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Biomedical subjects

H Koizumi

Publications and source records attributed to H Koizumi.

At least 55 records · Page 3Linked to original sources

Nuclear expression of the p16CDKN2 gene product during senescence of human pharyngeal epithelial cells.

OBJECTIVE: It has been proposed that a gene mapping to human chromosome 9p21 plays a critical role in cellular senescence. CDKN2 is a tumor suppressor gene on chromosome 9p21. It encodes a nuclear protein, p16, which inhibits the D-type cyclin/cyclin-dependent kinase complexes that phosphorylate the retinoblastoma protein, thus blocking cell cycle progression through G1. The purpose of this study was to determine whether nuclear p16 expression is altered during the senescence of human pharyngeal epithelial cells (HPECs) m vitro. METHODS: An immunocytochemical study was performed to examine a panel of cultured HPECs with a finite lifespan for the nuclear p16 expression. All HPEC cultures were also subjected to a histochemical assay that identifies senescent cells by their positive beta-galactosidase activity. RESULTS: Nuclear p16 was undetectable when HPECs were initially cultured in serum-free low-calcium medium. However, nuclear p16 was clearly detected when the cultured HPECs exhibited beta-galactosidase activity in the same medium. CONCLUSION: These results suggest that immunocytochemically detectable amounts of nuclear p16 are associated with senescence of HPECs in vitro.

Calcium↗

Estimating neural sources from each time-frequency component of magnetoencephalographic data.

We have developed a method that incorporates the time-frequency characteristics of neural sources into magnetoencephalographic (MEG) source estimation. This method, referred to as the time-frequency multiple-signal-classification algorithm, allows the locations of neural sources to be estimated from any time-frequency region of interest. In this paper, we formulate the method based on the most general form of the quadratic time-frequency representations. We then apply it to two kinds of nonstationary MEG data: gamma-band (frequency range between 30-100 Hz) auditory activity data and spontaneous MEG data. Our method successfully detected the gamma-band source slightly medial to the N1m source location. The method was able to selectively localize sources for alpha-rhythm bursts at different locations. It also detected the mu-rhythm source from the alpha-rhythm-dominant MEG data that was measured with the subject's eyes closed. The results of these applications validate the effectiveness of the time-frequency MUSIC algorithm for selectively localizing sources having different time-frequency signatures.

Acoustic Stimulation↗

Assessment of heating effects in skin during continuous wave near infrared spectroscopy.

Near infrared spectroscopy is an increasingly important tool for the investigation of human brain function, however, to date there have been few systematic evaluations of accompanying thermal effects due to absorption. We have measured the spatial distribution of temperature changes during near infrared irradiation (789 nm) as a function of laser power, in both excised tissue (chicken meat and skin) and in the forearm of an awake human volunteer. Light was applied using a 1 mm optical fiber which is characteristic of the topographic system. The temperature of excised chicken tissue increased linearly with power level as 0.097 and 0.042 degrees C/mW at depths of 0 and 1 mm, respectively. Human forearm studies yielded temperature changes of 0.101, 0.038, and 0.030 degrees C/mW at depths of 0.5, 1.0, and 1.5 mm, respectively. Due to direct irradiation of the thermocouple all measurements represent the maximum temperature increase from the laser. In all cases the estimated heating effects from continuous wave optical topography systems were small and well below levels which would endanger tissue cells. The close similarity between ex vivo and in vivo measurements suggests negligible contributions from blood flow in the skin which was further supported by measurements during cuff ischemia. Heating effects decreased sharply with both depth and lateral position; thus, for optode spacings greater than a few millimeters, fibers can be treated independently. Finite element analysis confirms that the experimental results are consistent with a simple heat conduction model.

Animals↗

Activation of the visual cortex imaged by 24-channel near-infrared spectroscopy.

