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Biomedical subjects

S Ishikawa

Publications and source records attributed to S Ishikawa.

At least 145 records · Page 8Linked to original sources

Association of hyperthyroidism with serum leptin levels.

The present study was undertaken to determine whether thyroid hormones affect serum leptin levels in patients with hyperthyroidism. In 32 female patients with hyperthyroidism and 30 body mass index (BMI)-matched control subjects, there was no difference in serum leptin concentrations (9.0+/-1.0 v 8.2+/-0.9 microg/L). The serum leptin levels were compared with the expected values for serum leptin derived from the corresponding BMI with the formula for the control subjects (serum leptin [micrograms per liter] = 0.976 x BMI [kilograms per square meter] - 11.933, P < .001) and are expressed as the percent deviation (%leptin). There was a weak but significant positive correlation between serum free thyroxine (T4) levels and %leptin in the combined analysis of patients with hyperthyroidism and control subjects (r = .28, P < .05). Multiple regression analysis also revealed the independent contribution of free T4 levels to serum leptin. Antithyroid therapy ameliorated the hyperthyroidism and increased the BMI by 7.8% and the percent body fat by 9.9% in a subgroup of 21 patients with hyperthyroidism. However, serum leptin levels did not change during the 2-month therapeutic period (from 9.8+/-1.4 to 8.7+/-1.0 microg/L), and accordingly, %leptin significantly decreased from 133%+/-16% to 98%+/-11% (P < .05). A total of 6 months of observation in 12 hyperthyroid patients showed the same alterations in the anthropometric indexes, serum leptin, and %leptin. These results indicate that serum leptin is slightly increased in subjects with moderate hyperthyroidism, possibly due to the direct action of thyroid hormone, and the levels decline in accordance with the attainment of euthyroidism.

Adipose Tissue↗

Developmental changes in pharmacokinetics and pharmacodynamics of warfarin enantiomers in Japanese children.

OBJECTIVE: To clarify developmental changes in the pharmacokinetics and dynamics of warfarin enantiomers to establish rational pediatric dosage. METHODS: Plasma concentrations of unbound warfarin enantiomers, vitamin K1 and vitamin K-dependent proteins (that is, prothrombin fragments 1+2, protein C, and the protein-induced by vitamin K absence) and international normalized ratio were measured in 38 prepubertal (1 to 11 years), 15 pubertal (12 to 18 years), and 81 adult (37 to 76 years) patients given long-term warfarin therapy. Unbound oral clearance values for warfarin enantiomers and its body weight-, body surface area-, and liver weight-normalized values, as well as the pharmacodynamic parameters, were compared among the groups. RESULTS: The prepubertal, pubertal, and adult patients exhibited comparable mean plasma concentrations of unbound warfarin enantiomers for pharmacologically more active (S)-warfarin. Although the unbound oral clearance of (S)-warfarin for the prepubertal patients was significantly (P < .01) less than that for the adult group (346 versus 637 mL/min), the body weight-normalized unbound oral clearance for the prepubertal patients was significantly (P < .01) greater than that for the adults and showed a negative correlation (P < .05) with age. In contrast, no differences were observed in the liver weight-normalized unbound oral clearance for (S)-warfarin between the prepubertal and adult groups. The prepubertal patients showed significantly (P < .01 or .05) lower plasma concentrations of protein C and prothrombin fragments 1+2 and greater international normalized ratio and international normalized ratio/dose than the adults. In contrast, the pubertal patients showed largely similar pharmacokinetic and pharmacodynamic properties to adults. CONCLUSION: Liver weight may be a better parameter than body weight for estimating the warfarin doses for prepubertal patients on the basis of the corresponding adult values. Augmented responses to warfarin in children should also be taken into account for estimating warfarin doses for children.

Adolescent↗

Comparison of two automatic staplers for closing the bronchial stump after pulmonary resection.

