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Biomedical subjects

H Nakahashi

Publications and source records attributed to H Nakahashi.

At least 19 recordsLinked to original sources

Widespread crystalline inclusions affecting podocytes, tubular cells and interstitial histiocytes in the myeloma kidney.

Numerous crystalline inclusions were observed in glomerular and tubular epithelial cells in a 46-year-old female patient with multiple myeloma and renal dysfunction. On light microscopy, epithelial cells were filled with homogenous materials and were remarkably swollen. Infiltrations of histiocytes with expanded cytoplasm were also seen in the interstitium of the kidney and bone marrow. On electron microscopy, cytoplasmic inclusions had crystalline structure showing rhomboid and oval shapes. Immunofluorescence study revealed that these cells were positive for IgG-kappa. The combination chemotherapy followed by autologous stem cell transplantation led to a partial resolution of her renal dysfunction, continued by a slight reduction in the number of crystalline-containing podocytes at the second renal biopsy. Crystal inclusions in the kidney are rarely found and cause renal impairment in multiple myeloma.

Bone Marrow Cells↗

Duodenal metastasis from large cell carcinoma of the lung: report of a case.

Duodenal metastasis from primary lung cancer is extremely rare. It rarely shows any symptoms, and the prognosis for this condition is poor. We herein describe the case of a 46-year-old woman with primary lung cancer who underwent a left upper lobectomy. Severe anemia was observed about 20 days after lobectomy. Gastroduodenoscopy showed duodenal metastasis. Simultaneously, brain metastasis was also detected using magnetic resonance imaging. The patient underwent a local resection of the duodenum and a tumor resection of the brain. Postoperative irradiation of the brain metastases and systemic chemotherapy of the lung metastases were performed, and complete remission occurred. However, abdominal lymph node metastasis recurred, and the patient died 1 year after the lobectomy.

Brain Neoplasms↗

[Decortication in chronic thoracic empyemas--a report of three cases].

Three cases of chronic thoracic empyema treated by decortication are reported with special reference to the indications for surgery. The first patient was a 68-year-old man who had right chronic thoracic empyema with a bronchopleural fistula. He underwent open thoracostomy, and decortication was performed after 8 months. The second patient was a 74-year-old man who had right chronic empyema without bronchopleural fistula. Open thoracostomy was also performed and decortication was done after 2 months. Postoperative pulmonary function was significantly improved in both patients. The third patient was a 66-year-old man who had left chronic empyema with a bronchopleural fistula. He underwent open thoracostomy and left lower lobectomy, and then decortication and the omental pedicle flap method were performed after 4 months. All three patients are still doing well currently. It is concluded that decortication significantly improves pulmonary function in properly selected patients, and that computed tomography is helpful for assessing the re-expansion ability of the collapsed lung.

Aged↗

[T 0 N 2 M 0 small cell lung cancer in a patient with Lambert-Eaton myasthenic syndrome].

We report an unusual case of T 0 N 2 M 0 small cell lung cancer in a patient with Lambert-Eaton myasthenic syndrome (LEMS). A 52-year-old man began to notice muscle weakness in a left limb in January 1996, which was followed by muscle weakness in his left arm and fingers, appetite loss, and general fatigue. An electromyogram (EMG) showed the waxing phenomenon in response to high-frequency repetitive stimulation. Lambest-Eaton myasthenic syndrome was diagnosed, based on his symptoms and EMG findings. Chest computed tomography (CT) was done, and left paratracheal, tracheobronchial, subaortic, and hilar lymphadenopathy were found. No mass was seen in either lung field. Cytologic examination of the sputum and bronchial lavage fluid were done, but no malignant cells were found Small cell lung cancer was diagnosed after thoracoscopic resection of the subaortic lymph nodes. No metastases were detected by bone scintigraphy, abdominal CT, or magnetic resonance imaging of the brain. Complete response and resolution of symptoms were obtained by chemotherapy and irradiation.

