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Biomedical subjects

K Honma

Publications and source records attributed to K Honma.

At least 91 records · Page 5Linked to original sources

Midday exposure to bright light changes the circadian organization of plasma melatonin rhythm in humans.

Effects of bright light exposure at midday were examined on plasma melatonin rhythm in humans under controlled living conditions. Bright light of 5000 1x was provided from the ceiling at midday (1100-1700 h) for 3 consecutive days and the circadian rhythm in plasma melatonin was determined from the fourth to fifth day. The control study was performed in the same subjects who spend four days under dim light conditions (less than 200 1x). The subjects were allowed to sleep from 2400 to 0800 h. The onset phase, but not the end phase, of plasma melatonin rhythm was significantly phase-advanced by bright light exposure. Furthermore, the area under the curve of nocturnal melatonin rise was significantly larger under bright light exposure than under dim light. These findings indicate that midday exposure to bright light for 3 consecutive days changes the circadian organization of plasma melatonin rhythm in humans.

Adult↗

Silicosis, mixed dust pneumoconiosis, and lung cancer.

A total of 764 autopsy cases with a pathological diagnosis of nonasbestos pneumoconiosis were investigated in a search for lung cancer: 146 patients bore 148 lung cancers (19.1%). The incidence of a lung cancer was associated positively with aging longer occupational exposures, and smoking habits. A reverse correlation was found between carcinogenesis and the severity of pneumoconiosis. A statistically significant increase in the incidence of certain types of lung cancer (squamous cell carcinoma + small cell carcinoma) was found in silicotic lungs with massive fibrosis as compared to lungs with mixed dust pneumoconiosis of comparable severity. Although there appears to be no dose-response relationship in general between silicosis and lung cancer, it is advisable to consider the possibility that a presumptive silica-induced carcinogenesis might be masked by the severe fibrosis of a silicotic type, which obliterates the lung tissue in a different way from asbestosis, which is associated with epithelial proliferation.

Aged↗

Cloning and sequence analysis of the fimbriae associated protein (fap) gene from Actinobacillus actinomycetemcomitans.

Fimbrial-associated protein, an attachment factor of Actinobacillus actinomycetemcomitans, was genetically analysed by cloning. The plasmid obtained was found to harbor a 1.7kb fragment which contained a 228bp open reading frame encoding 76 amino acids (7.970kDa). The fimbriae associated protein gene (fap) was strongly expressed in fimbriated A. actinomycetemcomitans 310a but not in non-fimbriated strains.

Aggregatibacter actinomycetemcomitans↗

Malignant fibrous histiocytoma arising from a calcifying enchondroma--a case report.

A man, 79 years of age, developed a malignant fibrous histiocytoma which arose in relation to a calcifying enchondroma of the distal femur. Radiographs showed a fracture through an intensely calcified bony tumour with no bony destruction. The clinical diagnosis was a dedifferentiated chondrosarcoma. Histology showed an anaplastic sarcoma with calcified tissue showing extensive areas of necrosis and degeneration. No chondrosarcomatous foci were found.

Aged↗

A study on lung toxicity of respirable hard metal dusts in rats.

The aetiology of hard metal lung disease has not been clarified so far. The pulmonary toxicity of respirable dusts collected in a hard metal factory was studied in vivo in rats. The effect of the samples was examined 1, 4, 7 and 30 days after single intratracheal injection. Lactate dehydrogenase (LDH), acid phosphatase (AP), protein and phospholipid were determined in cellfree bronchoalveolar lavage (BAL) and lung tissue. The lungs and regional lymph nodes were processed histologically. Lung toxicity of the samples collected during hard metal production varied. Samples containing considerable amount of cobalt dissolved upon acid treatment were found to induce inflammation. It has been established that the biological effect of samples of identical composition is changed by heat treatment and pre-sintering. Our examinations seem to prove that cobalt plays a prominent role in the development of pathological alterations.

