Intestinal receptor for heat-stable enterotoxin of Escherichia coli is tightly coupled to a novel form of particulate guanylate cyclase.

A novel form of particulate guanylate cyclase tightly coupled by cytoskeletal components to receptors for heat-stable enterotoxin (ST) produced by Escherichia coli can be found in membranes from rat intestinal mucosa. Intestinal particulate guanylate cyclase was resistant to solubilization with detergent alone, with only 30% of the total enzyme activity being extracted with Lubrol-PX. Under similar conditions, 70% of this enzyme was solubilized from rat lung membranes. The addition of high concentrations of sodium chloride to the extraction buffer resulted in greater solubilization of particulate guanylate cyclase from intestinal membranes. Although extraction of intestinal membranes with detergent and salt resulted in greater solubilization of guanylate cyclase, a small fraction of the enzyme activity remained associated with the particulate fraction. This activity was completely resistant to solubilization with a variety of detergents and chaotropes. Particulate guanylate cyclase and the ST receptor solubilized by detergent retained their abilities to produce cyclic GMP and bind ST, respectively. However, ST failed to activate particulate guanylate cyclase in detergent extracts. In contrast, guanylate cyclase resistant to solubilization remained functional and coupled to the ST receptor since enzyme activation by ST was unaffected by various extraction procedures. The possibility that the ST receptor and particulate guanylate cyclase were the same molecule was explored. ST binding and cyclic GMP production were separated by affinity chromatography on GTP-agarose. Similarly, guanylate cyclase migrated as a 300,000-dalton protein, while the ST receptor migrated as a 240,000-dalton protein on gel filtration chromatography. Also, thiol-reactive agents such as cystamine and N-ethylmaleimide inhibited guanylate cyclase activation by ST, with no effect on receptor binding of ST. These data suggest that guanylate cyclase and the ST receptor are independent proteins coupled by cytoskeletal components in membranes of intestinal mucosa.     

Dopaminergic mechanisms controlling urethral function in rats

AIMS: To investigate the role of dopamine receptor subtypes in the control of urethral activity. METHODS: Simultaneous recordings of intravesical and urethral perfusion pressure (UPP) were performed in rats under urethane anesthesia. Changes in coordinated activity of the bladder and urethral sphincter were examined following intravenous (i.v.), intrathecal (i.t.), or intracerebroventricular (i.c.v.) administration of dopamine D1- and D2-like receptor agonists (SKF38393 and quinpirole, respectively) and antagonists (SCH23390 and remoxipride, respectively). RESULTS: Quinpirole (0.03, 0.1, and 0.3 mg/kg i.v.) dose-dependently decreased baseline urethral pressure to 45.33 +/- 5.8, 33.7 +/- 3.3 (P < 0.05, n = 6), and 27.7 +/- 3.3 cm H(2)O (P < 0.05, n = 5) from the control value (46.0 +/- 4.0 cm H(2)O), respectively. i.c.v. injection of quinpirole (1 microg) decreased baseline urethral pressure to 33.6 +/- 5.0 cm H(2)O (P < 0.05, n = 4) from the control value (51.4 +/- 4.9 cm H(2)O) in contrast to the insignificant effects of i.t. administration of the drug (3 microg). The decrement of baseline pressure induced by quinpirole (0.1 mg/kg i.v.) was suppressed by alpha-bungarotoxin (BGT), a neuromuscular blocking agent. SCH23390 (1 and 3 mg/kg, i.v.) dose-dependently decreased the frequency of high frequency oscillation (HFO) of the urethral sphincter. SKF38393 or remoxipride did not have significant effects on any parameters of bladder and urethral activity. CONCLUSIONS: These results indicate that activation of D2-like dopamine receptors at a supraspinal site can suppress activity of the striated muscle urethral sphincter. Thus, decreased urethral resistance induced by D2 dopamine receptor activation might aggravate urge incontinence symptoms often seen in patients with Parkinson's disease (PD).     

Muscle function in 164 men and women aged 20--84 yr

PURPOSE: The purpose of the present study was to investigate the effect of aging in men and women on muscle functional properties, i.e., muscle force and force per unit of cross-sectional area (force/CSA). METHODS: A total of 164 volunteers participated in this study and were divided into five groups according to their chronological age as follows: 20s (20--39 yr old), 40s, 50s, 60s, and 70s (70--84 yr old). Isokinetic (0, 60, 180, and 300 degrees.s(-1)) knee extensor and flexor peak torque, and CSA of the quadriceps femoris (QF) muscle of the mid-thigh were measured. RESULTS: Peak torque during knee extension and flexion was inversely related to age in both men and women. This was the case irrespective of the speed of contraction in both genders (men: r = -0.797 to -0.756, all P < 0.001, women: r = -0.639 to -0.530, all P < 0.001). A significant correlation was observed between CSA of QF and peak torque during isometric knee extension in men (r = 0.827, P < 0.001) and women (r = 0.657, P < 0.001). During isometric contraction, the force/CSA exhibited a significant decrease with increasing age in men (r = -0.518, P < 0.001) but not in women (r = -0.207, NS). CONCLUSION: These results thus suggest that muscle strength losses would be mainly due to a decline in muscle mass in both genders, whereas age-related decline in muscle function in men may also be the result of neural factors, such as muscle recruitment and/or specific tension.     

