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Biomedical subjects

K Honma

Publications and source records attributed to K Honma.

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

Pneumoconiosis-related lung cancers: preferential occurrence from diffuse interstitial fibrosis-type pneumoconiosis.

It has been reported that patients with pneumoconiosis occasionally have a diffuse interstitial fibrosis (DIF) that resembles interstitial pneumonia, but little is known about the relation between pneumoconiosis-associated DIF and the risk of lung cancer. In the present study, we evaluated the incidence of DIF by chest CT and its contribution to lung cancer in 563 patients with nonasbestos pneumoconiosis. Fifty-five (10%) of the 563 patients had DIF. Pneumoconiosis with DIF had an exceedingly high concurrence of lung cancers when compared with pneumoconiosis without DIF (29 [53%] of 55 versus 78 [15%] of 508, p < 0.001). Squamous cell carcinomas (SCCs) of the lung from pneumoconiosis with DIF exclusively comprised peripheral-types, as compared with SCCs from pneumoconiosis without DIF (13 [100%] of 13 versus 33 [72%] of 46, p = 0.03). In addition, lung cancers arose frequently from the area of DIF in pneumoconiosis with DIF (20 [74%] of 27). Furthermore, our pathologic examination revealed that dysplasias from pneumoconiosis with DIF were significantly more frequently observed in peripheral bronchioli than were dysplasias from pneumoconiosis without DIF (11 [69%] of 16 versus 20 [30%] of 66, p = 0.01). p53 expression evaluated by immunohistochemistry was frequently observed in dysplasias from pneumoconiosis with DIF, although it was not significantly different compared with that in dysplasias from pneumoconiosis without DIF (5 [50%] of 10 versus 12 [38%] of 32). Taken together, these results may suggest a positive causal relationship between pneumoconiosis and peripheral-type SCCs of the lung, and further indicate a pivotal role of diffuse fibrosis for the excess incidence of lung cancers, especially peripheral-type SCCs, in DIF-type pneumoconiosis.

Aged↗
PubMed2000

In vitro and in vivo tests for determination of the pathogenicity of quartz, diatomaceous earth, mordenite and clinoptilolite.

The effects of samples of crystalline quartz, diatomaceous earth, mordenite and clinoptilolite were investigated in vitro (as concerns erythrocyte haemolysis and lactate dehydrogenase (LDH) release from peritoneal macrophages) and in vivo (on LDH, protein and phospholipids in rat bronchoalveolar lavage (BAL), and phospholipids in rat lung tissue). The respirable mineral samples were instilled intratracheally. Determinations in the BAL were carried out after 15, 60 and 180 days, and in the lung tissue after 90, 180 and 360 days. Quartz DQ and quartz FQ induced acute, subacute and chronic inflammation and progressive fibrosis. However, due to the Al2O3 contamination on the surface of the particles quartz FQ caused a delayed response in vivo. Diatomaceous earth produced acute/subacute inflammation that gradually became more moderate after 60 days. Clinoptilolite was inert, whereas the other zeolite sample, mordenite, was cytotoxic in vivo. The reason for this was presumably the needle and rod-shaped particles in the mordenite samples. The investigation revealed that different in vitro and in vivo methods canprovide valuable data concerning the pulmonary toxicity of minerals.

Aluminum Silicates↗
PubMed2000

[A case of congenital cystic adenomatoid malformation of the lung in a 4-year-old child].

A case of congenital cystic adenomatoid malformation (CCAM) of the lung is reported. A 3-year-old boy was admitted for elevation of infiltrative shadow in the right lower lung field on a chest X-ray. The clinical diagnosis was emphysematous bullae with inflammation. After 6 months, he had recurrent infected bullae, and was admitted. He received chemotherapy with antibiotics prior to the operation. Right lower lobectomy was performed on February 2, 1998. The resected lung was composed of multiple cysts with thin wall measuring 10-60 mm in diameter. The histological examination of specimen revealed CCAM (Stocker type I), which is rare in this age. The patient has been well for 16 months postoperatively.

