Phosphorylation of human histamine H(1) receptors and its role in agonist-induced receptor internalization and down-regulation.
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Animals↗
Biomedical subjects
N Kawakami
Publications and source records attributed to N Kawakami.
Expression of histamine H(1) receptor in placenta.
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Animals↗
Inhibition of histamine H1 receptor downregulation by KT5823, a protein kinase G inhibitor.
The role of various protein kinases in the downregulation of histamine H(1) receptors was studied by using their inhibitors and activators. Human histamine H(1) receptors (H(1)Rs) expressed in CHO cells were downregulated by histamine in a dose- and time-dependent manner, and this downregulation continued to increase over a 24-h period. KT5823, an inhibitor of protein kinase G, remarkably but not completely reversed the histamine-induced H(1)R downregulation over 24 h. HA1004, another inhibitor of protein kinase G, showed a similar inhibitory effect. However, both 8-Br-cGMP and 8-pCPT-cGMP, membrane-permeable analogues of cGMP, did not show any effects on H(1)R downregulation in the absence or presence of histamine. Ro 31-8220, an inhibitor of protein kinase C (PKC), did not affect histamine-induced downregulation of H(1)R; nor did phorbol 12-myristate 13-acetate, a PKC-activating phorbol ester. Similarly, histamine-induced downregulation of H(1)R was unaffected by either H-89, an inhibitor of protein kinase A, or 8-Br-cAMP, a membrane-permeable analogue of cAMP.
8-Bromo Cyclic Adenosine Monophosphate↗
Direct phosphorylation of histamine H1 receptor by various protein kinases in vitro.
Phosphorylation of G protein-coupled receptors (GPCRs) by various kinases is suggested to be an important step in initiating receptor desensitization. Some reports have indirectly demonstrated the involvement of protein kinase C (PKC)-mediated receptor phosphorylation in the desensitization of the histamine H1 receptor (H1R). In this study, human c-myc-epitope-tagged H1R (hm mcH1R) was expressed in Sf9 cells, and an in vitro approach was taken to obtain direct evidence that H1R could be phosphorylated by various kinases. When hm mcH1R, which had been immunoprecipitated with anti-c-myc antibody from Sf9 cell membranes, was incubated with PKC, cAMP-dependent protein kinase (PKA), calcium/calmodulin-dependent protein kinase II (CaMKII) or cGMP-dependent protein kinase (PKG), the immunoprecipitated receptor was phosphorylated by these kinases. Membrane-bound hm mcH1R, whose conformation is closer to its physiological state than that of the immunoprecipitated receptor, was also phosphorylated by PKC, PKA, CaMKII and PKG. Phosphorylation of immunoprecipitated and membrane-bound hm mcH1R was inhibited by kinase inhibitors. These data are the first demonstration of the phosphorylation of H1R by four protein kinases, i.e., PKC, PKA, CaMKII and PKG, and provide fundamental information to help us further understand the relationship between H1R phosphorylation and desensitization of this receptor.
Animals↗
A prospective cohort study of soy product intake and stomach cancer death.
The relationship between intake of soy products and death from stomach cancer was examined in a community-based prospective study of Japanese men and women in Takayama, Japan. Over 7 years of follow-up, 121 deaths from stomach cancer (81 men and 40 women) occurred among 30,304 (13,880 men and 16,424 women) participants who were at least 35 years of age. Diet including the intake of soy products and isoflavones was assessed by a validated semiquantitative food-frequency questionnaire at the beginning of the study. In men, the highest compared to the lowest tertile of total soy product intake was significantly inversely associated with death from stomach cancer after controlling for covariates (hazard ratios=0.50; 95% confidence intervals (CIs) 0.26-0.93, P for trend=0.03). Decreased hazard ratios for the highest compared to the lowest tertiles of total soy product intake (hazard ratios=0.49; 95% CI 0.22-1.13) was observed in women, although this association was of marginal significance. These data suggest that soy intake may reduce the risk of death from stomach cancer.
Chemoprevention↗
Correlation between the age of pinealectomy and the development of scoliosis in chickens.
