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Biomedical subjects

R Ito

Publications and source records attributed to R Ito.

At least 55 records · Page 3Linked to original sources
PubMed2000

Blasticidin A derivatives with highly specific inhibitory activity toward aflatoxin production in Aspergillus parasiticus.

Blasticidin A (1), an antibiotic, has strong inhibitory activity toward aflatoxin production by Aspergillus parasiticus. We prepared some derivatives of 1 and examined their biological activities. Among them, derivatives 3 and 4 without the tetramic acid moiety of 1 maintained inhibitory activity toward aflatoxin production, but did not show antifungal activity or toxicity. RT-PCR experiments indicated that derivatives 3 and 4 as well as 1 significantly reduced the expression of genes encoding aflatoxin biosynthetic enzymes (pksA, ver-1 and omtA) and a regulatory gene (aflR) in A. parasiticus. These results suggested that derivatives 3 and 4 can inhibit aflatoxin production more specifically than 1 by inhibiting an early step prior to the expression of aflR in the pathway of aflatoxin biosynthesis.

Aflatoxins↗
PubMed2000

[Genome analysis of Helicobacter pylori by pulsed-field gel electrophoresis].

The molecular epidemiology of total 121 isolates of Helicobacter pylori was analyzed by pulsed-field gel electrophoresis method with restriction enzyme Spe I. Seventy-seven isolates were separated from the clinical samples, 36 isolates from pyloric antrum and the body of stomach of 18 patients and 8 isolates from pyloric antrum of 4 patients that include one colony before and after sterilizing treatment to each patient. Seventy-five in 77 isolates showed different genomic types respectively, and the other 2 isolates had the same genomic type and were suspected to be caused by intersective infection of medical workers or the instruments that used in examination because they were from patients who were examined by gastric microscope in same time and same laboratory. In isolates from 4 patients who were treated by sterilizing method, 2 patients showed same genomic types with that observed before the treatment, and one patient showed an incomplete treatment because the genomic type of its colony was is similar, and another patient could be infected again because its isolates showed different genomic type. In 18 patients whose isolates were separated from pyloric antrum and body of the stomach respectively to each person, isolates of 3 patients showed different genomic types in the two different part of stomach indicating that they had two and more clones of H. pylori.

Cloning, Molecular↗
PubMed1999

Effect of cilostazol, a phosphodiesterase III inhibitor, on experimental thrombosis in the porcine carotid artery.

Thrombus formation in the carotid artery is one of the common causes of transient ischemic attacks and stroke. Platelet aggregation seems to be an essential component in these processes. The present study was conducted to determine the ability of cilostazol, a phosphodiesterase III inhibitor, to prevent formation of totally occlusive thrombus in a porcine carotid artery, in comparison with ticlopidine. Castrated male Yorkshire pigs were allocated to control (n=8), cilostazol (30 mg/kg, twice a day [b.i.d] for 2 days, n=8), and ticlopidine (50 mg/kg, b.i.d. for 3 days, n=7) groups. The endothelium of the right common carotid artery was injured with electrical stimulation (150 microA) without constriction and blood flow in this region was monitored by Doppler flow probe. Arterial blood was sampled during electrical stimulation for the measurement of platelet aggregation. Total occlusion rates within 240 minutes were 87.5% (7:8), 37.5% (3:8), and 85.7% (6:7) in the control, cilostazol, and ticlopidine groups, respectively. Compared with the control group, the time to total occlusion was significantly prolonged in the cilostazol group, but not in the ticlopidine group. Consistently, platelet aggregation was significantly inhibited only in the cilostazol group. Because ticlopidine increases blood flow in the intact carotid artery before injury to a greater extent than cilostazol, direct antiplatelet action is thought to be responsible for cilostazol's beneficial effect in preventing thrombotic occlusion. These results suggest that cilostazol may be useful for the inhibition of the thrombus formation in the carotid artery and for the prevention of cerebral ischemic events.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1999

Effect of 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)- quinolinone (vesnarinone) on the growth of gastric cancer cell lines.

