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Biomedical subjects

K Nishihara

Publications and source records attributed to K Nishihara.

At least 19 recordsLinked to original sources

Adenosquamous carcinoma of the gall-bladder with gastric foveolar-type epithelium.

An 80 year old Japanese man had adenosquamous carcinoma of the gall-bladder characterized by an adenocarcinoma (AC) in the gall-bladder lumen and a squamous cell carcinoma (SCC) in the invaded region of the liver. In the AC, the tumor cells consisted of atypical columnar epithelium with pseudostratification, mimicking gastric foveolar epithelium, while atypical signet-ring cells were scattered within the SCC. There was an abrupt transition between the AC and SCC areas. The tumor cells in the AC area were intensely positive for galactose oxidase-Schiff staining, and paradoxical concanavalin A staining revealed these tumor cells to have Class II mucins. Immunohistochemically, the tumor cells in foveolar-type adenocarcinoma were diffusely positive for cathepsin D. Flow cytometrical analysis of DNA content showed the AC area to be diploid and the SCC area to be aneuploid. The S-phase fraction of the SCC area (46.9%) was larger than that of the AC area (19.5%). The positive rate of immunostaining for proliferating cell nuclear antigen in the SCC area (mean 50.627%) was larger than that of the AC area (mean 3.048%, P < 0.01). These results suggest that the AC area of this tumor, histochemically and immunohistochemically, showed gastric foveolar-type characteristics, the SCC component was squamous cell metaplasia of the pre-existing AC, and that the SCC area had a greater proliferating capacity than the AC area.

Aged

[Enzyme immunoassay of drug in blood (serum)].

Antiepileptic drugs, cardiac glycosides (digoxin, etc.), theophylline, antiarrhythmic agents (quinidine, procainamide, lidocaine, etc.) and aminoglycosides have narrow therapeutic range and large interindividual variations have been reported for their pharmacokinetics. Therefore, to obtain the appropriate therapeutic effects without undesirable effects, monitorings of above drug concentrations are useful (therapeutic drug monitoring). There are many assay methods (high-performance liquid chromatography, immunoassay, enzyme immunoassay, etc.) to determine drugs in serum. In those assays various enzyme immunoassays, enzyme-multiplied immunoassay technique (EMIT), enzyme-linked immunosorbent assay (ELISA), apoenzyme reactivation immunoassay (ARIS), radial partition immunoassay (RPIA), etc., are developed and widely used in many clinical laboratories. These assay systems offer convenience and great rapidity of assay and satisfactory accuracy and reproducibility but lack a little specificity of antibody.

Drug Monitoring

Increased in vitro and in vivo tumoricidal activity of a macrophage cell line genetically engineered to express IFN-gamma, IL-4, IL-6, or TNF-alpha.

Genetically engineered monocytes and macrophages may have potential as effector cells for the adoptive immunotherapy of cancer. As a first step, we have transfected the genes encoding either mouse interferon (IFN)-gamma, human interleukin (IL)-6, mouse IL-4, or mouse tumor necrosis factor (TNF)-alpha into the mouse macrophage cell line, J774A.1 cells using retroviral vectors. In vitro activation of J774A.1 cells by gene modification was assessed by morphological changes, proliferative activity was determined by [3H]-TdR uptake, and cytolytic activity was assessed using an 18-hour chromium-51 (51Cr) release assay. In vivo tumoricidal activity was studied by means of local adoptive immunotherapy using intratumoral injection of transfected effector cells. IFN-gamma gene-transfected J774A.1 [J7(IFN-gamma)] cells developed filamentous processes, increased doubling times, and enhanced tumoricidal activity against three tumor cell lines: the TNF-sensitive fibrosarcoma line WEHI 164 and the TNF-alpha-resistant cell lines B16 melanoma and C1300 neuroblastoma. IL-6-, TNF-alpha-, and IL-4-gene-transfected J774A.1 cells also had augmented tumoricidal activity but did not display any changes in morphology or growth. Cytolytic activity was markedly reduced after the addition of anti-TNF-alpha antibodies. Cytolytic J7(IFN-gamma) cells showed upregulated expression of TNF-alpha messenger RNA. After intratumoral injection of J7(IL-4) and J7(IFN-gamma) cell mixtures, 50% of established B16 melanomas were rejected by C57BL/6 mice, thereby demonstrating synergistic killing. Further studies on gene-transfected macrophages should better define their potential usefulness in tumor immunotherapy.

3T3 Cells

[A case report of a metaplastic carcinoma of the breast diagnosed by the preoperative needle biopsy].

