Urinary levels of nuclear matrix protein 22 in patients with urinary diversion.

OBJECTIVES: To evaluate the influence of various types of urinary diversion on urinary nuclear matrix protein 22 (U-NMP22) levels. METHODS: U-NMP22 values were determined for 38 urinary diversion patients without upper urinary tract cancer. The patients were divided into three groups: tubeless cutaneous ureterostomy (n = 12), ileal conduit (n = 15), and continent urinary reservoir (n = 11). The mean values and false-positive rates of U-NMP22 (cutoff value 12 U/mL) were compared among the three groups. RESULTS: The mean +/- standard error U-NMP22 value for the ureterostomy, ileal conduit, and reservoir groups was 20.1 +/- 5.8 U/mL, 335.6 +/- 63.5 U/mL, and 671.8 +/- 220.4 U/mL, respectively (P = 0.0030). The false-positive rate of U-NMP22 for the ureterostomy, ileal conduit, and reservoir groups was 41.7%, 100%, and 100%, respectively. In the ureterostomy group, the exclusion of patients with pyuria improved the false-positive rate of U-NMP22 from 41.7% to 12.5%. CONCLUSIONS: U-NMP22 levels may be useful in the diagnosis of upper urinary tract cancer in patients with a tubeless cutaneous ureterostomy. However, in patients with urinary diversion using a bowel segment, U-NMP22 has no diagnostic value because of the high U-NMP22 levels.

Controlling the direction of kinesin-driven microtubule movements along microlithographic tracks.

Motor proteins are able to move protein filaments in vitro. However, useful work cannot be extracted from the existing in vitro systems because filament motions are in random directions on two-dimensional surfaces. We succeeded in restricting kinesin-driven movements of microtubules along linear tracks by using micrometer-scaled grooves lithographically fabricated on glass surfaces. We also accomplished the extraction of unidirectional movement from the bidirectional movements along the linear tracks by adding arrowhead patterns on the tracks. These "rectifiers" enabled us to construct microminiturized circulators in which populations of microtubules rotated in one direction, and to actively transport microtubules between two pools connected by arrowheaded tracks in the fields of micrometer scales.

[The present state of blindness in the world].

PURPOSE: To investigate the present state of blindness around the world. METHODS: The article reviews significant studies by WHO and literature on the topic. RESULTS: Current global estimates indicate that blindness affects close to 45 million people, with nine out of ten blind people living in developing countries. Two-thirds or more of all blindness is avoidable, in that the causes are preventable or treatable. Cataract is the major cause of blindness in the world and the number of cases is increasing. The second cause is glaucoma, and the third is trachoma. The extent of disability of blindness itself is very high compared to that of other illnesses. Also, in terms of the burden of diseases in society, blindness is a relatively huge problem in the developing world. CONCLUSIONS: Intervention should be focused on the factors that have the higheat possibility of change. Manpower development is the most important countermeasure. The aid required to support developing countries is what can make them stand on their own in long term ophthalmic care.

Alcohol and eye diseases: a review of epidemiologic studies.

OBJECTIVE: Epidemiologic evidence for the associations of alcohol consumption with eye diseases was gathered. METHOD: A literature review was conducted. RESULTS: In addition to alcohol-induced ocular anomalies among children with fetal alcohol syndrome, epidemiologic studies in the past two decades have demonstrated that chronic alcoholism is associated with a significantly increased risk of cataract, keratitis, color vision deficiencies and corneal arcus. Moderate alcohol use, however, has been reported to be possibly protective against age-related macular degeneration, cataract and diabetic retinopathy. CONCLUSIONS: It is evident that through its biologic effects and effects on nutrient deficits alcohol plays a role in a variety of eye diseases. Information on the patient's drinking history can be clinically valuable and should be collected on a routine basis.

Ambient temperatures preferred by humans acclimated to heat given at a fixed daily time.