The incidence of complications following pulmonary resection using an automatic stapler was studied in 348 consecutive patients. A parallel-jaw stapler with two staple lines was used in group A (133 males, 101 females, mean age 66 years) between 1990 and 1995, and a hinged-jaw stapler with three staple lines in group B (70 males, 44 females, mean age 67 years) in 1995-1997. The incidence of bronchopleural fistula was 0.4% (1 patient) in group A and nil in group B. The incidence of intraoperative air leak requiring interrupted suture closure was 4.7% (11 patients) in group A and nil in group B (p < 0.05). Postoperative bronchopleural fistula did not develop in any of the cases, and there was no mortality. For management of the bronchial stump after pulmonary resection, the newer device firing three rows of staples is superior to the two-row device.

Adult↗

Repeat intervention for in-stent restenosis: re-expansion of the initial stent is a predictor of recurrence of restenosis.

BACKGROUND: In-stent restenosis has become a significant clinical problem as use of stents has increased. The optimal strategy for dealing with in-stent restenosis needs to be evaluated. OBJECTIVE: To compare the acute and late results of interventions for in-stent restenosis according to the device used, and to analyze the clinical and procedural variables of the lesions treated and identify the determinants of recurrence of restenosis and target lesion revascularization (TLR). METHODS: Procedural and late outcomes for 58 lesions in 50 patients who underwent repeat intervention for in-stent restenosis were analyzed. The results of interventions according to the device employed were compared. The predictors of recurrence of restenosis and TLR within 6 months were analyzed. The ratio of balloon diameter in repeat intervention to minimal lumen diameter after initial stenting (MLD0) was used as an index of re-expansion of stents. Serial intravascular ultrasound imaging was performed before and after repeat intervention for 33 lesions, and re-expansion of the initial stent was evaluated. RESULTS: Repeat intervention was successful in treating all lesions. Angiographic follow-up was possible for 49 lesions (84%). The overall incidences of recurrence of restenosis and TLR were 40.1 and 27.6%, respectively. Despite the immediate results having been good, the late results of stenting for in-stent restenosis were not favorable. Diffuse-type in-stent restenosis, early in-stent restenosis, and balloon diameter:MLD0 ratio > 1.25 are independent predictors of poor late results. Intravascular ultrasound findings have shown that expansion of the initial stent leads to recurrence of restenosis and TLR. CONCLUSIONS: Re-expansion of the initial stent can cause further vascular injury and there is a risk of recurrence of restenosis. Alternative therapeutic strategies that work without dilating the initial stent may be necessary for treating lesions with high risk of recurrence of restenosis.

Aged↗

Constitutively expressed phoP inhibits mouse-virulence of Salmonella typhimurium in an Spv-dependent manner.

In Salmonella typhimurium, the transcription of several virulence genes including spvB is regulated by the PhoP/PhoQ regulatory system. To further examine the relationship between the PhoP/PhoQ and Spv systems for virulence in mice, we examined a non-polar phoP mutation combined with different virulence plasmid genotypes for effects on virulence of S. typhimurium in the mouse model. PhoP-/Spv+ and PhoP-/Spv- mutants were not detectably recovered from the spleens of subcutaneously or orally inoculated mice. The phoP gene constitutively expressed from the lacZ promoter of a low copy number vector (phoP(C)) only partially complemented the non-polar phoP mutation for mouse-virulence in both the Spv+ and Spv- backgrounds; both PhoP(C) strains exhibited virulence equal only to a PhoP+/Spv- strain. Interestingly, in a PhoP+ background, the phoP(C) gene reduced splenic infection of the Spv+ but not Spv- salmonellae after subcutaneous or oral inoculation compared with the PhoP+ parents. Additionally, the phoP(C) gene in an Spv+ background reduced the net growth of salmonellae in macrophages in vitro; phoP(C) in an Spv- background was without effect. These data suggest that the constitutive expression of the phoP gene attenuates the virulence of S. typhimurium in mice in an Spv-dependent manner.

ADP Ribose Transferases↗

Earlier detection of human immunodeficiency virus type 1 p24 antigen and immunoglobulin G and M antibodies to p17 antigen in seroconversion serum panels by immune complex transfer enzyme immunoassays.

