Observation of inflammatory responses in mice orally fed with bacteriophage T7.

AIMS: Analysis of inflammatory immune response upon bacteriophage intake in mice. METHODS AND RESULTS: Bacteriophage therapy is emerging as an effective alternative to conventional antibiotics. However, its safety when applied to humans and animals remains a prime concern. This study investigated the inflammatory responses in mice fed orally with bacteriophages. The mice were fed with either murine norovirus (MNV) or bacteriophage T7 for 10 days and then sacrificed. No behavioural changes related to diet, movement or defecation were observed in either group. The inflammatory cytokine profiling showed an increased level of interleukins 1α (IL-1α), 1ß (IL-1ß), 2 (IL-2), 10 (IL-10), 12 (IL-12), 17A (IL-17A), interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α), granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating factor (GM-CSF) in the serum from the mice fed with MNV, whereas only a slight increase in IL-17A was observed in the serum from the mice fed with bacteriophage T7. A histopathological analysis of tissue samples from the stomach, small intestine and colon revealed no significant pathological change. CONCLUSIONS: The bacteriophage diet only caused a minimal inflammatory response in the mice. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides insights into safety concerns of orally fed bacteriophage therapy.

Photon-assisted tunneling through self-assembled InAs quantum dots in the terahertz frequency range.

We have investigated terahertz (THz) photon-assisted tunneling in single self-assembled InAs quantum dots (QDs). Two types of photon-assisted tunneling processes have been observed in the THz range: ground state resonance and photon-induced excited state resonance, depending on the relative magnitude between the orbital quantization energy of the QDs and the THz photon energy. Furthermore, we could realize a very high coupling efficiency between THz waves and QDs and observed multiphoton absorption up to the fourth-order during the tunneling process, resulting in almost complete lifting of the Coulomb blockade.

Chip- and board-level optical interconnections using rigid flexible optical electrical printed circuit boards.

A new optical interconnection scheme based on a rigid flexible optical electrical printed circuit board (RFOE-PCB) is suggested. The easily installed RFOE-PCB can be universally applied for both chip- and board-level optical interconnections. This letter describes the detailed fabrication process, optical properties, and heat-resisting property of the RFOE-PCB. The fabricated RFOE-PCB was also successfully demonstrated with a 2.5-Gb/s data transmission through a 45 degrees-ended optical waveguide embedded in the RFOE-PCB.

Interactive effect of central obesity and hypertension on cognitive function in older out-patients with Type 2 diabetes.

AIM: Central obesity, hypertension and diabetes mellitus have been related individually to cognitive dysfunction. We aimed to study the interactive effects of these co-occurring risk factors on cognitive decline, which remain unclear in older patients with diabetes. METHODS: We assessed metabolic profiles and neuropsychological functions in 60 older out-patients with Type 2 diabetes to examine the associations of central obesity with cognitive functions, while controlling for other confounding factors in these subjects. RESULTS: Waist circumference was associated with poor performance in digits forward (r2 = 0.11, P = 0.02), choice reaction time (r2 = 0.08, P = 0.04) and cognitive reaction time (r2 = 0.07, P < 0.05) even after adjustment for potential confounders including age, gender, education and HbA1c. There were also significant interactions between central obesity and hypertension with respect to performance of digits forward (P = 0.04) and delayed verbal cued recall (P = 0.03). CONCLUSION: Our findings suggest that, in addition to glycaemic control, central obesity and hypertension influence cognitive functions, such as attention and psychomotor speed in older patients with Type 2 diabetes.

The relationship between serum ammonia level and neurologic complications in patients with acute glufosinate ammonium poisoning: A prospective observational study.

