Search PubMed⌕ Search

Biomedical subjects

N Hirai

Publications and source records attributed to N Hirai.

At least 109 records · Page 6Linked to original sources

A cytotoxic substance (CTS-51) produced by human buffy coat cultures stimulated by staphylococcal enterotoxin B: further characterizations and combined action with interferon.

A recently recognized unique cytotoxic substance, CTS-51, was tested for the hear or acid stability, trypsin digestion and dialysis. Moreover, influences of elevated incubation temperatures or serum concentrations of medium on the cytotoxic activity of CTS-51, and the combination effects of CTS-51 and human leucocyte interferon (HuIFN-alpha (Le)) were investigated. The cytotoxic activity of CTS-51, which is promoted by a small molecule easily passable the dialysis membrane, was found to be very stable to heat (even at 100 degrees C for 30 min) or acid (pH 2.0 for 24 hr at 4 degrees C) treatments. The treatment with 0.75% trypsin for 1 hr did not diminish the CTS-51 activity. The susceptibility of Daudi lymphoma cells to the antiproliferative action of HuIFN-alpha (Le) was further potentiated by treating the cells with CTS-51 for 16 hr. On the other hand, the CTS-51 activity which was revealed to be prescribed by its concentration in the medium, was not potentiated at 39 degrees C when compared to that at 37 degrees C in contrast to HuIFN-alpha (Le) action, and was reduced according to the increase of the fetal calf serum concentration in the medium.

Biological Products↗

Epstein-Barr virus-enhancing plant promoters in east Africa.

The extracts of a certain African plant species, Euphorbia tirucalli, were found to have markedly enhancing effects on the activation of latent Epstein-Barr virus (EBV) genomes in the EBV carrying lymphoblastoid cells and also on EBV-induced transformation of human lymphocytes. The Euphorbia tirucalli was especially noticeable in highly endemic areas of Burkitt's lymphoma (BL), an EBV-associated malignancy, in Kenya and Tanzania. The activation of the latent EBV genome and the EBV-induced transformation enhancement were also observed with the soil and drinking water taken around the plants, strongly indicating that the people living in BL endemic areas are frequently exposed to such an EBV-enhancing plant promoter substance.

Africa, Eastern↗

[Study of local shiftings of the brain stem in increased intracranial pressure by a supratentorial balloon].

The study of the mechanism of pressure transmission is important for the treatment of rapid deterioration of a patient's condition with increased intracranial pressure (ICP) from a space taking lesion in neurosurgical practice. The aim of this experiment is to clarify the mechanism of pressure transmission during supratentorial balloon inflation, by continuously monitoring local shiftings of the brain using strain gauge sensors. Mongrel dogs and macaca fuscatas were fixed in stereotaxic head frames with light anesthesia. Brain shiftings were evaluated by sensors discriminating two dimensional directions, sagittal and coronal planes, at the cerebrum. Brain stem shift was measured as displacement from the midline at the midbrain and ventro-dorsal shifting in the pons. ICP was raised by inflation of a supratentorial balloon located in the frontal lobe in one group or the temporal lobe in other group. As parameters detecting the changes in the functions of the brain stem, systemic blood pressure (SAP), respiration and pupil size were simultaneously monitored. Shifting of the brain stem occurred in four staged in both groups. During a minimum increment of ICP shifts to the antiballoon side were observed at the occipital lobe and the midbrain. The pons showed no shift in stage I. During the further inflation of the balloon stage II, the pons started to shift to the ventral side. In this stage the temporal lobe, in addition to the occipital lobe, shifted to the antiballoon side. There was a tendency for stage II to last longer for the frontal balloon than for the temporal balloon.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Antiviral and antiproliferative activities of human leukocyte interferon potentiated by cimetidine in vitro.