Near-infrared spectroscopy (NIRS) is a noninvasive technique for continuous monitoring of the amounts of total hemoglobin (total-Hb), oxygenated hemoglobin, (oxy-Hb) and deoxygenated hemoglobin (deoxy-Hb). The purpose of the present study was to demonstrate the utility of NIRS in functional imaging of the human visual cortex. A new NIRS imaging system enabled measurements from 24 scalp locations covering a 9 cm sq area. Topographic images were obtained from interpolations of the concentration changes between measurement points. Five healthy subjects between 25 and 49 years of age were investigated. After a resting baseline period of 50 s, the subjects were exposed to a visual stimulus for 20 s, followed by a 50 s resting period in a dimly lit, sound attenuating room. The visual stimulus was a circular, black and white, alternating checkerboard. In four of five subjects the visual cortex was the most activated area during visual stimulation. This is the first reported use of a NIRS-imaging system for assessing hemodynamic changes in the human visual cortex. The typical hemodynamic changes expected were observed; the total-Hb and oxy-Hb increased just after the start of stimulation and plateaued after 10 s of the stimulation period.

Adult↗

Noninvasive cerebral blood volume measurement during seizures using multichannel near infrared spectroscopic topography.

Near infrared spectroscopic topography (NIRS) is widely recognized as a noninvasive method to measure the regional cerebral blood volume (rCBV) dynamics coupled with neuronal activities. We analyzed the rCBV change in the early phase of epileptic seizures in 12 consecutive patients with medically intractable epilepsy. Seizure was induced by bemegride injection. We used eight-channel NIRS in nine cases and 24 channel in three cases. In all of the cases, rCBV increased rapidly after the seizure onset on the focus side. The increased rCBV was observed for about 30-60 s. The NIRS method can be applied to monitor the rCBV change continuously during seizures. Therefore, this method may be combined with ictal SPECT as one of the most reliable noninvasive methods of focus diagnosis.

Adult↗

Expression of prolactin mRNA in rat mammary gland during pregnancy and lactation.

We studied the expression of prolactin (PRL) mRNA in the mammary gland of resting, pregnant, lactating, and weanling rats using in situ and solution reverse transcriptase-polymerase chain reaction (RT-PCR). In mid- to late pregnancy and throughout lactation, PRL mRNA was detected in both in situ and solution RT-PCR. These PRL mRNA signals were clearly identified in the cytoplasm of alveolar and ductal mammary epithelial cells by the in situ RT-PCR method. In mid- to late pregnancy, such as at the initiating point of PRL mRNA expression, we confirmed in some cases a lack of PRL mRNA by solution RT-PCR. In addition, in the early weaning phase, no signals were detected by solution RT-PCR. However, slight focal signals were detected in some poorly vacuolated cytoplasm of regressing acinar cells by in situ RT-PCR. These findings suggest that PRL mRNA in rat mammary gland begins in mid- to late pregnancy in parallel with the development of the mammary gland, continues throughout lactation, and declines in the early phase of weaning, with regression of mammary epithelial cells.

Animals↗

[Coronary revascularization in a patient with bilateral internal carotid artery stenosis and aneurysm of brachiocephalic artery: a case report].

A 67-year-old man with a twenty-year history of effort angina was referred to our hospital. He underwent successful PTCA for the right coronary artery and diagonal branch. However, his angina recurred three months after PTCA due to restenosis and he was recommended to undergo CABG. Because he had concomitant bilateral internal carotid artery stenosis and aneurysm of the brachiocephalic artery, we chose two-staged operation strategy to avoid cerebrovascular complication during CABG. First, he underwent bilateral carotid endarterectomy (CEA), and then he underwent concomitant CABG and grafting of brachiocephalic artery 12 days after CEA. After these operations he recovered uneventfully without neurological complication.

Aged↗

[A case of collapsing variant of FSGS].

