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Biomedical subjects

H Kohno

Publications and source records attributed to H Kohno.

At least 37 records · Page 2Linked to original sources

[An analysis of fever of unknown origin defined by newly proposed practical criteria. A prospective study of 56 cases].

The criteria proposed by Petersdorf has been in use internationally to define the fever of unknown origin (FUO) since 1961 and the research of FUO has progressed with this criteria. Mean-while, new diagnostic methods have been developed and illness behavior of febrile patients has changed considerablly. Accordingly, the definition by Petersdorf is becoming less matched to current clinical situation. Therefore, we have developed a new practical criteria of FUO; i.e., out-patients who are febrile more than 2 weeks, documented temperature higher than 37.5 degrees C at least on one occasion and undetermined diagnosis and in-patients who are febrile more than 1 week with documented temperature higher than 37.5 degrees C, and undetermined diagnosis. Between October 1, 1993, and October 31, 1996, we prospectively collected a series of febrile patients who fulfilled our new criteria. We identified 56 patients by our criteria (23 male and 33 female, age: 49.7 +/- 20.6. range 15 to 88). Of this 56 patients, 19 (32%) were found to have infections, 18 (31%) had collagen disorders, 5 (9%) had malignancy and 6 (10%) had died. Of 56 patients, 38 (68%) were in the newly added group. Of these 38 patients, 4 patients had subacute necrotizing lymphoadenitis, 4 cytomegalovirus infection, 3 polymyalgia rheumatica, 3 tuberculosis. Four patients (10%) died. With our criteria, febrile patients who previously had not been included were found to have as poor a prognosis as with the Petersdorf group.

Adolescent

FK506 with portal decompression exerts beneficial effects following extended hepatectomy in dogs.

The present study was designed to elucidate the effectiveness of portal decompression and FK506 (FK) pretreatment in extended hepatectomy in dogs. In the first set of experiment the effect of portal decompression was evaluated in two groups of dogs which underwent extended hepatectomies (80%) with or without (control) a side-to-side portacaval shunt. The presence of the shunt significantly (p < 0.05) improved the 7-day survival of the animals (57.1%) when compared with those of the control group (28.6%) and eventually the portal pressure was significantly lower and mean arterial pressure was significantly higher in the shunt group (p < 0. 05). Moreover, the animals with lower portal pressure (</=220 mm of saline) had a significantly improved 7-day survival rate than those with higher portal pressure (p < 0.001). To evaluate the role of FK pretreatment in extended hepatectomy, a more severe model of 90% hepatectomy was used in four different groups: portacaval shunt, shunt and FK pretreatment, FK pretreatment, and hepatectomy only (control). Although the shunt improved the survival rate in the 80% hepatectomy model, neither shunt (8.3%) nor FK pretreatment (0%) independently improved the survival of the animals when the hepatectomy was extended to 90%. FK pretreatment significantly improved the survival (33.3%, p < 0.05) and hepatic functions of the animals only in the presence of a shunt. Also hepatic microcirculation measured with a laser Doppler flowmeter was significantly better in the remnant liver of all treated groups than in the control group (p < 0.01). In conclusion, extended hepatectomy (90%) could be performed in otherwise normal liver after FK pretreatment and a side-to-side portacaval shunt, which improve the regenerative response in a stable hemodynamic animal.

Animals

nm23 in the primary and metastatic sites of gastric carcinoma. Relation to AFP-producing carcinoma.

Tumor metastasis is the major cause of treatment failure and death in cancer patients. The present study was designed to extrapolate the association of nm23 expression with acquisition of metastatic potential of gastric carcinoma with special reference to the alpha-fetoprotein-producing gastric carcinoma (APGC). The primary tumor with surrounding normal mucosa and metastatic lymph nodes of 30 patients with APGC and 29 randomly selected matched controls of non-AFP gastric carcinoma (NAGC) were immunostained for nm23 and an image analyzer system was used for quantitative evaluation. Overexpression of nm23 was noted in 71% (42/59) of the primary tumors and 18% (10/55) of the metastatic tumors and there was no difference between the APGC and NAGC groups. The overexpression of nm23 in the primary tumors correlated with tumor invasion, metastasis and progression in all cases and similar results were obtained in the APGC and NAGC groups except for the tumor stage which was insignificant in the APGC group. The patient survival was adversely affected by the overexpression of nm23 in the primary sites and downregulation in the metastatic sites in all cases but lost their significance in the multivariate analysis. However, nm23 status did not affect patient survival in the APGC group.

