A 10 Minute Self-Care Program May Reduce Breast Cancer-Related Lymphedema: A Six-Month Prospective Longitudinal Comparative Study.

Patients with breast cancer-related lymphedema (BCRL) need a life-long self-care program that they can adhere to enable them to manage their lymphedema. The objective of this study was to assess the effectiveness of a holistic BCRL self-care program that patients could easily adhere to and comply with. A prospective, longitudinal, comparative study between affected arms and unaffected arms in unilateral breast cancer patients was implemented over a six-month period. Both the lymphedematous and unaffected arms of 23 patients with unilateral BCRL were followed and measured. The daily 10-minute holistic BCRL self-care program consisted of modified Japanese rajio taiso (Japanese radio calisthenics), a gentle arm exercise combined with deep breathing, skin moisturizing care using a traditional lymphatic drainage technique, and basic self-care education. Arm and edema volume, relative volume change, resistance of the skin to compression (fibrosis), lymphedema-related symptoms, skin condition, and self-care were assessed. At the end of six-months the volume of all limb segments and resistance of the tissues to compression at all measurement points of the affected arm were significantly reduced. On the unaffected side, only the volume of the forearm and the whole arm was significantly reduced and fibrosis significantly reduced only in the forearm. There was no significant difference in edema volume and relative volume change. Lymphedema-related symptoms significantly improved. Perceived adherence, effectiveness, burden, score and average time for self-care significantly increased. Our results demonstrate that this 10-minute self-care program may improve BCRL and its self-care.

Diaphragm pacing with a spinal cord stimulator: current state and future directions.

Diaphragm pacing with electrical stimulation of the phrenic nerve is an established treatment for central hypoventilation syndrome. The device, however, is not readily available. We tested the same spinal cord stimulator we use for pain control in phrenic nerve stimulation. We implanted a spinal cord stimulator (Itrel 3 or X-trel, Medtronic, MN) in 6 patients with chronic hypoventilation because of brainstem or high cervical cord dysfunction. The stimulation electrode was placed along the right phrenic nerve in the neck, and the device was implanted in the anterior chest. We used the cyclic mode, and set the parameters at I second ramp up, 2 seconds on, 3 seconds off. The pulse width and the frequency were set at 150 microseconds and 21 Hz, respectively. The amplitude of the output was adjusted to obtain sufficient tidal volume and to maintain PaCO2 at around 40 mm Hg. During a follow-up period up to four years, stable and sufficient ventilation was observed in all patients without any complications. Although further long follow-up is necessary, diaphragm pacing with the spinal cord stimulator is feasible and effective for the treatment of the central hypoventilation syndrome.

Clinical application of drug pump for spasticity, pain, and restorative neurosurgery: other clinical applications of intrathecal baclofen.

Intrathecal baclofen has been successfully used for control of severe spasticity. Baclofen, an agonist of GABA-B receptor, has other potential effects on pain and recovery from coma. Sporadic episodes of dramatic recovery from persistent vegetative state are reported after intrathecal administration of baclofen. There are also reports on the use of baclofen for neuropathic pain including post-stroke central pain syndrome. Baclofen is also used for control of dystonia due to cerebral palsy or reflex sympathetic dystrophy. On the other hand, epidural spinal cord stimulation has been used for pain, spasticity, dystonia, or attempt to improve deteriorated consciousness, though the effects seem variable and modest. Similarity between baclofen and spinal cord stimulation is interesting in that both involves in spinal GABAergic system. The GABAergic system in the spinal cord plays a pivotal role in various clinical effects of these procedures.

Diaphragm pacing with the spinal cord stimulator.

BACKGROUND: Diaphragm pacing with electrical stimulation of the phrenic nerve is an established treatment for central hypoventilation syndrome. The device, however, is not readily available, at least, in Japan. We applied the spinal cord stimulator for pain control to phrenic nerve stimulation. The purpose of this study is to evaluate the efficacy and feasibility of phrenic pacing with the compromise method. METHOD AND PATIENTS: We implanted a spinal cord stimulator in five patients with chronic central hypoventilation. The stimulation electrode was placed along the phrenic nerve in the neck, and the device was implanted in the anterior chest. We used the cyclic mode, and set the parameters at 1 second ramp up, 2 seconds on, 3 seconds off. The pulse width and the frequency were set at 150 microsec and 21 Hz respectively. The amplitude was adjusted to obtain sufficient tidal volume and to maintain PaCO2 at around 40 mmHg. FINDINGS: During the follow-up period from 3 to 34 months (mean 23), stable and sufficient ventilation were observed in all patients without complications. INTERPRETATION: Although longer follow-up is necessary, diaphragm pacing with the spinal cord stimulator is feasible for treatment of central hypoventilation syndrome.