A case of the metaplastic carcinoma, a rare type of the breast cancer, was reported. A 49-year-old woman noticed the left breast lump. Ultrasonography revealed a well circumscribed hypoechoic mass measuring 3 cm in diameter. The preoperative needle biopsy showed the invasive carcinoma with chondrometaplasia. The modified radical mastectomy along with the lymph node dissection was performed. There have been few reports of the metaplastic breast carcinoma diagnosed preoperatively.

Biopsy, Needle

Relationship between peripheral portal blood flow and liver function in patients with liver cirrhosis. Pulsed Doppler ultrasonographic study.

BACKGROUND: The relationship between portal hemodynamics and liver function in patients with liver cirrhosis remains unclear. METHODS: Using pulsed Doppler ultrasonography, we investigated portal hemodynamics in the trunk and the intrahepatic peripheral vessels and its relation to liver function in cirrhotic patients. RESULTS: The portal blood flow in the right anterior branch (RAB) in cirrhotic patients (n = 40) was significantly lower (p < 0.01) than that in normal subjects (n = 40). In the cirrhotic patients the portal blood flow in the RAB was significantly correlated with the values of serum albumin, total bilirubin, cholesterol, cholinesterase, prothrombin time, and ICG R-15, and that in group C (Child's grading) was significantly decreased (p < 0.01) compared with that in group A. No such difference was found in the main portal vein, the right posterior branch, or the umbilical portion of the left portal vein. CONCLUSIONS: The decrease in blood flow in the RAB is closely related to the impairment of liver function in cirrhotic patients.

Adult

Sensitive determination of cystathionine and assays for cystathionine beta- and gamma-lyase, as well as cystathionine beta-synthase, using high-performance liquid chromatography.

Cystathionine was cleaved into 2-ketobutyric acid, cysteine and ammonia by cystathionase. 2-Ketobutyric acid was converted into 3-ethyl-2-hydroxy-6,7-dimethoxyquinoxaline (EHDQ) by reaction with 1,2-diamino-4,5-dimethoxybenzene. When EHDQ was measured in a mobile phase of pH 2.1 using high-performance liquid chromatography with ultraviolet detection, 250 pmol of L-cystathionine in 250 microliters of the reaction mixture could be determined. Because EHDQ has a strong fluorescence in a mobile phase of pH 6.5 at 447 nm, on excitation at 365 nm, as little as 2.5 pmol of cystathionine in 250 microliters of the reaction mixture could be determined by high-performance liquid chromatography with fluorimetric detection. Cystathionase activity was assayed on the basis of the same principle by determining cystathionine in as little as 63 ng of rat liver by fluorimetric detection. Cystathionine beta-synthase activity was measured by the same method by determining cystathionine formed in only 113 ng of wet weight of rat liver. Using these methods, both cystathionine beta- and gamma-lyase activities in Saccharomyces cerevisiae were determined, because quinoxaline derivatives from pyruvate and 2-ketobutyrate could be measured simultaneously by high-performance liquid chromatography.

Animals

Non-icteric pancreas head carcinoma fares worse than icteric pancreas head carcinoma.

A total of 22 patients with non-icteric pancreas head carcinoma were retrospectively compared with 61 patients with icteric pancreas head carcinoma. No significant difference was found regarding age, sex, greatest diameter, macroscopic type, microscopic type, stage, lymphatic permeation, perineural infiltration, venous invasion, lymph node metastasis, and the presence of cancer cells at the surgical margins. The main location of pancreas head carcinoma could be divided into two sites: the superior (pericholedochal), and inferior or distal (excholedochal) areas of the pancreas head. Sixteen (73%) of the 22 non-icteric pancreas head carcinomas were located in the inferior or distal area (excholedochal), while 28 (46%) of the 61 icteric pancreas head carcinomas were situated in the superior portion (pericholedochal) (P less than 0.05). One (5%) of the 22 non-icteric pancreas head carcinomas was small pancreas carcinoma, compared with 11 (18%) of the 61 icteric pancreas head carcinomas. The cumulative 2-year and 4-year survival rates of the 22 patients with non-icteric pancreas head carcinoma were significantly worse than those of the 61 patients with icteric pancreas head carcinoma [7.9% vs. 24.6% (P less than 0.05) and 0% vs. 13.4% (P less than 0.01)]. These findings suggest that non-icteric pancreas head carcinomas normally arise in an area far from the biliary tree, and include a greater number of large tumors. Any resulting difficulty and delay in the diagnosis and treatment of this disease will usually lead to a worsening of the clinical course of non-icteric pancreas head carcinoma.

Age Factors

Long- and short-term survivors after pancreatoduodenectomy for ampullary carcinoma.

