Changes of enzyme activity levels in red blood cells in hemodialysis patients by recombinant human erythropoietin.

In a phase II clinical trial to test the ability of recombinant human erythropoietin (r-HuEPO) to reverse the anemia of patients undergoing hemodialysis, the changes of enzyme activity in red blood cells were evaluated in 5 hemodialysis anemic patients who were treated with r-HuEPO. Concerning the activity levels measured, the following conclusions are drawn. 1) HK, ALD, TPI, G6PD and 6PGD were statistically significantly increased at the time when the hematocrit has risen by 8% with the use of r-HuEPO. 2) The enzyme activity levels of PFK, GA3PD, MPGM, ENOL, PK, GR and ADA were higher than normal already before the r-HuEPO treatment. 3) The increases of HK and G6PD by r-HuEPO, as age dependent enzymes, may reflect the generation of young red blood cells. 4) In view of the fact that they are related to ATP production in the glycolysis cycle, we infer that increases of red blood cell enzymes by r-HuEPO may play at least some part in bringing a sensation of "well-being" to severely anemic patients undergoing hemodialysis.     

Transient enlargement and spontaneous regression of interhemispheric cysts--a case report

We report a 5-year-old male patient with interhemispheric cysts which showed spontaneous reduction in size. The patient was consulted to our hospital at 2 days of life for the evaluation of intracranial cysts found by fetal ultrasonography. Magnetic resonance imaging (MRI) on admission disclosed multiple cysts in the interhemispheric region and agenesis of the corpus callosum. MRI performed later disclosed the association of pachygyria and heterotopia. On follow-up MRIs, the cysts peaked in size at 5 month of age and gradually reduced thereafter. He showed transient hypertonia but had neither neurological deficits nor signs of increased intracranial pressure except transient hypertonia throughout the course. The present case is the first with interhemispheric cysts showing spontaneous reduction in size. While the present case suggested that an interhemispheric cyst dose not necessarily need a surgical treatment, and that it is difficult to determine surgical indication based on clinical manifestations.     

A new periodogram using one-way analysis of variance for circadian rhythms

A new periodogram was proposed using one-way analysis of variance (ANOVA), termed ANOVA periodogram, in order to reveal a precise significant periodicity. Thirty 3-day complex computer-simulated time series with known periodicity (24 h) and three 2-h data-missing occurring periodically (23 h, 20 min) were used to compare the ANOVA periodogram with Enright's one. In results, the ANOVA periodogram was superior to Enright's periodogram in the accuracy of assessing the major periodicity.     

Exposure to 1-bromopropane causes ovarian dysfunction in rats.

Although 1-bromopropane has been used in chemical and electronic industries as an alternative to ozone layer-depleting solvents, its toxicity on female reproductive organs has not been fully elucidated. The aim of this experiment was to determine the effect of 1-bromopropane on female reproductive function in rats. Forty female Wistar rats were divided into four equal groups. Each group was exposed daily to 0, 200, 400, or 800 ppm of 1-bromopropane for eight h a day. After exposure for 7 weeks, all rats in the 800-ppm group became seriously ill and were sacrificed during the 8th week. The other dose groups were exposed for 12 weeks. In the 800-ppm group, but not in the other two exposed groups, body weight was significantly less than the control at each time point from 2 to 7 weeks after the beginning of exposure. Tests of vaginal smears showed a significant increase in the number of irregular estrous cycles with extended diestrus in the 400- and 800-ppm groups. Histopathological examination of the ovary showed a significant dose-dependent reduction of the number of normal antral follicles and a decrease in the number of normal growing follicles in the 400-ppm group. No significant change was found in plasma concentrations of LH or FSH in any group when compared with the control. Our results indicate that 1-bromopropane can induce a dose-dependent ovarian dysfunction in nonpregnant female rats associated with disruption in follicular growth process.     

Suppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the high-affinity antibody response in C57BL/6 mice.

In the humoral immune response to an invasion of foreign antigens, B cells differentiate into low-affinity antibody-forming cells (AFCs) that mainly secrete IgM or, through germinal center (GC) formation, into high-affinity AFCs that secrete IgG-class antibodies with a higher affinity for the antigen. Previous studies have established the suppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on low-affinity antibody responses to antigens. However, whether and how TCDD affects the high-affinity antibody response to antigens has not yet been clarified. In this paper we investigate the effects of TCDD on GC formation, high-affinity AFC generation, and high-affinity antibody production in the primary humoral immune response. C57BL/6 mice were orally administered 0 or 20 microg/kg of TCDD and subsequently immunized with alum-precipitated ovalbumin (OVA) on day 0. Then the GC formation in the spleen and OVA-specific antibodies in the plasma, was evaluated until day 14 postimmunization. TCDD exposure reduced the production of OVA-specific IgG1 on days 10 and 14. GC formation in the spleen was also suppressed by TCDD exposure, and the suppression persisted from day 7 until day 14. In TCDD-administered mice, on day 7, cellular proliferation in the GCs was significantly suppressed, although apoptosis was not markedly affected. In order to measure high-affinity antibody and high-affinity AFCs, the mice were administered TCDD followed by immunization with alum-precipitated (4-hydroxy-3-nitrophenyl) acetyl linked to chicken gamma-globulin (NP-CG). The frequency of high-affinity NP-specific AFCs that bind to low-haptenated antigen was clearly shown to be reduced in the spleen on days 10 and 14. Furthermore, the high-affinity anti-NP IgG1 levels on days 10 and 14 postimmunization were significantly reduced by TCDD exposure. Taken together, the results of this paper demonstrate that TCDD exposure inhibits the generation of high-affinity AFCs and high-affinity antibody production during the primary humoral immune response and suggest that these alterations were caused by the suppression of antigen-responding B-cell proliferation induced by TCDD during GC formation.     