High expression of the novel endothelin-converting enzyme genes, Nbla03145/ECEL1alpha and beta, is associated with favorable prognosis in human neuroblastomas.

The clinicobiological feature of neuroblastoma is enigmatic because spontaneous regression often occurs in early stages of tumors of the patients under 1 year of age, while rapid growth usually occurs in the tumors of the patients over 1 year of age. Such difference in the clinical behavior may be caused by the difference in the pattern of gene expression among the subsets of neuroblastoma. To understand the molecular basis of neuroblastoma biology, we decided to identify the novel genes expressed differentially between favorable and unfavorable neuroblastomas. The oligo-capping cDNA libraries were constructed from different subsets of neuroblastomas. After random selection and DNA sequencing, the differentially expressed genes between favorable and unfavorable neuroblastomas were screened by reverse transcriptase-PCR. The clinical significance of gene expression was evaluated based on the results of Northern blot analysis. We have identified a novel gene Nbla03145 (alpha), also cloned and termed by another group as ECEL1, which encodes a new member of putative zinc-binding metalloendopeptidase (endothelin-converting enzyme) with unknown substrate. We also cloned a COOH-terminally truncated Nbla03145/ECEL1beta which is expressed only in thymus. In primary NBLs, the alpha isoform is more preferentially expressed than the beta isoform. High levels of Nbla03145/ECEL1 expression were significantly correlated with a younger age (p=0.0005), lower stages (p=0.0019), high level of TrkA expression (p

Absence of Z-chromosome inactivation for five genes in male chickens.

In order to examine if Z-chromosome inactivation, which is analogous to X-chromosome inactivation in mammals, takes place in male birds having ZZ sex chromosomes, five Z-linked genes of chickens which are expressed in both sexes in certain tissues were selected: i.e. genes for growth hormone receptor, nicotinic acetylcholine receptor beta3, aldolase B, beta1,4-galactosyltransferase I, and iron-responsive element-binding protein (also known as cytosolic aconitase). Antisense or sense riboprobe was prepared from an intronic sequence of each gene and subjected to fluorescence in situ hybridization to nascent transcripts of each gene in a nucleus. Each antisense riboprobe hyridized to two spots of nascent RNA which corresponded to its gene loci on the two Z chromosomes in a majority of nuclei in a tissue of the male. The efficiency of detection of two spots per nucleus was comparable to that for the glyceraldehyde-3-phosphate dehydrogenase gene, an autosomal housekeeping gene. These results suggest strongly that Z-chromosome inactivation, i.e. virtual silence of transcription at one of the alleles, does not take place for these five Z-linked genes in male chickens.

Prostanoids in the preoptic hypothalamus mediate systemic lipopolysaccharide-induced hyperalgesia in rats.

The systemic administration of lipopolysaccharide (LPS), an experimental model of systemic bacterial infection is known to modulate nociception. It increases the prostaglandin E(2) (PGE(2)) levels in the preoptic area of the hypothalamus (POA) and the microinjection of PGE(2) into the POA and the neighboring basal forebrain induces hyperalgesia. We, therefore, hypothesized that the PGE(2) synthesized in these regions mediates intravenous (i.v.) LPS-induced hyperalgesia. To test this hypothesis, we microinjected cyclooxygenase (COX) inhibitors into several sites in the rat hypothalamus and observed their effects on the LPS (0.1-100 microg/kg, i.v.)-induced changes in nociceptive behavior as assessed by a plantar test. LPS (10 and 100 microg/kg, i.v.) reduced the paw-withdrawal latency at 90 min and 45-60 min after injection, respectively, both thus indicating a hyperalgesic effect. This hyperalgesia was observed only in the period before the development of fever which started 120-135 min after the LPS injection. The LPS (100 microg/kg, i.v.)-induced hyperalgesia was completely abolished by pretreatment with the microinjection of diclofenac (an inhibitor of COX-1 and 2) at 1.0 ng into the bilateral POA. Furthermore, it was also blocked by the microinjection of NS-398 (a selective COX-2 inhibitor) at 1.0 ng into the bilateral POA and the horizontal limb of the diagonal band of Broca (DBB), but not the lateral hypothalamic area, the paraventricular hypothalamic nucleus, and the ventromedial hypothalamic nucleus. These findings suggest that LPS (i.v.)-induced hyperalgesia is mediated predominantly through a COX-2 induced prostanoids in the POA and the DBB in rats.

