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Biomedical subjects

T Morinaga

Publications and source records attributed to T Morinaga.

At least 55 records · Page 3Linked to original sources

Effect of conventional mechanical ventilation and jet ventilation on airway pressure in dogs and plastic models with tracheal stenosis.

OBJECTIVE: To evaluate the effect of jet ventilation on tracheal stenosis in dogs and plastic models. DESIGN: Prospective, randomized trial in dogs, and multitrial tests in tracheal stenosis models. SETTING: Animal laboratory in a university setting. INTERVENTIONS: Tracheal stenosis was surgically created around the middle of the trachea. Conventional mechanical ventilation and jet ventilation were compared at the same value of Paco2 in dogs and at the same tidal volume in tracheal stenosis models. SUBJECTS: Twelve mongrel dogs and four types of plastic models with combinations of short or long stenosis and fluid or nonfluid stenosis. MEASUREMENTS AND MAIN RESULTS: Canine Studies. Mean peak peak airway pressure values at the distal and proximal portion of the stenosis, and the end-expiratory pressure at the distal portion of the stenosis, were significantly higher during conventional mechanical ventilation than during jet ventilation. The mean values of arterial pressure, pulmonary arterial pressure, central venous pressure, and cardiac output did not change significantly between conventional mechanical ventilation and jet ventilation, except for the pulmonary artery occlusion pressure valve. Plastic Mold Studies. peak airway pressure and end-expiratory airway pressure at the poststenotic trachea during jet ventilation with the model lung were significantly lower than during conventional mechanical ventilation. The difference in peak airway pressure, and end-expiratory airway pressure values between jet ventilation and conventional mechanical ventilation increased more in short stenosis and nonfluid stenosis. CONCLUSIONS: The jet flow that struck the portion of the stenosed wall reversed direction, even during early expiration. Therefore, the expiration during jet ventilation was facilitated more by the reversed flow than by the expiration during conventional mechanical ventilation. This reversed flow may provide lower end-expiratory airway pressure at the poststenotic portion with jet ventilation than with conventional mechanical ventilation. We conclude that jet ventilation was a useful method of ventilation in cases with tracheal stenosis, especially nonfluid and short stenosis.

Animals↗

[Reproductive and developmental toxicity studies of prulifloxacin (NM441)(1)--A fertility study in rats by oral administration].

A study of fertility and fetal development of prulifloxacin, a new antibacterial agent, was conducted in Sprague-Dawley rats. Male rats were given the drug orally from 63 days before mating to the end of the mating period. Female rats were given from 14 days before mating to day 7 of pregnancy. The dose levels for both males and females were 0 (control), 30, 170 and 1000 mg/kg. The females were sacrificed on day 20 of pregnancy for examination of their fetuses. In the 170 mg/kg group, water consumption increased in the female rats, and food consumption decreased and the cecum increased in weight and was enlarged in the males and the females. In the 1000 mg/kg group, body weight gain was suppressed in the males, and food consumption decreased, water consumption increased and cecum increased in weight and enlarged in the males and the females. Moreover, this dose caused white spots and rough surface of the kidney in the males. Prulifloxacin had no adverse effects on reproductive function of the parent animals, and also on development of the fetuses. These results show that the NOAEL of prulifloxacin are 30 mg/kg for general toxicity in parent animals, 1000 mg/kg for reproductive function of parent animals and for development of fetuses.

Administration, Oral↗

[Reproductive and developmental toxicity studies of prulifloxacin (NM441)(2)--A teratogenicity study in rats by oral administration].