A clinical study of posttraumatic hydrocephalus

From 1989 to 1998, 721 patients with head injury were admitted to our department and 22 (3.1%) of them developed posttraumatic hydrocephalus. These patients included 16 males and 6 females, ranging in age from 17 to 86 years (mean age, 66 yrs) with peak incidence in the eighth decade. CT scan on admission immediately after head injury showed subarachnoid hemorrhage (SAH) in 18 cases. The other 4 cases without SAH had once suffered head injuries severe enough to give rise to consciousness disturbance. The typical clinical symptoms of hydrocephalus were observed in only 5 (23%) patients, and in the other 17 cases prolonged or deteriorated of consciousness disturbance were the main symptoms. Hydrocephalus was diagnosed between 1 and 3 months in 15 cases and in 7 cases after 4 months. Clinical improvement has been seen in 17 (77%) cases and marked recovery of consciousness was achieved in 12 cases after V-P shunt, but 5 cases with severe disturbance of consciousness revealed no improvement of clinical signs even after decrease of ventricular size. These results indicate that elderly patients with traumatic SAH should be followed up for at least 4 to 5 months, paying attention to development of hydrocephalus, and V-P shunt would be effective to improve consciousness disturbance in most of the cases.     

Gene transfer into rat renal cells using adeno-associated virus vectors

Adeno-associated virus (AAV) vectors have a number of attractive features, including lack of cytotoxicity, ability to transduce nondividing cells, and long-term transgene expression. We investigated whether rat renal cells could be efficiently transduced with AAV vectors. Rat glomerular mesangial cells were transduced with AAV-lacZ vector containing beta-galactosidase gene in vitro, and the expression of beta-galactosidase was evaluated by X-gal staining and ELISA. For ex vivo experiments, sections of rat kidneys were incubated with AAV-lacZ, and then evaluated by X-gal histochemical staining. The level of beta-galactosidase expression in cultured rat mesangial cells increased in a dose-dependent manner (ranging from 1 x 10(5) to 5 x 10(6) particles/cell). When transduced with 5 x 10(6) vector particles/cell of AAV-lacZ, about 50% of mesangial cells were stained positively with X-gal, and the level of beta-galactosidase expression reached 9.9 +/- 1.5 ng/mg protein. Expression was detectable during the culture period for at least 7 days. X-gal histochemical examination of the ex vivo transduced renal tissue revealed tubular cell and interstitial tissue staining. However, gene transfer was not clearly observed in glomeruli. These findings suggest that AAV vectors have the potential for gene therapy of renal diseases.     

Haemodynamic comparison of propofol-fentanyl anaesthesia with midazolam-fentanyl anaesthesia in CABG patients without preoperative heart failure

This study was designed to compare prebypass haemodynamics under total intravenous anaesthesia (TIVA) using midazolam-fentanyl (group M) and propofol-fentanyl (group P) combinations. Sixteen adult patients undergoing CABG were studied with patients in group M and P (n = 8 each) given intravenous midazolam 0.1 mg.kg-1.h-1 and propofol 4 mg.kg-1.h-1 with fentanyl 25 micrograms.kg-1 until sternotomy, respectively. Following induction of anaesthesia, cardiac index and heart rate decreased significantly (30% and 20% in both groups, p < 0.05) these variables returned to baseline on completion of sternotomy. In addition, in group P mean arterial pressure decreased significantly (about 15%) following induction and there were no ischaemic signs. Overall for MAP there was no significant difference between the two groups. LVSWI and RVSWI were reduced by around 25% in both groups. Only the change in LVSWI reached statistical significance (p < 0.05). This reduction may have exert a caridioprotectant action by decreasing myocardial oxygen consumption. We conclude that both TIVA techniques represent an acceptable anaesthetic regimen for use in cardiac anaesthesia.     

Age-specific effects of noradrenergic alpha-2 agonist clonidine on the development of amygdaloid kindling in developing rats

The effects of clonidine on the development of amygdaloid kindling were studied in rats of various ages (14, 21, 28 and 70 postnatal days). Administration of clonidine (0.2, 0.5 mg/kg i.p.) caused a significant retardation of kindling development in the 28-day-old rats as well as in the adult rats, whereas, in the 14-day-old rats, the development of kindling was significantly facilitated by clonidine. No significant effect of clonidine was observed in the 21-day-old rats. These results indicate that in rats the effects of clonidine on the development of amygdaloid kindling vary during development.