Functional organization of vestibulofastigial projection in the horizontal semicircular canal system in the cat

Spike potentials of fastigial nucleus neurons were recorded extracellularly in decerebrate, unanesthetized cats. The neurons responding to head rotation in the horizontal plane with a type I fashion were located mainly in the middle and caudal regions of the fastigial nucleus. Three fourth of these fastigial type I neurons were antidromically activated by stimulation of the contralateral vestibular nuclei. These neurons were excited transsynaptically from the ipsilateral vestibular nerve or nuclei. Intra cellular recordings were made from those neurons which were located in the caudal half of the fastigial nucleus and were activated antidromically from the contralateral vestibular nuclei. Stimulation of the ipsilateral vestibular nerve produced EPSPs in these neurons with latencies of 1.0-6.6 msec. The shortest conduction time along primary vestibular aggerents from the labyrinth to the ipsilateral fastigial nucleus was 0,7 msec. The EPSPs with the shortest latency of 1.0 msec were therefore postulated to be due to monosynaptic connections of primary vestibular afferents with fastigial neurons. Stimulation of ipsilateral vestibular nuclei also produced monosynaptic EPSPs in fastigial neurons. These EPSPs were facilitated by conditioning stimulation of the ipsilateral vestibular nerve, indicating the existence of polysynaptic activation of fastigial neurons from the ipsilateral vestibular nerve through the vestibular nuclei.     

Expression of estrogen receptor alpha (ER alpha) in the rat temporomandibular joint

Numerous epidemiological studies have pointed out a higher frequency of temporomandibular disorder (TMD) in women than in men, which indicates the involvement of a sex hormone, such as estrogen, in the pathogenesis of TMD. Although estrogen is known to play pivotal roles in osteoarthrosis or rheumatoid arthritis in systemic joints, there have been few reports about the role of estrogen in the temporomandibular joint (TMJ). The effect of estrogen is generally mediated by the estrogen receptors (ERs) ER alpha (the predominant type) and ER beta. In this study we examined the expression of ER alpha protein and mRNA in the TMJ of adult male rats by immunocytochemistry and in situ hybridization histochemistry. Intense ER alpha immunoreactivity was localized in the synovial lining cells, stromal cells in the articular disc, and chondrocytes in the TMJ. These ER alpha-immunopositive synovial lining cells are characteristic of cytoplasmic processes identified with confocal and immunoelectron microscopy, which indicates that they are synovial type B cells. In situ hybridization histochemistry confirmed intense signals for ER alpha in the synovial lining cells and the sublining fibroblasts at mRNA levels. The nuclei of chondrocytes showed an intense immunoreaction for ER alpha in the maturative and hypertrophic layers of the articular cartilage. In addition to the nuclear localization of ER alpha, a weak immunoreaction appeared in the cytoplasm of some ER alpha-positive cells. These findings support the hypothesis that TMJ tissue-at least in the male rat-has the potential to be an estrogen target tissue.     

Isolation,characterization and chromosomal mapping of an actin gene from the primitive red alga Cyanidioschyzon merolae

Based on the results of cytological studies, it has been assumed that Cyanidioschyzon merolae does not contain actin genes. However, Southern hybridization of C. merolae cell-nuclear DNA with a yeast actin-gene probe has suggested the presence of an actin gene in the C. merolae genome. In the present study, an actin gene was isolated from a C. merolae genomic library using a yeast actin-gene probe. The C. merolae actin gene has no intron. The predicted actin is composed of 377 amino acids and has an estimated molecular mass of 42003 Da. Southern hybridization indicated that the C. merolae genome contains only one actin gene. This gene is transcribed at a size of 2.4 kb. When Southern hybridization was performed with C. merolae chromosomes separated by pulsed-field gel electrophoresis, a band appeared on unseparated chromosomes XI and XII. A phylogenetic tree based on known eucaryote actin-gene sequences revealed that C. merolae diverged after the division of Protozoa, but before the division of Fungi, Animalia and Chlorophyta.     

Sequence analyses of the 3' genome end and NP gene of human parainfluenza type 2 virus: sequence variation of the gene-starting signal and the conserved 3' end

We cloned and determined the nucleotide sequences of cDNAs against nucleocapsid protein (NP) mRNA and the genomic RNA of human parainfluenza type 2 virus (PIV-2). The 3' terminal region of genomic RNA was compared among PIV-2, mumps virus (MuV), Newcastle disease virus (NDV), measles virus (MV), PIV-3, bovine parainfluenza type 3 virus (BPIV-3), Sendai virus (SV), and vesicular stomatitis virus (VSV), and an extensive sequence homology was observed between PIV-2 and MuV. Although no significant sequence relatedness was observed between PIV-2 and other viruses, the terminal four nucleotides were identical in the viruses compared, implying a specific role of these nucleotides on the replication of paramyxoviruses. A primer extension analysis elucidated the major NP mRNA initiation site with the sequence UCUAAGCC, which showed a moderate homology with the gene-starting consensus sequences of other paramyxoviruses. On the other hand, the NP mRNA was terminated at the nucleotide stretch AAAUUCUUUUU, and this sequence was conserved in all the PIV-2 genes, indicating that the oligonucleotides will form a part of the gene attenuation signal of PIV-2. Comparisons of NP protein sequence indicated a possible subgrouping of the paramyxoviruses into two groups, one of which is a group including PIV-2, PIV-4, MuV, and NDV, and another is a group including PIV-3, BPIV-3, and SV. This result supports an idea from our previous studies using polyclonal and monoclonal antibodies. Furthermore, our data indicated that the PIV-2 NP protein sequence was more closely related to MV and CDV than to other parainfluenza viruses, PIV-3 and SV.     