We investigated preferred ambient temperatures (T(pref)) of heat-acclimated humans to assess their behavioral thermoregulation. Seven male volunteers were exposed to an ambient temperature (T(a)) of 42 degrees C and relative humidity (RH) of 40% for 4 h (14:00-18:00 h)/day for 9-10 consecutive days. Rectal temperature (T(re)) was measured, and T(pref) was determined at two distinct times of day, 09:00-11:00 h (AM test) and 14:00-16:00 h (PM test), in both heat- and nonheat-acclimated (control) conditions. Heat acclimation significantly decreased T(re) only in the PM test. There was no difference in the T(pref) between the two tests in the control condition. However, T(pref) in the PM test was significantly lower than that of the AM test in the heat-acclimated condition. The findings suggest that repeated heat exposure in humans for 4 h at a fixed time daily alters the core temperature level and behavioral thermoregulatory function, particularly during the period when the subjects had previously been exposed to heat.

Functional characterization of vertebrate nonmuscle myosin IIB isoforms using Dictyostelium chimeric myosin II.

The alternatively spliced isoform of nonmuscle myosin II heavy chain B (MHC-IIB) with an insert of 21 amino acids in the actin-binding surface loop (loop 2), MHC-IIB(B2), is expressed specifically in the central nervous system of vertebrates. To examine the role of the B2 insert in the motor activity of the myosin II molecule, we expressed chimeric myosin heavy chain molecules using the Dictyostelium myosin II heavy chain as the backbone. We replaced the Dictyostelium native loop 2 with either the noninserted form of loop 2 from human MHC-IIB or the B2-inserted form of loop 2 from human MHC-IIB(B2). The transformant Dictyostelium cells expressing only the B2-inserted chimeric myosin formed unusual fruiting bodies. We then assessed the function of chimeric proteins, using an in vitro motility assay and by measuring ATPase activities and binding to F-actin. We demonstrate that the insertion of the B2 sequence reduces the motor activity of Dictyostelium myosin II, with reduction of the maximal actin-activated ATPase activity and a decrease in the affinity for actin. In addition, we demonstrate that the native loop 2 sequence of Dictyostelium myosin II is required for the regulation of the actin-activated ATPase activity by phosphorylation of the regulatory light chain.

Effects of Spore Availability, Spore Germinability, and Shoot Susceptibility on Gall Rust Infection of Pine.

Temporal changes in three factors (shoot susceptibility, spore availability, and spore germinability) were evaluated to estimate their effects on the infection of lodgepole pine (Pinus contorta var. latifolia) by Endocronartium harknessii. Germinability of rust spores from sori free of hyperparasites remained above 80% during the growing season and thus would not have significantly limited infection. In contrast, there was a slight, but statistically insignificant, increase in estimated susceptibility as infection increased from 94% of maximum at 45% shoot elongation to maximum susceptibility at 90% shoot elongation. This was followed by a precipitous decline in estimated susceptibility to 57% of maximum when shoots were 95% elongated. Spore availability was 24% of maximum when shoots were 45% elongated, and thus may have been limiting at the beginning of the growing season. At the end of the growing season, spore availability declined prior to, or simultaneous with, the decline in susceptibility. The combined effect of both factors drastically reduced the number of infections estimated to occur once shoots are more than 95% elongated. As shoots elongated, relatively more infections formed higher on the shoot, supporting the hypothesis that periderm is important in limiting infection.

Secondary keratoconus with corneal epithelial iron ring similar to Fleischer's ring.

