blood lymphocytes were unresponsive to fluke antigens by these in vitro tests. Investigations into the cause of this unresponsiveness found no evidence to suggest a selective loss of the IL-2 producing lymphocyte sub-population or that macrophages were responsible for the suppression or that antigen responsive cells were being sequestered in the spleen and mesenteric lymph nodes. Tests carried out on culture supernatants demonstrated the production during this unresponsive period of factors capable of suppressing in vitro responses to PHA. Although further tests failed to show antigen specific suppressor factors the presence of MHC restricted suppressor factors could not be ruled out. The early and transient appearance of CMI during F. hepatica infection of cattle indicates that delayed type hypersensitivity is unlikely to be important in protective immunity in cattle.

Physiological changes governing the onset of sexual receptivity in male mosquitoes

The effectors which erect antennal hairs in male mosquitoes are shown to be unresponsive to the neurotransmitter that triggers antennal hair erection until 12–24 hr after emergence. The unresponsive period can be prolonged by transfusion of haemolymph from newly-emerged males, or by injection of 20-hydroxyecdysone. This suggests that the hormone persisting after the metamorphosis from pupa to adult, affects the duration of the post-emergence delay in antennal hair erection and is indirectly responsible for timing the onset of sexual receptivity in male mosquitoes.

H reflex studies in patients with Parkinson's disease

The H reflex was studied in 13 patients with Parkinson's disease, and the results compared with those obtained in 22 control subjects. Pairs of identical stimuli near threshold intensity were delivered and the unresponsive period and time course of recovery of the amplitude of the H reflex were determined. The duration of the unresponsive period was significantly shorter in the patients with Parkinson's disease. In 10 patients the studies were repeated after treatment with l-dopa for six months. There was a significant increase in the period of unresponsiveness of the H reflex after treatment. The findings suggest that there is an increase in alpha motoneurone excitability in Parkinson's disease, and that it is reduced by treatment with l-dopa.

The receptor potential and its functional relationship to the nerve impulse analysed in a sense organ by means of thermal and electrical stimuli

1. The receptor potential (RP) which occurs at the level of tuberous organs in the mormyrid fish (Gnathonemus petersii andG. stanleyanus) was investigated using simultaneous thermal and electrical stimuli (Part I). Its functional relationship to the propagated potential (PP) in the afferent nerve fiber was analysed (Part II). 2. Two types of spontaneously occurring potentials were recorded extracellularly at the level of these organs: 1) small (100 μV) slow potentials of variable amplitude and 2) large (several mV) diphasic initially positive spike-like potentials (RP) with constant amplitude and duration. The behaviour of the two types of potential to thermal and electrical stimuli indicates that the slow potential is the generator potential of the RP. 3. The spontaneous as well as the electrically provoked RP obeys the “all or none” law. In contrast, the RP as well as its generator potential, both are graduable with combined electrical and thermal stimuli. 4. The amplitude of the RP diminishes with decreasing temperature, whereas its duration remains constant. Tested with paired electrical stimuli, the RP does not show any unresponsive period; also, the RP can be driven by repetitive stimulation to several thousands cycles/s. Thus, the RP does not show the characteristics of a nerve-spike. 5. Simultaneous recordings of RP and correlated propagated potentials (PP) show that the RP is a local phenomenon arising at the sensory cell membrane. 6. Without being the generator potential, the RP is indispensable for the advent of the nerve impulse; the RP and PP are strictly phase related. 7. The generation of the nerve impulse is not related to the amplitude of the RP. 8. Considering the morphological features of the junction between the sensory cells and the afferent nerve fiber, it is suggested that the RP provokes the release of transmitter substances present in the presynaptic area, which in turn depolarizes the post-junctional membrane.

Visual adaptation in the retina of the skate.