Glufosinate ammonium poisoning can cause neurological complications even after a symptom-free period. We prospectively investigated the predictors of neurologic complications in acute glufosinate ammonium poisoning and the change of serum ammonia level as a predictor of patient's presence and recovery of neurologic complication. This prospective observational study collected data from consecutive patients diagnosed with acute glufosinate ammonium poisoning between September 2014 and June 2016. Serum ammonia was serially measured. The patients were divided into two groups: the neurologic complication group and the nonneurologic complication group. We also defined 25 other insecticide- or herbicide-poisoned patients as controls. The neurologic complication group included 18 patients (72.0%). The latency period for neurologic complications was within 48-h postingestion. The peak ammonia level was statistically higher in the neurologic complication group than in the control group ( p < 0.001) and the nonneurologic complication groups ( p = 0.001). There was a statistical difference between the nonneurologic complication group and the neurologic complication group ( p = 0.0085) in terms of ingested amount. The peak ammonia was the only predictor for the development of neurologic complications (the optimal cutoff: 90 µg/dL). In patients with mental changes, the mean serum ammonia levels before and after recovery of the mental changes were statistically different ( p = 0.0019). In acute glufosinate ammonium poisoning, serial serum ammonia level measurements are needed and a serum peak ammonia level greater than 90 µg/dL is a predictor of neurologic complications. Also, it is important to treat the hyperammonemia in acute glufosinate ammonium poisoning.

Serum neuron-specific enolase as an early predictor of delayed neuropsychiatric sequelae in patients with acute carbon monoxide poisoning.

Delayed onset of neuropsychiatric symptoms after apparent recovery from acute carbon monoxide (CO) poisoning has been described as delayed neuropsychiatric sequelae (DNS). To date, there have been no studies on the utility of serum neuron-specific enolase (NSE), a marker of neuronal cell damage, as a predictive marker of DNS in acute CO poisoning. This retrospective observational study was performed on adult patients with acute CO poisoning consecutively treated over a 9-month period. Serum NSE was measured after emergency department arrival, and patients were divided into two groups. The DNS group comprised patients with delayed sequelae, while the non-DNS group included patients with none of these sequelae. A total of 98 patients with acute CO poisoning were enrolled in this study. DNS developed in eight patients. The median NSE value was significantly higher in the DNS group than in the non-DNS group. There was a statistical difference between the non-DNS group and the DNS group in terms of CO exposure time, Glasgow Coma Scale (GCS), loss of consciousness, creatinine kinase, and troponin I. GCS and NSE were the early predictors of development of DNS. The area under the curve according to the receiver operating characteristic curves of GCS, serum NSE, and GCS combined with serum NSE were 0.922, 0.836, and 0.969, respectively. In conclusion, initial GCS and NSE served as early predictors of development of DNS. Also, NSE might be a useful additional parameter that could improve the prediction accuracy of initial GCS.

The usefulness of diffusion-weighted magnetic resonance imaging performed in the acute phase as an early predictor of delayed neuropsychiatric sequelae in acute carbon monoxide poisoning.

Delayed onset of neuropsychiatric symptoms after apparent recovery from acute carbon monoxide (CO) poisoning has been described as delayed neuropsychiatric sequelae (DNS). No previous study has determined whether early use of diffusion-weighted magnetic resonance imaging (DWI) can predict which patients will develop DNS in the acute CO poisoning. This retrospective observational study was performed on adult patients with acute CO poisoning consecutively treated over a 17-month period. All included patients with acute CO poisoning underwent DWI to evaluate brain injury within 72 h after CO exposure. DWI was evaluated as follows: (1) presence of pathology, (2) number of pathologies, (3) asymmetry, and (4) location of pathology. Patients were divided into two groups. The DNS group was composed of patients with delayed sequelae, while the non-DNS group included patients with no sequelae. A total of 102 patients with acute CO poisoning were finally enrolled in this study. DNS developed in 10 patients (9.8%). Between the DNS group and the non-DNS group, presence of pathology on DWI and initial Glasgow Coma Scale (GCS) showed significant difference. There was also a statistical difference between the non-DNS group and DNS group in terms of CO exposure time, troponin I, rhabdomyolysis, acute kidney injury, and pneumonia. The presence of pathology in DWI and initial GCS (cutoff: <12) at the emergency department served as an early predictors of DNS.