A study of the effect of prulifloxacin, a new antibacterial agent, during the period of organogenesis was conducted in Sprague-Dawley rats. Female rats were given prulifloxacin orally at dose levels of 0 (control), 30, 300, and 3000 mg/kg from day 7 to day 17 of pregnancy. Twenty-four or twenty-five female rats per dose level were sacrificed on day 20 of pregnancy for examination of their fetuses, and the pregnant rats (12-15 per dose levels) were allowed to deliver naturally for postnatal examination of their offspring. In the 300 or 3000 mg/kg groups, the food consumption decreased and water consumption increased in the dams. In the 3000 mg/kg group, the body weight gain was suppressed in the dams. In the 300 and 3000 mg/kg groups, the weights of cecum increased and the enlargement of cecum was observed. In the 3000 mg/kg group, white spots and rough surface of the kidney and renal tubular nephrosis with crystalline substance were observed and the weight of the kidney increased in the dams, and the body weight decreased and retarded ossifications in the fetuses. Prulifloxacin had no effect on the number of corpora lutea and implantations, or on fetal mortality, sex ratio, or external and visceral development of the fetuses. Prulifloxacin also did not affect delivery and the number of live newborns and birth index, or have any adverse effects on the postnatal development of the first generation offspring (F1) such as differentiation, functional development, emotionality, motor ability, learning ability or reproductive performance. Prulifloxacin also had no adverse effects of the second generation offspring (F2). These results show that the NOAEL of prulifloxacin are 30 mg/kg for general toxicity in mother animals, 3000 mg/kg for pregnancy and delivery of mother animals and 300 mg/kg for development of their offspring.

Abnormalities, Drug-Induced↗

[Reproductive and developmental toxicity studies of prulifloxacin (NM441)(3)--A teratogenicity study in rabbits by oral administration].

A study of the effect of prulifloxacin, a new antibacterial agent, during the period of organogenesis was conducted in New Zealand White rabbits. Female rabbits were given prulifloxacin orally at dose levels of 0 (control), 10, 30 and 100 mg/kg from day 6 to 18 of pregnancy. Female rabbits were sacrificed on day 29 of pregnancy for examination of their fetuses. In the 30 mg/kg group, food and water consumption decreased. In the 100 mg/kg group, soft stool was observed and body weight gain, food consumption and water consumption decreased. Premature delivery (2/16) occurred and enlargement of cecum and increased weight of cecum were observed. The number of fetal death increased in the 100 mg/kg group. However, prulifloxacin had no effects on the number of corpora lutea, implantations and live fetuses, and on body weight, placental weight, sex ratio, and external, visceral and skeletal development of live fetuses. These results show that the NOAEL of prulifloxacin are 10 mg/kg for general toxicity in mother animals, 30 mg/kg for pregnancy of mother animals and for development of fetuses.

Abnormalities, Drug-Induced↗

[Reproductive and developmental toxicity studies of prulifloxacin (NM441)(4)--A perinatal and postnatal study in rats by oral administration].

A peri- and postnatal study of prulifloxacin, a new antibacterial agent, was conducted in Sprague-Dawley rats. Female rats were given prulifloxacin orally at dose levels of 0 (control), 30, 100 and 300 mg/kg from day 17 of pregnancy to day 21 after delivery. All pregnant rats were allowed to deliver naturally for postnatal examination of their offspring. Food consumption in the period of pregnancy decreased in the dams given 100 and 300 mg/kg, and food and water consumption during lactational period increased in the dams given 300 mg/kg. The weight of the cecum of the dams increased in 100 and 300 mg/kg groups, and these doses caused enlargement of the cecum. Prulifloxacin had no effects on general sign, delivery, nursing, body weight gain, and kidney. Prulifloxacin also did not affect the number of live newborns and birth index, and have any adverse effects on the postnatal development of the first generation offspring (F1) such as differentiation, functional development, emotionality, motor ability, learning ability and reproductive performance. Prulifloxacin also had no adverse effects on the second generation offspring (F2). These results show that the NOAEL of prulifloxacin are 30 mg/kg for general toxicity in mother animals, 300 mg/kg for pregnancy and delivery of mother animals and development of their offspring.

Administration, Oral↗

Neural connection between the ventral portion of the lumbar intervertebral disc and the groin skin.

