Roles of Department of Clinical Laboratory in infection control

The Department of Clinical Laboratory plays an important role in the hospital and has much information about patients and pathogens. Laboratory data are essential to support clinical physicians who diagnose and treat patients. For nosocomial infections, laboratory-based surveillance is recognized as essential to confirm outbreaks. Therefore, the role of the Department of Clinical Laboratory is very important in infection control. In Tohoku University Hospital, we have an Infection Control Unit located in the Department of Clinical Laboratory. The core role of the Infection Control Unit is diagnosis, treatment and preventative healthcare associated with infections. The Infection Control Team (ICT) performs rounds in the hospital (The ICT members are ICN, ICD, a microbiological technologist and a dietician), consultations about clinical cases, infection control, and organize the regional infection control network, "Miyagi Infection Control Network". The ICT rounds are performed once a week in two wards, and two times a year for one ward. The consultations are an important role of the ICD, and concern clinical infection cases and infection control in our hospital and the other regional hospitals, and produce advice on appropriate clinical information. The regional network is important for the collection of information about the pathogens and the susceptibility of antimicrobial agents in the region. "Miyagi Infection Control Network" has held a forum 5 times a year from 1999, and 300-400 healthcare workers join the forum and discuss infection control.     

The relationships between autonomic function and heart rate in essential hypertension

The circadian variation of blood pressure (BP) may be mediated at least in part by circadian variation of autonomic nervous system activity. In the present study power spectral analysis of hourly R-R intervals for 24 hours was done to obtain the low frequency variability (LF: 0.04 to 0.15Hz) and high frequency variability(HF: 0.15 to 0.40Hz) in 93 patients with untreated essential hypertension. LF/HF ratio and HF were considered to be an index of sympathetic nervous activity and parasympathetic nervous activity, respectively. The relationship between heart rate (HR) and systolic blood pressure (SBP), diastolic blood pressure (DBP), HF, and LF/HF was examined. Both SBP and DBP were correlated positively with HR(r = 0.28, p < 0.05 and r = 0.27, p < 0.05, respectively) in the daytime. HF was correlated negatively and significantly with HR in both daytime and nighttime (r = -0.40, p < 0.05, and r = -0.38, p < 0.05 respectively). After averaging for SBP of 24 hours, HR in the patients whose SBP was 135mmHg or more was significantly higher than that in the patients whose SBP was less than 135mmHg. These results suggest that the decreased parasympathetic nervous activity seems to be responsible for the rise in BP.     

Heat shock proteins play a crucial role in tumor-specific apoptosis by REIC/Dkk-3

We recently showed that overexpression of REIC/Dickkopf-3 (Dkk-3), a tumor suppressor gene, induced apoptosis in a tumor cell-specific manner. The aim of the present study was to determine the mechanisms underlying the selective induction of apoptosis. At first, we found a mouse renal carcinoma cell line, RENCA, to be extremely sensitive to an adenovirus carrying REIC/Dkk-3 (Ad-REIC), and we showed that activation of c-Jun N-terminal kinase (JNK) was a critical step in cell death, i.e. a process similar to that in human prostate and testicular cancer observed in our previous studies. Among the proteins interfering with the activation of JNK, heat shock protein (Hsp)70/72 was reduced in expression in RENCA cells compared with that in NIH3T3 cells. An Hsp70/72 inducer protected RENCA cells from Ad-REIC-induced apoptosis, while an Hsp70/72 inhibitor sensitized NIH3T3 cells for apoptosis induction. These results indicate that functionally active Hsp70/72 is a key factor in tumor cell-specific induction of apoptotic cell death and that analyses of the expression levels of Hsp70/72 may be essential in determining the significance of Ad-REIC-based gene therapy against human cancer.     

Type III hyperlipoproteinema with apolipoprotein E2/2 genotype in Japan

Limited information is available concerning type III hyperlipoproteinemia (HLP) in the Asian population. Therefore, clinical and biochemical characteristics of type III HLP were examined in 16 Japanese patients. Mean plasma triglyceride (TG) and total cholesterol (chol) levels were 381 mg/dl and 253 mg/dl, respectively, and the mean very low density lipoprotein (VLDL)-chol/plasma TG ratio was 0.27, which were lower than those reported in Western countries. Eighty percent of the patients had high plasma remnant-like particles (RLP)-chol levels above 50 mg/dl and a high RLP-chol/plasma TG ratio above 0.1. Twelve patients (75.0%) were obese. Seven patients (43.8%) had type 2 diabetes mellitus and four patients (25.0%) had impaired glucose tolerance. Six patients (37.5%) had coronary heart disease (CHD), but none had peripheral vascular disease or xanthomas. TG-rich lipoproteins from type III HLP patients with diabetes mellitus stimulated cholesteryl ester synthesis by human macrophages significantly (p < 0.001) more than those from type III HLP patients without diabetes mellitus. In conclusion, the Japanese type III HLP patients had lower plasma TG and total chol levels and a lower VLDL-chol/plasma TG ratio, but CHD was more common. The patients were characterized by a high frequency of obesity and/or glucose intolerance. The TG-rich lipoproteins from type III HLP patients with diabetes mellitus were more atherogenic.     