STUDY DESIGN: Pinealectomy induces experimental scoliosis in chickens. This study analyzed the correlation between the age at which pinealectomy was performed and the development of scoliosis in chickens. OBJECTIVE: To investigate the differences in the rate or magnitude of scoliosis and the type of curvature in chickens pinealectomized at different times after hatching. SUMMARY OF BACKGROUND DATA: Scoliosis develops in almost all chickens pinealectomized within 3 days after hatching, but there are no data on whether the condition will develop in chickens pinealectomized earlier or later after hatching. METHODS: In this study, 106 female white leghorn chickens were divided into six groups: four pinealectomy groups (pinealectomy was performed 2, 4, 11, or 18 days after hatching in Groups P-2, P-4, P-11, and P-18, respectively), a control group (Group C), and a sham operation group (Group S). Ventrodorsal radiographs of the spine were taken at 4-week intervals until the age of 12 weeks. At 12 weeks, a 1-mL sample of blood was taken from the heart at the middle of the dark cycle, and the serum melatonin concentration was measured by radioimmunoassay. RESULTS: At the age of 12 weeks, scoliosis was present in 63.6% of the chickens in Group P-2, 72.7% in Group P-4, 81% in Group P-11, and 70% in Group P-18, and the Cobb angles in the scoliotic chickens averaged 32.6, 29.8, 23.8, and 22.3 degrees in the respective groups. There were no significant differences in the rate or magnitude of scoliosis and the type of curvature among the pinealectomy groups at the age of 12 weeks. At the age of 12 weeks, the serum melatonin levels at the middle of the dark cycle in the pinealectomized chickens were significantly lower than those of chickens in Groups C and S. However, there were no differences in the serum melatonin levels between scoliotic and nonscoliotic pinealectomized chickens. CONCLUSIONS: Findings from this study show that scoliosis develops in 60% to 80% of chickens pinealectomized within 18 days after hatching, and that scoliotic development is not influenced by the age at which pinealectomy is performed. However, this study suggests that melatonin plays a complicated role in spinal development, inasmuch as the serum melatonin levels after pinealectomy approximated zero. Yet scoliosis did not develop in all pinealectomized chickens.
Aging↗
Soy product intake and hot flashes in Japanese women: results from a community-based prospective study.
The association between soy product intake and the occurrence of hot flashes was examined in a cohort of 1,106 female residents of Takayama, Gifu, JAPAN: The women were aged 35-54 years and premenopausal at their entry into the study in 1992. Diet, including intake of soy products and isoflavones, was assessed by means of a validated semiquantitative food frequency questionnaire at study entry. A follow-up mail questionnaire asking about experiences of hot flashes was sent in 1998. During the 6 years of the study period, 101 women had new moderate or severe hot flashes according to the Kupperman test of menopausal distress. After data were controlled for age, total energy intake, and menopausal status, hot flashes were significantly inversely associated with consumption of soy products in terms of both total amount (highest tertile of soy product intake (g/day) vs. lowest: hazard ratio = 0.47; 95% confidence interval: 0.28, 0.79; p for trend = 0.005) and isoflavone intake (highest tertile of isoflavone intake (mg/day) vs. lowest: hazard ratio = 0.42; 95% confidence interval: 0.25, 0.72; p for trend = 0.002). These data suggest that consumption of soy products has a protective effect against hot flashes.
Adult↗
Analysis of cartilage-derived retinoic acid-sensitive protein in cerebrospinal fluid From patients With spinal diseases.
STUDY DESIGN: The expression of cartilage-derived retinoic acid-sensitive protein (CD-RAP) was measured in cerebrospinal fluid from patients with spinal diseases. OBJECTIVES: To quantify the levels of CD-RAP in human cerebrospinal fluid and to clarify its character. SUMMARY OF BACKGROUND DATA: Cartilage-derived retinoic acid-sensitive protein is a newly discovered, secreted molecule that is expressed during the chondrogenesis phase of endochondral bone formation and in articular cartilage. In recent studies CD-RAP has been detected in the serum of patients with melanoma and breast cancer, and it has been used to monitor tumor activity. However, the function of CD-RAP is unknown, and the expression of CD-RAP in human cerebrospinal fluid has never been reported. METHODS: The concentration of CD-RAP in human cerebrospinal fluid was measured by enzyme-linked immunosorbent assay with antihuman CD-RAP antibodies. Cerebrospinal fluid samples were collected from two groups of patients. Group 1, the control group, consisted of 40 patients: 22 with trauma and 18 with gynecologic diseases. Group 2 consisted of 172 patients with spinal diseases: 5 with meningioma, 5 with neurinoma, 5 with arachnoid cyst, 30 with cervical spondylotic myelopathy, 35 with lumbar disc herniation, 56 with lumbar canal stenosis, and 36 with scoliosis. RESULTS: The concentration of CD-RAP in the control group was 16.5 +/- 8.3 ng/mL. The concentrations of CD-RAP in Group 2 were: 35.3 +/- 14.7 ng/mL in meningioma, 23.5 +/- 7.41 ng/mL in neurinoma, 26.0 +/- 22.2 ng/mL in arachnoid cyst, 41.7 +/- 22.3 ng/mL in cervical myelopathy, 27.8 +/- 14.7 ng/mL in lumbar disc herniation, 36.5 +/- 18.4 ng/mL in lumbar canal stenosis, and 13.4 +/- 7.48 ng/mL in scoliosis. The concentrations of CD-RAP in cervical myelopathy, lumbar canal stenosis, and lumbar disc herniation were significantly higher than in the control group (P < 0.001). CONCLUSIONS: The CD-RAP concentration was low in the control group, whereas it was significantly higher in spinal diseases that cause spinal stenosis. CD-RAP is expressed in cerebrospinal fluid as a result of damage to or stressing of neural structures and could be a marker for spinal diseases.