Animals↗

Identification of an epitope derived from human proteolipid protein that can induce autoreactive CD8+ cytotoxic T lymphocytes restricted by HLA-A3: evidence for cross-reactivity with an environmental microorganism.

The demyelination process that occurs in the central nervous system (CNS) of patients with multiple sclerosis (MS) is in part due to an inflammatory response in which CD4+ and CD8+ T cells and macrophages infiltrate white matter. In this study, we have identified a peptide sequence derived from the CNS-specific myelin protein proteolipid protein (PLP) which could bind to HLA-A3 and induce a HLA-A3-restricted CD8+ CTL response from HLA-A3+ donors. These PLP peptide-specific CTL could lyse HLA-A3+ target cells pulsed with a homologous peptide derived from the CRM1 protein of Saccharomyces cerevisae. These findings demonstrate the immunogenic potential of a PLP-derived peptide for generation of autoreactive HLA-A3-restricted CD8+ CTL, and further show that these CTL can be activated by a peptide derived from a common environmental microorganism.

Adult↗

DNA vaccination followed by macromolecular multicomponent peptide vaccination against HIV-1 induces strong antigen-specific immunity.

The induction of a strong and long-lasting immunity characterized by both a humoral and cell-mediated immune (CMI) response is one of the most important considerations in developing an effective HIV vaccine. In previous studies, we have independently developed both DNA vaccine and macromolecular multicomponent peptide vaccine (VC1) candidates. In the present study, we attempted to optimize the vaccination protocol using mice, guinea pigs, rabbits and Macaca fuscata monkeys. Repeated vaccination with VC1 induced a substantial level of multivalent antibodies which neutralized various HIV-1 strains, as determined using a p24 inhibition assay. On the other hand, repeated immunization with DNA vaccine induced and sustained high levels of cytotoxic T lymphocytes (CTLs). In addition, when DNA vaccination was followed by multicomponent peptide vaccination, levels of both humoral immunity and CMI increased, and this effect continued for at least 10 months. These data clearly demonstrate that for inducing HIV-1 specific immunity, immunization with DNA vaccine followed by VC1 boosting produces better results than immunizing with either vaccine alone.

AIDS Vaccines↗

Genetic control of immune response to a synthetic fimbrial antigen of Actinobacillus actinomycetemcomitans.

The incidence of infection by Actinobacillus actinomycetemcomitans, one of the important pathogens in human periodontal diseases, has been reported to be associated with racial background and genetic factors. We attempted to determine the genetic regulation of immune responses to A. actinomycetemcomitans fimbriae, an attachment factor, using various inbred strains of mice. For this purpose, we synthesized an oligopeptide antigen using the amino acid sequence of the fimbriae and conjugated this antigen to branched lysine polymer resin beads. After immunization with the synthetic A. actinomycetemcomitans fimbrial antigen, serum antibody levels and the delayed-type hypersensitivity (DTH) reaction to the antigen were measured by enzyme-linked immunosorbent assay (ELISA) and footpad swelling responses, respectively. The strains of mice found to be high-IgG responders to the antigen were B10.HTT, B10.RIII, B10.A (5R) and B10.S (9R). These results indicate that mice with E(beta s):E(alpha k), E(beta r):E(alpha r) and E(beta b):E(alpha k) respond strongly to the synthetic peptide. All of the high-IgG responders showed a high DTH response. A cell transfer experiment confirmed that CD4 T cells mediated with DTH response to the synthetic peptide. Thus, the results of this study demonstrate that the immune responses to A. actinomycetemcomitans fimbriae are genetically controlled.

Aggregatibacter actinomycetemcomitans↗

Free-running circadian rhythm of melatonin in a sighted man despite a 24-hour sleep pattern: a non-24-hour circadian syndrome.

