Biomedical subjects

S Ishikawa

Publications and source records attributed to S Ishikawa.

At least 55 records · Page 3Linked to original sources

PubMed2002

Apparent diffusion coefficient mapping predicts mortality and outcome in rats with intracerebral haemodynamic disturbance: potential role of intraoperative diffusion and perfusion weighted magnetic resonance imaging to detect cerebral ischaemia.

BACKGROUND: Usefulness and ability of diffusion and perfusion weighted magnetic resonance images (DWI and PWI) to detect intracerebral haemodynamic disturbance have not been fully evaluated. METHODS: After the right common carotid artery had been ligated, rats were exsanguinated to maintain a mean arterial pressure of 35, 42, or 50 mm Hg (n=6, each group). Apparent diffusion coefficient (ADC) maps were calculated from DWIs and lesion volume (area) was defined based on ADC values (ADC lesion volume (area)). RESULTS: ADC lesion volume during exsanguination in the 35 mm Hg group (417 (111) mm(3), P<0.01) was significantly larger than in the 42 mm Hg group (87 (84) mm(3)) and 50 mm Hg group (42 (58) mm(3)). The low relative cerebral blood flow area, calculated from PWI, was significantly larger during exsanguination in the 35 mm Hg group than in the other groups. ADC lesion volume in the six rats that died within 3 days of the MRI study was significantly larger (median 421 mm(3), range 205-476 mm(3), P<0.005) than in the 12 rats that survived for 3 days (median 26 mm(3), range 3-517 mm(3)). Rats with an ADC lesion area over 14 mm(2) on the coronal slice including the caudate putamen during exsanguination died within 3 days or revealed a more severe histopathological outcome than those that survived for 3 days. CONCLUSIONS: Incomplete cerebral ischaemia created by the combination of common carotid artery occlusion and exsanguination could be detected by DWI and PWI both qualitatively and quantitatively. The size of the lesion on ADC mapping was found to correlate with mortality and outcome.

Animals↗

PubMed2002

An endocrinopathy characterized by dysfunction of the pituitary-adrenal axis and alopecia universalis: supporting the entity of a triple H syndrome.

We demonstrate the rare disorder of triple H syndrome in a 25-year-old man. He was pointed out as having short stature, at -5.9 s.d., and diagnosed as GH deficient at 6 years old. Approximately a year ago, he noticed systematic hair loss. He lost body weight by 7 kg during the last half year. He was admitted to Jichi Medical School Hospital because of unconsciousness. Physical findings showed disturbance of consciousness with Japan Coma Scale I-3. He had emaciation and alopecia universalis. Laboratory findings showed plasma glucose was as low as 1.11 mmol/l. GH and ACTH deficiency with hypoadrenocorticism were clarified. His intelligence was in the low normal range with a WAIS IQ of 70, and anterograde amnesia was suggested in the presence of a little, but not significant, morphological change in the hippocampus on a magnetic resonance imaging scan. Replacement by a physiological dose of hydrocortisone normalized plasma glucose, and restored body weight and growth of hair during the 7 month therapeutic period. The present finding strongly supports a clinical entity of triple H syndrome, including ACTH deficiency, alopecia universalis and anterograde amnesia, and that there may be some variation of the triad among the subjects.

Adrenal Glands↗

PubMed2002

Lung impairment following cardiac surgery in patients with pulmonary hypertension.