Adolescent↗
Proliferative activity of the parathyroid cells in rats with secondary hyperparathyroidism.
Proliferative kinetics of parathyroid cells in secondary hyperparathyroidism (HPT) are still unknown. We examined the histopathological changes and proliferative activity of parathyroid cells in spontaneously hypercholesterolemic (SHC) rats that exhibit secondary HPT and in normal Sprague Dawley (SD) rats from 3 weeks to 32 weeks of age. Proliferative activity [proliferating cell nuclear antigen(PCNA) labeling index], evaluated by means of immunohistochemical examination of PCNA, declined in SD rats with age from 10.8% at 3 weeks of age to 0.15% at 32 weeks of age. In SHC rats, a PCNA labeling index of 11.6% declined to 3.12% at 14 weeks of age and rebounded to 6.15% at 26 weeks of age. Parathyroid glands increased in size as determined by the maximum cross-sectional area, but in SHC rats, the increase was significantly greater, paralleling the progression of renal dysfunction, and at 32 weeks they were almost three times larger than in SD rats. Parathyroid hormone (PTH) levels in SHC rats also rose sharply after 20 weeks and reached 611 pg/ml at 32 weeks, while PTH in SD rats remained unchanged at approximately 110 pg/ml. This study showed that in the course of developing HPT in SHC rats, there is a large increase in the size of the parathyroid gland, a concomitant increase in PTH levels, and a PCNA labeling index that is higher than in normal SD rats.
Animals↗
Soy product intake and premenopausal hysterectomy in a follow-up study of Japanese women.
OBJECTIVE: The estrogenicity of dietary soy may increase the risk of diseases, such as uterine leiomyoma and endometriosis, which originate from uterine tissue and are predominant indications for hysterectomy. We sought to determine whether soy product intake is associated with an increased risk of premenopausal hysterectomy. DESIGN: Prospective cohort study. SETTING: Takayama City, Gifu, Japan. SUBJECTS: A cohort of 1172 female residents randomly selected from participants in the Takayama Study who were aged 35-54 and premenopausal at the time they entered the study in 1992. MEASUREMENTS: Diet including soy product and isoflavone intake was assessed by a validated semiquantitative food frequency questionnaire at baseline. Information on the onset of menopause and hysterectomy were obtained by a follow-up mail questionnaire in 1998. RESULTS: During the 6 y study period, 31 women underwent premenopausal hysterectomies. The second tertile of isoflavone intake was significantly associated with an decreased risk of premenopausal hysterectomy compared to the lowest tertile of intake after controlling for age and total energy (rate ratio=0.35, 95% confidence interval 0.13-0.97), although the dose-response relationship was not statistically significant. CONCLUSIONS: It is possible that soy product intake may be inversely associated with diagnoses leading to hysterectomy. Future studies focusing on specific diseases will be required to examine this possibility. SPONSORSHIP: Grants from the Ministry of Education, Science, Sports and Culture, Japan.
Adult↗
Distinct functions of the two protein tyrosine phosphatase domains of LAR (leukocyte common antigen-related) on tyrosine dephosphorylation of insulin receptor.