This study was designed to investigate neural mechanisms of referred pain in lumbar intervertebral disc lesions. Patients with a degenerative disc in lower lumbar segments occasionally complain of groin pain, which cannot be explained anatomically as having a radicular origin. In rats pretreated with intravenous application of Evans blue dye, the dye extravasation appeared in the groin skin after application of capsaicin to the ventral portion of the L5-6 intervertebral disc. This response occurred even in rats with a sectioned L-5 spinal nerve and sympathetic trunks, but did not occur in rats with a sectioned genitofemoral nerve. Capsaicin topically applied to the sciatic nerve did not cause dye extravasation in the hindpaw. Therefore, groin dye extravasation was not due to a direct effect of capsaicin but, rather, presumably was caused by an "antidromic axon reflex" of dichotomizing C fibers or to a segmental sympathetic reflex causing vascular permeability. The present results indicate that the ventral portion of the lumbar discs is neurally connected to the groin skin via the upper (L-2) lumbar spinal nerves in rats. Groin pain coincident with low-back pain may be explained as referred pain, indicating that a lesion is present in the ventral portion of the lumbar intervertebral disc space.

Animals↗

Cloning and characterization of an ATBF1 isoform that expresses in a neuronal differentiation-dependent manner.

The human ATBF1 cDNA reported previously, now termed ATBF1-B, encodes a 306-kDa protein containing 4 homeodomains and 18 zinc fingers including one pseudo zinc finger motif. Here, we report the isolation of a second ATBF1 cDNA, 12 kilobase pairs long, termed ATBF1-A. The deduced ATBF1-A protein is 404 kDa in size and differs from ATBF1-B by a 920-amino acid extention at the N terminus. Analysis of 5'-genomic sequences showed that the 5'-noncoding sequences specific to ATBF1-A and ATBF1-B transcripts were contained in distinct exons that could splice to a downstream exon common to the ATBF1-A and ATBF1-B mRNAs. The expression of ATBF1-A transcripts increased to high levels when P19 and NT2/D1 cells were treated with retinoic acid to induce neuronal differentiation. Preferential expression of ATBF1-A transcripts was also observed in developing mouse brain. Transient transfection assays showed that the 5.5-kilobase pair sequence upstream of the ATBF1-A-specific exon (exon 2) supported expression of the linked chloramphenicol acetyltransferase gene in neuronal cells derived from P19 cells but not in undifferentiated P19 or in F9 cells, which do not differentiate into neurons. These results showed that ATBF1-A and ATBF1-B transcripts are generated by alternative promoter usage combined with alternative splicing and that the ATBF1-A-specific promoter is activated during neuronal differentiation.

Alternative Splicing↗

Genotype, slow decrease in virus titer during interferon treatment and high degree of sequence variability of hypervariable region are indicative of poor response to interferon treatment in patients with chronic hepatitis type C.

In a study assessing factors associated with a good or a poor response to interferon treatment in patients with chronic hepatitis type C, we analyzed serum samples taken from 26 interferon-treated patients and found further evidence that infection with genotype II is associated with a poor response. Whereas all seven patients with group III genotype tested showed a good response (normalization of alanine aminotransferase level for more than 6 months), only 10 of 19 (53%) patients infected with group II genotype showed a good response. We also observed that 16 of 17 (94%) patients who exhibited a rapid virus titer decrease during the first 2 weeks of treatment later showed a good response. In contrast, only three of nine (33%) patients with an initially slow viral decrease eventually showed a good response (p<0.04). None of the 26 control patients exhibited a marked virus decrease or normalization of serum alanine aminotransferase level. Interestingly, high degrees of sequence variability were seen in three patients with group II hepatitis C virus who responded poorly to the therapy. All three showed slow decreases in virus titer during the first 2 weeks of treatment. In contrast, patients with genotype II who showed a good response to treatment were seen to have very few mutations. In three patients with genotype III who had responded well to interferon treatment, all showed very little amino acid sequence variability in the hypervariable region compared with patients with genotype II who had responded poorly to interferon treatment. These data suggest that a slow decrease in virus titer during the beginning of interferon treatment and a high degree of sequence variability, both of which are often seen in patients with group II genotype, are associated with poor response to interferon treatment.