We report a case of collapsing variant of FSGS. An 82-year-old man without HIV-1 infection or a history of intravenous drug abuse was admitted to our hospital with the chief complaints of acute onset of generalized edema and loss of appetite. Laboratory findings were consistent with nephrotic syndrome. He developed acute renal insufficiency. Initially, we suspected minimal change nephrotic syndrome and started steroid pulse therapy but the nephrotic syndrome was refractory and a renal biopsy was performed. The pathologic findings were judged to be consistent with a collapsing variant of focal segmental glomerulosclerosis (FSGS). This form was described by Weiss et al. in 1986 as a clinically and pathologically distinct variant of FSGS. Valeri et al. further reported that the incidence of this idiopathic collapsing type of FSGS which is devoid of evidence of HIV-1 infection or intravenous drug abuse has progressively increased over the past two decades. They reported that cyclosporin is effective for the treatment of this type of FSGS with a remission rate of about 30%. The present case also had a nearly complete remission after 2 month-cyclosporin treatment. In Japan, no adult case of this type of FSGS has been reported according to our review of the literature.

Aged↗

[Positive rate of anti-mitochondrial antibody in Japanese corporate workers].

Anti-mitochondrial antibody(AMA) has been reported to be detectable in approximately 85% of patients with primary biliary cirrhosis(PBC). Therefore, a test for AMA is acceptable to be essential for diagnosing PBC. However, the positive rate in Japanese general population has not yet been determined. We tested sera from 1,145 corporate workers who took an annual health check and evaluated the liver of AMA-positive subjects. An indirect immunofluorescence method was used for screening AMA. ELISA and immunoblotting method were used for detecting anti-M2 in AMA-positive cases. AMA was detected in 5 of 1,145(0.44%) corporate workers. AMA positive rate was higher in females than in males(0.91% and 0%, respectively) and the AMA-positive people are all females over age 40. All of the AMA-positive sera are also positive for Anti-M2. Liver biopsy was performed in two AMA-positive cases and the histology was compatible with PBC in both cases.

Adolescent↗

Temporal patterns of trigeminal respiratory activity in rat brainstem-spinal cord in vitro.

Respiratory activity in trigeminal (V) motoneurons was studied in rhythmically active en bloc brainstem-spinal cord preparations isolated from neonatal rats (P0-P3). In the majority of preparations (83%), the temporal pattern of V activity consisted of spontaneous inspiratory phasic discharge with onset delayed or coincident with onset of phrenic motoneuron discharge. Blockade of alpha-2 noradrenergic receptor activation shifted onset of V respiratory discharges earlier than phrenic discharges, while elevation of extracellular potassium concentration or blockade of GABAergic and glycinergic inhibitory synaptic transmission had little effect on temporary pattern of V respiratory discharges. We conclude V motoneurons in the in vitro preparation generate respiratory activity during inspiratory phase, and their temporal patterns are modulated by inhibitory noradrenergic synaptic transmission.

Animals↗

Apoptosis in favourable neuroblastomas is not dependent on Fas (CD95/APO-1) expression but on activated caspase 3 (CPP32).

The mechanisms of apoptosis in neuroblastomas have been investigated by examining the expression profiles of Fas, Fas ligand (FasL), and caspase 3 in 42 primary tumour tissues. Immunohistochemically, no or weak Fas expression was detected in 25 out of 29 neuroblastomas (86 per cent), whereas high levels of expression of FasL and pro-caspase 3 were noted in 30 and 29 of 42 tumours, respectively (approximately 70 per cent). Overexpression of pro-caspase 3, but not FasL, correlated significantly with a younger age and low tumour stage. Western blot analysis of ten neuroblastomas confirmed the lack of Fas expression and the presence of strong FasL expression in all samples and pro-caspase 3 expression in five tumours, of which four belonged to the favourable type. These favourable tumours also showed vigorous Asp-Glu-Val-Asp (DEVD) hydrolytic, or caspase 3-like activities, while the unfavourable tumour lacked such activity. Moreover, immunostaining for the p17 subunit of the caspase 3 heterodimer showed that active caspase 3 was mainly localized in apoptotic tumour cells. Combined together, our results suggest that caspase 3, activated via a Fas-independent pathway, may play important roles in apoptosis, suppression of growth, and, in some cases, regression of favourable neuroblastomas.