Sleep and plasma melatonin rhythms were measured longitudinally in a sighted young man (21 years old) under a day-right environment. At each measurement, the responsiveness of the melatonin rhythm to a single light pulse was examined in addition to the 24-hour profile. In experiment 1, the timing of sleep was decided by the subject himself. Although most sleep episodes were observed between 21:02 h and 10:55 h, the plasma melatonin rhythm free-ran for a period of 24.18 h. In experiment 2, the sleep-wake schedule of the subject was strictly fixed. The subject was instructed to go do bed at 24:00 h and wake up, at the latest, before 8:00 h for 40 days. The melatonin rhythm, however, continued to free-run for a period of 24.12 h. Nocturnal melatonin level could not be suppressed by a 3-hour light pulse of 500 lx, but was suppressed by a pulse of 1000 lx. It is concluded that internal desynchronization occurred in this particular sighted subject where the sleep-wake rhythm was entrained by the 24-hour day-night environment, whereas the plasma melatonin rhythm free ran, and that a forced sleep schedule did not act as a strong zeitgeber.

Adult↗

A sighted man with non-24-hour sleep-wake syndrome shows damped plasma melatonin rhythm.

Twenty-four-hour profiles of plasma melatonin, cortisol and rectal temperature were measured longitudinally in a sighted man who has been suffering from sleep disorders for more than 10 years. The sleep-wake rhythm of this subject free-ran, despite his routine life, and occasionally showed a sign of internal desynchronization, where sleep was lengthened up to 30 h. These states were classified into the non-24-hour sleep-wake syndrome. Plasma melatonin concentrations in the subjective night remained at a low level and showed a damped circadian rhythm. At the same time, robust circadian rhythms were detected in plasma cortisol and rectal temperature, indicating that the circadian pacemaker was intact. The causal relationship between the damping of nocturnal melatonin rise and a failure of entrainment of the sleep-wake cycle is discussed.

Adult↗

Daily melatonin intake resets circadian rhythms of a sighted man with non-24-hour sleep-wake syndrome who lacks the nocturnal melatonin rise.

Effects of daily melatonin intake on the circadian rhythms of sleep and wakefulness, rectal temperature and plasma cortisol were examined in a sighted man who had suffered from the non-24-hour sleep-wake syndrome. The subject lacked the nocturnal melatonin rise in plasma, but showed robust circadian rhythms in rectal temperature and plasma cortisol. The sleep-wake rhythm free-ran with a period longer than 24 hours. Daily melatonin intake at 21:00 h concentrated sleep episodes in the nocturnal period (24:00-8:00 h), and increased the length of the episodes. A single oral dose (3 mg) of melatonin increased plasma melatonin levels to about 1300 pg/mL within one hour and remained at pharmacological levels for approximately 6 hours. The trough of rectal temperature and the circadian rise of plasma cortisol were fixed to the early morning. A higher dose of melatonin (6 mg) did not improve the general feature. After the cessation of melatonin intake, the sleep-wake rhythm began to free-run together with the circadian rhythms in rectal temperature and plasma cortisol. It is concluded that daily intake of melatonin at early night time resets the circadian rhythms in a sighted man who lacked the nocturnal melatonin rise and showed free-running circadian rhythms in routine life.

Administration, Oral↗

Immunohistochemical localization of endothelin-1, endothelin-3 and endothelin receptors in human pheochromocytoma and paraganglioma.