Aged

Possible neural mechanisms involved in footshock stress-induced enhancement of exploratory behavior in mice.

The effect of inescapable footshock stress on open-field activity, as measured by the number of ambulations, was studied in male mice. Ambulations significantly increased after footshock stress, the most significant effect appeared after 20 min-stimulation and the effect decreased as footshock time lengthened. The footshock stress-induced enhancement of ambulation was inhibited by haloperidol (0.2, 0.5 and 1 mg/kg), phentolamine (5 and 10 mg/kg), mianserin (20 mg/kg), atropine (0.5, 1 and 2 mg/kg), naltrexone (10 mg/kg) and MK-801 (0.05, 0.1 and 0.2 mg/kg), but was not influenced by propranolol (5, 10 and 20 mg/kg) or diazepam (1, 2 and 5 mg/kg). Haloperidol (0.5 and 1 mg/kg) and mianserin (5, 10 and 20 mg/kg) also exerted an inhibitory effect on non-stressed normal mice. These results suggest that dopaminergic, alpha-adrenergic, cholinergic, opioidergic and N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission systems are involved in the footshock stress-induced ambulatory activation.

Animals

Doppler features of occlusion of the internal thoracic artery due to preoperative branch embolization.

A 61-year-old male was referred to the surgical ward by cardiologists because of a diagnosis of unstable angina with 3-vessel disease. On preoperative left internal thoracic arteriography, a large first intercostal branch was found at the proximal portion. Selective arterial embolization of the branch of the left internal thoracic artery (LITA) was carried out preoperatively. At 2 days after embolization, the Doppler peak flow velocity and diameter of the LITA were increased and enlarged compared with before the procedure. However, a large reverse wave following after the first systolic peak flow of the LITA was newly detected after embolization. Upon operation, the LITA was found to be occluded at the 2nd intercostal space due to thrombus formation. Therefore, the right internal thoracic artery was anastomosed to the left anterior descending artery and coronary reversed saphenous vein grafts were joined to segment 4PD of the right coronary artery. The postoperative course was uneventful. There has been no previous report of an LITA branch being embolized preoperatively. It was possible to diagnose the graft problem by detecting the altered Doppler wave form of the LITA.

Angina Pectoris

Relationship between coronary blood flow velocity waveform and transmural distribution of myocardial blood flow in coronary artery.

It is important to know the transmural distribution of myocardial blood flow in assessing the severity of ischemia in coronary heart disease. We analyzed the relation between phasic waveform of epicardial coronary flow velocity with a Doppler flow probe in the left anterior descending artery in dogs and regional myocardial blood flow using a colored microsphere technique. Time-velocity integral in an average of 5 cardiac cycles was measured as an index of coronary blood flow during diastole (TVId) and systole (TVIs). The diastolic fraction of coronary blood flow (%DF) was defined as TVId/(TVId + TVIs). Myocardial specimens were divided into inner (subendocardial), middle, and outer (subepicardial) layers, and the inner layer to outer layer myocardial blood flow ratio (endo/epi ratio) was used as an index of transmural distribution of myocardial perfusion. The mean endo/epi ratio and the mean %DF decreased as the pressure gradient increased. There was a moderate but significant correlation (r = 0.57) between the endo/epi ratio and the %DF. In conclusion, analysis of the phasic pattern of coronary blood flow velocity provides some information about the transmural distribution of blood flow in the myocardium. The %DF may be a useful index for evaluating subendocardial ischemia.

Animals

Antiangiogenic therapy of human esophageal cancers with thalidomide in nude mice.

