Determinants of Slow Walking Speed in Ambulatory Patients Undergoing Maintenance Hemodialysis

Walking ability is significantly lower in hemodialysis patients compared to healthy people. Decreased walking ability characterized by slow walking speed is associated with adverse clinical events, but determinants of decreased walking speed in hemodialysis patients are unknown. The purpose of this study was to identify factors associated with slow walking speed in ambulatory hemodialysis patients. Subjects were 122 outpatients (64 men, 58 women; mean age, 68 years) undergoing hemodialysis. Clinical characteristics including comorbidities, motor function (strength, flexibility, and balance), and maximum walking speed (MWS) were measured and compared across sex-specific tertiles of MWS. Univariate and multivariate logistic regression analyses were performed to examine whether clinical characteristics and motor function could discriminate between the lowest, middle, and highest tertiles of MWS. Significant and common factors that discriminated the lowest and highest tertiles of MWS from other categories were presence of cardiac disease (lowest: odds ratio [OR] = 3.33, 95% confidence interval [CI] = 1.26–8.83, P<0.05; highest: OR = 2.84, 95% CI = 1.18–6.84, P<0.05), leg strength (OR = 0.62, 95% CI = 0.40–0.95, P<0.05; OR = 0.57, 95% CI = 0.39–0.82, P<0.01), and standing balance (OR = 0.76, 95% CI = 0.63–0.92, P<0.01; OR = 0.81, 95% CI = 0.68–0.97, P<0.05). History of fracture (OR = 3.35, 95% CI = 1.08–10.38; P<0.05) was a significant factor only in the lowest tertile. Cardiac disease, history of fracture, decreased leg strength, and poor standing balance were independently associated with slow walking speed in ambulatory hemodialysis patients. These findings provide useful data for planning effective therapeutic regimens to prevent decreases in walking ability in ambulatory hemodialysis patients.     

Ability of various alkylating agents to induce adaptive and SOS responses: a study with lacZ fusion

We used alkA'-lacZ' and umuC'-lacZ' fused genes and determined the ability of various alkylating agents to induce adaptive and SOS responses. The degree of induction of expression of these genes was quantitatively measured by a simple colorimetric assay of beta-galactosidase activity. SN1 type methylating agents, such as N-methyl-N'-nitro-N-nitrosoguanidine and N-methyl-N-nitrosourea, were more effective inducers for the alkA than for the umuC system, while SN1 type ethylating agents, such as N-ethyl-N'-nitro-N-nitrosoguanidine and N-ethyl-N-nitrosourea, were more potent inducers for the umuC than for the alkA system. Similar but less striking effects on the two systems were obtained with SN2 type alkylating agents.     

Role of virus inhibitory factor or interferon in the antitumoral effect of whole-body hyperthermia

The interferon inducing effect of hyperthermia was studied in normal and tumor-bearing mice. Circulating interferon was temporarily detected one day after subcutaneous transplantation of 1.6 X 10(6) Ehrlich's ascites tumor cells. Hyperthermia of 43.5 degrees C for 5 min did not induce the interferon formation in mice with or without subcutaneous tumor of the cells. These findings showed that the induction of interferon formation was not main cause of the hyperthermia-induced tumor inhibition.     

A 5-bp Insertion in Mip Causes Recessive Congenital Cataract in KFRS4/Kyo Rats

We discovered a new cataract mutation, kfrs4, in the Kyoto Fancy Rat Stock (KFRS) background. Within 1 month of birth, all kfrs4/kfrs4 homozygotes developed cataracts, with severe opacity in the nuclei of the lens. In contrast, no opacity was observed in the kfrs4/+ heterozygotes. We continued to observe these rats until they reached 1 year of age and found that cataractogenesis did not occur in kfrs4/+ rats. To define the histological defects in the lenses of kfrs4 rats, sections of the eyes of these rats were prepared. Although the lenses of kfrs4/kfrs4 homozygotes showed severely disorganised fibres and vacuolation, the lenses of kfrs4/+ heterozygotes appeared normal and similar to those of wild-type rats. We used positional cloning to identify the kfrs4 mutation. The mutation was mapped to an approximately 9.7-Mb region on chromosome 7, which contains the Mip gene. This gene is responsible for a dominant form of cataract in humans and mice. Sequence analysis of the mutant-derived Mip gene identified a 5-bp insertion. This insertion is predicted to inactivate the MIP protein, as it produces a frameshift that results in the synthesis of 6 novel amino acid residues and a truncated protein that lacks 136 amino acids in the C-terminal region, and no MIP immunoreactivity was observed in the lens fibre cells of kfrs4/kfrs4 homozygous rats using an antibody that recognises the C- and N-terminus of MIP. In addition, the kfrs4/+ heterozygotes showed reduced expression of Mip mRNA and MIP protein and the kfrs4/kfrs4 homozygotes showed no expression in the lens. These results indicate that the kfrs4 mutation conveys a loss-of-function, which leads to functional inactivation though the degradation of Mip mRNA by an mRNA decay mechanism. Therefore, the kfrs4 rat represents the first characterised rat model with a recessive mutation in the Mip gene.     