Apoptosis↗

Moderate posttraumatic hypothermia decreases early calpain-mediated proteolysis and concomitant cytoskeletal compromise in traumatic axonal injury.

Traumatic brain injury (TBI) in animals and man generates widespread axonal injury characterized by focal axolemmal permeability changes, induction of calpain-mediated proteolysis, and neurofilament side-arm modification associated with neurofilament compaction (NFC) evolving to axonal disconnection. Recent observations have suggested that moderate hypothermia is neuroprotective in several models of TBI. Nevertheless, the pathway by which hypothermia prevents traumatic axonal injury (TAI) is still a matter of debate. The present study was conducted to evaluate the effects of moderate, early posttraumatic hypothermia on calpain-mediated spectrin proteolysis (CMSP), implicated in the pathogenesis of TAI. Using moderate (32 degrees C) hypothermia of 90 min duration without rewarming, the density of CMSP immunoreactive/damaged axons was quantified via LM analysis in vulnerable brain stem fiber tracts of hypothermic and normothermic rats subjected to impact acceleration TBI (90 min postinjury survival). To assess the influence of posthypothermic rewarming, a second group of animals was subjected to 90 min of hypothermia followed by 90 min of rewarming to normothermic levels when CMSP was analyzed to detect if any purported CMSP prevention persisted (180 min postinjury survival). Additionally, to determine if this protection translated into comparable cytoskeletal protection in the same foci showing decreased CMSP, antibodies targeting altered/compacted NF subunits were also employed. Moderate hypothermia applied in the acute postinjury period drastically reduced the number of damaged axons displaying CMSP at both time points and significantly reduced NFC immunoreactivity at 180 min postinjury. These results suggest that the neuroprotective effects of hypothermia in TBI are associated with the inhibition of axonal/cytoskeletal damage.

Animals↗

Postoperative complications in patients of esophageal cancer after neoadjuvant chemotherapy.

We examined the effects of neoadjuvant chemotherapy on surgery by evaluating postoperative complications in 50 patients who had undergone neoadjuvant chemotherapy (Group A) and in 108 patients who had undergone surgery without neoadjuvant chemotherapy (Group B). Toxicity of grade 3 by chemotherapy were WBC in 3 patients (6%), alopecia in 3 patients (6%), and anorexia in 22 patients (44%). There were 4 patients with anastomotic leakage (8%) (all in minor), 5 patients with infection of wound (10%), 6 patients with arrhythmia (12%), no patients with postoperative bleeding, 2 patients with respiratory complications (4%), and no patients who died due to complications in Group A. In Group B, there were 13 patients with anastomotic leakage (13%) (all in minor), 12 patients with infection of the wound (11%), 11 patients with arrhythmia (10%), 2 patients with postoperative bleeding (2%), 8 patients with respiratory complications (7%), and 2 patients who died due to complications (2%). There was no significant difference in the incidence of postoperative complications between the patients who had undergone surgery after neoadjuvant chemotherapy, such as CDDP + 5FU therapy and FAP therapy, and the patients who had undergone surgery without neoadjuvant chemotherapy, in patients who had been diagnosed as being able to undergo relative non-curative resection or better, who had Ccr 60 ml/min or more and no severe complication, and whose stomach could be used for reconstruction of the esophagus, on the condition that surgery would be performed on NC patients at the end of first-course treatment.

Alopecia↗

Recurrence of medulloblastoma 19 years after the initial diagnosis.

A 25-year-old woman presented with recurrent medulloblastoma. She had been diagnosed with cerebellar medulloblastoma and treated for it at the age of 5 years. The new tumor was partially resected and chemotherapy was begun. However, a disseminated tumor of the spine was discovered and, despite radiotherapy, the patient became comatose and died. Histological examination of the tumor specimen showed characteristics similar to those of the first tumor. Late recurrence of medulloblastoma is rare, and a latency period of 19 years is the longest reported. This case violates Collins' rule and exceeds other proposed periods of risk. Extension of the period of follow-up in patients with medulloblastoma is advocated.