The influence of cimetidine on antiviral activity of leukocyte interferon (IFN-alpha (Le] was studied in plaque-reduction assays using Utrecht (U) amnion cells challenged with vesicular stomatitis virus (VSV) and in CPE inhibition assays using A549 cells challenged with encephalomyocarditis (EMC) virus and WISH cells challenged with VSV. The IFN-alpha (Le)-induced antiviral activity was slightly enhanced in cells treated with cimetidine, whereas cimetidine treatment alone did not show any antiviral effect. The observed titer (OT) was significantly higher (p less than 0.05) in cells treated with cimetidine together with IFN-alpha (Le) compared with the control without cimetidine. The effect of cimetidine on IFN-alpha (Le)-induced cell growth inhibition was studied on Daudi (a Burkitt's lymphoma cell line) and on G361 (a melanoma cell line) cells. The growth of these cells was slightly suppressed by cimetidine alone. When cells were treated with IFN-alpha (Le)/cimetidine, the cell growth inhibition rates were significantly higher (p less than 0.02) than the rates obtained with IFN-alpha (Le) or cimetidine alone. These results indicate that cimetidine can enhance the antiviral as well as the antiproliferative activities of IFN-alpha (Le) in "in vitro" studies.

Cell Division↗

Cimetidine enhances interferon induced augmentation of NK cell activity and suppresses interferon production.

Effects of cimetidine on the augmentation of natural killer (NK) cell activity by human leukocyte interferon (Hu IFN-alpha (Le] and on the IFN production from donor leukocytes were investigated in vitro. NK cell activity of PBL was suppressed after 16 hours pretreatment with 0.3, 3.0, and 30.0 micrograms/ml of cimetidine. On the other hand, there was dose dependent suppression of Hu IFN-alpha (Le) production in PBL by cimetidine. The NK cell activity of PBL augmented by Hu IFN-alpha (Le) was further enhanced when the effector cells were pretreated with cimetidine or when cimetidine was added together with IFN. K562, G361, and PLC/PRF/5 cells were used as target cells. Our results suggest that a 16 hour treatment with cimetidine alone may suppress NK cell activity of PBL, probably due to reduced IFN production by leukocytes. On the other hand, cimetidine may enhance the IFN induced NK augmentation in PBL in vitro.

Cells, Cultured↗

Effects of cimetidine on various biological activities of human leucocyte interferon and on interferon production in lymphocytes.

In vitro effects of cimetidine on the antiviral, the antiproliferative and the natural killer (NK) cell stimulating activities of human leucocyte interferon (IFN-alpha (Le], and on the Sendai virus induced interferon production in lymphocytes were investigated. The antiviral activity of IFN-alpha (Le) was dosedependently enhanced by cimetidine, which alone did not demonstrate any antiviral action. The observed titer of the same IFN preparation titrated with 60 micrograms/ml of cimetidine was significantly higher (p less than 0.05) than that without cimetidine. Cimetidine slightly but dosedependently inhibited the growth of Daudi or G-361 cells. The combination effects of these two agents were revealed to be statistically additive or synergistic. The NK cell activity of peripheral blood lymphocytes (PBL) was suppressed after a 16 hr pretreatment with cimetidine. Furthermore, the interferon production in normal lymphocyte cultures was suppressed dosedependently by cimetidine. On the other hand, the augmentation of the NK cell activity by interferon was further potentiated by cimetidine.

Cell Division↗

A cytotoxic substance (CTS-51) produced by human buffy coat cultures stimulated by staphylococcal enterotoxin B: specificity to malignant cells and kinetics of action.

A unique cytotoxic substance (CTS-51), which is rather specific to malignant cell cultures in vitro, was found to be produced together with human immune interferon and interleukin-2 in buffy coat cultures stimulated with staphylococcal enterotoxin B. CTS-51, which is stable at 100 degrees and has a molecular weight of 8,000-10,000, was found to have biological properties distinct from those of known cytotoxic cytokines. CTS-51 was able to kill four human malignant cell lines at concentrations that did not affect normal or non-malignant cell lines. The mode of CTS-51 action was found to be cytotoxic rather than cytostatic. Several kinetic studies showed that the cell killing activity seemed to be dose-dependent, and the appearance of the activity required about 24 hr. The minimum effective exposure time of the target cells to CTS-51 also seemed to be dose-dependent.

Cell Cycle↗

[Evaluations of regional cerebral blood flow (rCBF) by 133Xenon i.v. method in patients with occlusions of bilateral internal carotid arteries].