BACKGROUND: Postoperative respiratory management following cardiac surgery is sometimes troublesome in patients with pulmonary hypertension. We retrospectively studied the relationship between the etiology of preoperative pulmonary hypertension and the postoperative decline of blood oxygenation capacity by focusing on the postoperative intravascular fluid volume. METHODS: Sixteen adult patients with an atrial septal defect (preload group) and 17 patients with solitary mitral valve disease (afterload group) were studied. The mean age of the patients in the preload and afterload group was 51 and 52 years old, respectively. RESULTS: Preoperative pulmonary-systemic pressure ratio and pulmonary artery resistance index were significantly higher in the preload group than in the afterload group. The respiratory index (RI) and the pulmonary shunt ratio (Qs/Qt) measured immediately after the operation was larger in the afterload group than in the preload group. Postoperative RI and Qs/Qt remained high until postoperative day 3 in both groups. In the preload group RI on postoperative day 1 had a reverse correlation with the central venous pressure (CVP). Meanwhile, the RI in the afterload group on postoperative day 1 was slightly larger in patients with a high CVP and pulmonary capillary wedged pressure. Similar relationships were seen in the relations between pulmonary capillary wedged pressure and RI in the afterload group. CONCLUSIONS In conclusion, a preoperative pulmonary vascular change and a postoperative precipitous decrease of pulmonary blood flow may have caused postoperative lung oxygenation impairment in the preload group. An extended period of extracorporeal circulation associated with cardiac arrest and postoperative volume overload may have caused lung impairment in the afterload group. In aspect of postoperative management, low CVP is beneficial to the patients in the afterload group, however, hypovolemia should be avoided in patients of the preload group.

Blood Gas Analysis↗

PubMed2002

[Congenital tracheoesophageal fistula; report of an adult case].

We experienced an adult case of congenital tracheoesophageal fistula which was successfully treated by surgical intervention. A 69-year-old female was admitted with complaint of coughing and fever. The patient previously had had several episodes of pneumonia. Esophagography and thoracic CT demonstrated a tracheoesophageal fistula in the upper of the thoracic esophagus. Following the resection of the fistula, the trachea was closed with one layer suture and the esophagus was closed with two layer sutures. A pedicled fifth intercostal muscle was interposed between the tracheal and esophageal suture lines. There was mild inflammatory change in surrounding tissues of the fistula. Pathological examination revealed that the fistula was covered with the squamous epithelium, and had the muscularis mucosa. Her postoperative course was uneventful.

Aged↗

PubMed2002

Peripheral pulmonary atelectasis and oxygentation impairment following coronary artery bypass grafting.

BACKGROUND: Severe pulmonary oxygenation impairment occurred in some patients with pleurotomy during the harvest of the internal mammary artery graft followed by coronary artery bypass grafting (CABG). Peripheral pulmonary atelectasis in the postoperative chest X-ray was detected in these patients. We studied the efficacy of intraoperative positive end-expiratory airway pressure (PEEP) therapy for the prevention of postoperative pulmonary oxygenation impairment. METHODS: The pleural cavity was intraoperatively opened in 40 patients with solitary CABG procedure performed during 5 years since January 1992. These patients were divided into two groups. Intraoperative PEEP therapy, which is initiated just after pleurotomy, was not used in 32 patients before May, 1996 (control group) and used for recent 8 patients with pleurotomy (PEEP group). The mean age of patients was 60 years old in the control group and 68 in the PEEP group. RESULTS: Respiratory insufficiency (A-aDO2 >400 mmHg and RI >1.5) was detected in 6 patients in the control group. Three out of these 6 patients required long-term mechanical respiratory support over a week. No respiratory insufficiency occurred in patients of the PEEP group. Values of PaO2, A-aDO2, respiratory index and shunt ratio were significantly worse in the control group than in the PEEP group. CONCLUSIONS: In conclusion, PEEP therapy may prevent pulmonary atelectasis and oxygen impairment after CABG.

Aged↗

PubMed2002

[Resection for pulmonary metastasis of gastrointestinal stromal tumor of the stomach at 10 years after gastrectomy; report of a case].

A 70-years-old male, who had received gastrectomy for leiomyosarcoma of the stomach 10 years ago, was found to have a left lung tumor on chest X-ray and computed tomography (CT). The tumor was diagnosed to be a pulmonary metastasis of gastric leiomyosarcoma. On admission, another tumor was detected at left occipital region by brain CT and was thought to be meningioma. Left lower lobectomy and brain tumor resection were performed serially. The histologic and immunohistochemical findings showed that both tumors were metastases of gastrointestinal stromal tumor (GIST) of the stomach after long disease-free interval. Compared with the primary tumor, cellular density, mitotic figures, bizarre nuclei, and necrotic foci were prominent in the metastatic tumors. This case suggest that GIST may recurrent as pulmonary metastasis after long disease-free interval and should be follow up longer after resection. Patient prognosis with pulmonary metastases is considered to be reflected more exactly in biological malignant potential of metastatic tumor rather than that of primary tumor.