For earlier diagnosis of human immunodeficiency virus type 1 (HIV-1) infection, the sensitivities of immune complex transfer enzyme immunoassays for HIV-1 p24 antigen and antibody immunoglobulin G (IgG) to HIV-1 p17 antigen were improved approximately 25- and 90-fold, respectively, over those of the previous immunoassays by performing solid-phase immunoreactions with shaking and increasing the serum sample volumes, and immune complex transfer enzyme immunoassay of antibody IgM to p17 antigen was also performed in the same way as the improved immunoassay of antibody IgG to p17 antigen. By the improved immunoassays, p24 antigen and antibody IgG to p17 antigen were detected earlier in 32 and 53%, respectively, of the HIV-1 seroconversion serum panels tested than before the improvements, and p24 antigen was detected as early as or earlier than HIV-1 RNA by reverse transcriptase-PCR (RT-PCR) in all of the panels tested. In 4 panels out of 19 tested, antibody IgG to p17 antigen or both antibodies IgG and IgM to p17 antigen were detected earlier than p24 antigen and RNA, although the antibody levels declined slightly before their steep increases usually observed after p24 antigen and RNA. Thus, the window period in diagnosis of HIV-1 infection can be shortened by detection of p24 antigen with the improved immunoassay as much as by detection of RNA with RT-PCR and, in some cases, more by detection of antibodies IgG and IgM to p17 antigen with the improved immunoassays than by detections of p24 antigen with the improved immunoassay and RNA with RT-PCR.

Gene Products, gag↗

Renal resistance to vasopressin in poorly controlled type 1 diabetes mellitus.

To investigate the hypothesis that diabetes induces nephrogenic diabetes insipidus, we studied the urine-concentrating ability in response to vasopressin (AVP) in 12 patients with insulin-dependent diabetes mellitus (IDDM) and 12 nondiabetic controls. Subjects were euglycemic-clamped, and after oral water loading, AVP was infused intravenously for 150 min. AVP induced a greater (P<0.001) rise in urine osmolality in controls (67.6+/-10.7 to 720+/-31.1 mosmol/kg, P<0.001) than in IDDM patients (64.3+/-21.6 to 516.7+/-89.3 mosmol/kg, P<0.001). Urinary aquaporin-2 concentrations after AVP infusion were higher in controls (611.8+/-105.6 fmol/mg creatinine) than in IDDM (462.0+/-94.9 fmol/mg creatinine, P = 0. 003). Maximum urine osmolality in IDDM was inversely related to chronic blood glucose control, as indicated by Hb A(Ic) (r = -0.87, P = 0.002). To test the hypothesis that improved glycemic control could reverse resistance to AVP, 10 IDDM subjects with poor glycemic control (Hb A(Ic) >9%) were studied before (B) and after (A) intensified glycemic control. Maximum urine osmolality in response to AVP increased with improved glycemic control (B, 443.8+/-49.0; A, 640.0+/-137.2 mosmol/kg, P<0.001), and urinary aquaporin-2 concentrations after AVP increased from 112.7 +/-69 to 375+/-280 fmol/mg creatinine (P = 0.006), with improved glycemic control. Poorly controlled IDDM is associated with reversible renal resistance to AVP.

Adolescent↗

Synthesis and properties of novel bifunctional nitrosamines with omega-chloroalkyl groups.