Vesnarinone (OPC-8212; 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-quinolinone ) is a synthetic oral cardiotonic agent that has been used for the treatment of patients with congestive heart failure. Six days of treatment with 30 microg/ml of vesnarinone induced 20-80% growth inhibitions in five out of six gastric carcinoma cell lines examined. Cell cycle analysis revealed that the vesnarinone-sensitive TMK-1 gastric cancer cell line exhibited a significant G0-G1 arrest without evidence of apoptotic cell death induction after 48 h of treatment. Interestingly, this phenomenon was preceded by a marked reduction in the expression of cyclin A, D1 and E as well as cyclin-dependent kinase 2 (CDK2). On the other hand, no significant change was observed in the expression of p21(Waf1/Cip1), p27Kip1 nor various growth factors and their receptor genes. Overall these results indicate that vesnarinone inhibits the growth of gastric cancer cells by down-regulating G1 cyclins and CDK2 to induce G0-G1 arrest through a pathway different from that of cyclin inactivation by p21(Waf1/Cip1) or p27Kip1.

Antineoplastic Agents↗
PubMed1999

Immunohistochemistry of myoepithelial cells during development of the rat salivary glands.

Using a battery of monoclonal antibodies specific for rat proteins, immunohistochemistry was carried out on the developing myoepithelial cells (MECs) of the rat major salivary glands. The proteins examined were alpha-smooth muscle actin (alphaSMA), h1-calponin (calponin), keratin 14 (K14), beta subunit of S-100 protein (S-100beta), vimentin and glial fibrillary acidic protein (GFAP). The MECs exhibited immunoreactivity for alphaSMA, calponin and K14, but not that for S-100beta, vimentin and GFAP. Immunoreactivity for alphaSMA appeared in the MECs from the time when the microfilaments were initially deposited in these cells, i.e., at 20 days in utero in the sublingual and submandibular glands and at birth in the parotid gland. Calponin immunoreactivity was seen 1 day earlier than alphaSMA. The appearance was almost at the same time as the onset of the MEC differentiation in each gland. A small number of the MECs expressed weak K14 immunoreactivity from the time when the acinus-intercalated duct structure was established, i.e., at 21 days in utero in the sublingual gland, at 5 days after birth in the perotid gland and after 5 weeks post-natally in the submandibular gland. In addition, K14 immunoreactivity was observed in the basal cells of the striated and excretory ducts. The first appearance of K14 in these cells again coincided with the emergence of the duct system in each gland, i.e., at 20 days in utero in the sublingual gland, at 21 days in utero in the submandibular gland and at 3 days after birth in the parotid gland. Finally, the MECs in all the glands were found to redistribute as the acini matured. As the acini grew rapidly during the weaning period in the parotid and the sublingual glands, the MECs ceased to surround the acini. Thereafter, they disappeared from the acini in the parotid gland, whereas they reappeared in the sublingual gland. In the submandibular gland, the MECs were confined to the terminal tubules until 4 weeks after birth. Thereafter, the acini were established and invested by the MECs. In conclusion, immunohistochemistry of calponin and alphaSMA is a useful tool for identification of the MEC during its earliest differentiation, which has hitherto been possible only electron microscopically. In addition, it is suggested that the MEC is heterogeneous and the functionally differentiated MEC appears after weaning around acini of the mucous and seromucous glands.

Animals↗
PubMed1999

Small cell undifferentiated carcinoma of the submandibular gland: immunohistochemical evidence of myoepithelial, basal and luminal cell features.

A primary small cell undifferentiated carcinoma of the submandibular gland is reported. Histological studies revealed that the major part of this tumor was composed of cells slightly larger (10-14 microm) than lymphocytes. These tumor cells showed myoepithelial-cell differentiation, which was confirmed by the immunohistochemical and ultrastructural findings. Furthermore, some of them showed luminal-cell and basal-cell differentiation immunohistochemically. However, there was no evidence of neuroendocrine differentiation. These findings demonstrated that the tumor had the features of all the salivary ductal components (myoepithelial, basal, and luminal cells) and supported that the tumor might arise from the salivary duct. Furthermore, it supports the hypothesis of multipotential stem cells as the origin for small cell undifferentiated carcinomas in salivary glands.

Actins↗
PubMed1999

Visual impairment and REP-1 gene mutations in Japanese choroideremia patients.