18F-fluoromisonidazole positron emission tomography before treatment is a predictor of radiotherapy outcome and survival prognosis in patients with head and neck squamous cell carcinoma

Objective  

To evaluate the usefulness of [¹⁸F]fluoromisonidazole ([¹⁸F]FMISO)-positron emission tomography (PET) prior to the treatment of head and neck squamous cell carcinoma.     

N-Isopropyl-p-iodoamphetamine receptors in normal and cancerous tissue of the human lung

N-Isopropyl-p-iodoamphetamine (IMP) receptors in normal human lung tissue were characterized using a radioligand binding assay with iodine-125 IMP as the ligand. Saturation binding studies revealed the presence of two binding sites with dissociation constant (K _d) values of 53 ± 2 and 4687 ± 124 nM and maximum binding capacity (Bmax) values of 7 ± 1 and 133 ± 27 pmol/mg protein (n=5) respectively. The IC₅₀ values of various amines were as follows: IMP, 9 × 10^–5 M; propranolol, 5 × 10^–4 M; haloperidol, 6 × 10^–4 M; ketamine, 9 × 10^–3 M; dopamine, 1 × 10^–2 M. The IMP receptors of cancerous tissue obtained from human lung also had two binding sites with K _d values of 54 ± 2 and 5277 ± 652 nM and Bmax values of 7±1 and 103 ± 21 pmol/mg protein (n = 3) respectively. There was no significant difference in binding parameters between normal and cancerous lung tissue. These results demonstrate the existence of IMP receptors and suggest that cancer does not affect the nature of IMP receptors in human lung tissue.Correspondence to: E. Tanaka     

Primary staging of laryngeal and hypopharyngeal cancer: CT,MR imaging and dual-energy CT

Laryngeal and hypopharyngeal cancer, in particular T4a disease associated with cartilage invasion and extralaryngeal spread, needs to be evaluated accurately because treatment can impact heavily on a patient's quality of life. Reliable imaging tools are therefore indispensible. CT offers high spatial and temporal resolution and remains the preferred imaging modality. Although cartilage invasion can be diagnosed with acceptable accuracy by applying defined criteria for combinations of erosion, lysis and transmural extralaryngeal spread, iodine-enhanced tumors and non-ossified cartilage are sometimes difficult to distinguish. MR offers high contrast resolution for images without motion artifacts, although inflammatory changes in cartilage sometimes resemble cartilage invasion. With dual-energy CT, combined iodine overlay images and weighted average images can be used for evaluation of cartilage invasion, since iodine enhancement is evident in tumor tissue but not in cartilage. Extralaryngeal spread can be evaluated from CT, MR or dual-energy CT images and the routes of tumor spread into the extralaryngeal soft tissue must be considered; (1) via the thyrohyoid membrane along the superior laryngeal neurovascular bundle, (2) via the inferior pharyngeal constrictor muscle, and (3) via the cricothyroid membrane. Radiologists need to understand the advantages and limitations of each imaging modality for staging of laryngeal and hypopharyngeal cancer.     

The relationships among self-identity,self-esteem and attitude towards sexual behavior in university students

PURPOSE: It has been reported that the young people of today tend to engage in sexual behavior at an early age and the abortion rate is high. The purpose of this study was to investigate the attitudes of post-adolescents with regard to sexual behaviors and the relationship to self-identity and self-esteem. METHODS: The subjects were 234 males (mean +/- SD 20.2 +/- 1.1 years) and 460 females (mean +/- SD 19.5 +/- 1.1 years) 4-year university students aged 18 to 23 years in Aichi Prefecture. An anonymous, self-report questionnaire was used to survey the subjects with regard to self-identity ("Establishment of Self" scale), self-esteem (Rosenberg Self-Esteem Scale), and sexual attitude and behavior. The scores on both scales and subscales of the "Establishment of Self" scale, "Foundation of Identity (Foundation)" and "Establishment of Identity (Establishment)", were calculated and intercompared, along with sexual attitude and behavior, controlled for age and school type. RESULTS: The mean total score of the "Establishment of Self" scale for males was 55.3 (SD9.2) and for females 52.2 (SD9.3), while those for the Rosenberg Self-Esteem Scale were 27.2 (SD5.5) and 25.7 (SD5.2), respectively. There was significant positive correlation all scales in both sexes. Both male and female students had positive attitude towards sex and a negative view of "traditional gender roles" particularly females. Of the subjects, 82.4% of males and 69.5% of females were thinking of accepting a request for sexual intercourse from their partners. Many students understood the "need for contraception", that is a component of contraceptive behavior. Most of them, however, didn't acquire the other components. A total of 68.3% of males and 48.2% of females had experienced sexual intercourse during the last year. Of these, 50.6% of males and 58.2% of females consistently used contraception. The score on the "Establishment of Self" scale was higher among both the male and female students who responded positively to having "communication ability," "learning ability," and "acquisition ability." Significant differences were found in total and "Establishment" scales among males, and all scales among females. The score on the Rosenberg Self-Esteem Scale was significantly higher with "learning ability" among males, and with "communication ability" and "learning ability" among females. However, no significant relationship was found between actual contraceptive behavior and any of the scales. CONCLUSION: In dealing with contraception, a gap exists between university students' attitudes and actual behavior. The scores on the "Establishment of Self" scale and the Rosenberg Self-Esteem Scale were found to be significantly higher for those who exhibited higher values for components of contraceptive behavior.