Distribution of respiration-related neuronal activity in the thoracic spinal cord of the neonatal rat: An optical imaging study.

The inspiratory motor outputs are larger in the intercostal muscles positioned at more rostral segments. To obtain further insights into the involvement of the spinal interneurons in the generation of this rostrocaudal gradient, the respiratory-related neuronal activities were optically recorded from various thoracic segments in brainstem-spinal cord preparations from 0- to 2-day-old rats. The preparation was stained with a voltage-sensitive dye, and the optical signals from about 2.5s before to about 7.7s after the peak of the C4 inspiratory discharge were obtained. Respiratory-related depolarizing signals were detectable from the ventral surface of all thoracic segments. Since the local blockage of the synaptic transmission in the thoracic spinal cord induced by the low-Ca(2+) superfusate blocked all respiratory signals, it is likely that these signals came from spinal neurons. Under the-low Ca(2+) superfusate, ventral root stimulation, inducing antidromic activation of motoneurons, evoked depolarizing optical signals in a restricted middle area between the lateral edge and midline of the spinal cord. These areas were referred to as 'motoneuron areas'. The respiratory signals were observed not only in the motoneuron areas but also in areas medial to the motoneuron areas, where interneurons should exist; these were referred to as 'interneuron areas'. The upper thoracic segments showed significantly larger inspiratory-related signals than the lower thoracic segments in both the motoneuron and interneuron areas. These results suggest that the inspiratory interneurons in the thoracic spinal cord play a role in the generation of the rostrocaudal gradient in the inspiratory intercostal muscle activity.

Transient O2-dependent effects of CO2 on ventilation in the anesthetized mouse.

In this study we sought to determine the effects of background hyperoxia on the ventilatory response to hypercapnia. We addressed this issue by examining the temporal profile of the first minute transients of minute ventilation, and its frequency and tidal components, in response to 5% and 10% CO2 each co-applied with the natural (balanced with air) and hyperoxic (balanced with O2) levels of oxygen. The study was performed on the urethane-anesthetized, tracheostomized, spontaneously breathing mouse, placed in a flow-through body plethysmograph. We identified an early suppressant effect of CO2-in-O2 on breathing frequency. The frequency declined to 88.5 +/-1.4% and 87.8 +/-1.9% relative to the pre-test, baseline level for 5% and 10% CO2, respectively. There was a compensatory rise in tidal volume and no major change in the overall ventilation. In contrast, CO2-in-Air resulted in ventilatory stimulation caused in equal measure by frequency and tidal components. Thus, the inhibitory effect on breathing frequency of the CO2-in-O2 resulted from the O2 content in the mixture and had the temporal characteristics consistent with carotid body function. In conclusion, transient O2-dependent effects can bear on the nascent hypercapnic ventilatory response. The complexity of the O2-CO2 interaction regarding the breathing pattern components should be taken into account while designing the optimal conditions for a hypercapnic test.

Involvement of central histaminergic neurons in polypnea induced by hyperthermia in rabbits.

A role of central histamine in the preoptic area/anterior hypothalamus (POA/AH) for the regulation of hyperthermia-induced polypnea was examined in anesthetized, paralyzed, vagotomized and artificially ventilated rabbits. Phrenic nerve activities were recorded to monitor respiratory neuronal output. Hyperthermia increased respiratory frequency by reductions of inspiratory time (T(I)) and expiratory time (T(E)). Pyrilamine, an H1 receptor antagonist, which was applied to the POA/AH reduced polypnea under hyperthermia. The effect of S+alpha-fluoromethylhistidine, a specific inhibitor of histidine decarboxylase, applied in a lateral ventricle was comparable to the effect of pyrilamine on polypnea. Moreover, histamine dihydrochloride applied into the POA/AH at a normal body temperature produced polypnea by reductions of T(I) and T(E). The results suggest that central histamine in the POA/AH contributes to the generation of polypnea in hyperthermia through H1 receptors.

Intervention of thymus and activation-regulated chemokine attenuates the development of allergic airway inflammation and hyperresponsiveness in mice.

Thymus- and activation-regulated chemokine (TARC; CCL17) is a lymphocyte-directed CC chemokine that specifically chemoattracts CC chemokine receptor 4-positive (CCR4(+)) Th2 cells. To establish the pathophysiological roles of TARC in vivo, we investigated here whether an mAb against TARC could inhibit the induction of asthmatic reaction in mice elicited by OVA. TARC was constitutively expressed in the lung and was up-regulated in allergic inflammation. The specific Ab against TARC attenuated OVA-induced airway eosinophilia and diminished the degree of airway hyperresponsiveness with a concomitant decrease in Th2 cytokine levels. Our results for the first time indicate that TARC is a pivotal chemokine for the development of Th2-dominated experimental allergen-induced asthma with eosinophilia and AHR. This study also represents the first success in controlling Th2 cytokine production in vivo by targeting a chemokine.

Central histamine contributed to temperature-induced polypnea in mice.

Breathing pattern is influenced by body temperature. However, the central mechanism for changing breathing patterns is unknown. Central histamine is involved in heat loss mechanisms in behavioral studies, but little is known about its effect on breathing patterns. We examined first the effect of body temperature on breathing patterns with increasing hypercapnia in conscious mice and then that of the depletion of central histamine by S(+)-alpha-fluoromethylhistidine hydrochloride (alpha-FMH) (100 mg/kg ip), a specific inhibitor of histidine decarboxylase, at normal and raised body temperatures. A raised body temperature increased respiratory frequency with reductions in both inspiratory and expiratory time and decreased tidal volume. On the other hand, alpha-FMH lowered respiratory frequency with a prolongation of expiratory time at the raised temperature; however, this was not observed at a normal temperature. These results indicate that central histamine contributes to an increase in respiratory frequency as a result of a reduction in expiratory time when body temperature is raised.