The electroretinogram (ERG) and single-unit ganglion cell activity were recorded from the eyecup of the skate (Raja erinacea and R. oscellata), and the adaptation properties of both types of response compared with in situ rhodopsin measurements obtained by fundus reflectometry. Under all conditions tested, the b-wave of the ERG and the ganglion cell discharge showed identical adaptation properties. For example, after flash adaptation that bleached 80% of the rhodopsin, neither ganglion cell nor b-wave activity could be elicited for 10-15 min. Following this unresponsive period, thresholds fell rapidly; by 20 min after the flash, sensitivity was within 3 log units of the dark-adapted level. Further recovery of threshold was slow, requiring an additional 70-90 min to reach absolute threshold. Measurements of rhodopsin levels showed a close correlation with the slow recovery of threshold that occurred between 20 and 120 min of dark adaptation; there is a linear relation between rhodopsin concentration and log threshold. Other experiments dealt with the initial unresponsive period induced by light adaptation. The duration of this unresponsive period depended on the brightness of the adapting field; with bright backgrounds, suppression of retinal activity lasted 20-25 min, but sensitivity subsequently returned and thresholds fell to a steady-state value. At all background levels tested, increment thresholds were linearly related to background luminance.

Immunological unresponsiveness to helminth parasites: III. Challenge of rats previously infected at an early age with Nippostrongylus brasiliensis

We have previously shown that when rats are infected when young with 500 N. brasiliensis larvae worm expulsion does not occur as in adult rats; instead rats so infected remain unresponsive to their intestinal worm burdens well into adult life. It was subsequently shown that this state is to a certain extent dose dependent in that infections of a greater size do result in a measure of worm expulsion but that this ceases when a burden of approximately 200 is reached; this also persists into the adult life of the rats. In this paper the response of rats infected when young to a subsequent challenge infection has been studied. Three factors have been found to be of importance in determining the type of response elicited: 1. (1) The size of the first infection given when young. Young rats initially infected with a small dose of larvae (500) respond to a challenge of 1000 larvae in adult life by a pattern of worm expulsion similar to rats experiencing a primary infection of N. brasiliensis, whereas rats initially infected with a large dose (3200) show a secondary type of response. 2. (2) The size of the challenge infection. Whereas removal of the original worm population by thiabendazole and its replacement with a similar small number of new worms (either by infection with larvae or by adult worm transplant) results in a primary type of worm expulsion, a large challenge infection (3000) larvae is capable of eliciting a secondary type of expulsion response despite an initial small infection. 3. (3) The age of the rats at the challenge infection. The superimposition of a challenge infection on a primary infection where both occur during the original unresponsive period (i.e. up to 7 weeks) results merely in a continuation of the unresponsive state into adult life although the worm burden is again adjusted to bring it down to a level of around 200 worms. It was concluded on several grounds that immune tolerance in the classical sense is not responsible for the persistence into adult life of the relatively large worm burdens acquired from infection during the immunologically unresponsive period. Alternative explanations and the significance of the phenomenon are discussed.

Recovery cycles in the lemniscal system

Recovery of the evoked response to controlled peripheral nerve stimulation was studied in the cat at the medial lemniscus, internal capsule, and somatosensory cortex with the following findings: 1. 1. In the unanesthetized, alert animal, recovery proceeds quickly with no evidence of facilitatory or inhibitory peaks at all recording locations. 2. 2. Barbiturate anesthesia prolongs the latter part of the relatively unresponsive period (RUP) in the lemniscus, increases the absolutely unresponsive period (AUP) and uncovers a period of increased responsiveness in the capsule, and increases both the AUP and RUP of the cortex with no evidence of subsequent periods of increased or decreased responsiveness. 3. 3. Mild hypothermia (31–32°C) in the absence of anesthesia prolonged the RUP in the lemniscus and both the AUP and RUP in the capsule and cortex. In the anesthetized animal, these changes were more marked and the period of heightened responsiveness in the capsule disappeared. While some evidence of increased responsiveness was seen in the cortex, recovery of this responsiveness was polonged. 4. 4. A stimulus placed near the end of the AUP of the capsule and cortical response, itself ineffective in producing a response, prolonged recovery of a subsequent test response.

Dose related effects of pentobarbital on somatosensory evoked responses and recovery cycles

The interrelationships among the amplitude of primary evoked somatosensory responses, the recovery cycle of these responses and dose level of pentobarbital sodium were investigated. Although pentobarbital reduced both the amplitude and the degree of recovery of evoked potentials, only the recovery changes during the relative unresponsive period provided a dose sensitive indicator. Amplitude was affected only at maximum dose levels. These results were discussed in relation to previous work on the effects of state of alertness on the recovery cycle and to the formulation of King et al. (1957) with regard to the mechanism of action of barbiturates. It was concluded that state of alertness and barbiturates probably affect the recovery cycle through mechanisms in the brain stem reticular formation that are at least partially independent. Low doses of barbiturates probably affect reticular mechanisms controlling recovery and higher doses probably exert an additional, depressant action on the thalamic relay nuclei.