The studies of changes in regional blood flow (rCBF) have been reported on different clinical courses in the five cases (mean 57.4 y.o.) showing bilateral occlusion or stenosis of internal carotid arteries. Values of rCBF using Fg (fast component in gray matter) were closely correlated with their clinical courses. The three patients (2 males and 1 female) showed bilateral focal decreased patterns of rCBF and their uneventful clinical courses except for mild attacks of transient cerebral ischemia. However, the rest two male patients showed bilateral decreased pattern of rCBF and moderate hemiparesis including attacks of loss of consciousness. The one died suddenly because of the thalamic hemorrhage and the other died also suddenly from the unknown etiology. Such differences between the classification of clinical course and hemodynamics evaluated by rCBF was discriminated more clearly by Fg (fast component in gray matter) than by F mean (mean rCBF). The authors concluded that the evaluation by Fg may be valuable to estimate prognosis of patients with bilateral occlusion of internal carotid artery. There are two patterns of decreased rCBF in our study. The patients with bilateral diffuse decreased patterns of rCBF should be followed up more carefully because of the sudden death from cerebral hemorrhage.

Aged↗

[Clinical studies on cefoxitin in the field of obstetrics and gynecology].

Clinical studies were done on cefoxitin (CFX), the first cephamycin antibiotic, in the field of obstetrics and gynecology and following results were obtained. CFX was administrated by intravenous drip infusion for average 6.9 days at a daily dose of 2--6 g to 58 patients; 15 with intrauterine infections, 5 with intrapelvic infections, 11 with adnexitis, 3 with mastitis, 5 with urinary tract infections, 2 with other infections and 17 for prophylaxis of postoperative infections. The clinical results were excellent in 8 cases, good in 39 cases, fair in 4 cases, poor in 6 cases and unknown in 1 case, with the efficacy of 82.5%. Total bacteriological effective rate was 88.9%. As to side effects, eruption was observed only in 1 case. From the results of the present study, the usefulness of CFX was demonstrated in the field of obstetrics and gynecology.

Adult↗

Biological and immunological properties of native species of human leukocyte interferon.

The successful purification of the native species of human leukocyte interferon (Hu IFN - alpha) has made it possible to perform a detailed biological immunological analysis which has been disclosed that the human interferon alpha species are represented by 13 individually separated species having molecular weights in the range of 16.6 to 33.5 kD (1-3). The stained interferon proteins were eluted individually from the gel slices and assessed for antiviral activity in the human, monkey and bovine cells, as well as for immunomodulatory effect in vitro on human lymphocytes. Interferon titrations were performed in human and in bovine cells and it was disclosed that one interferon species did not have any activity in the human system, at all (2). In contrast to the human activity, the bovine activity in each Hu IFN - alpha species increased along with decreasing molecular weights. Based on equal amounts of human interferon units, the "immunological efficacy" of the 13 different human IFN alpha species yielded the following in cellular immune systems (4): 1) potentiation of the natural killer cell (NK) function was a property of all species, although the two lower species (16.6 kD and 16.9 kD) were clearly less efficient having "titers" in the NK system reduced 25-fold; 2) enhanced expression of HLA on lymphocyte membranes was induced by all of the Hu IFN alpha species to the same extent; and, 3) addition of interferon to mixed lymphocyte reaction (MLR) augmented the cytotoxic mediated lympholysis (CML) outcome of the cultures. In this system all 13 species exerted their effort equally well.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A physiological study of identification, axonal course and cerebellar projection of spinocerebellar tract cells in the central cervical nucleus of the cat.