Effects of dopamine and metoclopramide in polycystic ovary syndrome.

A relative deficiency in dopamine has been suggested to explain the inappropriate gonadotropin secretion and postulated increased GnRH secretion characteristic of polycystic ovary syndrome (PCO). Previous studies demonstrated an exaggerated decrement in serum LH after large iv doses of dopamine (DA, 4-5 micrograms/kg X min). Normoprolactinemic patients with PCO and weight- and estrogen-matched normal women received iv infusions of DA in two doses (0.5 and 4 micrograms/kg X min). After DA, each subject also received iv metoclopramide (MCP; 10 mg). Serum LH decreased (P less than 0.05) during DA infusion to a similar degree in PCO [23 +/- 3% (+/- SE)] and normal women (20 +/- 2%). In PCO patients, the decrease in LH was similar with both DA doses. Serum PRL and TSH responses to DA were also similar in PCO and normal women. After MCP treatment, serum LH did not change, but serum PRL increased more in PCO (801 +/- 100%) than in normal women (467 +/- 73%; P less than 0.05), as did serum TSH. These data suggest that the sensitivity of LH to DA in patients with PCO is not increased. Further, increased responses of PRL and TSH to MCP may reflect increased dopaminergic activity or, in the case of PRL, the influence of chronic hyperestrogenism.

Features and prognosis of exertional syncope in light-chain associated AL cardiac amyloidosis.

Syncope is common in AL amyloid heart disease and in almost 1/3 of our patients who experienced syncope, it was precipitated by physiologic stress. Stress-precipitated syncope was associated with a poor prognosis in such patients, both in terms of their median survival of 2 months and was frequently a precursor of sudden cardiac death.

Electrocardiography and Doppler echocardiography in secondary (AA) amyloidosis.

The fibrils in AL and AA amyloidosis, although similar in appearance, have different biochemical composition and staining characteristics. Whereas electrocardiographic and echocardiographic features of heart involvement in AA amyloidosis resemble those for AL amyloidosis, our findings support the concept that the constituent amyloid fibrils may play a decisive role in the clinical pattern and significance of heart infiltration.

The effect of ellagic acid on xenobiotic metabolism by cytochrome P-450IIE1 and nitrosodimethylamine mutagenicity.

Ellagic acid (EA) is an inhibitor of the in vitro mutagenicity of N-nitrosodimethylamine (NDMA) in Salmonella typhimurium strain TA100 using pyrazole-induced rat liver 9000 x g supernatant (S-9). In order to understand this activity, the effect of EA on the metabolic hydroxylation of 4-nitrophenol, a substrate, as is NDMA, for cytochrome P-450IIE1 was studied using pyrazole induced rat S-9 and microsomal protein. It is shown that EA has an inhibitory effect on 4-nitrophenol hydroxylase with both enzyme preparations. This effect on cytochrome P-450IIE1 may be responsible, at least in part, for the inhibition of NDMA mutagenicity by EA.

Freezing immature oocytes.

The establishment of a long-term preservation system for mammalian oocytes is important for the development of both biological and medical sciences. A number of efforts have been made to develop this system. In human reproductive medicine, the development of an oocyte cryopreservation system can improve the efficacy of the current assisted reproductive technology (ART) for infertile patients with severe reproductive disorders. In this article, the technical development of cryopreservation programs for human oocytes and its biological background were reviewed. Clinical outcome after the use of this technology was further introduced.

An unusual venous anomaly of the placenta.