Out of 36 consecutive patients who underwent a pancreatoduodenectomy for carcinoma of the ampulla of Vater, eight patients (long-term survivors) survived more than 5 years after surgery, while eight other patients (short-term survivors) survived less than 12 months after intervention. Both the eight long-term survivors and eight short-term survivors were compared clinicopathologically. The long-term survivors did have some preferable factors such as a high value of peripheral lymphocytes, a low concentration of carcinoembryonic antigen, a small protruding tumor, a shallow depth of invasion, a well-differentiated histopathologic type, an infrequent venous invasion, and no perineural infiltration. However, these differences were not significant. A multivariate regression analysis regarding the 18 prognostic variables showed that both perineural invasion and the grade of histopathologic differentiation were significant parameters. Out of the eight long-term survivors, three patients lived more than 10 years while another died from ampullary carcinoma 74 months after surgery. Pancreatoduodenectomy not only produces long-term survivors but can also effect a complete cure in patients with ampullary carcinoma. A long clinical follow-up of more than 5 years after surgical intervention is thus warranted.

Adenocarcinoma

Relationships between epinephrine, waking time, and self-estimates for naps at night.

In a previous study, we established a basal regression line between epinephrine excretion and percent of waking time in bed-rested humans under conditions involving minimal stress. We suggested that this regression line might be clinically useful for observing insomnia. The present study was undertaken to examine whether epinephrine excretion during short-duration sleep, such as naps, is influenced by a transient insomniac state. Polysomnograms during a 2-hour nap from 0000 to 0200 were recorded three times for six healthy male subjects. Epinephrine excretion levels during sleep were found to increase along the basal regression line when percent of waking time went up. The subjects with over 30% waking time during this 2-hour period reported that their sleep was light and not satisfactory at all. These results support our position that the regression line can be useful for observing a transient insomniac state.

Adult

Solitary pancreatic metastasis of malignant fibrous histiocytoma treated by distal pancreatectomy.

A tumor in the body of the pancreas was detected in a 31-year-old man who had undergone a resection of a malignant fibrous histiocytoma (MFH) of the left distal femur 2 years before. The patient underwent a distal pancreatectomy with regional lymph node dissection. The surgical specimen revealed MFH metastatic to the pancreas. He is alive without recurrence or metastasis at 1 year after pancreatectomy. This case seems to be the first report of successfully resected pancreatic metastasis of a malignant fibrous histiocytoma in the published literature, as far as we can determine.

Adult

Long survivors after pancreatoduodenectomy for pancreas head carcinoma.

Twelve Japanese patients with pancreas head carcinoma who survived 3 years or more after a pancreatoduodenectomy and 50 who survived less than 12 months were reviewed clinicopathologically. The 12 patients who survived for greater than or equal to 3 years exhibited more favourable prognostic factors: a higher incidence of jaundice; a smaller mass; a higher prevalence of an earlier stage tumour and adenocarcinoma of differentiated type; and a lower incidence of venous invasion, lymph node metastasis, and cancer cells at the surgical margins. However the difference was not significant. Univariate log-rank analysis regarding 13 prognostic variables showed that histologic type was a significant factor but multivariate Cox regression analysis failed to reveal an independent significant parameter. Nine of the 12 long-term survivors showed lymph node metastasis and six of the 12 revealed cancer cells at the surgical margins. Six of the 12 long-term survivors died from local recurrence and/or distant metastasis 37-78 months after operation. Only two patients survived more than 5 years after the operation. At the time of writing, one of them was still alive and another was dead 78 months after the operation. Pancreatoduodenectomy for pancreas head carcinoma infrequently offers a permanent cure for the patients with pancreas head carcinoma but sometimes produces a worthwhile long-term survival, even if the resected margins were affected by malignant cells or the lymph node metastasis was evident.

Adenocarcinoma

[Involvement of lymph nodes and neural plexus in carcinoma of the pancreas].

We studied 428 lymph nodes attached to the head of the pancreas (13,14,17) in 18 patients with ductal carcinoma of the pancreatic head. These were classified into the small size of the lymph nodes less than 5mm (group S), the moderate size of the lymph nodes (group M) and the large size of the lymph nodes more than 10 mm (group L). The metastases were seen in 76 nodes, which consisted of 49 with group S, 14 with group M and 13 with group L. The lymph node involvement in group (14) S was found in 7 of 18 patients (38.9%), that in group (14) M was in 4 (22.2%) and that in group (14) L was in 2 (11.1%). In these involved cases, the primary tumors tended to be locate in the portion near the superior mesenteric artery, such as in the uncinate process. Invasion of extrapancreatic neural plexus was noted in 9 of 18 patients (50%). There was no significant correlation between nerve plexus invasion and lymphatic invasion by Spearman's rank correlation. In addition, any close relationship between plexus invasion and primary tumor location could not be indicated. These results suggested that neural invasion in pancreatic carcinoma is independent of lymphatic invasion, and the routes of cancer spread via the neural plexus are different from those via the lymphatic vessels. Those without liver metastases survived longer than those with liver metastases, which were characteristically multiple.