Spinocerebellar tract (SCT) neurones in and around the central cervical nucleus (CCN) were physiologically identified by antidromic activation of these cells on stimulation of the cerebellum. Among the spinocerebellar tract cells thus identified, those ascending the contralateral spinal funiculi were found in the CCN and ventralwards, whereas those ascending the ipsilateral funiculi existed mostly dorsal to the CCN partly overlapping with crossed cells in the nucleus. Mapping sites from which CCN cells were antidromically activated showed that axons of the CCN-SCT cross at the same segment, ascend the ventral funiculus initially, the lateral funiculus at rostral C1 and the lateral border of the medulla to reach the cerebellar peduncle, enter the cerebellum mainly via the restiform body but possibly also via the superior peduncle. Systematic mapping of stimulation within the cerebellum indicated that the CCN-SCT projects to the medial part of the anterior lobe and the posterior lobe bilaterally. Projection to lobules I-II was found in almost all CCN-SCT cells examined. Three fourths of CCN-SCT cells projected to the posterior lobe, as revealed by less extensive mapping. Mapping of axonal regions of the same single CCN-SCT cells showed that they project multifocally in the cerebellum, where projection to lobules I-II was common and that to other areas varied with individual cells. Conduction velocities decreased within the cerebellum probably as the result of repeated branching. Mossy fibre responses evoked on stimulation of the C2 dorsal root in cats with the transected dorsal funiculi were shown to be mediated mostly via the CCN-SCT. Mapping the field potential showed that the response was by far the largest in lobules I-II. This suggested that the terminals provided by the CCN-SCT are the densest in these lobules.

Afferent Pathways↗

Neck muscle afferent input to spinocerebellar tract cells of the central cervical nucleus in the cat.

Extracellular and intracellular recordings were made from spinocerebellar tract neurones of the central cervical nucleus (CCN) in C1-C3 segments of the anaesthetized cat. These neurones were identified by antidromic activation from the cerebellar peduncle. Stimulation of the ipsilateral dorsal root elicited extracellular spikes or EPSPs with a monosynaptic latency in almost all CCN neurones in the same segment (segmental input). Late excitatory effects were also observed in about one third of CCN neurones. The monosynaptic EPSP was occasionally followed by an IPSP. The excitatory input from the dorsal root to CCN neurones was extended over several segments for some CCN neurons (extrasegmental input). Monosynaptic excitation was evoked in CCN neurones after stimulation of dorsal neck muscle nerves as well; i.e. splenius (SPL), biventer cervicis and complexus (BCC), rectus capitus dorsalis, and obliquus capitus caudalis. Thresholds for this excitation were near the threshold of the nerve, suggesting that it originated from group I fibres. The component of excitation added after strong stimulation of neck muscle nerves would be attributed to group II fibres. When a CCN neurone received excitatory input from the nerve of one muscle, it was generally not affected by stimulation of other nerves in the same segment. Such muscle specificity of segmental input was the principal pattern of connexion of neck muscle afferents with CCN neurones. In some cases, however, excitatory convergence from SPL and BCC nerves onto single CCN neurones or excitation from the SPL nerve and inhibition from the BCC nerve were also observed. Nearly half of the CCN neurones received input from one muscle nerve of the same segment and not from the afferent of the same muscle of different segments, indicating a segment specificity of input. In the remaining CCN neurones, weaker excitatory effects were induced from afferents of different segments as well. In such extrasegmental effects, inputs to CCN neurones from caudal segments predominated in frequency over those from rostral segments. The origin of extrasegmental input was generally confined to the same muscle. Low threshold muscle afferents from the SPL and BCC were intraaxonally stained with HRP. The collaterals of the stained fibre distributed branchlets and terminals to the CCN, laminae VII, VIII, and motor nuclei. Two fibres responding to local muscle prodding or stretch showed a similar morphology. The findings indicated that muscle spindle afferents from primary endings projected to the CCN.

Afferent Pathways↗

Superior vestibular nucleus neurones related to the excitatory vestibulo-ocular reflex of anterior canal origin and their ascending course in the cat.

Stimulation of the superior vestibular nucleus and the anterior canal nerve evoked mono- and disynaptic excitatory postsynaptic potentials, respectively, in contralateral inferior oblique motoneurones of the cat. Combined stimulation revealed that the superior vestibular nucleus relayed excitatory anterior canal signals to the motoneurones. Thirty-six superior vestibular neurones receiving anterior canal inputs were activated antidromically by microstimulation of the contralateral inferior oblique motoneurone pool. Their axons ascended neither in the brachium conjunctivum nor in the medial longitudinal fasciculus, but proceeded rostrally in the ventral part of the brain stem.

Animals↗

Axon collaterals of anterior semicircular canal-activated vestibular neurons and their coactivation of extraocular and neck motoneurons in the cat.