Accumulation pattern of amino acid substitutions in protein evolution

Summary A simple method for the evolutionary analysis of amino acid sequence data is presented and used to examine whether the number of variable sites (NVS) of a protein is constant during its evolution. The NVSs for hemoglobin and for mitochondrial cytochrome c are each found to be almost constant, and the ratio between the NVSs is close to the ratio between the unit evolutionary periods. This indicates that the substitution rate per variable site is almost uniform for these proteins, as the neutral theory claims. An advantage of the present analysis is that it can be done without knowledge of paleontological divergence times and can be extended to bacterial proteins such as bacterial c-type cytochromes. It is suggested that the NVS of cytochrome c has been almost constant even over the long period (ca. 3.0 billion years) of bacterial evolution but that at least two different substitution rates are necessary to describe the accumulated changes in the sequence. This two clock interpretation is consistent with fossil evidence for the appearance times of photosynthetic bacteria and eukaryotes.     

Effect of volume expansion on hemodynamic variables in nephrectomized dogs

We have previously demonstrated that blood pressure elevation by acute blood volume expansion is volume-dependent during the infusion period and resistance-dependent in the post-infusion period in normal anesthetized dogs, and that such an increase in blood pressure is associated with a potentiation of the pressor response to norepinephrine. To evaluate the possible renal contribution to these hemodynamic changes, blood volume expansion was performed for 1 h with dextran dissolved in lactated Ringer's solution (20 ml/kg) in 15 nephrectomized dogs. The mean blood pressure, cardiac output and total peripheral resistance at the end of infusion were 126%, 225% and 60%, respectively; 3 h after volume expansion they were 126%, 151%, and 92% respectively. However, in 4 dogs, there was an increase in mean blood pressure (138%) 3 h after volume expansion. This was thought to result from an increase in the total peripheral resistance (133%) associated with the recovery of cardiac output (106%). The pressor response to norepinephrine (0.5 microgram/kg) was potentiated after volume expansion. These results indicate that the handling of volume by the kidney contributed to the maintenance of an elevated level of cardiac output. However, nephrectomy did not seem to interfere with the hemodynamic switching of the causative factor for blood pressure elevation from increased cardiac output to increased total peripheral resistance. Neither was the potentiation of pressor response to norepinephrine affected.     

Gender, age and circadian blood pressure variation of apparently healthy rural vs metropolitan Japanese

Interim chronobiologic cardiovascular reference data have been described; 353 clinically healthy Japanese subjects were monitored every 15 min for 24h on 2 occasions. Special attention was paid to the difference between metropolitan and rural areas. Not only the MESORs of SBP and DBP, but also the circadian amplitudes, were higher in the Tokyo than in a rural area (Komaki, Aichi Prefecture). Age-related alterations in the circadian profile of cardiovascular variables were noted for women but not for men. The average MESOR remained similar for SBP in men, whereas in women the average MESOR increased with advancing age in both urban and rural areas. The average circadian amplitude of SBP also increased with age in women, but not in men. No significant deviations of acrophase with age were found for SBP and DBP in men, whereas in rural women the acrophase tended to occur earlier with increasing age.     

Experimental and clinical chronocardiology

Recent advances of the chronobiologic approach to experimental and clinical cardiology was reviewed. First, the maximum entropy method (MEM) was introduced as one of the statistical methods analyzing the circadian periodicity. The MEM power spectrum showed a remarkable resolution property. It will play an important role in chronocardiology in cooperation with the cosinor method. Secondly, recent investigations of the relationship between sleep states and cardiac arrhythmias were mentioned from the viewpoints of both experimental and clinical chronocardiology. Next, recent remarkable advance on myocardial ischemia was reviewed. A marked circadian rhythm in the frequency of myocardial infarction onset and sudden cardiac death has been observed. Lastly, a reference has been made to the recent development of ambulatory BP monitoring. A chronobiologic approach to the analysis of time-series data in cardiology will lead to many advantages in clinical practice.