Adult↗

Evaluation of the accuracy of preoperative staging in thoracic esophageal cancer.

BACKGROUND: Exact clinical staging before treatment of esophageal cancer has become increasingly important in the evaluation and comparison of the results of different treatment modalities, including surgery, chemotherapy, and radiotherapy. METHODS: The accuracy of preoperative tumor staging by using an esophagography, esophagoscopy, percutaneous and endoscopic ultrasonography, and computed tomography was assessed in 224 patients with resectable esophageal cancer. The results of tumor staging by these tests were compared prospectively with the pathologic stage of the esophagectomy specimens with respect to the T and N categories defined by the International Union Against Cancer TNM classification. RESULTS: For the T category, the overall accuracy was 80%. For the N category, overall accuracy was 72%, with a sensitivity of 78%, a specificity of 60%, and a positive predictive value of 78%. Overall, the accuracy of stage grouping was 56%. CONCLUSIONS: Either the T or N categories can be predicted reliably by clinical staging techniques. However, the preoperative stage grouping might not be valid in resectable, localized esophageal cancer.

Adult↗

Monokine stimulation of interleukin-11 production by human vascular smooth muscle cells in vitro.

Human vascular smooth muscle cells (VSMC) are a component of blood vessels, and secrete a variety of cytokines in atherosclerotic loci. Interleukin-11 (IL-11), a member of IL-6-like cytokines, is reported to be involved in inflammation and tissue remodeling, both of which are observed in atherosclerosis. However, no information is available as to the production of IL-11 by VSMC. Therefore, the expression of IL-11 in VSMC is investigated. The amounts of IL-11 protein and mRNA were determined by enzyme-linked immunosorbent assay (ELISA) and Northern blot analysis, respectively. The expression of IL-11 in VSMC was also immunohistochemically determined. IL-1 alpha, transforming growth factor-beta (TGF beta) and, to a lesser extent, tumor necrosis factor-alpha (TNF alpha) stimulated the IL-11 production by VSMC, and the stimulatory effects of IL-1 alpha and TGF beta on IL-11 production were dose-dependent. IL-1 alpha and TNF alpha synergistically augmented TGF beta-stimulated IL-11 production by VSMC. Immunohistochemical staining also revealed the expression of IL-11 protein in VSMC. Furthermore, IL-1 alpha, TGF beta, and TNF alpha induced IL-11 gene expression in VSMC. Because IL-6-like cytokines are reported to be cytoprotective, monokine-stimulated IL-11 may have a potent protective role in atherosclerotic lesions.

Arteriosclerosis↗

H2 histamine receptor-mediated increase in intracellular Ca2+ in cultured human keratinocytes.

Histamine is present in the epidermis in intracellular and extracellular area and is released from mast cells and keratinocytes in the early stage of inflammation of the skin. Such release may contribute to common itching or intensify the inflammatory responses. Histamine binds to its receptors and participate in regulation of the inflammatory responses by acting on endothelial cells, nerve endings, lymphocytes, monocytes, and leukocytes. Histamine has direct effects on keratinocytes as well. Histamine modulates the proliferation of keratinocytes. The binding of histamine to the receptor on keratinocyte membrane induces activation of adenylate cyclase and phospholipase C through GTP binding protein. We previously reported that histamine induces transient increase in intracellular Ca2+ in cultured normal human epidermal keratinocytes (NHEK) and normal epidermis. H1 and H2 histamine receptors are widely distributed in many tissues and cells. In this study, we investigated which types of histamine receptors are related to the increase in intracellular Ca2+ by histamine stimulation in cultured human epidermal keratinocytes. NHEK were cultured in serum-free KGM medium. With H1 antihistamines, mepyramine and diphenhydramine, histamine responses were moderately but not statistically significantly inhibited. With H2 antihistamine, cimetidine, histamine response was significantly inhibited. Epinephrine response was not affected by these antihistamines. Thus, it is considered that H2 antihistamines specifically block histamine-mediated increase in intracellular Ca2+ of cultured normal human keratinocytes.

Calcium↗