Antineoplastic Combined Chemotherapy Protocols↗

[Interstitial pneumonia caused by manidipine HCl].

A 62-year-old woman was given a diagnosis of rheumatoid lung in 1993. She began receiving manidipine HCl (10 mg per day) on June 19, 1996 to treat hypertension. The next day fever, coughing and dyspnea developed. She was admitted to our hospital on June 28. A chest radiograph showed diffuse reticulo-nodular shadows in all lung fields and arterial blood gas analysis revealed severe hypoxemia. Administration of manidipine HCl was stopped and treatment with methylprednisolone was started. The symptoms and the radiographic evidence of infiltrates disappeared. A drug lymphocyte stimulation test for manidipine HCl was positive. We know of no previous report of pneumonia caused by manidipine HCl.

Antihypertensive Agents↗

Production of recombinant human monoclonal antibody using ras-amplified BHK-21 cells in a protein-free medium.

A ras oncogene-amplified recombinant BHK-21 cell line (ras-rBHK-IgG) has been established, and was shown to hyperproduce the recombinant IgG chimeric human monoclonal antibody (hMAb) AE6F4, which recognizes lung cancer cells. We found that the ras-rBHK-IgG cell could be easily cultured in a protein-free ERDF medium supplemented with iron(III) nitrate, hydroxyethyliminodiacetic acid, and non-protein synthetic attachment factor as well as in a serum-free ERDF medium supplemented with insulin, transferrin, ethanolamine, and sodium selenite. The productivity of recombinant hMAb from the cells cultured in dishes at high cell densities was higher in protein-free medium than in serum-containing medium. True high density culture of the ras-rBHK-IgG cells was done in protein-free medium using the Tecnomouse, which is a novel hollow fiber bioreactor system. After culture for 30 days in protein-free culture, a total amount of about 14 mg of the recombinant hMAb AE6F4 was obtained, and was shown to be reactive against lung cancer cells in tissues.

Animals↗

Lung cancer-reacting human recombinant antibody AE6F4: potential usefulness in the sputum cytodiagnosis.

Human monoclonal antibody (hMAb) AE6F4 has been shown to be potentially useful for immunocytological detection of lung cancer cells in sputum. By recombinant DNA technology, IgM type hMAb AE6F4 was switched to lgG. The IgG mimic recombinant AE6F4 antibody expression plasmid was assembled using the antibody heavy chain gene, which ligated the gene encoding VH and CH1(mu) domains of hMAb AE6F4 heavy chain to the gene encoding CH2(gamma 1) and CH3(gamma 1) domains of human IgG heavy chain, and the antibody light chain gene of hMAb AE6F4. The recombinant antibody expressed by baby hamster kidney (BHK)-21 cells showed molecular size equivalence to IgG, and consisted of human mu-gamma hybrid heavy and kappa light chains. The immunological specificity of the recombinant antibody was the same as that of hMAb AE6F4 by immunoblotting analysis to the 14-3-3 protein, the putative antigen of hMAb AE6F4, and by immunohistochemical and immunocytological analyses using tissue sections and sputa of lung cancer patients. The transfected BHK-21 cells produced the recombinant antibody persistently and the productivity was greater than 20 times that by human-human hybridoma producing hMAb AE6F4.

14-3-3 Proteins↗

Specific reactivity of human monoclonal antibody AE6F4 against cancer cells in tissues and sputa from lung cancer patients.

In vitro immunization of normal human peripheral lymphocytes by the co-cultivation with A549 cells (a human lung adenocarcinoma cell line), followed by the hybridization with the partner cell line A4H12, resulted in the efficient generation of hybridomas which produce human monoclonal antibodies of IgG or IgM isotype. Immunohistochemical and immunocytological studies showed that one of those monoclonal antibodies, termed AE6F4, was specifically reactive to lung cancer tissues as well as cancer cells in sputa.

Antibodies, Monoclonal↗

[Clinical analysis of benign tumors of the lung].