Physiological and anatomical studies of development of superficial axodendritic synaptic pathways in neocortex

Neocortical axodendritic synaptic organizations involved in the production and spread of evoked superficial cortical responses (SCR's) have been studied in kittens ranging in age from the late fetal stage to 6 weeks. Electrophysiological data are correlated with the salient morphological features of cortical neurons at various developmental stages. Graded, long-duration (50–80 msec) SCR's are detectable 5 to 7 mm from the site of stimulation during the first postnatal week and 8 to 10 mm after this period. Short-duration (10–20 msec) responses, similar to those recorded in mature animals, are detectable in perinatal animals at the site of stimulation but not at distances greater than 2 mm from stimulating electrodes until the third postnatal week. Linear changes in latency with distance are observed at all stages of development. Distant SCR's exhibit reinforcement during the second postnatal week. The appearance of reinforced responses is associated with a change in the early phase of the SCR activity cycle characterized by progressive shortening of the absolute unresponsive period. The distinctive electrographic characteristics of SCR's in neonatal animals are attributed to summation of 10 to 20 msec postsynaptic potentials generated in densely packed apical dendrites of pyramidal neurons and dendrites of embryonic Cajal-Retzius cells. Regression of the dendritic system of the latter cells, decrease in apical dendritic density, increase in conduction velocity of axons in the molecular layer and changes in the SCR-activity cycle are considered the major factors associated with maturation of superficial neocortical neuropil.

The responses of single units of the inferior colliculus of the cat to acoustic stimulation.

Discharges of single units of the inferior colliculus in response to acoustic stimulation have been studied in anaesthetized and decerebrate cats by means of extracellularly placed electrodes. A tonal stimulus may cause a unit to discharge either with a short burst of spikes or with a slowly adapting train of spikes. For each unit there is a ‘characteristic frequency’ at which the threshold is lowest, with rising thresholds for frequencies on either side. In response to tonal stimuli presented to one ear, some units (classed as Group A units) may respond over a relatively wide range of the audible spectrum, while other units (classed as Group B units) are only activated by tonal frequencies within a narrow band of the spectrum. Some Group B units, however, may be activated by two separate bands of frequencies at different parts of the spectrum; this occurs even though the unit can only be activated by stimuli delivered to one ear. An increase in the intensity of the stimulus causes an increase in the rate of firing of the unit, and also a broadening in the range of tonal frequencies which can activate the unit. This takes place to a greater extent for Group A units than for Group B units. Masking of the unitary responses to clicks by different tonal backgrounds was examined. A click response may be abolished by a particular tonal frequency: on either side of this frequency the characteristics of the responses (i. e. the mean latency and number of spikes per discharge) are altered. This may take place over a large or small range of the audible spectrum. Tonal stimuli delivered to either ear may activate the same unit. In such cases, the unit may have two ‘characteristic frequencies’, but these lie close to one another. The range of tonal frequencies which activates the unit, however, differs for the two sides. Click stimulation alone presented to either ear may activate the same unit. When click stimuli are delivered in succession to the two ears, there is revealed an absolutely unresponsive period during which the second stimulus cannot evoke a detectable response. The duration of this unresponsive period is dependent upon which ear is stimulated first, and is not the same for the two sides. For most units, the absolutely unresponsive period was longer when the contralateral ear was stimulated first. With progressive increase in the interval between the two stimuli there is a relatively unresponsive period during which the characteristics of the responses are altered, until finally a constant response to the second stimulus is obtained. If the two stimuli are separated by short intervals, summation of the two responses may take place. When the sound source is moved in a semicircular horizontal plane in front of the head, and click stimuli are delivered at every 15°, an asymmetrical distribution with respect to the latency is revealed. For those units which are activated by click stimuli delivered to either ear, a progressive and linear change in the mean latency of the response occurs as the source is moved from one ear to the opposite ear. When the sound source is placed at the midline, however, there is a deviation from the linear relationship and the mean latency is significantly decreased. This decrease does not occur for responses from units activated by stimuli presented to one ear alone. The significance of these findings is discussed, particularly in relation to central mechanisms for the localization of sound in space.