Child, Preschool↗
PubMed2000

Clock genes outside the suprachiasmatic nucleus involved in manifestation of locomotor activity rhythm in rats.

Chronic treatment of methamphetamine (MAP) in rats desynchronized the locomotor activity rhythm from the light-dark cycle. When the activity rhythm was completely phase-reversed with respect to a light dark-cycle, 24 h profiles were examined for the clock gene (rPer1, rPer2, rBMAL1, rClock) expressions in several brain structures by in situ hybridization, and for the pineal as well as plasma melatonin levels. In the MAP-treated rats, the rPer1 expression in the suprachiasmatic nucleus (SCN) showed a robust circadian rhythm which was essentially identical to that in the control rats. Circadian rhythms in pineal as well as plasma melatonin were not changed significantly in the MAP-treated rats. However, robust circadian rhythms in the rPer1, rPer2 and rBMAL1 expressions detected in the caudate-putamen (CPU) and parietal cortex were completely phase-reversed in the MAP-treated rats, compared with those in the control rats, indicating desynchronization from the SCN rhythm. Such desynchronization was not observed in the circadian rhythms of clock gene expression in the nucleus accumbens and cingulate cortex. The circadian rClock expression rhythm in the MAP-treated rats was not phase-reversed in the CPU and parietal cortex. These findings indicate that the locomotor activity rhythm in rats is directly driven by the pacemaker outside the SCN, in which rPer1, rPer2 and rBMAL1 in the CPU and parietal cortex are involved.

Animals↗
PubMed1999

Circadian rhythms and light responsiveness of mammalian clock gene, Clock and BMAL1, transcripts in the rat retina.

Circadian expression and light-responsiveness of the mammalian clock genes, Clock and BMAL1, in the rat retina were examined by in situ hydbribization under constant darkness. A small but significant daily variation was detected in the Clock transcript level, but not in BMAL1. Light increased the Clock and BMAL1 expressions significantly when examined 60 min after exposure. The light-induced gene expression was phase-dependent for Clock and peaked at ZT2, while rather constant throughout the day for BMAL1. These findings suggest that Clock and BMAL1 play different roles in the generation of circadian rhytm in the retina from those in the suprachiasmatic nucleus. Different roles are also suggested between the two genes in the photic signal transduction in the retina.

ARNTL Transcription Factors↗
PubMed1999

Characterization of three splice variants and genomic organization of the mouse BMAL1 gene.

The BMAL1 gene encodes a member of the basic helix-loop-helix/PER-ARNT-SIM (bHLH/PAS) family of transcription factors. It is a key regulator of circadian rhythms. Using sequence information from human BMAL1 (hBMAL1) cDNAs previously reported by our laboratory, we have isolated and characterized cDNAs encoding three splice variants of the mouse BMAL1 (mBMAL1) gene. Of the three splice variants, mBMAL1b extends for 1878 bp in the coding sequence, which is 91% identical to that of hBMAL1b; its deduced amino acid sequence is 626 residues long and is 98% identical to that of hBMAL1b, and sequence identities in the bHLH, PAS-A, and PAS-B regions are 98, 100, and 100%, respectively. mBMAL1b' arises from alternative usage of exon 2, which results in a 7-amino-acid insertion and alternative splice acceptor usage at the intron 9/exon 10 splice junction, which causes an alanine residue deletion. mBMAL1b' encodes 632 amino acids and contains the bHLH/PAS domains. mBMAL1g' is generated by alternative splice acceptor usage at the intron 6/exon 7 splice junction, which results in a 28-bp deletion adjacent to the 5' end of the PAS domain. Since the 28-bp deletion shifts the reading frame, mBMAL1g' is predicted to encode a product of only 222 amino acids that lacks the PAS domain. The tissue distributions of the three splice variants showed some variation. The variations in the tissue distributions and predicted amino acid sequences suggest that the three splice variants may have different functions. Direct sequencing of the genomic mBMAL1 clones indicated that the coding sequence of mBMAL1 spans 32 kb and includes 17 exons. An unusual exon/intron donor sequence was found in intron 14, which begins with GC at the 5' end. Comparison with the bHLH/PAS family genes revealed that the intron/exon splice pattern of mBMAL1 most closely matches that of the mAhr, which suggests that BMAL1 and Ahr belong to the same subclass and may be derived from a common primordial gene.