Choroideremia (CHM), an X-linked recessive hereditary disease, is an intractable chorioretinal dystrophy. The rate of disease progression of CHM reportedly shows considerable variability. A number of mutations involving the gene that codes for Rab escort protein-1 (REP-1) have been detected in CHM patients. We have analyzed REP-1 gene mutations of Japanese CHM patients. The present study was designed to investigate the clinical variability and the genotype to phenotype relationship in 15 Japanese CHM patients referred to the Department of Ophthalmology of Juntendo University Hospital. The clinical investigation of visual acuity, visual field, color vision and refraction revealed inter-individual variability. Mutation analyses of the REP-1 gene revealed 10 types of mutations in 13 patients from 11 families, including an insertion, small deletions, nonsense mutations and an A to CC mutation. In 13 CHM patients with detectable REP-1 gene mutations, no relationship of genotype to phenotype was detected. At present, we consider the REP-1 genotype to be an unreliable prognostic factor for counseling of CHM patients. In two patients from one family, no mutations were detected in coding regions of the REP-1 gene. These patients may have intron mutations of the REP-1 gene, not detectable by the techniques employed in this study, or other causative genes. Both were observed to have somewhat slower disease progression than the other 13 patients. More advanced analyses are necessary to answer questions regarding the genotype-phenotype relationship in CHM patients.

Adaptor Proteins, Signal Transducing↗
PubMed1999

[Effects of bright light on cognitive disturbances in Alzheimer-type dementia].

We investigated the effectiveness of bright light therapy on cognitive disturbances and its effect on circadian (sleep-wake) rhythm in Alzheimer-type dementia (ATD). Twenty-seven patients with ATD were treated with bright light therapy in the morning for 4 consecutive weeks. We evaluated the cognitive functions and circadian rhythms of the patients as a whale, and as members of two groups (one: questionable and mild dementia: the other: moderate and severe dementia; both groups classified by the severity criteria of Clinical Dementia Rating). We assessed circadian rhythms by actigraphy and cognitive states by Mini-Mental-State Examination (MMSE) and Alzheimer's Disease Assessment Scale (ADAS) before and after light therapy. Bright light therapy improved circadian rhythm. Although bright light therapy had no Significant effect on the Severity of dementia, it improved the MMSE scores, cognitive functions of ADAS scores (memory > language) and non-cognitive functions of ADAS scores (behavior = mood), especially in the questionable and mild dementia group. These results suggest that bright light therapy improves cognitive functions with the modification of circadian rhythm, especially in the early stages of ATD.

Aged↗
PubMed1999

Increased susceptibility of mice to malarial infection following UV-B irradiation.

Using a mouse model, we examined whether UV-B was a risk factor for malarial infection. Two mouse strains, susceptible (BALB/c) and resistant (C57BL/10) to murine malaria (Plasmodium chabaudi), were UV-preirradiated and infected with a sub-lethal dose of malaria parasite (104 and 105, respectively). Parasite growth was assayed with tail-blood smears counting parasitized red blood cells. Mice resistant to malaria were bled by heart puncture and the plasma cytokines were determined. Our results showed that UV-B irradiation worsened the malarial infection and 100% of the malaria-resistant mice strains died due to a usual infection at sub-lethal dose following UV-B irradiation. In the resistant mice strain infected with the parasite, the plasma IFN-gamma production was inhibited by UV-B irradiation and the maximum titer was about one-fifth of the non-irradiated mice. Furthermore, activation of macrophages from UV-irradiated mice also decreased compared with that of non-irradiated mice. IFN-gamma administration prevented the death of UV-B irradiated resistant mice and the cure ratio was 60%. In conclusion, UV-B increased the susceptibility of both strains of mice and impaired IFN-gamma production in the malaria-resistant mice strain.

Animals↗
PubMed1999

FSH-initiated differentiation of newt spermatogonia to primary spermatocytes in germ-somatic cell reaggregates cultured within a collagen matrix.

We previously cultured fragments of newt testes in chemically defined media and showed that mammalian follicle-stimulating hormone (FSH) stimulates proliferation of spermatogonia as well as their differentiation into primary spermatocytes (Ji et al., 1992; Abe and Ji, 1994). Next, we indicated in cultures composed of spermatogonia and somatic cells (mainly Sertoli cells) that FSH stimulates germ cell proliferation via Sertoli cells (Maekawa et al., 1995). However, the spermatogonia did not differentiate into primary spermatocytes, but instead died. In the present study, we embedded large reaggregates of spermatogonia and somatic cells (mainly Sertoli cells) within a collagen matrix and cultured the reaggregates on a filter that floated on chemically defined media containing FSH; in this revised culture system, spermatogonia proliferated and differentiated into primary spermatocytes. The viability and percentage of germ cells differentiating into primary spermatocytes were proportional to the percentage of somatic cells in the culture, indicating that differentiation of spermatogonia into primary spermatocytes is mediated by Sertoli cells.