Adult↗

[Reproductive and developmental toxicity studies of montirelin hydrate (1)--Fertility study in rats by intravenous administration].

A study of fertility and early embryonic development to implantation of montirelin hydrate (NS-3), a new drug for the treatment of disturbance of consciousness, was conducted in Sprague-Dawley rats. Male rats were given the drug intravenously from 63 days before mating to the end of mating period and female rats from 14 days before mating to day 7 of pregnancy; the dose levels for both males and females were 0 (control), 0.02, 1 and 50 mg/kg. The females were sacrificed on day 20 of pregnancy for examination of their fetuses. In the 50 mg/kg group, tremor, disappeared within some minutes, was observed during administration period in all animals. Food and water consumptions increased in the females and body weight gain was suppressed in the males. Moreover prolonged estrus cycle was observed at early period of the administration in the females, but it recovered at late period of the administration. However, there were no toxicities in the males and females in the 1 mg/kg or less groups. The drug had no adverse effects on reproductive function of the parent animals, or on development of fetuses. These results show that the NOAEL of montirelin hydrate are 1 mg/kg for general toxicity in parent animals, and 50 mg/kg for reproductive function of the parent animals and for development of fetuses.

Animals↗

[Reproductive and developmental toxicity studies of montirelin hydrate (2)--Teratogenicity and postnatal study in rats by intravenous administration].

A study of the effect of montirelin hydrate (NS-3), a new drug for the treatment of disturbance of consciousness, during the period of organogenesis was conducted in Sprague-Dawley rats. Female rats were given the drug intravenously at dose levels of 0 (control), 0.02, 1 and 50 mg/kg from day 7 to day 17 of pregnancy. Twenty-three or twenty-five female rats per dose level were sacrificed on day 20 of pregnancy for examination of their fetuses, and the pregnant rats (13-15 per dose levels) were allowed to deliver naturally for postnatal examination of their offspring. In the 1 or 50 mg/kg group, water consumption and the weights of adrenals of the dams increased and the weights of the thymus of the dams decreased. In addition, tremor, disappeared within some minutes, was observed from day 7 to day 16 of pregnancy in all dams given 50 mg/kg. Moreover, food consumption increased and the weights of the submaxillary glands of the dams given 50 mg/kg increased. The drug had no effect on the number of corpora lutea and implantations, on fetal mortality, on fetal body weights, on sex ratio, or on external, visceral and skeletal development of the fetuses. The drug also did not affect delivery. The drug did not have any adverse effects on the newborn such as the number of live newborns, birth index and body weights of live newborn, or on the postnatal development of the first generation offspring (F1) such as differentiation, functional development, emotionality, motor ability, learning ability or reproductive performance. The drug also had no adverse effects of the second generation offspring (F2). These results show that the NOAEL of montirelin hydrate are 0.02 mg/kg for general toxicity in mother animals, 50 mg/kg for pregnancy and delivery of mother animals and 50 mg/kg for development of their offspring.

Animals↗

[Reproductive and developmental toxicity studies of montirelin hydrate (3)--Teratogenicity study in rabbits by intravenous administration].

A study of the effect of montirelin hydrate (NS-3), a new drug for the treatment of disturbance of consciousness, during the period of organogenesis was conducted in New Zealand white rabbits. Female rabbits were given the drug intravenously at dose levels of 0 (control), 0.01, 0.1 and 1 mg/kg from day 6 to day 18 of pregnancy. Female rabbits were sacrificed on day 29 of pregnancy for examination of their fetuses. In the 0.1 mg/kg group, food consumption decreased slightly. In the 1 mg/kg group, tachypnea, salivation and rhinorrhea were observed, and body weight and food consumption decreased and water consumption increased. The drug had no effect on the number of corpora lutea and implantations, or on fetal mortality, on fetal body weights, on placental weight, on sex ratio, or on external, visceral and skeletal development of the fetuses. These results show that the NOAEL of montirelin hydrate are 0.1 mg/kg for general toxicity in mother animals, and 1 mg/kg for pregnancy of mother animals and for development of fetuses.