BACKGROUND: Thalidomide (alpha-N-phthalimidoglutarimide) is attracting new attention because of its antiangiogenic effect in corneal neovascularization models. However, the effect of this agent on esophageal carcinoma is yet to be established. METHODS: The human esophageal squamous cell carcinoma strains ES63 and ES80 implanted subcutaneously in nude mice were used to evaluate the antiangiogenic effect of thalidomide (200 mg/kg/d) after daily gavage or intraperitoneal administration. Tumor size was measured, and assessment of microvessel density was performed histochemically with Griffonia simplicifolia lectin I. Characterizations of angiogenic growth factors, vascular endothelial growth factor, basic fibroblast growth factor, and thymidine phosphorylase in ES63 and ES80 tumors were done by immunohistochemical staining and reverse transcription-polymerase chain reaction. RESULTS: ES63 strongly expressed 3 angiogenic factors, but ES80 showed moderate expression of thymidine phosphorylase and only weak or no expression of vascular endothelial grown factor and basic fibroblast growth factor at protein and messenger RNA levels. In ES63 intraperitoneal injection of thalidomide produced significant (P < .05) inhibition of tumor growth, but there was no effect after gastric gavage. Also, a significantly (P < .0005) lower microvessel density was encountered in the intraperitoneal thalidomide group. However, in the ES80 tumor strain thalidomide had no antiangiogenic effect after either intraperitoneal or oral administration. CONCLUSIONS: These data indicate that thalidomide exerts an antiangiogenic effect on solid tumor after intraperitoneal administration. Thalidomide might be one of the hopeful antiangiogenic drugs for solid tumors.

Animals

[Management of patient with acute myocardial infarction due to left main trunk obstruction].

Between April 1995 and March 1998, we experienced 13 cases of Acute Myocardial Infarction due to Left Main Trunk Obstruction (LMT-AMI). Two cases died before emergent intervention. Eight cases underwent emergent intervention (Plain Old Balloon Angioplasty (POBA) in five cases, Stenting in 3 cases); 2 cases died of acute occlusion of POBA site, 1 case survived by only POBA, and the other 5 cases underwent following Coronary Artery Bypass Grafting (CABG). 3 cases underwent only CABG with stable hemodynamics condition by Intraaortic balloon pumping (IABP) support. In a result, seven of eight CABG cases survived. Emergent stenting made the hemodynamics before CABG stable, and six-month's follow up angiogram showed occluded bypass grafts and patent stented sites in two of three cases. The combination therapy of emergent stenting and CABG will have to be evaluated in future.

Adult

[A case of chordoid meningioma].

Chordoid meningioma is a very rare variant, especially in adults. We report an adult case of chordoid meningioma. A 52-year-old man was admitted to our hospital due to right hemiparesis. MRI revealed a left temporal convexity mass that showed two structures; the cerebral layer was shown as an isointensity area on T1WI and T2WI, and the dural layer seemed relatively hypointense on T1WI and hyperintense on T2WI. The tumor was well enhanced with gadolinium, especially on the dural side. A left external carotid arteriogram showed tumor stains with feeding vessels from the left middle meningeal artery. The tumor was totally removed via fronto-temporal craniotomy. Histological examination of the surgical specimen revealed two different structural components, meningothelial meningioma on the cerebral side, and chordoid meningioma on the dural side, consisting of clustering spindled cells and partly vacuolated ones in the mucoid stroma. In immunohistochemical examination, tumor cells showed positive staining for vimentin and epithelial membrane antigen (EMA), and negative for cytokeratin. From the above findings, this case was diagnosed as chordoid meningioma in an adult, a very rare variant of meningioma.

Chordoma

Molecular characterization of a newly identified heme-binding protein induced during differentiation of urine erythroleukemia cells.

A heme-binding protein with a molecular mass of 22 kDa, termed p22 HBP, was purified from mouse liver cytosol, using blue Sepharose CL-6B. We identified a cDNA encoding p22 HBP, and sequence analysis revealed that p22 HBP comprises 190 amino acid residues (Mr 21,063) and has no homology to any other known heme-binding protein. The p22 HBP mRNA (approximately 1.0 kilobases) is ubiquitously expressed in various tissues and is extremely abundant in the liver. cDNA allows for expression of active p22 HBP, with a high affinity for 55Fe-hemin, with a Kd of 26 +/-1.8 nM. The Bmax of hemin binding to p22 HBP was 0.55 +/- 0.021 mol/mol of protein, a value consistent with one heme molecule binding per molecule of protein. The order of potency of different ligands to compete against 55Fe-hemin binding to p22 HBP was hemin = protoporphyrin IX > coproporphyrin III > bilirubin > palmitic acid > all-trans-retinoic acid. Treatment of mouse erythroleukemia (MEL) cells with dimethyl sulfoxide or hemin resulted in an increase in p22 HBP mRNA. The immunoblot analysis showed that p22 HBP increased with time in dimethyl sulfoxide- and hemin-induced MEL cells. Conversely, transfer of antisense oligonucleotides to p22 HBP cDNA resulted in a decrease of p22 HBP in dimethyl sulfoxide-treated MEL cells, and the heme content in these cells decreased to 66-71% of sense oligonucleotides-transferred cells. Thus, this newly identified heme-binding protein, p22 HBP, may be involved in heme utilization for hemoprotein synthesis and even be coupled to hemoglobin synthesis during erythroid differentiation.