The authors present an unusual vascular anomaly of the placenta. The placenta was very large, weighing 1,490 g. On the fetal surface, numerous dilated and tortuous vessels were observed on and under the chorionic membrane, of which three branches arose from a vein that was connected to the umbilical vein. One of them had a 5 x 2.5 cm aneurysmal dilatation, where three secondary branches arose. These venous channels were dilated and tortuous. The longest secondary branch was 133 cm in length and 1.2 cm in mean diameter and led into the placenta. Multiple, severely coiled or straight small branches arising from these vessels were also observed as vascular tangles. Some of these smaller vessels also led into the placenta. All abnormal vessels were veins. The umbilical cord was also normal except for a membranous insertion, and the placenta was unremarkable except for its large size.

Isolation, characterization, and mapping of the stay green mutant in rice.

Leaf color turns yellow during senescence due to the degradation of chlorophylls and photosynthetic proteins. A stay green mutant was isolated from the glutinous japonica rice Hwacheong- wx through N-methyl-N-nitrosourea mutagenesis. Leaves of the mutant remained green, while turning yellow in those of the wild-type rice during senescence. The stay green phenotype was controlled by a single recessive nuclear gene, tentatively symbolized as sgr(t). All the phenotypic characteristics of the mutant were the same as those of the wild-type lines except for the stay green trait. The leaf chlorophyll concentration of the mutant was similar to that of the wild-type before heading, but decreased steeply in the wild-type during grain filling, while very slowly in the mutant. However, no difference in photosynthetic activity was observed between the stay green mutant and the yellowing wild-type leaves, indicating that senescence is proceeding normally in the mutant leaves and that the mutation affects the rate of chlorophyll degradation during the leaf senescence. Using phenotypic and molecular markers, we mapped the sgr(t) locus to the long arm of chromosome 9 between RFLP markers RG662 and C985 at 1.8- and 2.1-cM intervals, respectively.

Multifrequency bioelectrical impedance fails to quantify sequestration of abdominal fluid.

Multifrequency bioelectrical impedance analysis (MFBIA) was used to determine the intracellular (ICW) and extracellular water (ECW) compartments in rats. Resistance and reactance were measured on various body segments with frequencies ranging from 1 KHz to 1 MHz. After initial measurements, 0.9% NaCl was injected intravenously or intraperitoneally, and changes in ECW and ICW were estimated by MFBIA. Important differences were found between segments. In the leg, estimated ECW increased in proportion to the volume of intravenous fluid infused, whereas estimated ICW changed minimally. However, in the trunk region, both estimated ECW and ICW were increased with intravenous and intraperitoneal injections. Our findings indicate that MFBIA has important limitations for quantifying fluid compartments in the trunk and thus in whole body, especially when applied to ill patients in whom sequestration of fluid in the trunk region frequently occurs.

Window operation: an alternative treatment method for Bartholin gland cysts and abscesses.

Recently, we developed the "window operation" as a more effective way to treat Bartholin gland cysts and abscesses. The window operation was used to treat 25 Bartholin cysts and 22 Bartholin abscesses during a 3-year period from October 1, 1986 to September 30, 1989. Under local anesthesia, a small piece of skin including the cyst wall was excised in an oval shape, and suturing was performed along the excised margin. Postoperative antibiotics were given in cases of acute inflammation. A new mucocutaneous junction was observed at the 4-week postoperative checkup. No complications or recurrences have been observed during the study period. The window operation can be an alternative method of treatment for Bartholin gland cysts or abscesses.

Interrupted circular suture: bleeding control during cesarean delivery in placenta previa accreta.

Rapid accumulation of blood from the placental separation site during cesarean delivery for placenta previa obscures the surgical field and quickly leads to deterioration of the patient's vital signs. We used the following technique in eight cases of intractable bleeding among 49 cesareans for placenta previa. Following failure to control the bleeding by suture at the placental separation site via the lower segment cesarean incision, the vessels were ligated using interrupted 2-3-cm sutures at 1-cm intervals in a circle around the bleeding area on the serosal surface of the uterus. The sutures were placed as deeply as possible in order to reach the endometrium. This led to a marked decrease in bleeding and allowed the small vessels to be easily identified and ligated. The amount of blood transfused and the operation time were gradually reduced as we became adept in the use of this procedure. Our experience suggests that this technique could reduce the use of hysterectomy in cesarean for placenta previa.