Novel N-nitroso-N-(acetoxymethyl)-omega-chloroalkylamines were synthesized and their chemical and biological properties were evaluated. The nitrosamines were expected to decompose through omega-chloroalkyldiazohydroxides in aqueous solution, and then to alkylate various cellular macromolecules. N-Nitroso-N-(acetoxymethyl)-2-chloroethylamine rapidly decomposed in aqueous solution, and the reaction rate was apparently independent of the pH of the solution. On the other hand, the rate of decomposition of chloropropyl and chlorobutyl homologs was pH-dependent, and increased in alkaline solution. When mutagenicity was assayed in Salmonella typhimurium TA1535 and TA92 for preliminary evaluation, all three compounds were directly mutagenic. The mutagenicity in Salmonella typhimurium TA1535, which can detect base-pair change mutation, clearly showed that these compounds induced DNA alkylation in vivo. The increase of alkyl chain length in chloroalkyl compounds increased the mutagenic activity, and the activities were stronger than those of the corresponding simple alpha-acetoxy nitrosamines lacking a chloro group, N-nitroso-N-(acetoxymethyl)alkylamines. Furthermore, the positive result in TA92 suggested that chlorinated nitrosamines cross-linked DNA like antitumor chloroethylnitrosoureas and that they are expected to be new lead compounds for antitumor agents.

Alkylation↗

Five-year intra-individual variability in C-reactive protein levels in a Japanese population-based study: the Jichi Medical School Cohort Study at Yamato, 1993-1998.

C-reactive protein (CRP) is an acute-phase reactant that is related to future cardiovascular events. However, little is known about the long-term intra-individual stability of CRP in community residents. The 5-year intra-individual correlation of CRP levels was examined in the Jichi Medical School Cohort Study in Japan. CRP measurements were obtained in 1993 and in 1998 from 388 presumptively healthy individuals aged 30-69 years at baseline. The Pearson's correlation coefficient of CRP between baseline and follow-up measurements was 0.43 (95% confidence interval (CI): 0.34-0.51). Additional analyses by sex and smoking status at baseline revealed similar coefficients. The correlation coefficient of CRP was lower than that of other classical risk factors, such as body-mass index (BMI), blood pressure, and total and high-density lipoprotein (HDL) cholesterol. A subgroup of individuals with higher levels of CRP at both baseline and follow-up measurements had higher BMI, hemoglobin Alc, and plasma fibrinogen, and lower levels of HDL-cholesterol than others, even after adjusting for age, sex, and smoking status in a multiple logistic model. In conclusion, the stability of CRP levels was statistically significant in a long-term population-based study. A subgroup with higher levels of CRP who had an aggregation of cardiovascular risk factors was identified by the 2 measurements.

Adult↗

Prediction of embolism in atrial fibrillation: classification of left atrial thrombi by transesophageal echocardiography.

The current study was undertaken to clarify the relationship between cerebral/arterial embolism and the morphology of left atrial thrombi. Forty-one patients with atrial fibrillation and left atrial thrombi were followed for 1 year, using transesophageal echocardiography (TEE) to study how the shape, site, movability, number and maximum dimension of left atrial thrombi are related to embolism. Left atrial thrombi were classified by their shape and movability into movable ball (MB) type (n=13), fixed ball (FB) type (n=17) and mountain (MN) type (n=11). The thrombi were also classified by location into the interior section (n=3), middle section (n=8), and the entrance section (n=19) of the left atrial appendage, and the section outside of the left atrial appendage (n=11). The rate of embolism in the MB-type group was significantly higher than that in the other groups (ie, MB 76.9% vs FB 17.6% (p<0.01) vs MN 9.1%; p<0.01), which indicates that the MB-type thrombus is an important risk factor for cerebral/arterial embolism.

Adult↗

Lipoprotein(a) is a potential coronary risk factor.