Animals↗
PubMed1999

The central distribution pattern of primary afferent fibers innervating the thigh muscle posterior iliotibialis in the chicken.

The anatomical relationship between motoneuron dendrites and primary afferent fibers innervating the same muscle were examined by using a modified cholera toxin tracing method. The cholera toxin B subunit conjugated with latex beads was injected into the posterior iliotibial muscle (PIT) of chicken. Both motoneuron dendrites and primary afferent fibers were intensely labeled. Labeled primary afferent fibers innervating the PIT were mainly located in laminae I (ventral part), V (lateral part), VI, VII (except ventromedial part) and lateral motor column (LMC, lamina IX) of the lumbar spinal cord. Numerous labeled primary afferent fibers were observed in proximity to the motoneuron pool of the PIT located in the dorsolateral region of the LMC; primary afferent fibers were closely apposed to somatic profiles of the PIT motoneurons.

Afferent Pathways↗
PubMed1999

[Functional MRI of the human brain responses to olfactory stimulation].

Image artifacts such as signal loss or distortion due to intravoxel phase dispersion at the skull base are problematic in analysis by functional MRI (fMRI). Since the olfactory center of the brain is located in the medial temporal and basal frontal areas, it is a challenge to try to detect the Blood Oxygenation Level Dependent (BOLD) effect during fMRI at olfactory stimulation. We examined 20 normal volunteers with a 1.5-T MR system, employing multishot, interleaved echo-planar imaging (EPI). Olfactory stimulation was performed with 2-methyl-1, 3-cyclo-pentanedione, a caramel-like fragrance, by presenting it for 20 seconds with two cycles of rest-stimulus paradigm. Sites of functional activation were identified by correlation analysis with a threshold of p < 0.01. Most commonly activated areas were the orbitofrontal and primary olfactory cortices. Mild activation was also observed in the cingulate gyrus, lateral temporal cortex, cerebellum, parietal and occipital lobes. These results indicate that olfactory stimulation participates in the emotion and behavior processes. Interestingly, broad activation in the "silent" area of the frontal and temporal lobe was also observed in some cases. Multishot EPI was a useful method to evaluate brain activation at the basal level on fMRI.

Adult↗
PubMed1998

Serotonin2A receptor-like immunoreactivity in rat cerebellar Purkinje cells.

In the present study we examined the distribution pattern of serotonin2A (5-HT2A) receptors in the rat cerebellum. A strong immunoreaction against 5-HT2A receptor protein was observed in Purkinje cells. A dense cluster of immunopositive dendritic profiles of Purkinje cells was located beneath the pia matter of cerebellar cortex. Somal profiles in the cerebellar nuclei had weak to moderate immunoreactions.

Animals↗
PubMed1998

The cellular localization of 5-HT2A receptors in the spinal cord and spinal ganglia of the adult rat.

The localization of serotonin2A (5-HT2A) receptors in the adult rat spinal cord and dorsal root ganglia was examined by using a polyclonal antibody that recognizes the C-terminus peptides of the mouse 5-HT2A receptor. Positive cell bodies of 5-HT2A receptor were found in several regions of the spinal cord. Generally, large-to-intermediate sized neuronal cell bodies were intensely immunolabeled. Motoneurons in the ventral horn were the most intensely labeled. Dot-like immunoreactive profiles were located beneath the cell membrane of motoneurons. Neuronal somata in the intermediolateral nucleus of the thoracic spinal cord were moderately labeled. The immunoreactivity in the dorsal horn was weak. A considerable number of glial cell bodies in the white matter were immunostained. The majority of both small and large sized neurons were 5-HT2A immunopositive in the dorsal root ganglion.

Age Factors↗
PubMed1998

Twenty-four-hour ambulatory oxygen desaturation and electrocardiographic recording in obstructive sleep apnea syndrome.