ARNTL Transcription Factors↗
PubMed1999

Daily variation and light responsiveness of mammalian clock gene, Clock and BMAL1, transcripts in the pineal body and different areas of brain in rats.

Expression patterns of mammalian clock genes, Clock and BMAL1, were examined by in situ hybridization in the pineal body, olfactory bulb, hippocampus and cerebellum in rats under constant darkness. In the pineal, the level of Clock transcript was significantly higher at ZT18 (subjective night) than at ZT6 (subjective day), while the level of BMAL1 transcript was significantly higher at ZT6 than at ZT18. A 30 min light pulse did not affect the transcript levels of Clock nor of BMAL1. The Clock expression in the cerebellum was significantly increased at ZT6 than at ZT18, while no difference was detected in the olfactory bulb and hippocampus at these two phases. The BMAL1 expressions in these areas were similar to the case in the pineal. These findings indicate that the mammalian clock gene, Clock and BMAL1, are expressed differently in the different areas of the brain and the pineal.

ARNTL Transcription Factors↗
PubMed1999

Expression of saliva-binding epitopes of the Porphyromonas gingivalis FimA protein on the surface of Streptococcus gordonii.

Porphyromonas gingivalis, a gram-negative oral anaerobic bacterium, has been implicated in the onset and development of periodontitis. The P. gingivalis fimbriae which mediate bacterial adherence to host oral sites and induce host inflammatory responses have been suggested as a potential antigen candidate. for vaccine development. This study was undertaken to generate Streptococcus gordonii vectors expressing the major subunit protein (FimA) of P. gingivalis fimbriae for testing as a potential live vaccine against periodontitis. We report here the expression of the C-terminal saliva-binding epitopes of P. gingivalis FimA on the surface of S. gordonii and demonstrate that domains containing free cysteine residues are poorly expressed on the surface of S. gordonii.

Bacterial Proteins↗
PubMed1999

Phase-dependent induction by light of rat Clock gene expression in the suprachiasmatic nucleus.

To clarify the role of Clock in the photic signal transduction of rat circadian clock, we cloned and sequenced rat Clock and examined the effect of a single light pulse on the Clock mRNA expression in the suprachiasmatic nucleus (SCN) by in situ hybridization. Rats were exposed to a 30 min light pulse ( approximately 300 lx) at one of six circadian phases in constant darkness (DD), and sacrificed 60 min after the light on. In the rats without light exposure, the mRNA level in the SCN was high at ZT (Zeitgeber time) 6 and low at ZT 18 and 22. Light exposure increased Clock mRNA level in the SCN in phase dependent manner. The mRNA level was significantly increased during the subjective night (ZT10-22). The light had no effect on the mRNA level during the subjective day (ZT2 and 6). The Clock mRNA was also detected in the piriform cortex (PC), and increased by light at ZT14. These results suggest that Clock transcription in the SCN is involved in the photic signal transduction of circadian clock in rats.

ARNTL Transcription Factors↗
PubMed1999

Functional diversities of two activity components of circadian rhythm in genetical splitting mice (CS strain).