Lack of temperature-induced polypnea in histamine H1 receptor-deficient mice.

Breathing patterns are influenced by body temperature. However, the central mechanism for changes of breathing patterns is unknown. We previously showed that central histamine contributed to temperature-induced polypnea in mice (Izumizaki, M., Iwase, M., Homma, I., Yanai, K., Watanabe, T. and Watanabe, T., Central histamine contributed to the temperature-induced polypnea in mice, Neurosci. Res., 23 (1999) S282). In this study we examined the role of central histamine H1 receptors in temperature-induced polypnea using wild and mutant mice lacking histamine H1 receptors. Breathing patterns were characterized at two different body temperatures during hypercapnia under conscious conditions. In wild mice a raised body temperature increased respiratory frequency mainly due to a reduction in expiratory time, whereas in mutant mice respiratory frequency did not increase even though the body temperature was elevated. These results indicate that central histamine contributes to an increase in respiratory frequency due to a reduction in expiratory time through histamine H1 receptors when body temperature is raised.

[A case of AIDS with disseminated Mycobacterium kansasii infection in which Mycobacterium, avium complex was also detected from his sputum repeatedly].

A 43 year-old Japanese male was admitted to our hospital because of productive cough and fever. He was diagnosed as acquired immunodeficiency syndrome (AIDS) in 1994. Laboratory findings were as follows: WBC was 3200/microliter, CD4+ T lymphocyte count was 22/microliter. His chest X-ray film taken on admission showed infiltration with small cavity lesion in middle left lung field. Tuberculin skin reaction was negative. He was treated with isoniazid 0.4 g, rifampicin 0.45 g, and ethambutol 0.75 g each daily. Sputum smear was positive for acid fast bacilli. The cultured isolates were identified as Mycobacterium kansasii (M. kansasii) and Mycobacterium avium complex (MAC). Urine smear was also positive for acid fast bacilli. The cultured isolates were identified as M. kansasii. He was diagnosed as disseminated M. kansasii infection and suspected MAC infection. About one hundred days later, his chest X-ray film showed reticular shadow. His clinical symptoms improved and the sputum smear and culture converted to negative for acid fast bacilli. Based on these findings, his MAC discharge was considered not as MAC infection, but MAC colonization. He returned to the former hospital for AIDS treatment, and he died in August 1996.

[Prevalence of coexisting diabetes mellitus among patients with active pulmonary tuberculosis].

We investigated the prevalence of coexisting diabetes mellitus among patients with active pulmonary tuberculosis by the time of admission, sex and age among 2659 active pulmonary tuberculosis patients admitted to National Chiba Higashi Hospital during the 8 years period from 1987 to 1994. Out of total patients, 352 patients were diagnosed as having coexisting diabetes mellitus and the rate was 13.2%. Prevalence of coexisting diabetes mellitus among active pulmonary tuberculosis during the period from 1991 to 1994 was significantly higher than that from 1987 to 1990. The prevalence in male was higher than that in female significantly. The prevalence was particularly higher in male of 40s (22.0%), and 50s (21.3%), than that in the other age groups.

[A case of AIDS with miliary tuberculosis].

A 22 year-old Thai male was admitted to our hospital because of chest pain and dyspnea. In 1989, he met with a traffic accident and was injured his head and the arm, and was given a blood transfusion in Thai. Laboratory examinations on admission revealed that serolopositivity for HIV, and CD4+T lymphocyte count was 17/microliter. Chest X-ray on admission showed bilateral diffuse nodular shadow, and he was diagnosed as miliary tuberculosis with AIDS. On the chest X-ray, in the right upper middle lung fields, the shadow was rough and partly influent. In the left lung, the nodular shadow were smaller and distributed evenly. As there was a difference in the distribution of nodular shadows between the left and right lung, the chest X-ray findings of this case was atypical of miliary tuberculosis.

[A study on the background factors of cases died of pulmonary tuberculosis detected by symptomatic visit].

Forty three patients detected by symptomatic visit and died of active pulmonary tuberculosis were investigated on their social background factors. As to age of 43 cases, 17 cases (40%) were fortieth of fiftieth; namely in young productive age. Sixteen were male and 13 cases lived alone and thirteen cases had no regular occupation when they were admitted. Three were too serious to talk about their case histories. Among other 13 cases, none visited a hospital within three months from the appearance of their symptoms and 8 cases visited a hospital after six months or long from the appearance of their symptoms. Thus, the patient's delay was obvious, and this was actually the cause of death in this cases.

[A case of posterior tuberculous spondylitis of the lumbar vertebra with the skull inoculated by acupuncture].

A 77-year-old male consulted an orthopedist with complaints of lumbago and a lumbar swelling, and was treated with acupuncture. As the symptoms deteriorated, and smear of a specimen aspirated from the lumbar swelling was positive for acid fast bacilli which were later identified as Mycobacterium tuberculosis, he was hospitalized in the National Chiba Higashi Hospital. On admission to our hospital, CT-scan of lumbar vertebrae showed the destructive change of spinous process of the third lumbar vertebra accompanied by the abscess formation, and an occipital swelling with the destructive change of skull was also detected. Whole body examinations with CT-scan and bronchoscopy did not reveal any other abnormal findings suspective of tuberculous lesions. The above lesions were both gradually improved by antituberculous chemotherapy with INH, RFP, and EB. He was finally diagnosed as posterior tuberculous spondylitis of the lumbar vertebra with cold abscess, and also clinically diagnosed as skull tuberculosis caused presumably by the inoculation of tubercle bacilli from the lumbar lesion by acupuncture.