BACKGROUND: Fleischer's ring is considered to be a characteristic of keratoconus, but we have seen a ring similar to Fleischer's ring in patients with secondary keratoconus, in which the cornea becomes thinner secondarily for undetermined reasons. CASES: We report 6 cases of secondary keratoconus with a corneal epithelial ring similar to the Fleischer's ring pattern. OBSERVATIONS: In these 6 cases (2 men and 4 women), the causes of secondary keratoconus were trachoma in 2 cases, trauma in 2 cases, keratitis in 1 case and unknown etiology in one case. All showed thinning of the cornea and a corneal iron ring similar to Fleischer's ring pattern. The corneal button obtained after keratoplasty in 1 case showed the deposition of hemosiderin in the corneal epithelium after staining with Prussian blue. At the same time we confirmed the existence of iron in the corneal epithelium by x-ray ultimate analysis. CONCLUSIONS: All 6 patients we encountered had a past history of corneal disease in their childhood except for 1 case with unknown etiology. Primary keratoconus is also considered to develop by the early teens at the latest. These facts led us to an assumption that the occurrence of some abnormalities in the cornea during the growth period may result in iron deposition in the epithelium and thinning of the stroma. In light of these facts, abnormalities of the iron metabolism must be thoroughly investigated in considering the etiology of keratoconus.

Autonomic and behavioural thermoregulation in starved rats.

1. We investigated the mechanism of starvation-induced hypothermia in rats. 2. Threshold core temperatures (Tcor) for tail skin vasodilatation and cold-induced thermogenesis were determined after a 3 day starvation using a chronically implanted intravenous thermode. Food deprivation significantly lowered the threshold Tcor for heat production, but did not affect the heat loss threshold. 3. Thermogenic response to a fall in Tcor below its threshold was enhanced by starvation. 4. Preferred ambient temperatures (Tpref) and Tcor were measured before and during a 3 day starvation in a thermal gradient. The 3 day starvation significantly lowered Tcor only in the light phase of the day. The level of hypothermia was the same throughout the fasting period, while Tpref gradually increased during the 3 days of starvation. 5. When rats were starved at a constant ambient temperature of 25 C (no thermal gradient), their Tcor levels were comparable with those of the rats kept in the thermal gradient. 6. The results suggest that, in rats, hypothermia caused by starvation was not due to a decrement in thermogenic capability, but was due to a decrease in the threshold for the activation of thermogenesis.

[Clinical significance of urothelial dysplasia concomitant with superficial bladder cancer].

OBJECTIVE: Retrospective analysis was carried out to evaluate the prognostic value of urothelial dysplasia with superficial bladder cancer. PATIENTS AND METHODS: 62 patients with bladder cancer of pTa or pT1 who had been treated by transurethral resection (TUR-Bt), underwent random mucosal biopsies in the urinary bladder. The results of random biopsies were classified into 3 groups: negative group, dysplasia group and CIS group. The recurrence rate, progression rate and type of recurrences (true recurrence/new occurrence) were compared among the 3 groups. RESULTS: The results of random biopsies were as follows; negative group was found in 42 (68%), dysplasia group in 17 (27%) and CIS group in 3 (5%). There were no significant difference in the characteristics of the patients among the 3 groups. The recurrence rates at 1, 2 and 5 years after TUR-Bt were 3%, 12% and 21%, respectively, for negative group, and 37%, 51% and 67%, respectively, for dysplasia group (p < 0.01). For CIS group, 2 of 3 cases (67%) recurrenced within 1 year after TUR-Bt. Non of negative group progressed to muscle invasion, whereas 57% of dysplasia group invaded bladder muscle after 6 years post operatively (p < 0.001). No significant relationship was observed between the absence or presence of concomitant dysplasia and the rate of true recurrence. Dysplasia group revealed a higher rate (47.1%) of new occurrence than negative group (2.4%) (p = 0.0001). CONCLUSION: The presence or absence of concomitant dysplasia of superficial bladder cancer seems to be an important prognostic factor for future new ocurrence and progression after TUR-Bt.

Prophylactic intravesical instillation chemotherapy against recurrence after a transurethral resection of superficial bladder cancer: a randomized controlled trial of doxorubicin plus verapamil versus doxorubicin alone. The Kyushu University Urological Oncology Group.