Benign tumors of the lung occur in low frequency, but its differential diagnosis from malignant tumors such as lung cancer is important. This paper presents as analysis of clinical features of 26 cases operated on for benign tumor of the lung. Histologically there were 15 hamartomas, 8 sclerosing hemangiomas, 2 inflammatory pseudotumors and one clear cell tumor. The roentgenographic appearances were well defined circumscribed solitary nodules in 17 cases (65%), and lobulation and spiculation in 9. Histological diagnosis of benign tumors was not obtained in all cases preoperatively. Minimal resection procedures were performed in 22 cases (85%). No postoperative complications developed.

Adolescent↗

Pharmacokinetics of cisplatin instilled into the pleural cavity following panpleuropneumonectomy in patients with malignant pleurisy due to lung cancer.

The pharmacokinetics of cisplatin instilled into the pleural cavity in patients with malignant pleurisy due to lung cancer were studied. Higher concentrations of total and free platinum in pleural effusion have been maintained for longer than 72 hours in patients who were subjected to panpleuropneumonectomy than in those who received simple drainage. Early rapid drop of total platinum within 6 hours was significant in the drainage group. Total platinum level in the serum of the panpleuropneumonectomy group gradually increased during 1-72 hours, however, that of the drainage group was highest at 1 hour after instillation and declined gradually with time. Free platinum in the serum was also present at lower concentrations in the panpleuropneumonectomy group than in the drainage group. These facts may be ascribed to the absorptive activity of parietal pleura which is present in the drainage group but absent in the panpleuropneumonectomy group. In summary, removal of the parietal pleura by panpleuropneumonectomy could cause cisplatin to be not only more active but also less toxic in patients with malignant pleurisy due to lung cancer.

Adenocarcinoma↗

Effect of postoperative intrapleural instillations of interleukin-2 in patients with malignant pleurisy due to lung cancer.

Thirteen patients with resectable lung cancer and concomitant malignant pleurisy which could not be detected by preoperative chest roentgenograms were treated with surgical resection of the primary lesions and postoperative intrapleural instillations of interleukin-2 (IL-2). All of the patients demonstrated disappearance of cancer cells from pleural effusion after the IL-2 therapy. Four of the 13 patients survived over 5 years and 2 of them are in disease free state at this moment (January 31, 1993). The first recurrent sites were distant organs in 8 of 11 patients with recurrence and lymph nodes in 3 of them. No pleural recurrence was observed. These results indicate that the postoperative intrapleural IL-2 therapy may be one of hopeful adjuvant therapies in patients with resectable lung cancer and concomitant malignant pleurisy, although distant metastasis and lymph node recurrence could not be suppressed completely.

Adenocarcinoma↗

Quantification of human splenic blood flow (quantitative measurement of splenic blood flow with H2(15)O and a dynamic state method: 1).

Positron emission tomography (PET) by means of a dynamic state method and H2(15)O was performed to quantify splenic blood flow in 20 patients who had no hepatic functional disorders. Non-linear regression analysis was applied to determine splenic blood flow. In calculating arterial input function for the spleen, our original exponential method was used to facilitate computerization. Mean splenic blood flow per 100 g of spleen (SBF) was 168.0 ml/min/100 g with a standard error (SE) of 12.4 ml/min. The mean spleen-blood partition coefficient for water (rho) was 0.767 with a SE of 0.020. Significant correlations were noted between the values for SBF obtained by the exponential method and linear method in which individual increasing values for arterial 15O concentration were used rectilinearly (r = 0.96, p < 0.005) and also between the values for rho obtained by the two methods (r = 0.95, p < 0.005). In order to validate the application of a one compartment model to an organ with a large blood volume such as the spleen, a further experiment was performed with a water flow model simulating splenic circulation. We succeeded in quantifying regional splenic blood flow by PET. It was thought that the quantification of splenic blood flow by our method would be beneficial in the study of splenic circulation, which is expected to be altered under conditions of portal hypertension, liver dysfunction and shock, etc.

Adult↗

Relationship between liver function and splenic blood flow (quantitative measurement of splenic blood flow with H2(15)O and a dynamic state method: 2).