Morphological evidence for neural interactions between leptin and orexin in the hypothalamus.

Both leptin and orexin have been recently discovered as peptides involved in feeding regulation. The morphological evidence of neural interaction between leptin and orexin, one considered to inhibit food intake and the other to stimulate it in the central nervous system (CNS), was studied by use of double immunostaining method. The leptin receptor-like immunoreactive (LR-LI) neurons in the hypothalamic arcuate nucleus and ventromedial nucleus were innervated by orexin-like immunoreactive (OX-LI) neurons. The distribution of LR-LI neurons in the hypothalamus was very similar to that of OX-LI neurons. These results may suggest that leptin and orexin are intimately correlated with each other and that they reciprocally regulate feeding at the hypothalamic level.

Molecular cloning of a novel brain-type Na(+)-dependent inorganic phosphate cotransporter.

We have isolated a human cDNA encoding a protein, designated DNPI, that shows 82% amino acid identity and 92% similarity to the human brain-specific Na(+)-dependent inorganic phosphate (Na(+)/P(i)) cotransporter (BNPI), which is localized exclusively to neuron-rich regions. Expression of DNPI mRNA in Xenopus oocytes resulted in a significant increase in Na(+)-dependent P(i) transport, indicating that DNPI is a novel Na(+)/P(i) cotransporter. Northern blot analysis shows that DNPI mRNA is expressed predominantly in brain, where the highest levels are observed in medulla, substantia nigra, subthalamic nucleus, and thalamus, all of which express BNPI mRNA at low levels. In contrast, DNPI mRNA is expressed at low levels in cerebellum and hippocampus, where BNPI mRNA is expressed at high levels. No hybridizing signal for DNPI mRNA is observed in the glia-rich region of corpus callosum. In other regions examined, both mRNAs are moderately or highly expressed. These results indicate that BNPI and DNPI, which coordinate Na(+)-dependent P(i) transport in the neuron-rich regions of the brain, may form a new class within the Na(+)/P(i) cotransporter family.

Induction of dog sperm capacitation by glycosaminoglycans and glycosaminoglycan amounts of oviductal and uterine fluids in bitches.

Ejaculated sperm collected from 12 beagle dogs were incubated in canine capacitation medium (CCM), supplemented with 5 microg/ml chondroitin sulfate A (CS), 5 microg/ml hyaluronic acid (HA), or 5 microg/ml heparin (HP) for 7 hr at 38 degrees C in a 5% CO2 in air atmosphere to investigate the effects of glycosaminoglycans (GAGs) on dog sperm capacitation. The percentages of motile sperm, hyperactivated sperm (%HY), and acrosome-reacted sperm (%AR) in all media were examined after 4 hr and 7 hr of incubation. The oviducts and uteri of 9 anestrous and 18 estrous beagle bitches were removed under halothane inhalation anesthesia to measure the total GAG amounts in oviductal and uterine fluids. The lumens of the ampulla of the oviducts, isthmus of the oviducts, and the uterine horns were each flushed with 1 ml HEPES-EDTA fluid. Total GAG amounts in the flush fluids obtained were measured with a spectrophotometer. Sperm motility (51-59%), %HY (79-86%), and %AR (31-36%) in CCM supplemented with CS, HA, or HP were significantly higher after 7 hr of incubation than when incubated in CCM without GAGs (P<0.01 or 0.05). The mean total GAG amounts in the fluids from the ampulla and isthmus of the oviducts and the uterine horns in the estrous bitches were higher than in the anestrous bitches. These results indicate that GAGs in the oviductal and uterine fluids in estrous bitches are associated with in vivo sperm capacitation.

Estimation of generator sources of human sleep spindles by dipole tracing method.