Humans

Improved delineation of the gallbladder wall with ultrasonography: its value in assessment of the depth of carcinoma invasion.

We examined 30 surgically removed gallbladders with ultrasound using a 10 MHz transducer in a water bath. The sonographic structure of gallbladder wall was imaged as 5 layers. The layer 3, a well-defined hyperechoic zone, was confirmed histologically as corresponding to the boundary between subserosa and muscularis. Since the spreading of gallbladder carcinoma beyond the muscle coat is an important prognostic indicator, high resolution images may well be used to advantage in assessing gallbladder wall penetration intraoperatively, enabling the surgeon to choose the proper operative procedure.

Adenocarcinoma, Papillary

Carcinoma of the cystic duct.

Carcinoma of the cystic duct is a rare neoplasm, and we herein report four cases of carcinoma of the cystic duct. The patients consisted of a 69 year old and 71 year old woman and a 61 year old and 93 year old man. They complained of either abdominal pain or abdominal mass. All the tumors were microscopically well-differentiated adenocarcinoma, mostly limited to the wall, that showed no lymph node or distant metastasis. Three patients who had undergone resection were doing well 20 days, 67 months, and 125 months after the operation, respectively. These findings may suggest that not only the early development of symptoms caused by obstruction of the narrow lumen of the cystic duct, but also slow growth and late metastasis produce a favorable clinical course in patients with carcinoma of the cystic duct.

Aged

The anti Mac-1 monoclonal antibody inhibits neutrophil sequestration in lung and liver in a septic murine model.

We investigated the mechanism by which leukocytes adhere to the pulmonary and liver microvascular endothelium in a septic murine model. After C57BL/6 mice were intraperitoneally (ip) injected with lipopolysaccharide (LPS), a striking peripheral leukocytopenia occurred as neutrophils accumulated rapidly in the lung and liver. When the anti-Mac-1 monoclonal antibody (mAb) was administered intravenously (iv) 2 hr before the ip administrated LPS, leukocytopenia and neutrophil accumulation in the lung and liver were inhibited significantly at 3 hr after the LPS injection. An immunofluorescence study revealed that Mac-1 expression on leukocytes from LPS-injected mice were greatly increased when compared to that of controls. Additionally, an in vitro assay demonstrated that LPS-activated serum increased neutrophil Mac-1 expression and neutrophil adhesion to the endothelial monolayer and that these phenomena are inhibited by pretreatment of neutrophils with anti-Mac-1 mAb. These results indicate that a marked increase in Mac-1 antigen expression by leukocytes plays a crucial role in striking neutrophil attachment to the vascular endothelium and is likely to be the cause of neutrophil accumulation in the lung and liver during endotoxemia.

Animals

Giant pseudoaneurysm of the extracranial vertebral artery successfully treated using intraoperative balloon catheters.

Traumatic pseudoaneurysms of the extracranial vertebral artery rarely occur, because of its deeply protected anatomical location. Because the direct surgical approach has resulted in high morbidity and mortality rates, ligation of the vertebral artery has been adopted, but this can cause an ischemia in the vertebrobasilar system. We report the case of a 73-year-old woman with a huge pseudoaneurysm of the right vertebral artery that occurred after attempted placement of a cardiac pacemaker. The aneurysm was 7 x 7 x 5 cm in size and its neck was situated just distal to the right subclavian artery. Direct surgical repair of the injured vessel and removal of the aneurysm were successfully performed using balloon catheters placed intraoperatively in both the innominate artery and the right vertebral artery.

Aged

Tubular adenoma of the gallbladder with squamoid spindle cell metaplasia. Report of three cases with immunohistochemical study.

Three cases of tubular adenoma of the gallbladder with squamoid spindle cell metaplasia are reported. Two of the three patients, who were middle-aged Japanese, had a solitary polyp in the gallbladder, and the other had three polyps. All the lesions were detected incidentally by ultrasonography. The polyps were pedunculated with a fine or frail stalk, and ranged from 0.5 to 3.9 cm in diameter. Histologically, they were tubular adenomas accompanied by scattered foci composed of a compact collection of short-spindle or oval cells with mild atypia. These cells did not retain intercellular bridges, and lacked intracellular keratinization. Immunohistochemically, the spindle cells stained positively for high-molecular-weight cytokeratin (EAB 903, a marker of squamous cell differentiation), whereas adenoma cells lining the tubules were negative for this antigen. Therefore, the spindle cell component is considered to represent squamoid metaplasia of adenoma cells.

Adenoma