Anterior urethral recurrence of superficial bladder cancer: its clinical significance

The aim of this study was to reveal the clinical features of anterior urethral recurrence in patients with superficial bladder cancer, and to determine the appropriate treatment. Three hundred and three patients with superficial bladder cancer, who were newly diagnosed and initially treated conservatively in our hospital between 1965 and 1990, were followed for at least 5 years and their clinical outcomes were analyzed. Clinical factors, including anterior urethral recurrence, were evaluated statistically regarding tumor progression. Eight patients (2.6%) had anterior urethral recurrence following superficial bladder cancer. Twenty-four patients (7.9%) had tumor progression and 149 (49.2%) had tumor recurrence. In a multivariate analysis using a logistic model, anterior urethral recurrence was the most important factor, followed by histological grade. Four of 5 patients who were treated for anterior urethral recurrent tumors by transurethral resection showed progression and died of the cancer within one year. Two of the remaining three patients who underwent radical cysto-urethrectomy at the time of anterior urethral recurrence survived. Anterior urethral recurrence following superficial bladder cancer is a predictor for rapid subsequent malignant progression. Once there is anterior urethral recurrence, radical intensive therapy, including radical cysto-urethrectomy, should be carried out immediately.     

Medial profrontal cortex and anterior cingulate cortex in the generation of alpha activity induced by transcendental meditation: a magnetoencephalographic study

Previous EEG studies have shown that transcendental meditation (TM) increases frontal and central alpha activity. The present study was aimed at identifying the source of this alpha activity using magnetoencephalography (MEG) and electroencephalography (EEG) simultaneously on eight TM practitioners before, during, and after TM. The magnetic field potentials corresponding to TM-induced alpha activities on EEG recordings were extracted, and we attempted to localize the dipole sources using the multiple signal classification (MUSIC) algorithm, equivalent current dipole source analysis, and the multiple spatio-temporal dipole model. Since the dipoles were mapped to both the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC), it is suggested that the mPFC and ACC play an important role in brain activity induced by TM.     

Long‐term observation of a Japanese mucolipidosis IV patient with a novel homozygous p.F313del variant of MCOLN1

Mucolipidosis type IV (MLIV) is an autosomal recessively inherited lysosomal storage disorder characterized by progressive psychomotor delay and retinal degeneration that is associated with biallelic variants in the MCOLN1 gene. The gene, which is expressed in late endosomes and lysosomes of various tissue cells, encodes the transient receptor potential channel mucolipin 1 consisting of six transmembrane domains. Here, we described 14‐year follow‐up observation of a 4‐year‐old Japanese male MLIV patient with a novel homozygous in‐frame deletion variant p.(F313del), which was identified by whole‐exome sequencing analysis. Neurological examination revealed progressive psychomotor delay, and atrophy of the corpus callosum and cerebellum was observed on brain magnetic resonance images. Ophthalmologically, corneal clouding has remained unchanged during the follow‐up period, whereas optic nerve pallor and retinal degenerative changes exhibited progressive disease courses. Light‐adapted electroretinography was non‐recordable. Transmission electron microscopy of granulocytes revealed characteristic concentric multiple lamellar structures and an electron‐dense inclusion in lysosomes. The in‐frame deletion variant was located within the second transmembrane domain, which is of putative functional importance for channel properties.     

New medical education of laboratory medicine at Tohoku University

The purpose of this paper is to give an insight into the medical education program of our division at Tohoku University. Laboratory medicine in medical education is a field of learned basic clinical tests. Students have to learn the clinical laboratory through early clinical exposure in the first grade and try clinical technology through small-group learning in the fifth grade. Finally, they learn laboratory medicine such as infection control in our or another clinical hospital. The objects of our course are to encourage and promote the highest standards of training and post-graduate education of physicians and scientists at our university.     

Neuropsin is essential for early processes of memory acquisition and Schaffer collateral long-term potentiation in adult mouse hippocampus in vivo

Long-term potentiation (LTP) is thought to be particularly important in the acquisition of hippocampus-associated memory, in part because it develops quickly and persists for indefinite periods. Extracellular proteolysis has been hypothesized to contribute to LTP by modifying adhesive relations of synapses and thus the morphology of excitatory synapses. Here we report that neuropsin (NP), an extracellular serine protease, is critically involved in the formation of both the potentiation effect and hippocampus-dependent forms of memory. NP-knockout mice were significantly impaired in the Morris water maze and Y-mazes and failed to exhibit early phase LTP induced by a single tetanus. Potentiation was also impaired or completely blocked by in vivo application of a specific inhibitor or a neutralizing monoclonal antibody for NP. Intriguingly, recombinant (r-) NP alone, without tetanic stimulation, elicited either long-lasting potentiation or depression, depending on the applied dose. The r-NP-elicited potentiation was occluded by prior induction of LTP, while theta-burst-elicited LTP was occluded by application of r-NP alone, suggesting that the two forms of plasticity have a common signalling pathway. r-NP-elicited potentiation and depression increased phosphorylation at different sites on the GluR1 subunit of the AMPA receptor that had previously been associated with LTP or long-term depression. Thus, we conclude that NP is necessary for establishment of LTP and has a significant role in memory acquisition.