Animals↗

[Reproductive and developmental toxicity studies of montirelin hydrate (4)--Perinatal and postnatal study in rats by intravenous administration].

A study of the effect of montirelin hydrate (NS-3), a new drug for the treatment of disturbance of consciousness, during the perinatal and lactation periods was conducted in Sprague-Dawley rats. Female rats were given the drug intravenously at dose levels of 0 (control), 0.02, 1 and 50 mg/kg from day 17 of pregnancy to day 21 after delivery. All pregnant rats were allowed to deliver naturally for postnatal examination of their offspring. In the 1 and 50 mg/kg groups, food and water consumptions decreased after delivery and the weights of adrenals of the dams increased. In addition, tremor, disappeared within some minutes, was observed during administration period in all dams given 50 mg/kg. Moreover, body weight gain was suppressed after delivery, and the weights of submaxillary glands increased, and the weights of thymus and liver decreased in the dams given 50 mg/kg. The drug did not affect delivery. The drug did not have any adverse effects on the newborn including the number of live newborns, birth index and body weights of live newborn. In the 1 or 50 mg/kg group, body weight gains were suppressed and food consumption decreased in the offspring. The drug did not have any adverse effects on the postnatal development of the offspring such as differentiation, functional development, emotionality, motor ability, learning ability or reproductive performance. These results show that the NOAEL of montirelin hydrate are 0.02 mg/kg for general toxicity in mother animals, 50 mg/kg for reproductive function in mother animals and 0.02 mg/kg for their offspring.

Animals↗

Prognostic value of electroencephalogram (EEG) in anoxic encephalopathy after cardiopulmonary resuscitation: relationship among anoxic period, EEG grading and outcome.

We studied the prognostic applicability of electroencephalograms (EEGs) of seventy-nine patients within 24 hours after successful cardiopulmonary resuscitation. The EEGs were classified into five grades according to a modified Hockaday's scale. The EEGs of grades I and II implied full recovery, while those of grade III gave a varied but generally unfavorable prognosis. Patients with grades IV and V EEGs survived in a vegetative condition or died without awakening. Eighteen patients showed EEG with periodic patterns, all of which led to a fatal or vegetative outcome. One case showed EEGs associated with periodic triphasic waves and repetitive sharp transients in the same record. Several cases showed EEGs with different periodic patterns in consecutive records. We conclude that an EEG is a good indicator of patient prognosis after cardiopulmonary resuscitation. However, the clinical significance of morphological differences of various periodic patterns that can occur during an EEG remains to be established.

Adult↗

ATBF1, a multiple-homeodomain zinc finger protein, selectively down-regulates AT-rich elements of the human alpha-fetoprotein gene.

ATBF1 is a 306-kDa protein containing four homeodomains, 17 zinc finger motifs, and several segments potentially involved in transcriptional regulation (T. Morinaga, H. Yasuda, T. Hashimoto, K. Higashio, and T. Tamaoki, Mol. Cell. Biol. 11:6041-6049, 1991). At least one of the homeodomains of ATBF1 binds to an AT-rich element in the human alpha-fetoprotein (AFP) enhancer (enhancer AT motif). In the present work, we analyzed the transcriptional regulatory activity of ATBF1 with respect to the enhancer AT motif and similar AT-rich elements in the human AFP promoter and the human albumin promoter and enhancer. Gel retardation assays showed that ATBF1 binds to the AFP enhancer AT motif efficiently; however, it binds weakly or not at all to other AT-rich elements in the AFP and albumin regulatory regions studied. Alterations of the enhancer AT motif by site-specific mutagenesis resulted in the loss of binding of ATBF1. Cotransfection experiments with an ATBF1 expression plasmid and the chloramphenicol acetyltransferase (CAT) gene fused to AFP promoter or enhancer fragments showed that ATBF1 suppressed the activity of AFP enhancer and promoter regions containing AT-rich elements. This suppression was reduced when the mutated AT motifs with low affinity to ATBF1 were linked to the CAT gene. The ATBF1 suppression of AFP promoter and enhancer activities appeared to be due, at least in part, to competition between ATBF1 and HNF1 for the same binding site. In contrast to the AFP promoter and enhancer, the albumin promoter and enhancer were not affected by ATBF1, although they contain homologous AT-rich elements. These results show that ATBF1 is able to distinguish AFP and albumin AT-rich elements, leading to selective suppression of the AFP promoter and enhancer activities.