Aged↗

PubMed2002

Effect of phosphodiesterase III inhibitor (Olprinone) on thoracic duct lymph flow in anesthetized sheep with experimentally induced heart failure by endothelin-1.

We investigated the short-term effects of a phosphodiesterase III inhibitor (Olprinone) on hemodynamics and thoracic duct lymph flow in anesthetized open-chest sheep with heart failure induced by endothelin-1 (cardiogenic shock). Ultrasound transit-time flow probes were attached to the thoracic duct, the ascending aorta and the renal artery. Arterial, pulmonary and central venous pressures were monitored. Endothelin-1 was infused intravenously at a dosage that reduced cardiac output to 50% or more of baseline (n=11). The effects of Olprinone were examined (n=5) by intravenous infusion after endothelin-1 administration. Other sheep (n=6) were used as controls. Olprinone significantly increased cardiac output that had been decreased by endothelin-1 and further increased thoracic duct flow that had been increased by endothelin-1. Increased arterial and pulmonary pressures induced by endothelin-1 administration were rapidly decreased by Olprinone. Renal arterial flow and central venous pressure were, however, unchanged by Olprinone. Overall, Olprinone acutely improved experimental cardiogenic shock (heart failure) induced by endothelin-1, and maintained thoracic duct lymph flow at a high level after endothelin-1 administration.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2001

Life-threatening orthostatic hypotension in a case with bulbo-myelo-radiculo-neuropathy.

A 59-year-old female developed acute autonomic failure accompanied by life-threatening orthostatic hypotension. Reduced plasma noradrenaline levels and enhanced pressure response to noradrenaline infusion were compatible with a diagnosis of acute pan-dysautonomia. However, nerve conduction tests clearly revealed motor and sensory nerve involvement and abnormal F-responses. A sural nerve biopsy and catecholamine fluorescence study of the rectal mucosa revealed relatively preserved postganglionic unmyelinated nerve fibers. Six weeks later, the patient developed another episode of bulbar palsy and right hemiparesis; the MRI showed lesions in the medulla oblongata and right cervical spinal cord. The prognosis of acute pan-dysautonomia is usually unsatisfactory, but the present patient showed good steroid-responsiveness probably because impaired preganglionic sympathetic myelinated fibers and medulla oblongata recovered quickly.

Acute Disease↗

PubMed2001

Optimal alveolar oxygen concentration for cold storage of the lung.

BACKGROUND: Ischemia of the lung is different from that of solid organs because the lung contains gas in the alveoli. However, the optimal gas composition in the alveoli during cold storage remains uncertain. We investigated the relationship between the alveolar oxygen concentration and reperfusion injury. METHODS: The lungs inflated with 0% O2, 5% O2, room air, 50% O2, or 100% O2 were reperfused after 8 hR storage at 4 degrees C and pulmonary functions were measured for 120 min using an ex vivo rat lung model. The levels of high-energy phosphate and lipid peroxidation of the lung were analyzed after a PA flush, preservation, and reperfusion. Additionally, respiration of the mitochondria in the lungs was measured after preservation. RESULTS: The pulmonary functions were significantly superior in the 5% O2 group than those in the 0% O2, 50% O2, and 100% O2 groups. Pulmonary edema developed in the 0% O2, 50% O2, and 100% O2 groups, but not in the 5% O2 group. After preservation, the energy level in the lungs decreased only in the 0% O2 group. Although lipid peroxidation of the lungs did not increase in any group after preservation, significant increases were observed in the room air, 50% O2 and 100% O2 groups after reperfusion. State 3 and 4 ratios of the mitochondrial respiration significantly decreased in the lungs of the room air, 50% O2 and 100% O2 groups. CONCLUSIONS: Although the cold-preserved lungs require oxygen, hyperoxygenation induced mitochondrial dysfunction and increased lipid peroxidation and led to deleterious lung function after reperfusion. Therefore, hypoxic conditions that can maintain the energy level of the lung during cold storage would be optimal.