BACKGROUND: Although nocturnal pulseoximetry is routinely performed in obstructive sleep apnea syndrome (OSAS), pulseoximetry over a 24-h period has not been studied. HYPOTHESIS: The purpose of the study was to determine whether simultaneous 24-h oxygen desaturation and electrocardiographic (ECG) recording might be used to screen for daytime sleep sequelae in patients with OSAS. METHODS: Simultaneous recording of arterial oxygen saturation (SpO2) and ECG was conducted over a 24-h period in 18 male patients with OSAS (mean age 51.3 years) who were diagnosed by standard polysomnography (PSG), and in 15 age-matched healthy subjects (mean age 52.7 years) as controls to evaluate circadian variation of these parameters. The measures of heart rate variability (HRV) were calculated from 24-h ambulatory ECGs. Seventeen patients with OSAS showed excessive daytime sleepiness (EDS). We calculated the duration in which SpO2 decreased to < 90% (duration of SpO2 < 90%). The number of apnea/hypopneas per hour (AHI) during sleep was investigated with Apnomonitors (Chest MI, Co., Tokyo) on the same day as the SpO2 recordings. RESULTS: Controls showed no episodes of oxygen desaturation. In patients with OSAS, driving (33.3% of patients with OSAS) was the most common activity in which SpO2 decreased to < 90%, followed by daytime napping (27.8%) and resting after meals (22.2%). The duration of SpO2 < 90% over a 24-h period correlated significantly with the duration levels recorded during sleep (r = 0.99, p < 0.05) and in the afternoon (r = 0.62, p < 0.05), and with the AHI (r = 0.55, p < 0.05), but not with the duration of SpO2 < 90% in the morning. The number of ventricular premature beats correlated significantly with the duration of SpO2 < 90% for a 24-h period, but not with measures of HRV. Ventricular tachycardia was found in two (11.1%) and ST-T depression in three patients (16.6%) with underlying cardiac diseases. CONCLUSION: Our results suggest that daytime sleep attacks accompanied by oxygen desaturation in patients with moderate to severe OSAS may contribute to the occurrence of traffic or cardiovascular accidents. We conclude that 24-h ambulatory recordings of SpO2 and ECG are useful for screening for daytime sleep sequelae associated with the potential risk of this pathology in OSAS during social activities.

Adult↗
PubMed1998

Immunohistochemistry of carbonic anhydrase isozymes VI and II during development of the rat salivary glands.

Secreted carbonic anhydrase (isozyme VI; CA VI) was localized by immunohistochemistry in the developing postnatal rat submandibular and parotid glands using a specific monoclonal antibody to the rat enzyme. CA VI immunostaining was not detectable in the glands before birth. In the submandibular gland, granular immunostaining for CA VI was detectable in several terminal tubule cells of 1-day-old rats. At 1 week, the CA VI-positive cells were located at the periphery of the terminal tubules and appeared to be budding off the tubules. These cellular buds gradually increased, and, by 4 weeks, formed acini. CA VI was also detected in the duct lumen from day 1. The immunostaining in the parotid gland was detected sporadically in the acinar cells at 2 or 3 weeks. By 4 weeks, when the gland was almost indistinguishable from the adult one, the number of positive acinar cells had increased. Their number, however, was far smaller than in the adult gland, and the enzyme could not be detected in the duct lumen. CA II was also localized using specific antibodies to the rat isozyme. CA II was detectable in the inter- and intralobular striated ducts at 2 weeks after birth in the submandibular gland and at 3 weeks in the parotid gland. These results suggest that CA VI is secreted into saliva from soon after birth and that CA II appears in parallel with the functional maturation of the ducts. In addition, CA II was transiently expressed by the cellular buds of the submandibular gland at 2 and 3 weeks.

Animals↗
PubMed1998

Hypertension in Leigh syndrome--a case report.

A female patient, who was diagnosed with Leigh syndrome at 15 months of age, developed fulminating severe hypertension and died at 8 years of age. Hypertension has not been reported as an important clinical symptom in Leigh syndrome. Laboratory findings indicated that it was not associated with endocrinopathic diseases such as pheochromocytoma and aldosteronism, or renal diseases. Brain MRI scan showed symmetrical lesions in the basal ganglia and medulla oblongata including the nucleus tractus solitarius. This nucleus is known to play an important role in maintaining blood pressure. Since the medulla oblongata is a vulnerable site, potential development of hypertension should be taken into consideration when managing Leigh syndrome.

3-Iodobenzylguanidine↗