Endothelin (ET) and its receptor system have been shown to exert various biological effects on different types of cells in addition to their well-known vasoconstrictor activity. Recently ET-1, ET-3 and the ETB receptor have been shown to play an important role in the development of neural crest-derived cells and, in this context, pheochromocytomas have been reported to harbor ET-1. Endothelin-3 or ET receptor subtypes, however, have not been examined in pheochromocytoma and paraganglioma so far. In the present study the immunohistochemical localization of ET-1/big ET-1, ET-3/big ET-3 and the ETA and ETB receptors were investigated to clarify the biological characteristics of these two tumors using 32 pheochromocytomas and 11 extra-adrenal paragangliomas. Endothelin-1/big ET-1 was detected in 19 pheochromocytomas (59%) and eight paragangliomas (72%), while ET-3/big ET-3 was detected in 10 pheochromocytomas (31%) and three paragangliomas (27%). The ETA receptor was found in 21 pheochromocytomas (66%) and in eight paragangliomas (73%), while the ETB receptor was found in 25 pheochromocytomas (78%) and in eight paragangliomas (73%). Normal adrenomedullary cells lacked each antigen examined. Endothelin-immunoreactive tumor cells were distributed focally or in a manner scattered, while receptor-immunostained tumor cells were distributed with a focal pattern for the ETA receptor and with a focal or diffuse pattern for the ETB receptor. Endothelin and its receptor coexisted in the same tumor in 21 of 28 ET-positive pheochromocytomas and in eight of 10 ET-positive paragangliomas. In addition, seven pheochromocytomas and two paragangliomas revealed positivity of the receptor(s) irrespective of the absence of ET-immunoreactivity. In conclusion, ET and its receptor are frequently and concomitantly expressed in the pheochromocytoma and paraganglioma. From the highly frequent expression of this system or the receptor(s), ET-receptor-mediated signal transduction of these tumors concerning growth and/or cell survival is expected, although definite biological significance of this ligand-receptor system in these tumors awaits further investigation.

Adrenal Gland Neoplasms↗

Comparison of specificity between IgG, IgE and T cells to three casein components: implication for the role of circulating allergen-specific T cells in food allergy.

In order to investigate the role of food antigen-specific T cells circulating in the blood of patients with food allergy, we compared T cell response to three casein components (alpha s-, beta- and, kappa-casein) with specificities of IgG and IgE binding to the casein components in four milk-allergic patients (P1-4) with atopic dermatitis. In all patients the binding activities of IgG antibodies to alpha s-casein were most dominant, followed by those to beta- and to kappa-casein. The major component of casein bound by IgE antibodies was alpha s-casein in P1 and P3, kappa-casein in P2, and alpha s-casein as well as kappa-casein in P4; the order of casein components bound by IgE antibodies was different from that by IgG antibodies. Proliferative responses of peripheral blood mononuclear cells (PBMC) to casein components were so low that the dominance of casein recognition could not be clearly demonstrated. However, short-term T cell lines that specifically respond to casein were successfully established from PBMC of the four patients and the proliferative responses of the T cell lines to the three components of casein were in accord with the IgE antibody specificity to casein components but not with that of IgG antibody specificity. When taken together, these results indicate that casein-specific T cells circulating in the blood are involved in or reflect an allergic reaction against casein.

Caseins↗

Vitamin B12 enhances the phase-response of circadian melatonin rhythm to a single bright light exposure in humans.

Eight young males were subjected to a single blind cross-over test to see the effects of vitamin B12 (methylcobalamin; VB12) on the phase-response of the circadian melatonin rhythm to a single bright light exposure. VB12 (0.5 mg/day) or vehicle was injected intravenously at 1230 h for 11 days, which was followed by oral administration (2 mg x 3/day) for 7 days. A serial blood sampling was performed under dim light condition (less than 200 lx) and plasma melatonin rhythm was determined before and after a single bright light exposure (2500 lx for 3 h) at 0700 h. The melatonin rhythm before the light exposure showed a smaller amplitude in the VB12 trial than in the placebo. The light exposure phase-advanced the melatonin rhythm significantly in the VB12 trail, but not in the placebo. These findings indicate that VB12 enhances the light-induced phase-shift in the human circadian rhythm.

Adult↗

Intertrabecular pattern of tumors metastatic to bone.