Adenine Nucleotides↗

PubMed2001

Aberrant high expression of B lymphocyte chemokine (BLC/CXCL13) by C11b+CD11c+ dendritic cells in murine lupus and preferential chemotaxis of B1 cells towards BLC.

We observed here that the expression of B lymphocyte chemokine (BLC/CXCL13) was markedly enhanced in the thymus and kidney in aged (NZB x NZW)F1 (BWF1) mice developing lupus nephritis, but not in similarly aged NZB and NZW mice. BLC-positive cells were present in the cellular infiltrates in the target organs with a reticular pattern of staining. CD11b+CD11c+ dendritic cells were increased in the thymus and spleen in aged BWF1 mice and identified as the major cell source for BLC. CD4+ T cells as well as B cells were dramatically increased in the thymus in aged BWF1 mice, whereas no increase was observed in aged NZB and NZW mice. B1/B2 ratio in the thymus was significantly higher than those in the spleen and peripheral blood in aged BWF1 mice. Interestingly, BLC showed preferential chemotactic activity for B1 cells derived from several mouse strains, including nonautoimmune mice. Cell surface CXCR5 expression on B1 cells was significantly higher than that on B2 cells. Thus, aberrant high expression of BLC by myeloid dendritic cells in the target organs in aged BWF1 mice may play a pivotal role in breaking immune tolerance in the thymus and in recruiting autoantibody-producing B cells in the development of murine lupus.

Aging↗

PubMed2001

Distribution of serum C-reactive protein and its association with atherosclerotic risk factors in a Japanese population : Jichi Medical School Cohort Study.

The distribution of serum C-reactive protein (CRP) levels and their association with age, sex, and atherosclerotic risk factors were studied in a large Japanese population between 1992 and 1995. The subjects consisted of 2,275 males and 3,832 females aged 30 years and over. CRP was measured by nephelometry. The distribution of CRP was highly skewed toward a lower level than that of previous studies and seemed to be a combination of two separate distribution curves. The increase in CRP with age was statistically significant, and males had higher CRP levels than did females. Males who were current smokers had higher CRP levels than did nonsmokers. Age, systolic blood pressure, diastolic blood pressure, triglycerides, fibrinogen, and body mass index were all positively associated with CRP in both sexes, while total cholesterol and blood glucose were positively related in females only. High density lipoprotein cholesterol was inversely related in both sexes. Multiple logistic regression analysis showed that sex, age, systolic pressure, high density lipoprotein cholesterol, triglycerides, fibrinogen, and body mass index were significant independent variables. In conclusion, the distribution of CRP among the Japanese was quite different from that among Westerners, although CRP levels correlated with other atherosclerotic risk factors, similar to those in Westerners.

Adult↗

PubMed2001

Interaction of MCC2, a novel homologue of MCC tumor suppressor, with PDZ-domain Protein AIE-75.

AIE-75 is a protein identified as an autoantigen in patients with autoimmune enteropathy and as a colon cancer-related antigen. It has recently been assigned to be a causative gene for Usher type 1C congenital syndromic hearing loss. The novel protein has three PSD-95/Dlg/ZO-1 (PDZ) protein-protein interaction domains and is therefore implicated to function as a molecular anchor or sorter. We have identified a novel protein that binds to AIE-75 by yeast two-hybrid screening. The protein has a high homology to the tumor suppressor MCC (mutated in colon cancer; or MCC1 hereafter) and was named MCC2. MCC2 protein binds the first PDZ domain of AIE-75 with its C-terminal amino acids -DTFL. Since the MCC1 does not bind to AIE-75 and the MCC2 displays different expression patterns in various organs compared to MCC1, they appear to play distinct roles in cells. The MCC2 gene is located on chromosome 19p13 in the vicinity of APCL gene, while MCC1 maps near to APC tumor suppressor gene. Because of negative expression of MCC2 in a panel of cancer cell-lines compared to the corresponding normal tissues, we suggest that further study is necessary to investigate a possible role of MCC2 as a tumor suppressor.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Arginine vasopressin inhibits apoptosis of rat glomerular mesangial cells via V1a receptors.