Bronchial hyperresponsiveness and airway inflammation in adolescents with asymptomatic childhood asthma

BACKGROUND: About 70% of childhood asthmatics become free of asthma-related symptoms during adolescence. Little is known about bronchial hyperresponsiveness (BHR) and airway inflammation in young adults with "outgrown" childhood asthma. METHODS: We studied 61 nonsmoking medical students (18 intermittent mild asthmatics, 23 students with outgrown childhood asthma but free of asthma-related symptoms for 10 years (asymptomatic asthmatics) and 20 healthy students). BHR and lung function were measured, and induced sputum samples analyzed for eosinophil count, eosinophilic cationic protein (ECP), granulocyte-macrophage colony stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha). RESULTS: BHR was still present in most asymptomatic asthmatics, but it was milder compared with healthy students. Only three subjects with previous asthma had no BHR and no signs of airway inflammation. Percentages of eosinophil, and ECP, TNF-alpha and GM-CSF concentrations in induced sputum of mild asthmatics and asymptomatic asthma groups were higher than in the healthy group. In asymptomatic asthmatics group, the duration of asthma, sputum eosinophil percentage, and the level of TNF-alpha in sputum correlated significantly with BHR. CONCLUSIONS: Only a few subjects with longstanding asymptomatic asthma could be considered as cured; most asymptomatic asthmatics continued to exhibit BHR and signs of airway inflammation. The outcome of childhood asthma and BHR was associated with the degree of airway inflammation and the duration of childhood asthma.     

Complete nucleotide sequence of the matrix gene of human parainfluenza type 2 virus and expression of the M protein in bacteria

The sequence of the M gene of human parainfluenza virus type 2 (PIV-2) has been determined. The sequence contained a large open reading frame with 1131 nucleotides encoding a protein with a calculated molecular weight of 42,312. Comparison of M protein sequence indicated that PIV-2 was more closely related to mumps virus and Newcastle disease virus than to other parainfluenza viruses, Sendai virus (SV), and parainfluenza virus type 3 (PIV-3), indicating a possible subdividing of the Paramyxovirus into two groups. This grouping is consistent with that obtained from analysis of the HN gene. Measles virus and canine distemper virus definitely belong to the subgroup composed of SV and PIV-3. No homology region was found in all the paramyxoviruses compared. However, a tertiary structure may be conserved in each subgroup of paramyxovirus. The M protein of PIV-2 was expressed in bacteria, and the product was recognized by a monoclonal antibody specific for the PIV-2 M protein. The bacterial-expressed protein, however, was heterogeneous and smaller in size.     

Computational studies on acquisition and adaptation of ocular following responses based on cerebellar synaptic plasticity

To investigate how cerebellar synaptic plasticity guides the acquisition and adaptation of ocular following response (OFR), a large-scale network model was developed. The model includes the cerebral medial superior temporal area (MST), Purkinje cells (P cells) of the ventral paraflocculus, the accessory optic and climbing fiber systems, the brain stem oculomotor network, and the oculomotor plant. The model reconstructed temporal profiles of both firing patterns of MST neurons and P cells and eye movements. Model MST neurons (n = 1,080) were set to be driven by retinal error and exhibited 12 preferred directions, 30 preferred velocities, and 3 firing waveforms. Correspondingly, each model P cell contained 1,080 excitatory synapses from granule cell axons (GCA) and 1,080 inhibitory synapses. P cells (n = 40) were classified into four groups by their laterality (hemisphere) and by preferred directions of their climbing fiber inputs (CF) (contralateral or upward). The brain stem neural circuit and the oculomotor plant were modeled on the work of Yamamoto et al. The initial synaptic weights on the P cells were set randomly. At the beginning, P cell simple spikes were not well modulated by visual motion, and the eye was moved only slightly by the accessory optic system. The synaptic weights were updated according to integral-differential equation models of physiologically demonstrated synaptic plasticity: long-term depression and long-term potentiation for GCA synapses and rebound potentiation for inhibitory synapses. We assumed that maximum plasticity was induced when GCA inputs preceded CF inputs by 200 ms. After more than 10,000 presentations of ramp-step visual motion, the strengths of both the excitatory and inhibitory synapses were modified. Subsequently, the simple spike responses became well developed, and ordinary OFRs were acquired. The preferred directions of simple spikes became the opposite of those of CFs. Although the model MST neurons were set to possess a wide variety of firing characteristics, the model P cells acquired only downward or ipsilateral preferred directions, high preferred velocities and stereotypical firing waveforms. Therefore the drastic transition of the neural representation from the population codes in the MST to the firing-rate codes of simple spikes were learned at the GCA-P cell synapses and inhibitory cells-P cell synapses. Furthermore, the model successfully reproduced the gain- and directional-adaptation of OFR, which was demonstrated by manipulating the velocity and direction of visual motion, respectively. When we assumed that synaptic plasticity could only occur if CF inputs preceded GCA inputs, the ordinary OFR were acquired but neither the gain-adaptation nor the directional adaptation could be reproduced.     