Equivalent dipole sources of two types of human sleep spindles (14 and 12 Hz) were investigated on five normal subjects. The present study showed that a sleep spindle can be represented by a single equivalent dipole. For both 14 and 12 Hz sleep spindles, the equivalent dipole sources were estimated near the thalamus. The orientation of the equivalent dipole of a 14 Hz sleep spindle was in the centro-parietal direction, while that of a 12 Hz sleep spindle was in the frontal direction. These results suggest that both types of sleep spindle activities are generated in the thalamus, and cortical de-arousal plays a modificatory role on their different topographical distributions.

Case of a non-24 h sleep-wake syndrome patient improved by phototherapy.

Polysomnography (PSG) and body temperature were examined in a patient with non-24 h sleep-wake syndrome who responded to phototherapy. The patient was a 17-year-old male who had been suffering from a free-running sleep-wake rhythm for 2 months. Phototherapy was administered to the patient while he was admitted to our hospital. This treatment immediately changed the free-running sleep-wake and body temperature rhythm of the patient to the environmental 24-h rhythm. On a polysomnography, total sleep time and stages 1 and 2 and REM sleep were decreased, and percentage stage 3+4 was increased by phototherapy. The time of minimum body temperature (mBT) was located at the latter half of the sleep phase through the clinical course of the patient.

Effects of phototherapy on the phase relationship between sleep and body temperature rhythm in a delayed sleep phase syndrome case.

We examined polysomnography (PSG) and body temperature of a patient with delayed sleep phase syndrome (DSPS) who was successfully treated with only phototherapy. This case showed a possible improvement of the phase relationship between sleep and body temperature rhythm given that the time of minimum body temperature (mBT) shifted to the latter portion of the sleep phase after constant phototherapy.

Hypothalamic mechanisms of pain modulatory actions of cytokines and prostaglandin E2.

A decrease and subsequent increase in nociceptive threshold in the whole body are clinical symptoms frequently observed during the course of acute systemic infection. These biphasic changes in nociceptive reactivity are brought about by central signal substances induced by peripheral inflammatory messages. Systemic administration of lipopolysaccharide (LPS) or interleukin-1 beta (IL-1 beta), an experimental model of acute infection, may mimic the biphasic changes in nociception, hyperalgesia at small doses of LPS, and IL-1 beta and analgesia at larger doses. Our behavioral and electrophysiological studies have revealed that IL-1 beta in the brain induces hyperalgesia through the actions of prostaglandin E2 (PGE2) on EP3 receptors in the preoptic area and its neighboring basal forebrain, whereas the IL-1 beta-induced analgesia is produced by the actions of PGE2 on EP1 receptors in the ventromedial hypothalamus. An intravenous injection of LPS (10-100 micrograms/kg) produced hyperalgesia only during the period before fever develops and was abolished by microinjection of NS-398 (an inhibitor of cyclooxygenase 2) into the preoptic area, but not into the other areas in the hypothalamus. The hyperalgesia induced by the cytokines PGE2 and LPS may explain the systemic hyperalgesia clinically observed in the early phase of infectious diseases, which probably warns the organisms of infection before the full development of sickness symptoms. The switching of nociception from hyperalgesia to analgesia accompanied by sickness symptoms may reflect changes in the host's strategy for fighting microbial invasion as the disease progresses.

Hypnagogic imagery and EEG activity.

The relationships between hypnagogic imagery and EEG activity were studied. 7 subjects (4 women and 3 men) reported the content of hypnagogic imagery every minute and the hypnagogic EEGs were classified into 5 stages according to Hori's modified criteria. The content of the hypnagogic imagery changed as a function of the hypnagogic EEG stages.

[Blood PCB analysis by capillary column-gas chromatograph/quadruple mass spectrometer--comparison with packed column-electron capture detector/gas chromatograph].