BACKGROUND: The prevalence of radiologically invisible metastatic tumors to bone is not known. To clarify this, the authors examined histologic sections, radiographs, bone scans, and magnetic resonance (MR) images of autopsied patients with bone metastases. METHODS: Complete slices of the vertebral column, including C3-S1, were obtained from 52 cadavers with metastatic tumors to the spine. Macroscopic and histologic features were compared with postmortem roentgenographs (52 patients), bone scans with 99mTc-labelled methylene diphosphonate (17 patients), and MR images (4 patients). Morphologic patterns were classified into intertrabecular, osteoblastic, osteolytic, mixed, small lesion, and compression fracture. RESULTS: Metastatic lesions were found in 734 of the 1194 vertebral bodies. The lesions were intertrabecular in 255 vertebrae, osteoblastic in 185, osteolytic in 114, mixed in 70, small lesion in 83, and compression fracture in 27. Postmortem radiographs demonstrated lesions in 367 (50%) of the 734 vertebrae, bone scans in 103 (34.7%) of the 297 vertebrae examined, and MR images in all 42 (100%) vertebral bodies imaged. Lesions showing an intertrabecular pattern were detected in only 7.1% of the radiographs and 4.5% of the bone scans. CONCLUSIONS: Radiographs and bone scans often fail to show metastatic lesions, especially those with an intertrabecular pattern. The intertrabecular pattern is a unique histologic form that is difficult to detect on radiographs and bone scans.

Adult↗

Persistence of circadian oscillation while locomotor activity and plasma melatonin levels became aperiodic under prolonged continuous light in the rat.

In order to examine the mechanism for a loss of circadian rhythms in several functions under prolonged continuous light (LL), rats were blinded following LL over 5 months, and the mode of reappearance of circadian rhythms were analyzed in locomotor activity and plasma melatonin levels. Locomotor activity and plasma melatonin levels in individual rats became aperiodic after the exposure to LL. On the day of blinding, plasma melatonin levels showed circadian rhythms having a peak coincided with the activity time of locomotor rhythm which was restored after blinding. The time of melatonin peak was not related to the time of blinding (onset of darkness) nor to the initial time of blood sampling. Circadian rhythm in plasma melatonin levels reappeared faster than those in locomotor activity. The findings suggest that aperiodism developed in these functions under prolonged LL is not due to disruption of the circadian oscillation but to uncoupling of overt functions from the circadian pacemaker.

Animals↗

Substance P receptor regulates the photic induction of Fos-like protein in the suprachiasmatic nucleus of Syrian hamsters.

Substance P (SP) is a candidate neurotransmitter or neuromodulator for conveying light information from the retina to the hypothalamic suprachiasmatic nucleus (SCN) where a circadian oscillator(s) is located in mammals. Immediate early gene c-fos has been demonstrated to be induced in the SCN with a brief light exposure at the subjective night, and suggested to play an important role in the photic entrainment of the oscillator. To clarify the possibility of an involvement of the SP receptor in the photic-induction of c-fos in the SCN, we examined effects of a SP receptor antagonist, spantide, on the light-induced Fos-like protein immunoreactivity (Fos-lir) in the SCN of Syrian hamster. The light-induced Fos-lir was inhibited with the pretreatment of spantide in a dose-related manner and in an anatomically distinctive way. The higher dose of spantide (8 nmol) blocked light-induced Fos-lir substantially in the rostral and central areas of the SCN, and in the dorsal portion of the caudal SCN. However, it blocked Fos-lir only slightly in the ventral portion of the caudal SCN. These results suggest that the SP is involved in conveying light information to induce Fos protein in the hamster SCN, and that different neurotransmitter systems are involved in the light-induced Fos-lir in the different portions of hamster SCN.

Animals↗

Methamphetamine stimulates the release of neuropeptide Y and noradrenaline from the paraventricular nucleus in rats.

Effects of methamphetamine (MAP) on the extracellular neuropeptide Y (NPY) and noradrenaline (NA) levels were examined in the vicinity of the paraventricular nucleus (PVN) of freely moving rats by means of push-pull perfusion. The NA and NPY levels increased significantly in 30-60 min and reached the maximum level in 90-120 min after intraperitoneal administration of MAP. The effects were dose-dependent. The maximum levels were 1.6-fold of the pretreatment level for NPY and 7-fold for NA, respectively, when 5.0 mg/kg b.w. of methamphetamine was administered. It is concluded that MAP stimulates the releases of paraventricular NPY and NA, but the effect is more strong for NA than for NPY.

Animals↗