Animals↗

Effect of lymphoblastoid alfa-interferon in patients with chronic hepatitis C having different genotypic subtype of hepatitis C virus.

Five subtypes of hepatitis C virus (Pt[I], K1[II], K2a[III], K2b[IV] and Tr[V]) have been suggested based on the nucleotide sequence of the non-structural five region. To assess the susceptibility of each subtype to interferon therapy, we developed a one-step method which allows quick determination of subtype using polymerase chain reaction with a mixed primer set deduced from the sequence of each subtype. We were able to determine the subtype of 69 of 80 (86.3%) Japanese patients who received natural alfa-interferon treatment. The incidence of each subtype was K1: 53 (76.8%), K2a: 14 (20.3%), K2b: 3 (4.3%) and Tr: 1 (1.4%). Interferon was administered to these patients and found to be effective in 28 of 51 (54.9%) patients with K1 subtype and in 16 of 18 (88.9%) patients with other subtypes (P < 0.01). These data show that K1 is a major subtype in Japan and relatively resistant to interferon treatment.

Adult↗

The nucleotide sequence and genome structure of mung bean yellow mosaic geminivirus.

Complete nucleotide sequences of the infectious cloned DNA components (DNA 1 and DNA 2) of mung bean yellow mosaic virus (MYMV) were determined. MYMV DNA 1 and DNA 2 consists of 2,723 and 2,675 nucleotides respectively. DNA 1 and DNA 2 have little sequence similarity except for a region of approximately 200 bases which is almost identical in the two molecules. Analysis of open reading frames revealed nine potential coding regions for proteins of mol. wt. > 10,000, six in DNA 1 and three in DNA 2. The nucleotide sequence of MYMV DNA was compared with that of bean golden mosaic virus (BGMV), tomato golden mosaic virus (TGMV) and African cassava mosaic virus (ACMV). The 200-base region common to the two DNAs of each virus had little sequence similarity, except for a highly conserved 33-36 base sequence potentially capable of forming a stable hairpin structure. The potential coding regions in the MYMV DNAs had counterparts in the BGMV, TGMV and ACMV, suggesting an overall similarity in genome organization, except for absence of 1L3 in MYMV DNA 1. The most highly conserved ORFs, MYMV 1R1, BGMV 1R1, TGMV 1R1 and ACMV 1R1, are the putative genes for the coat proteins of MYMV, BGMV, TGMV and ACMV, respectively. MYMV 1L1 has also a high degree of sequence similarity with BGMV 1L1, TGMV 1L1 and ACMV 1L1.

Base Sequence↗

Severe Guillain-Barré syndrome in aged patients: the effect of plasmapheresis.

We report two aged patients with Guillain-Barré syndrome (GBS), in whom the rapid progression necessitated the use of a respirator. The first case, a 72-year-old woman, needed a respirator on the 5th day after onset of illness and the second case, a 74-year-old woman, needed a respirator on the 23rd day. We treated the first patient with plasmapheresis; the second patient underwent plasmapheresis as well as a large dose of intravenous methylprednisolone. Both patients showed remarkable recovery and did not need the respirator from the early stages. It was suggested that plasmapheresis is beneficial for treatment of aged patients with severe GBS, who necessitate the support of a respirator, because it prevents the decline in functional status by shortening the period of hospitalization.

Aged↗