Amino Acid Sequence

Levels of soluble Fas in patients with myocarditis, heart failure of unknown origin, and in healthy volunteers.

This study showed that serum levels of sFas were elevated in patients with myocarditis, and that this elevation was correlated with sIL-2R level as a marker of T-cell activation. Therefore, sFas levels may be associated with T-cell activation in patients with myocarditis, and elevation of sFas may inhibit apoptosis in activated T cells, leading to persistent cell-mediated destruction of myocytes in myocarditis.

Adult

Suppression of cell proliferation and the expression of a bcr-abl fusion gene and apoptotic cell death in a new human chronic myelogenous leukemia cell line, KT-1, by interferon-alpha.

A new human leukemia cell line, KT-1, was established from a patient in the blastic crisis phase of chronic myelogenous leukemia (CML). This cell line had a positive reaction for intracytoplasmic myeloperoxidase and two Philadelphia chromosomes (Ph1) [t(9;22)(q34;q11)] and lacked normal copies of chromosomes 9 and 22. Molecular characterization of the breakpoint in the t(9;22)(q34;q11) showed that KT-1 had a bcr-2/abl-2 splice junction. When the KT-1 cells were cultured with interferon (IFN)-alpha or IFN-gamma, the growth of the cells were dose-dependently suppressed. IFN-alpha and IFN-gamma exerted synergistic suppressive effects on the growth of KT-1 cells. Furthermore, IFN-alpha suppressed the expression of the bcr-abl fusion gene in KT-1 cells, and induced G1 cell-cycle arrest and apoptotic cell death. The KT-1 cell line should be a valuable tool for studying the molecular mechanism of the suppression of Ph1 clone cells from CML by IFN.

Apoptosis

Modulation of endothelin and nitric oxide: a rational approach to improve canine hepatic microcirculation.

ET receptor blocker (TAK-044) and NO donor (FK409) were used to improve the hepatic microcirculation following ischemia-reperfusion injury. In the first experiment (60 minutes of ischemia), 15 dogs were divided into three groups: group A (control), saline; group B, TAK 5 mg/kg; and group C, FK 0.4 mg/kg. In the second experiment (90 minutes of ischemia), 38 dogs were divided into six groups that underwent 90 minutes of hepatic ischemia followed by reperfusion: group I (control), saline only; group II, TAK 5 mg/kg and FK 3.2 mg/kg; group III, TAK 5 mg/kg and FK 0.4 mg/kg; group IV, TAK 5 mg/kg; group V, FK 0.4 mg/kg; and group VI, FK3.2 mg/kg. All drugs were administered through the portal vein. Following 60 minutes of ischemia, both FK and TAK produced significant improvement in hepatic microcirculation and enzymatic status when compared with the control group. After 90 minutes of ischemia, low doses of FK and TAK significantly improved hepatic microcirculation and reduced portal pressure following reperfusion in group III compared with group I. Leakage of hepatic enzymes was prevented and tissue injury score was significantly lower in group III. In group VI, early protection was obtained to some extent; however, blood pressure was reduced significantly following reperfusion compared with group I. In contrast, hepatocellular function deteriorated and the tissue injury score was higher in group II animals. TAK pretreatment with low doses of FK provided the best protection for the hepatic microcirculation in ischemia-reperfusion injury of the liver.

Animals

Prognostic factors and rational approach in the treatment of submucosal cancer of the stomach.