CS mice, an inbred strain, showed two distinctive characteristics in the circadian rhythm of locomotor activity: (1) large variation in the freerunning period, and (2) spontaneous rhythm splitting under continuous darkness. In the splitting rhythm there was a positive correlation between the freerunning period of the evening component and the activity time of the morning component. The phase-shifting effect of a 15-min light pulse was examined on the two activity components of the splitting rhythm. There were significant differences in the amount of light-induced phase response between the two components. A light pulse during the late subjective night induced a phase advance shift only in the morning component, while a light pulse during the early subjective night induced a phase delay shift only in the evening component. These results indicate functional diversities of the two activity components in the circadian locomotor rhythm of CS mice, and suggest that the circadian system in CS mice consists of two mutually coupled oscillators which have different circadian periods and different responsiveness to light. The CS mouse is a useful model to explore a genetic background of oscillator coupling in the circadian system of nocturnal rodents.

Animals↗
PubMed1999

Computed tomographic evaluation of bone formation after secondary bone grafting of alveolar clefts.

PURPOSE: The purpose of this article was to evaluate the initial volume of alveolar clefts and the bone bridges formed in patients who had undergone secondary bone grafting. PATIENTS AND METHODS: Fifteen cleft patients were studied. Computed tomography (CT) scans were made at 2-mm slice sections immediately before operation and at 3 months and 1 year postoperatively. The volume of the alveolar clefts and bone bridges was calculated from stored images by using an image scanner and a personal computer. RESULTS: The mean cleft volume of the patients was 1.1 +/- 0.3 cm3. The corresponding volume of the bone bridges 3 months and 1 year postoperatively were 1.2 +/- 0.6 cm3 and 1.1 +/- 0.5 cm3, respectively. The value at 1 year was significantly decreased compared with that at 3 months. CONCLUSIONS: Adequate bone bridging was maintained for 1 year. However, it is suggested that the grafted site should be restored with a functioning tooth or a dental implant to place it under physiologic stress, because the volume of the bone bridges tends to decrease from 3 months to 1 year.

Adolescent↗
PubMed1999

Melatonin induces gamma-glutamylcysteine synthetase mediated by activator protein-1 in human vascular endothelial cells.

In the present study, we show that melatonin induces the expression of gamma-glutamylcysteine synthetase (gamma-GCS), the rate-limiting enzyme of glutathione (GSH) synthesis, in ECV304 human vascular endothelial cells. One micromolar melatonin induced the expression of gamma-GCS mRNA followed by an increase in the concentration of GSH with a peak at 24 h. An electrophoretic mobility shift assay showed that melatonin stimulates the DNA-binding activity of activator protein-1 (AP-1) as well as retinoid Z receptor/retinoid receptor-related orphan receptor alpha (RZR/RORalpha). ECV304 cells transiently transfected with a plasmid containing the gamma-GCS promoter-luciferase construct showed increased luciferase activity when treated with melatonin. The melatonin-dependent luciferase activity was found in the gamma-GCS promoter containing AP-1 site. The luciferase activity mediated by AP-1 was repressed in the promoter containing RZR/RORalpha site. In addition, cell cycle analysis showed that melatonin increases the number of cells in the G0/G1 phase; however, treatment of the cells with buthionine sulfoximine, a specific inhibitor of gamma-GCS, abolished the effect of melatonin on the cell cycle, suggesting induction of cell arrest by melatonin requires GSH. As conclusion, induction of GSH synthesis by melatonin protects cells against oxidative stress and regulates cell proliferation.

Buthionine Sulfoximine↗
PubMed1999

Salivary immunoglobulin A production against a synthetic oligopeptide antigen of Actinobacillus actinomycetemcomitans fimbriae.

Actinobacillus actinomycetemcomitans is an important pathogen in human periodontal diseases. We attempted to produce effective antibodies against A. actinomycetemcomitans fimbrial antigen, which was shown to be an attachment factor. An oligopeptide based on the amino acid sequence of A. actinomycetemcomitans fimbriae was synthesized and conjugated with branched lysine polymer resin beads. Mice were immunized with the synthetic antigen together with one or more of Freund's incomplete adjuvant, the Ribi adjuvant system, liposomes, mouse interleukin 4 expression plasmids, and cholera toxin. After immunization, salivary immunoglobulin A (IgA) and serum IgG levels against the synthetic oligopeptide antigen were determined by enzyme-linked immunosorbent assay. The serum IgG responses against the fimbrial antigen were significantly higher in animals immunized intramuscularly with the Ribi adjuvant system. A high salivary IgA response to the fimbriae was induced by intranasal mucosal immunization with cholera toxin and mouse interleukin 4 expression plasmids.