The contents of polychlorinated biphenyls (PCBs) in the blood of Yusho patients (Y) and normal subjects (N) were analyzed, using a gas-chromatograph equipped with a capillary column/quadruple mass spectrometer (capillary column GC/MS). While the average of the content of blood PCBs was 679 ppt in N, those were 2960, 1480 and 1090 ppt in Y diagnosed previously as A, B and C patterns, respectively. The contents of non-ortho coplanar PCBs (3,3',4,4' Tetra-, 3,3',4,4',5-Penta- plus 3,3',4,4',5,5'-Hexa-CB) were 0.9-2.1 ppt in Y, and 0.8 ppt in N. The contents of eight mono-ortho coplanar PCBs having the toxic equivalency factors (TEFs) were 118-424 (Y) and 78 ppt (N), respectively. The differences between Y and N in the species of mono-ortho coplanar PCBs contained were observed as follows: 2,3,3',4,4',5- and 2,3,3',4,4',5'-Hexa-CB were predominant in Y, whereas 2,3,4,4',5-Penta-CB was a major congener in N. The levels of di-ortho coplanar PCBs (2,2',3,4,4',5,5' plus 2,2',3,3',4,4'5-Hepta-CB) were determined to be 195-608 and 98 ppt in Y and N, respectively. In both groups, the content of the former isomer was greater than the latter. Total TEQ values were 0.214-1.226 ppt in Y, and 0.148 ppt in N. The analyses were also performed by a conventional method in which a GC equipped with a packed column/electron capture detector (packed column GC/ECD) was used, and the results obtained were compared with those by capillary column GC/MS method. The results showed that the total PCB levels obtained by capillary column GC/MS method were 56-61% in Y and 67% in N of those obtained by packed column GC/ECD method.

Structure, expression profile and chromosomal location of an isolog of DNA-PKcs interacting protein (KIP) gene.

A novel DNA-PKcs interacting protein, KIP (kinase interacting protein), was recently isolated using a two-hybrid analysis which showed a significant homology to calcineurin B. We found other ESTs showing significant similarity to KIP gene in the dbEST database and isolated a cDNA clone which encodes a 187 amino acid polypeptide from a human fetal brain cDNA library. This protein (termed KIP2 for kinase interacting protein 2) has sequence homology to KIP (46% identical and 64% similarity). RT-PCR analysis showed that the messenger RNA was ubiquitously expressed in various human tissues. Based on PCR-based analysis with a radiation hybrid cell panel and fluorescence in situ hybridization, the gene was localized to the q24 region of chromosome 15.

Isolation, tissue expression, and chromosomal assignment of a novel human gene which encodes a protein with RING finger motif.

We identified a novel gene encoding a RING finger (C3HC4-type zinc finger) protein from a human neuroblastoma full-length enriched cDNA library. This cDNA clone consists of 1919 nucleotides with an open reading frame of a 485-amino acid protein. From reverse transcription (RT)-polymerase chain reaction (PCR) analysis, the messenger RNA was ubiquitously expressed in various human adult tissues. The chromosomal location of the gene was determined on the chromosome 6p21.3 region by PCR-based analyses with both a human/rodent monochromosomal hybrid cell panel and a radiation hybrid mapping panel.

Neuroimmunomodulatory actions of hypothalamic interferon-alpha.

Recent studies have revealed that the brain produces interferon-alpha (IFN-alpha) in response to noninflammatory as well as inflammatory stress and that it might have a role in normal physiology. When administered intracerebrally, IFN-alpha causes diverse effects including fever, anorexia, analgesia and changes in the central neuronal activities. These responses are inhibited by the opioid receptor antagonist naloxone. This is consistent with the reports suggesting that recombinant human (rh) IFN-alpha binds to opioid receptors in rodent brain membrane. We revealed that rhIFN-alpha altered the activity of thermosensitive neurons in the medial preoptic area (MPO) and glucose-responsive neurons in the ventromedial hypothalamus in an opioid-receptor-dependent way. As a stress which produces opioid-dependent analgesia is known to suppress the cytotoxicity of splenic natural killer cells, we investigated whether the administration of beta-endorphin and rhIFN-alpha may induce a similar immunosuppression. We found that central, but not peripheral, injection of both compounds inhibited natural killer (NK) cytotoxicity. Further studies revealed that rhIFN-alpha decreased the activity of MPO neurons via opioid receptors and the altered activity of MPO neurons in turn resulted in the activation of corticotropin-releasing factor neurons, thereby suppressing NK cytotoxicity predominantly through activation of the splenic sympathetic nerve and beta-receptor mechanisms in splenocytes. Thus, IFN-alpha may alter the brain activity to exert a feedback effect on the immune system. Further detailed whole-cell clamping analyses on neuronal mechanisms in rat brain tissue slices showed that the inhibitory effect of rhIFN-alpha on N-methyl-D-aspartate-induced membrane current responses of MPO neurons was mediated not only by opioid receptors but also by the local production of reactive oxygen intermediates, nitric oxide and prostanoids, possibly due to neuron-glial cell interaction.