PURPOSE: We investigated whether verapamil (VR), a known chemosensitizing agent of P-glycoprotein-mediated multidrug resistance, could enhance the preventative effect of doxorubicin (Adriamycin, ADM) on both intravesical recurrence and disease progression after transurethral resection (TUR) of superficial bladder cancer. METHODS: The patients were randomized into two groups: one group received an intravesical instillation of ADM (30 mg) plus VR (15 mg) after TUR of superficial bladder cancer (19 times over 1 year), and the other group received ADM alone on the same treatment schedule. The nonrecurrence rate, the incidence of disease progression at the first recurrence and the side effects were compared over a median follow-up of 38.5 months. RESULTS: Of the 226 patients registered, 157 were evaluable. No significant differences were observed in the patients' characteristics between the two groups. Although the incidence of disease progression at the first recurrence was not significantly different between the two groups, the ADM plus VR instillation group did show a significantly higher nonrecurrence rate than the ADM-only instillation group, and such significance persisted even when any possible bias was allowed for in a multivariate analysis. In terms of side effects, the incidence and severity of bladder irritation symptoms were not significantly different between the two groups. CONCLUSIONS: Intravesical instillation chemotherapy with ADM plus VR was found to have a significantly greater beneficial effect than with ADM alone for preventing recurrence after TUR of superficial bladder cancer.

Reactivities of Cys707 (SH1) in intermediate states of myosin subfragment-1 ATPase.

To detect structural changes around the reactive Cys707 (SH1) in the myosin heavy chain during the ATPase reaction, the reactivity of SH1 in rabbit skeletal myosin subfragment-1 (S-1) was measured using a fluorescent reagent, 5-(iodoacetamidoethyl)aminonaphthalene-1-sulfonic acid, in the presence of various ATP analogs: adenosine 5'-(3-thiotriphosphate) (ATPgammaS), ADP-vanadate (ADP-Vi), ADP-BeFx, and ADP-AlF4. The SH1 reactivities in the S-1 complexes with ATPgammaS and ADP-BeFx, analogs of the E-ATP state, were very high, as well as that in the E-ADP state. In contrast, the SH1 reactivities in the S-1 complexes with ADP-Vi and ADP-AlF4, analogs of the E-ADP-P state, were extremely low. The structural changes around SH1 can be correlated to changes in the structure of the gamma-phosphate of ATP during the ATPase reaction or to the structure of the corresponding part of ATP analogs at the active site of ATPase. This is consistent with the crystal structure of S-1 in which the heavy chain structure around SH1 of S-1-ADP-BeFx is significantly different from those of S-1-ADP-Vi and S-1-ADP-AlF4 [Fisher et al. (1995) Biochemistry 34, 8960-8972; Smith and Rayment (1996) Biochemistry 35, 5404-5417].

Distribution of lymphoid tissue in the caecal mucosa of chickens.

In order to clarify the fundamental structure of the host defence mechanism in chicken caeca, a detailed analysis of the distribution of lymphoid nodules (LNs) was carried out on longitudinal sections of both the mesenteric (side of the ileocaecal ligament) and the antimesenteric mucosa. An overwhelming majority of solitary or aggregated LNs were located in the mesenteric mucosa, although a few were also found in the antimesenteric mucosa. Of the total LNs, 45.7% were detected at the proximal 7.8% section in the caecal tonsil. LNs (21.4%) were also concentrated in the distal 22.0% section corresponding to the apex. A moderate concentration of LNs (13.1%) was found at the transitional 20.0% region between the base and body. Approximately 80.2% of total LNs were found at the above 3 regions in the mesenteric mucosa. In many cases, the frequency of LNs in the caecal tonsils was opposite to that at the apices. Aggregated LNs were mainly found in the caecal tonsils, transitional region and apex. Almost all aggregated LNs consisted of fundamental nodular units possessing M cells in their follicle associated epithelia. The aggregated LNs in the above 3 regions therefore could provide immunological surveillance against caecal luminal contents. In particular, the cooperative function between LNs of the caecal tonsil and apex might be highly important in maintaining the caecal microenvironment.