Most receptor-like, transmembrane protein tyrosine phosphatases (PTPases), such as CD45 and the leukocyte common antigen-related (LAR) molecule, have two tandemly repeated PTPase domains in the cytoplasmic segment. The role of each PTPase domain in mediating PTPase activity remains unclear; however, it has been proposed that PTPase activity is associated with only the first of the two domains, PTPase domain 1, and the membrane-distal PTPase domain 2, which has no catalytic activity, would regulate substrate specificity. In this paper, we examine the function of each PTPase domain of LAR in vivo using a potential physiological substrate, namely insulin receptor, and LAR mutant proteins in which the conserved cysteine residue was changed to a serine residue in the active site of either or both PTPase domains. LAR associated with and preferentially dephosphorylated the insulin receptor that was tyrosine phosphorylated by insulin stimulation. Its association was mediated by PTPase domain 2, because the mutation of Cys-1813 to Ser in domain 2 resulted in weakening of the association. The Cys-1522 to Ser mutant protein, which is defective in the LAR PTPase domain 1 catalytic site, was tightly associated with tyrosine-phosphorylated insulin receptor, but failed to dephosphorylate it, indicating that LAR PTPase domain 1 is critical for dephosphorylation of tyrosine-phosphorylated insulin receptor. This hypothesis was further confirmed by using LAR mutants in which either PTPase domain 1 or domain 2 was deleted. Moreover, the association of the extracellular domains of both LAR and insulin receptor was supported by using the LAR mutant protein without the two PTPase domains. LAR was phosphorylated by insulin receptor tyrosine kinase and autodephosphorylated by the catalytic activity of the PTPase domain 1. These results indicate that each domain of LAR plays distinct functional roles through phosphorylation and dephosphorylation in vivo.
Animals↗
[Successful complete androgen blockade (CAB) therapy for prostatic cancer detected from multiple lung metastases: a case report].
Prostatic cancer is rarely diagnosed by detection of lung metastases. We report a case of prostatic cancer in a 73-year-old man detected by abnormalities in chest X-ray and serum prostate specific antigen (PSA) level. He was initially admitted to our hospital due to elevation of PSA level. On the first transperineal prostatic needle biopsy, prostatic cancer was not detected and he was followed. Seven months after the first biopsy, chest X-ray revealed multiple abnormal nodules in the lung fields bilaterally and PSA level was again elevated. A second prostatic biopsy and whole-body examination were performed, and he was diagnosed with moderately differentiated prostatic adenocarcinoma with multiple lung metastases. Complete androgen blockade therapy was performed immediately. Two months after the beginning of treatment, PSA level was normalized and the multiple lung metastases had completely disappeared. There has been no evidence of recurrence or PSA relapse 24 months after detection of the prostatic cancer. This is the 26th case of prostatic cancer diagnosed in Japan following detection of multiple lung metastases.
Adenocarcinoma↗
[Regional cerebral blood flow values measured by Xe-CT during the attack of transient global amnesia: a case report].
A 50-year-old right-handed woman was referred to our hospital for further examination of sudden global amnesia. The patient had no history of epilepsy, head injury or cerebral vascular diseases. There were no neurological deficits except for recent memory disturbance. We examined her cerebral blood flow(CBF) immediately during transient global amnesia(TGA) by stable xenon enhanced CT scans(Xe-CT) and twice thereafter. Xe-CT during the attack showed a significant diminution of regional blood flow from the right posterior temporal lobe to the occipital lobe. Conventional MRI scans also had been performed serially but it could not detect the local ischemic event. The ischemic lesion was clearly divided and larger than those cases reported using PET, SPECT, and diffusion-weighted MRI. TGA happens suddenly, and recovery is immediate. It becomes very difficult to study CBF during TGA attack. However stable Xe-CT is capable of examining CBF easily, so we concluded that CBF examination by Xe-CT in TGA patients would be helpful to reveal the mechanism of TGA.
Amnesia, Transient Global↗
[Two cases of elderly patients with ruptured AVM with contrast medium extravasation during cerebral angiography].
Two cases are reported of elderly patients who experienced intracranial extravasation of contrast medium (CM) during carotid angiography (CAG) for ruptured cerebral arteriovenous malformations (AVM). The first patient, an 87-year-old male with no history of hypertension, was admitted immediately following a loss of consciousness after swimming in a pool. CT scan revealed a large intracranial hematoma in the left frontal lobe. CAG performed 1 hour after his arrival revealed a small AVM, fed by the left anterior cerebral artery with concomitant extravasation of CM. The patient's condition subsequently deteriorated and he died the following day. The second patient, a 71-year-old female, was admitted to our hospital in a comatose state after complaining of a severe headache. CT scan revealed a right parietal lobe hemorrhage extending into the ventricles. CAG was performed and demonstrated a small AVM in the right parietal lobe with extravasation of CM. Following emergency removal of the hematoma and AVM, the patient regained consciousness although some motor deficits persisted. A literature review revealed that only 6 cases of CM extravasation with ruptured AVM have been previously reported. The 4 previous cases involved patients 9, 15, 33 and 66-year-old, the younger three of which had a good outcome. The patients reported here were much older, and had a much less favorable outcome. Thus, AVM with CM extravasation may have a better prognosis in younger individuals.