Lipoprotein(a) (Lp(a)) is recognized as a new coronary risk factor, but few studies have quantitatively assessed the relationship of serum Lp(a) levels with other coronary risk factors in many patients undergoing coronary cineangiography. Seventeen coronary risk factors were quantified (i.e., age, gender, hypertension, impaired glucose tolerance, cerebrovascular accident, hyperuricemia, smoking, family history of ischemic heart disease (IHD), history of hyperlipidemia, Lp(a), total cholesterol, high density lipoprotein (HDL)-cholesterol, triglyceride, low density lipoprotein-cholesterol, apolipoproteins(apo)A-I,B, E) to determine their relationship with the numbers of involved coronary vessels using multiple regression test in 1,006 patients who underwent coronary cineangiogram (280 non-IHD patients: 144 men, 136 women; 726 IHD patients: 460 men, 266 women; age 16-84 years, mean 60.5+/-0.3). Multiple regression test indicated R = 0.506 and items that showed high beta weight and significant p level were age, Lp(a), impaired glucose tolerance, total cholesterol, cerebrovascular accidents, HDL-cholesterol, smoking, gender, family history of IHD, and apo-A-I (0.221, p<0.001; 0.174, p<0.001; 0.616, p<0.001; 0.138, p<0.001; 0.122, p<0.001; -0.12, p<0.001; 0.092, p<0.01; 0.091, p<0.01; 0.067, p<0.05; -0.065, p<0.05; respectively). It was concluded that Lp(a) is an independent, potential, and modifiable coronary risk factor, and that reduction of serum Lp(a) is important in the clinical management of patients with IHD.

Adolescent↗

Crucial role of insulin in leptin maintenance: profound decrease in serum leptin by octreotide acetate in insulinoma subjects.

To further clarify the relationship between insulin and leptin, time course changes in plasma glucose, serum insulin and leptin levels were analyzed after subcutaneous administration of 100 microg octreotide acetate in two insulinoma subjects. Octreotide acetate induced a prompt decrease in serum insulin level, accompanied with an increase in plasma glucose in both patients. Following the decrease in serum insulin level, serum leptin concentrations were profoundly decreased by 66% and 44%, 8-12 hrs after octreotide injection; that is, the concentrations decreased from 41.1 to 13.8 ng/ml in patient 1, and from 17.5 to 9.8 ng/ml in patient 2. Daily profiles of plasma glucose, serum insulin and leptin without octreotide administration did not show such alterations in these indexes in patient 1. These data show that circulating leptin may be susceptible to decline dependent on the decrease in serum insulin, suggesting that insulin plays a crucial role in the maintenance of leptin secretion in humans.

Blood Glucose↗

Sclerosant therapy for delayed cardiac tampo-nade after coronary artery bypass grafting.

A 56-year-old Japanese male with delayed cardiac tamponade which occurred 13 months after coronary artery bypass grafting (CABG) is presented. The patient was admitted to our hospital suffering from dypnea due to cardiac tamponade. Pericardiocentesis yielded a viscous bloody fluid. The patient recovered after continuous drainage followed by an intra-pericardial administration of minocycline hydrochloride. Sclerosant therapy is considered to be a treatment of choice for delayed cardiac tamponade following CABG.

Cardiac Tamponade↗

Crescentic glomerulonephritis with positive antineutrophil cytoplasmic autoantibody specific for myeloperoxidase associated with autoimmune hemolytic anemia and thrombocytopenic purpura.

A 41-year-old woman was admitted to the hospital with severe uremia, hemolytic anemia, and thrombocytopenic purpura. Emergency hemodialysis with plasmapheresis was started in view of consideration of hemolytic uremic syndrome (HUS), which resulted in improvement of renal function and platelet count. Positive antineutrophil cytoplasmic autoantibody specific for myeloperoxidase (MPO-ANCA) suggested crescentic glomerulonephritis, which was pathologically evidenced by renal biopsy. The diagnosis of MPO-ANCA associated crescentic glomerulonephritis with autoimmune hemolytic anemia (AIHA) and thrombocytopenic purpura were confirmed. Three courses of steroid pulse therapy with heparin were successfully performed, followed by oral prednisolone and warfarin. Such a case has not been previously reported to our knowledge.

Adult↗

Urinary excretion of aquaporin-2 in pathological states of water metabolism.