Mortality of silicosis patients among migrant workers

Migrant workers known in Japanese as "dekasegi" refer to workers who migrate seasonally from their town of residence to areas where work is readily available. The eastern part of Toyama Prefecture is well known as a source of migrant workers who engage in jobs associated with dust exposure such as tunnel projects. Most of these workers suffered from silicosis. A total of 695 migrant workers suffering from silicosis who had underwent health screening between 1977 and 1982 were followed until the end of 1983. For cases of death, the cause and date of death were individually confirmed on the basis of death certificates. Based on these data, the person-years of risk and cause-specific mortality rates were calculated. The mean person-years of risk per person was 4.7. During this period of observation, there were 75 deaths among these silicosis patients, giving a mortality rate of 23.0 per 1,000 person-years of risk. When classified by the Japanese roentgenographic category of pneumoconiosis, the mortality rate was 10.5 for category 1, 21.3 for category 2, 38.6 for category 3 and 49.3 for category 4. The mortality rates of categories 3 and 4 were significantly higher than those of categories 1 and 2. The highest cause-specific mortality rate among silicosis patients per 1,000 person-years was 5.2 for malignant neoplasms followed by 3.7 for pulmonary tuberculosis, 3.1 for both cardiovascular diseases and pneumoconiosis, and 2.8 for pneumonia and bronchitis. High mortality rates in the 50-69 age group were found among silicosis patients belonging to categories 3 and 4. By cause of death, the mortality rates of all malignant neoplasms (especially lung cancer), pulmonary tuberculosis, and cerebrovascular diseases were relatively high in this age group. In the 70-89 age group, the mortality rate of those belonging to categories 2, 3 and 4 was high and by cause of death the mortality rates of pneumoconiosis, pulmonary tuberculosis, all malignant neoplasms (especially lung cancer), cardiovascular diseases and pneumonia and bronchitis were high. The mortality rates of silicosis patients with abnormal findings in %VC, FEV1% and AaDO2 by pulmonary function tests tended to be higher than those of silicosis patients without such abnormalities.     

Cyclosporine and partial liver allotransplants in a simplified rat model

We designed a simplified rat model to assess the effects of cyclosporine (CsA) on liver transplants. Auxiliary liver grafts consisting of 20 per cent of the whole liver were supplied with portal inflow and the bile was drained into the stomach. The cuff technique was used routinely for both end-to-end and end-to-side venous anastomoses. The host liver was totally deprived of portal inflow. Two inbred strains of rats, LEW and F344, were used for isograft (LEW----LEW) and allograft (F344----LEW). All survivors were killed at the end of the fourth week after transplantation. During four weeks, the isografts increased by 108 per cent in wet liver weight. Animals with allograft were treated with CsA given i.m., in a daily dose of 20 and 40 mg/kg for the first ten days post transplantation. The CsA-treated rats were free from parenchymal destruction of the allograft, as was characteristic of the allograft controls. The rats given CsA in the dose of 40 mg/kg showed a 173 per cent increase in the wet liver weight of the transplant, such being greater than allografts in rats on 20 mg/kg of CsA (100 per cent) and even than isografts. These results indicate that auxiliary partial liver grafts benefit from the use of CsA not only through suppression of allorejection but through a potential "hepatotrophic effect" of the agent.     

Total hip arthroplasty using hydroxyapatite-coated cementless cup for rapidly destructive coxarthrosis: Minimum 10-year follow-up

BackgroundPerforming total hip arthroplasty (THA) as early as possible is recommended for rapidly destructive coxarthrosis (RDC) as it causes pain that becomes progressively more severe. However, acetabular bone loss remains an issue in THA. Special devices, such as a Kerboull-type plate, may be used for acetabular bone defects, but the procedure is highly invasive and often the patients are elderly, further complicating matters. We retrospectively investigated the clinical and radiographic results of THA using conventional hydroxyapatite-coated cementless cup in RDC.MethodsA total of 32 patients (35 hips) with RDC were enrolled in the study with a minimum 10-year follow-up. All THAs were performed using conventional hydroxyapatite-coated cementless cup. All patients were evaluated clinically according to the Harris hip score (HHS). Acetabular bone deficiency was classified according to the American Academy of Orthopaedic Surgeons (AAOS) classification.ResultsEleven hips (31%) were AAOS type III, and none were type IV. Total HHS significantly improved from 36.5 to 79.4 (p < 0.01). Two cups exhibited loosening. The overall implant-associated survival rate after 10 years was 91.4%.ConclusionsClinical results of THA using conventional cementless implants for patients with RDC were acceptable. Thus, THA using conventional cementless implant is an effective and safe surgery for patients with RDC, minimizing surgical stress.