Aged↗
[A case of Sertoli cell tumor of the testis].
A 24-year-old man was admitted to our hospital with the complaint of a painless mass in the left testis. Gynecomastia was not present. The serum levels of alpha fetoprotein and human chorionic gonadotropin-beta were not elevated. Ultrasound sonography showed a hypoechoic lesion in the left testis. There was no evidence of retroperitoneal lymph node enlargement or distant metastasis on computerized tomography. With a diagnosis of left testicular tumor, left high orchiectomy was done. The tumor measured 10 x 11 mm in size within the testis and was histologically diagnosed as benign Sertoli cell tumor. Immunohistochemcal analysis revealed negative findings with the tumor markers inhibin, CAM 5.2, pancytokeratin, EMA, and PLAP. No adjuvant therapy was performed. Twenty-six cases of Sertoli cell tumor of the testis in the Japanese literature are reviewed.
Adult↗
Job stress, social support at work, and insomnia in Japanese shift workers.
A cross-sectional study was conducted to clarify the contribution of psychological job stress to insomnia in shift workers. A self-administered questionnaire concerning job stress, sleep, depressive symptoms and lifestyle factors was submitted to a sample of 530 rotating shift workers of age 18-59 years (mean age 27) in an electric equipment manufacturing company. Perceived job stress, i.e., job demands, job control and social support at work, was assessed using the Japanese version of the Job Content Questionnaire. Insomnia was regarded as prevalent if the workers had at least one of the following symptoms in the last year; less than 30 minutes to fall asleep, difficulty in maintaining sleep, or early morning awakening almost everyday. Overall prevalence was 37.8%. Logistic regression analyses while adjusting relevant factors showed that lower social support at work was significantly associated with a greater risk of insomnia than the higher social support (adjusted OR 2.5). Higher job strain with lower social support at work increased the risk, compared to lower strain with higher support at work (crude OR 1.8; adjusted OR 1.5). Our findings suggest the low social support at work independently associated with insomnia in shift workers.
Adolescent↗
Association of diet with the onset of menopause in Japanese women.
A prospective study was conducted in Takayama, Gifu, Japan, to evaluate the association between diet and the onset of menopause. A total of 1,130 female residents aged 35-54 years who were premenopausal and completed a validated semiquantitative food frequency questionnaire in 1992 were contacted by mail with a follow-up questionnaire in 1998 to update information on menopause. Onset of menopause was defined as a woman's age at the last menstrual period prior to stopping menstruation for 12 months. During the 6-year study period, 296 women experienced natural menopause. The Cox proportional hazards model was used to estimate hazard ratios of the onset of menopause after controlling for age, total energy, body mass index, years of smoking, and age at which regular menstrual cycle began. The authors found that green and yellow vegetable intake was significantly inversely associated with the 6-year incidence of menopause (hazard ratio = 0.71, 95% confidence interval: 0.54, 0.95 for the highest vs. lowest tertile of intake, p for trend = 0.02). Association of carotene intake with the incidence of menopause was of borderline significance (hazard ratio = 0.78, 95% confidence interval: 0.59, 1.04, p for trend = 0.07).
Adult↗
On-line automated high-performance liquid chromatographic determination of total riboflavin phosphates using immobilized acid phosphatase as a pre-column reactor.
An automated chromatographic detection system for the determination of total riboflavin phosphates using immobilized sweet potato acid phosphatase as a pre-column reactor is reported on. An immobilized enzyme reactor, incorporated in the on-line analytical system, hydrolysed riboflavin phosphates to riboflavin, and then lipophilic riboflavin was concentrated at the top of an ODS trap column. Enzymatically hydrolysed riboflavin was back-eluted from the trap column using a mobile phase containing methanol, and then subsequently chromatographed on an ODS analytical column. The effluents were monitored by UV absorption at 280 nm. The calibration graph for total riboflavin phosphates, determined by this method, was linear over the range 0.5-500 nmol/ml, with a correlation coefficient of 0.9999. The detection limit at a signal-to-noise ratio of 3 was 25 pmol/ml. The average conversion rate of riboflavin phosphates to riboflavin was estimated at 97%. The relative standard deviations of the intra- and inter-assay precision were 1.2 and 2.6%, respectively.
Acid Phosphatase↗