Aquaporin-2 (AQP-2) is an arginine vasopressin (AVP)-regulated water channel in renal collecting duct cells. Approximately 3 % of AQP-2 in collecting duct cells is excreted into urine. Urinary excretion of AQP-2 varies widely in different physiological conditions, and it has a positive correlation with plasma AVP levels. Urinary excretion of AQP-2 was significantly increased by the single injection of AVP in patients with central diabetes insipidus. The urinary excretion of AQP-2 was one-eighth over in patients with central diabetes insipidus and three times greater in patients with impaired water excretion than that in normal subjects. In a hypertonic saline test, the urinary excretion of AQP-2 promptly increased 6-12-fold in normal subjects, but remained low in patients with central diabetes insipidus. In addition, exaggerated urinary excretion of AQP-2 persisted after an acute water load in patients with impaired water excretion. These results indicate that urinary excretion of AQP-2 is a potent marker for the diagnosis of water metabolism disorders dependent on AVP.

Animals↗

Thoracic duct lymph flow and its driving pressure in anesthetized sheep.

We examined the relationship between thoracic duct lymph flow (TDF) and its driving pressure (DP) in six anesthetized sheep. DP was determined as the thoracic duct pressure (TDP) minus the innominate vein pressure (VP). TDF was measured using an ultrasound transit-time flow meter, placing a flow probe beside the caudal mediastinal lymph node. TDP was measured with a fine needle inserted near the flow probe. TDP increased linearly together with an increase in VP after balloon inflation in the cranial vena cava with a TDP/VP ratio of 0.79. DP decreased, therefore, with an increase in VP and this decrease in DP correlated directly with a fall in TDF. After rapid i.v. fluid infusion, TDF increased but DP varied among the six sheep. Nonetheless, after balloon inflation with expanded volume (i.e., i.v. fluid infusion), DP and TDF were positively correlated. We conclude that DP is the main factor determining TDF when VP rises in conjunction with increased lymph production.

Animals↗

[A case of polymyositis presenting pregnancy with acute respiratory failure].

A 33-year-old pregnant woman developed respiratory difficulty with bilateral pleural effusion 31 weeks into gestation. On admission she had an elevated serum level of creatine kinase, but muscle weakness in the extremities was mild. After an immediate and successful Cesarean section, she developed respiratory failure and mechanical ventilation was required. The patient was diagnosed as having polymyositis from the limb muscle biopsy. She was treated with dexamethasone at a dose of 8 mg, methylprednisolone++, 1 g daily for three days, and then prednisolone 60 mg daily. One week later the serum level of creatine kinase was normalized and the patient was weaned from ventilator support. The dose of prednisolone was tapered 10 mg every week and she was discharged two months after delivery without prednisolone. A chest CT scan revealed no interstitial pneumonitis or aspiration pneumonia, so her respiratory failure seemed to be ascribable to polymyositis-related respiratory muscle weakness and pleural effusion. However, severe involvement of respiratory muscles without generalized marked muscle weakness is extremely rare, and pleural complications have usually been described in association with pulmonary parenchymal diseases. During the following two years polymyositis has not recurred in this patient and there have been no data indicative of other overlapping collagen diseases. Reports of polymyositis which occurred during pregnancy are rare, and the pathogenesis and clinical outcome of these patients need to be carefully investigated.

Acute Disease↗

[An autopsy case of primary cerebellar-pontine angle epidermoid carcinoma].

A 65-year-old man developed right facial palsy and six months later experienced sudden unconsciousness and right hemiplegia. On admission he had severe nuchal rigidity, decreased visual acuity, and a hearing disturbance. A CT scan and angiography failed to reveal any lesions in the brain, but CSF cytology showed undifferentiated malignant cells with a high level of neuron-specific enolase. A postcontrast CT scan and MRI demonstrated diffuse meningeal enhancement and a faintly rim-enhanced cystic lesion at the cerebellopontine angle. The patient died four months after admission, and postmortem examination revealed meningeal dissemination of squamous cell carcinoma, probably arising from an epidermoid cyst at the cerebellopontine angle. Microscopic examination revealed squamous epithelial debris and a foreign body reaction in portions of the cyst wall and in the surrounding subarachnoid space near the base of the cyst. Rim enhancement of the cyst on MRI and the microscopic findings indicated that the recurrent headaches may have been the result of chemical aseptic meningitis caused by spontaneous leakage of the cyst's contents.

Aged↗