Multifrequency bioelectrical impedance estimates the distribution of body water.

Multifrequency bioelectrical impedance analysis was used to estimate the ratio of extracellular water (ECW) to total body water in subjects with end-stage renal disease. The body's resistance was measured at frequencies ranging from 1 kHz to 1 MHz. The impedance index (height2/resistance) determined at low frequency (5 kHz) correlated most closely with ECW (r = 0.886) using sodium bromide dilution as the standard of comparison. In contrast, the ratio of height squared to resistance determined at high frequency (500 kHz) correlated most closely with total body water (r = 0.974) using deuterium oxide dilution as the standard of comparison. The ratio of resistance at 500 kHz to resistance at 5 kHz was directly correlated (r = 0.767) with the ratio of ECW to total body water. Multifrequency bioelectrical impedance analysis may assist in the evaluation of body water distribution in endstage renal disease and other clinical disorders of fluid volume and/or distribution.

The clinical features of immunoglobulin light-chain (AL) amyloidosis with heart involvement.

We reviewed clinical presentation, investigations, therapy, prognosis and outcome of 232 patients with primary (AL) cardiac amyloidosis. There were 142 men and 90 women. Median age at presentation was 59 years (range 29-85). AL heart disease was unusual both in patients under the age of 40 (3.0%) and in non-Caucasians (6.5%). Fatigue and weakness were the commonest presenting symptoms. Hallmark features of periorbital ecchymoses and macroglossia were present in 12.5% and 27.2%, respectively. AL cardiac amyloidosis was unusual in isolation (3.9%), and most frequently patients had features of multiorgan dysfunction; heavy proteinuria and features of malabsorption predominating in this respect. Heart involvement represents the worst prognostic indicator, with a median survival from diagnosis of 1.08 years, falling to 0.75 years with the onset of heart failure. Current therapeutic procedures appear to prolong survival, with left ventricular wall thickness, mass and ejection fraction on echocardiography and late potentials on signal averaged electrocardiography of use in prognostic stratification. Cardiac involvement from AL amyloidosis is rapidly fatal. It should be suspected in all patients with heart failure who have wall thickening on echo, normal chamber sizes, low EKG voltages and evidence suggesting a multisystem disease.

Tissue-specific expression and activation of N-methylpurine-DNA glycosylase in thymic carcinomas of transgenic mice expressing the SV40 large T-antigen gene.

Simian virus 40 T-tumor antigen (SV40 T-ag) can induce a wide variety of tumors in hamsters and neonatal mice. These tumorigenic effects are predominantly due to the activity of early viral gene products, large T-antigen and small t-antigen. We have analyzed the expression of a DNA repair gene, N-methylpurine-DNA glycosylase (MPG), from different tissues of a non-transgenic (control) and SV40 T-ag expressing transgenic mice at the mRNA level. Expression of the transgene in thymus of adult mice was also detected by the presence of SV40 T-ag mRNA. Non-transgenic mice did not express the SV40 T-ag gene in their thymus, while the mRNA for MPG was found in thymus from both of transgenic and non-transgenic mice. The MPG gene was expressed in various tissues and is regulated in a tissue-specific manner. Northern blot analysis revealed that the transgenic mice showed considerably higher expression of MPG in the thymic carcinomas. The level of MPG mRNA in the thymic carcinoma was elevated about 5.7 fold, as compared with those found in the control thymus. MPG expression was significantly increased, either directly or indirectly, by the SV40 T-ag gene product. These findings provide the first in vivo observations that the SV40 T-ag gene induced thymic carcinomas associated with the activation of the DNA repair gene, MPG.