In early gastric cancer, lymph node metastasis is known to be a prognostic factor. A retrospective study of 134 patients with submucosal gastric cancer (SMGC) who had undergone gastrectomy with lymph node dissection was performed to evaluate the prognostic factors and indication of postoperative chemotherapy. Five-year disease-free survival rate for 121 patients without nodal metastasis was 100% with (n = 62) or without postoperative chemotherapy (n = 59). On the other hand, it was 72.9% for 13 patients with nodal metastases, although all patients had undergone D2 or D3 resection and received postoperative chemotherapy. Tumor recurrence occurred only in three patients (n = 3) with alpha-fetoprotein (AFP) producing cancer and lymph node metastasis. Multivariate analysis with the Cox's proportional hazard model revealed AFP positivity to be a new independent prognostic factor in addition to lymph node metastasis in the patients with SMGC. Our findings suggest that routine use of postoperative chemotherapy does not appear rational for the patients without nodal metastasis and that new modalities of operation and chemotherapy may be necessary for the patients with AFP producing SMGC with nodal metastasis. The necessity of chemotherapy in conventional-type SMGCs with nodal involvement remains to be studied in future.

Adenocarcinoma

Tumor vascularity predicts recurrence in differentiated thyroid carcinoma.

BACKGROUND: New prognosticators are necessary for optimizing the extent of thyroidectomy and adjuvant radiotherapy in differentiated thyroid carcinoma. METHODS: Tumor microvessel density (MVD), expression of thymidine phosphorylase (dThdPase) and CD68 stained macrophages were evaluated in 71 differentiated thyroid carcinomas by an immunohistochemical method. RESULTS: The recurrence-free survival was significantly (P <0.05) shorter in patients with hypervascular tumors but was not related to the dThdPase expression. Significant (R = 0.323, P <0.001) correlation between dThdPase expression score and increment in MVD was documented. Frequent high MVD and dThdPase expression were encountered in tumors >3 cm. Twenty-two of the 27 (82%) patients expressing high dThdPase were also evaluated positive for CD68 (P <0.001). CONCLUSIONS: Tumor MVD might be a new prognostic indicator of differentiated thyroid carcinoma, whereas dThdpase expression with high MVD might serve to identify a subgroup of thyroid carcinoma patients as potential candidates for adjuvant radiotherapy.

Adult

Serum carcinoembryonic antigen as a prognostic factor in resectable gastric cancer.

BACKGROUND: Carcinoembryonic antigen (CEA) has been widely accepted as a tumor marker useful in the diagnosis and management of colorectal cancer. When CEA levels are positive in gastric cancer patients, they could be useful prognostic indicators. However, the value of CEA as a tumor marker for gastric cancer remains a matter of controversy. STUDY DESIGN: We measured preoperative serum CEA levels in 196 patients with resectable gastric cancer between May 1986 and April 1996 and then evaluated the correlation between serum CEA levels, clinicopathologic features, and prognostic information. RESULTS: Serum levels of CEA were above the normal range in 29 of 196 (14.8%) surgically resected patients (range, 5.2-570 ng/mL). Among 100 early gastric cancers confined to the submucosal layer, only 7 patients (7.0%) had positive CEA levels, but among 96 advanced cancers, 22 patients (22.9%) had high CEA levels. The CEA positive patients had more macroscopically infiltrative tumors, a more prominent serosal invasion, more frequent lymph nodes involvement, and a more advanced stage than did the CEA negative patients. The 3- and 5-year cumulative disease-specific survival rates of patients positive for serum CEA were 39.6% and 31.7%, respectively; these rates for patients negative for CEA were 83.0% and 77.3%, respectively (p < 0.0001 for comparison of survival curves). In various clinicopathologic parameters, nine parameters (tumor size, macroscopic type, type and time of operation, Laurén classification, depth of invasion, lymph node involvement, CEA, alpha-fetoprotein [AFP], and carbohydrate antigen [CA] 19-9) showed statistically significant differences in the cumulative survival rates. Of these nine parameters, independent prognostic factors by multivariate analysis were depth of invasion (T1, 2 versus T3, 4, p < 0.0001), serum CEA levels (negative versus positive, p = 0.0003), and lymph node metastasis (negative versus positive, p = 0.0005). CONCLUSIONS: Preoperative serum CEA levels provide a predictive value in determining tumor stage and prognostic information for patients with potentially resectable gastric cancer during the preoperative period.

Adenocarcinoma