We studied the ascending and descending axonal trajectories of excitatory vestibular neurons related to the anterior semicircular canal, by means of local stimulation and spike-triggered signal averaging techniques in anesthetized cats. More than 200 vestibular neurons related to the ampullary nerve of the anterior semicircular canal (ACN) were identified as vestibulo-ocular neurons by antidromic stimulation of the contralateral inferior oblique (IO) muscle motoneuron pool. In the descending, medial and ventral lateral nuclei, about 60% of these vestibulo-ocular neurons were also activated antidromically by upper cervical spinal cord stimulation (vestibulo-ocular-collic (cervical) = VOC). These VOC neurons produced unitary EPSPs in the majority of neck extensor motoneurons located at the C1 segment. None of the VOC neurons had axons descending as far as the thoracic level. Most of these VOC neurons were activated monosynaptically following stimulation of the ACN. The conduction velocity of the descending axons of VOC neurons was approximately 63 m/s, which was significantly faster than that of the ascending axons. The remaining 40% of the vestibulo-ocular neurons were not activated antidromically following spinal cord stimulation at intensities of 1 mA or more (vestibulo-ocular = VO). Most of the VO neurons were activated polysynaptically by ACN stimulation. The superior vestibular nucleus contained VO neurons that were activated mono- and polysynaptically following ACN stimulation.

Animals↗

Floccular influence on excitatory relay neurones of vestibular reflexes of anterior semicircular canal origin in the cat.

Floccular influence on excitatory vestibular reflex arcs of anterior semicircular canal origin was examined in the anaesthetized cat. Stimulation of the anterior semicircular canal nerve (ACN) evoked disynaptic excitatory postsynaptic potentials (EPSPs) in all sampled inferior oblique (IO), superior rectus (SR), and biventor cervicis (BIV) muscle motoneurones of the contralateral side. Conditioning stimulus to the flocculus depressed the amplitude of the EPSPs in both IO and SR motoneurones by 50% on the average but not in any BIV motoneurones. The excitatory vestibulo-ocular neurones identified by orthodromic and antidromic responses to stimulation of the ACN and the contralateral IO motoneurone pool, respectively, were classified as VOC (vestibulo-ocular neurones with axons descending to the cervical segment) or VO (vestibulo-ocular proper) neurones on the basis of whether or not they responded antidromically to stimulation of the spinal cord in the C1 segment. All of the VO neurones in the superior vestibular nucleus (n = 19) were inhibited from the flocculus while the activities of three-fourths of the VO neurones (36/48) in the other vestibular nuclei were not suppressed by floccular stimulation. In contrast, none of VOC neurones (n = 49) received floccular inhibition. Besides inhibition, floccular stimulation induced the antidromic or orthodromic responses in some VO and VOC neurones.

Animals↗

Temperature influences on different human alpha interferon activities.

Influences of different incubation temperatures within the physiological range on three different biological activities of human leukocyte-derived alpha interferon (IFN) (the antiviral effect, the antiproliferative activity, and the augmentation of natural killer cell (NK) activity) were investigated in vitro. Using the plaque-reduction assay (U cells challenged with VSV), the antiviral activity by IFN was found to be lower at 35 degrees C and higher at 38 degrees C and 39 degrees C than at 37 degrees C. Using the CPE (cytopathogenic effect) inhibition technique (Vero cells challenged with VSV), the antiviral activity was slightly enhanced at 38 degrees C, 39 degrees C, and 40 degrees C, respectively, when compared with 37 degrees C. The antiproliferative activity on Daudi cells and G-361 melanoma cells was enhanced at elevated temperatures. On the other hand, the antiproliferative activity on PLC/PRF/5 hepatoma cells was lower at 38 degrees C and 39 degrees C than at 37 degrees C, but higher at 40 degrees C. NK activity of PBL after 2 h incubation at 41 degrees C was remarkably lower than that at 37 degrees C, while it was not affected by 2 h incubation at 35 degrees C and 39 degrees C, respectively. When PBL was treated with IFN for 2 h at the temperatures described above, NK activity was equally augmented at all temperatures tested. Our results suggest that elevated incubation temperature potentiates the antiviral and the antiproliferative activities, but does not affect the NK augmenting activity of HuIFN-alpha (Le).

Cell Division↗