Adjuvants, Immunologic↗
PubMed1999

Amplitude reduction of plasma melatonin rhythm in association with an internal desynchronization in a subject with non-24-hour sleep-wake syndrome.

The plasma melatonin rhythm was measured longitudinally in a subject with non-24-h sleep-wake syndrome, and the amplitude and area under the curve (AUC) of the melatonin rhythm were investigated in relation to the sleep-wake cycle. When the melatonin rhythm and sleep-wake rhythm were internally desynchronized, the amplitude and the AUC were reduced significantly. These parameters were not influenced by external melatonin administration. These results suggest that a causal relationship between the reduction of circadian oscillation and internal desynchronization exists in this subject.

Adult↗
PubMed1999

Temporomandibular joint symptoms and disc displacement in patients with mandibular prognathism.

Our objective was to find out the incidence of signs and symptoms of temporomandibular joint (TMJ) and disc displacement in patients with mandibular prognathism. Fifty-one patients were examined clinically and by axial computed tomography(CT). The incidence of TMJ signs and symptoms was 6/25(24%) in patients with simple mandibular prognathism and 12/26(46%) in patients with mandibular prognathism and asymmetry. No discs were displaced in patients with simple mandibular prognathism, but 15(58%) of the patients with mandibular prognathism and asymmetry had displaced discs. There was no association between signs and symptoms of TMJ and disc displacement. Patients with mild protrusion and severe asymmetry of the mandible had a high incidence of disc displacement, which interestingly was on the deviated side in 14 of the 15 patients affected. We conclude that skeletal morphology may have a role in the development of TMJ disorders but the mechanism is obscure.

Adolescent↗
PubMed1999

Light-induced uncoupling of multioscillatory circadian system in a diurnal rodent, Asian chipmunk.

Responses of the circadian locomotor rhythm to a single light pulse were examined in a diurnal rodent, Asian chipmunk, by exposing it to a 1-h light pulse of 2,000 lx under constant conditions. A light pulse given at the beginning and end of the subjective night produced a phase delay and advance shifts, respectively. When pulsed around the midpoint of the subjective night, the circadian rhythm was shifted as much as 12 h in most animals or became arrhythmic in some. In the latter case, an additional light pulse restored the circadian rhythm. Some animals were unresponsive to light. The phase response curve is categorized as type 0. A large phase-shift was sometimes followed by splitting of an activity band into two components. These results are best explained by an assumption that the chipmunk circadian system is composed of two mutually coupled major oscillators, each of which is constituted by multiple oscillators. Our results suggest that light affects the oscillatory coupling not only of the major oscillators but also of constitutional oscillators.

Animals↗
PubMed1999

Seasonal changes of human circadian rhythms in Antarctica.

The human circadian rhythms in sleep, activity, plasma melatonin, and rectal temperature were explored under two conflicting time cues in Antarctica: an extreme photoperiod and a strict work schedule. The nine healthy male subjects stayed at the Antarctic zone (latitude 66.5-90 degrees south) for 15 mo including a 13-mo wintering at the Dome station (latitude 77 degrees south). Neither the phases nor the amounts of sleep and daily activity underwent a seasonal change. On the other hand, the peak phase of melatonin rhythm was phase delayed by 4.1 h in winter compared with summer. When the analysis is limited to the Dome data, the seasonal difference was reduced to 1.3 h. Similarly the trough phase of rectal temperature rhythm in two of three subjects was phase delayed by approximately 2 h in winter. From these findings, the sleep or activity rhythm is concluded to be reset predominantly by the work schedule, whereas the circadian rhythm in plasma melatonin and rectal temperature is substantially influenced by the photoperiod.

Activity Cycles↗