Arginine vasopressin (AVP) promotes proliferation of glomerular mesangial cells. We examined whether AVP modulates an apoptosis of cultured rat glomerular mesangial cells at 3-17th passages. The agarose gel electrophoresis demonstrated that AVP attenuated a ladder formation stimulated by the serum deprivation. The quantitation of oligonucleosomes by ELISA also showed that AVP suppressed the serum deprivation-induced apoptosis. Such an antiapoptotic effect of AVP was dose-dependent. An AVP V1a receptor antagonist, d(CH2)5Tyr(Me)AVP, abolished the antiapoptotic effect of AVP. The inhibitory effect of AVP on the apoptosis was reduced by staurosporine and mimicked by phorbol-12-myristate-13-acetate. These results suggest that AVP inhibits serum deprivation-induced apoptosis of glomerular mesangial cells via V1a receptor-protein kinase C pathway.

Animals↗

PubMed2001

"Chemical preconditioning" by 3-nitropropionate reduces ischemia-reperfusion injury in cardiac-arrested rat lungs.

BACKGROUND: Chemical preconditioning was defined as the induction of resistance to massive disruption of energy metabolism through prior chemical suppression of oxidative phosphorylation, by which phenomena similar to those resulting from increased ischemic tolerance as a result of ischemic preconditioning can be induced. It could be induced by the inhibitor of either mitochondrial complex I or II. We investigated whether or not chemical preconditioning by 3-nitropropionate (an inhibitor of the mitochondrial complex II) can suppress ischemia-reperfusion injury in cardiac-arrested lungs, which will be the major problem in lung transplants donated from non-heart-beating cadavers. METHODS AND RESULTS: In an isolated rat lung perfusion model with fresh rat blood as perfusate, administration of 3-nitropropionate (20 mg/kg) immediately before the induction of cardiac arrest attenuated pulmonary dysfunction during reperfusion after 1 hr postmortem warm ischemia and 1 hr cold preservation. 3-Nitropropionate administration reduced the mitochondrial respiratory functions (state 3 and state 4 respiration, and the respiratory control ratio) before cardiac arrest and kept them at a lower level of activity than when decreased by ischemia alone. 3-Nitropropionate administration also reduced the ATP levels immediately after drug administration. However, 3-nitropropionate did not significantly reduce lipid peroxidation in the lung tissue and mitochondria. CONCLUSIONS: These results demonstrated that chemical preconditioning by 3-nitropropionate administration immediately before cardiac arrest suppressed succinate-related oxidation during postmortem warm ischemia and reduced ischemia-reperfusion injury in cardiac arrested rat lungs.

Adenine Nucleotides↗

PubMed2001

Involvement of pRB-related p107 protein in the inhibition of S phase progression in response to genotoxic stress.

pRB family pocket proteins consisting of pRB, p107, and p130 are thought to act as a set of growth regulators that inhibit the cell cycle transition from G1 to S phases by virtue of their interaction with E2F transcription factors. When cells are committed to progressing through the cell cycle at the late G1 restriction point, they are hyperphosphorylated by G1 cyclin-cyclin-dependent kinase and are functionally inactivated. Consistent with such a G1 regulatory role, pRB and p130 are abundantly expressed in quiescent cells. In contrast, p107 is present at low levels in the hypophosphorylated form in quiescent cells. As cells progress toward late G1 to S phases, the levels of p107 increase, and the majority become hyperphosphorylated, suggesting a possible role of p107 in post-G1 cell cycle regulation. In this study, we have demonstrated that a nonphosphorylatable and thus constitutively active p107 has the potential to inhibit S phase progression. The levels of the phosphorylation-resistant p107 required for the S phase inhibition are significantly less than those of endogenous p107. We further show herein that the exposure of cells to the DNA-damaging agent, cisplatin, provokes S phase arrest, which is concomitantly associated with the accumulation of hypophosphorylated p107. Furthermore, the S phase inhibitory response to cisplatin is augmented by the ectopic expression of wild type p107, although it is diminished by the adenovirus E1A oncoprotein, which counteracts the pocket protein functions. Because p107 is a major pRB family protein expressed in S phase cells, our results indicate that p107 participates in an inhibition of cell cycle progression in response to DNA damage in S phase cells.

Amino Acid Substitution↗

PubMed2001

Blockade of secondary lymphoid tissue chemokine exacerbates Propionibacterium acnes-induced acute lung inflammation.

Chemokine-chemokine receptor interaction plays an essential role in leukocyte/dendritic cell (DC) trafficking in inflammation and immune responses. We investigated the pathophysiological roles of secondary lymphoid tissue chemokine (SLC; CCL21) and macrophage inflammatory protein-2 (MIP-2) in the development of acute pulmonary inflammation induced by an intratracheal injection of Propionibacterium acnes in mice. Immunohistochemical studies revealed that SLC was constitutively expressed in the peribronchial areas and perivascular lymphatics in normal mice. MIP-2-positive cells were observed in alveolar spaces in mice challenged with P. acnes. Both neutralization Abs against MIP-2 and CXC chemokine receptor 2 alleviated the P. acnes-induced pulmonary inflammation when injected before P. acnes Ag challenge. On the other hand, polyclonal anti-SLC Abs (pAbs) exacerbated the pulmonary inflammation. The numbers of mature DCs (MHC class II +, CD11c+, and CD86+) as well as macrophages and neutrophils in the P. acnes Ag-challenged lungs were increased, whereas the number of CD4+ T cells, including memory T cells, was decreased. The numbers of mature and proliferating CD4+ T cells (bromodeoxyuridine(+)CD4+) in regional lymph nodes were decreased in mice injected with anti-SLC pAbs compared with those in mice treated with control Abs. An in vitro proliferation assay confirmed the impairment of the Ag-specific T cell response in regional lymph nodes of mice treated with anti-SLC pAbs. These results indicate for the first time a regulatory role for SLC-recruited mature DCs in bridging an acute inflammatory response (innate immunity) and acquired immunity in the lung.

Acute Disease↗

PubMed2001

Regulation by chemokines of circulating dendritic cell precursors, and the formation of portal tract-associated lymphoid tissue, in a granulomatous liver disease.

We have studied the recruitment and roles of distinct dendritic cell (DC) precursors from the circulation into Propionibacterium acnes-induced granulomas in mouse liver. During infection, F4/80(-)B220(-)CD11c(+) DC precursors appeared in the circulation, migrated into the perisinusoidal space, and matured within newly formed granulomas. Recruited DCs later migrated to the portal area to interact with T cells in what we term "portal tract-associated lymphoid tissue" (PALT). Macrophage inflammatory protein 1alpha attracted blood DC precursors to the sinusoidal granuloma, whereas secondary lymphoid organ chemokine (SLC) attracted mature DCs to the newly identified PALT. Anti-SLC antibody diminished PALT expansion while exacerbating granuloma formation. Therefore, circulating DC precursors can migrate into a solid organ like liver, and participate in the granulomatous reaction in response to specific chemokines.

Animals↗

PubMed2001

Stoichiometric and microenvironmental effects on hydrolysis of propantheline and oxyphenonium bromides in cyclodextrin solutions.

The effects of alpha-, beta-, and gamma-cyclodextrins (CDs) on the basic hydrolysis of propantheline bromide (PB) and oxyphenonium bromide (OB) are analyzed in terms of the stoichiometry and microenvironments of their complexes. The rate constant of each species is evaluated with binding constant data for the 1:1, 1:2, and 2:1 complexes. The dielectric constant of the binding site of PB is estimated from the ultraviolet maximum wavelength in reference with the ethanol-water and dioxane-water systems. The energy-optimized structures of some complexes of PB with beta- and gamma-CD are obtained by molecular mechanics. Because the ester linkage of PB in the 1:1 complex with alpha-CD and in the 2:1 complex with gamma-CD is located near hydroxyls of the CD rim, these complexes catalyze the hydrolysis of PB. In contrast, the hydrolysis is inhibited by the formation of the 1:1 and 1:2 complexes of beta-CD and the 1:1 complex of gamma-CD because the ester linkage of PB is rather deeply incorporated into the CD cavities for these complexes. All the CDs inhibit the hydrolysis of OB. The rate constant of the 1:1 complex of OB and CD is in the decreasing order alpha-CD > gamma-CD > beta-CD. This order is consistent with that of the local dielectric constants of the binding sites.

Binding Sites↗