We measured splenic blood flow in 55 patients by means of quantitative splenic positron emission tomography (PET), a novel, dynamic state method with H2(15)O as a tracer. Twenty-four of the 55 patients suffered from liver cirrhosis (LC), 25 showed no evidence of cirrhosis (NR) and 6 patients were diagnosed as having chronic hepatitis (CH). Splenic blood flow per 100 g weight of the spleen (SBF) was significantly correlated with splenic volume (r = -0.39, p < 0.005). The indocyanine green retention test at 15 min (r = -0.39, p < 0.005) and the hepaplastin test (r = 0.37, p < 0.025) also correlated significantly with SBF. The means and 95% confidence intervals for the LC, CH, and NR groups were 117.5 ml/min/100 g (96.6-138.4), 102.5 ml/min/100 g (60.6-144.4), and 160.3 ml/min/100 g (139.8-180.8), respectively. The differences in SBF between these 3 groups were significant (p < 0.01). We conclude that regional splenic blood flow is not proportionate to splenic volume, although the splenic volume does increase with the progressive chronic changes observed in hepatic diseases.

Adult↗

Difference in regional hepatic blood flow in liver segments--non-invasive measurement of regional hepatic arterial and portal blood flow in human by positron emission tomography with H2(15)O.

Organ blood flow can be quantitatively measured by positron emission tomography (PET). As the liver has dual blood supplies, arterial and portal, regional hepatic blood flow had not been measured quantitatively. However, we succeeded in simultaneously measuring both regional hepatic arterial and portal blood flow by PET in non-stressed patients. Mean regional portal hepatic blood flow in patients with normal liver and cirrhotic liver was 57.5 and 36.7 ml/minutes/100 g, respectively. Mean regional arterial blood flow was 42.5 and 30.7 ml/minutes/100 g, respectively. A significant difference between regional portal hepatic blood flows in normal and cirrhotic patients was noted. Mean regional portal hepatic blood flow in the lateral, medial, anterior, and posterior segments of the liver was 29.8, 43.4, 50.0, and 40.9 ml/minutes/100 g, respectively. Mean regional arterial blood flow in each liver segment was 37.6, 30.0, 28.2, and 31.6 ml/minutes/100 g, respectively. A significant difference between regional portal hepatic blood flows in lateral and anterior segment was noted. The p value was less than 0.025 and the 95% confidence interval of the difference between means was from -20.2 to -2.7 ml/minutes/100 g by ANOVA. These results showed that regional hepatic blood flow is not the same in all the liver segments.

Adult↗

Hemodynamic disturbances in cerebral ischemia: correlation between positron emission tomographic and angiographic findings.

Proper treatment of ischemic stroke requires better understanding of cerebral hemodynamic changes. The hemodynamic changes associated with ischemia were measured using positron emission tomography and related to angiographic findings in the subacute and chronic stages of 17 ischemia patients who showed symptoms of main trunk stenosis of the internal carotid artery system. The hemodynamic factors, cerebral blood flow, cerebral blood volume, cerebral metabolic rate for oxygen, oxygen extraction fraction, and flow/volume ratio, were measured in regions of interest determined from the angiographic stenosis (over 50%) and compared in each stage. The cerebral blood flow and flow/volume ratio in the territory downstream of the main trunk stenosis and cerebral metabolic rate for oxygen in the whole cortex were decreased in the subacute stage. In the chronic stage, cerebral blood flow and flow/volume ratio decreased mainly in borderzone areas.

Adult↗

Protein kinase C imaging using carbon-11-labeled phorbol esters: 12-deoxyphorbol 13-isobutyrate-20-[1-11C]butyrate as the potential ligand for positron emission tomography.

Protein kinase C plays a crucial role in signal transduction for a variety of biologically active substances which activates cellular functions and their proliferation. The actions are closely related to both normal and abnormal functions in the nervous system. Tumor-promoting phorbol esters can substitute for diacylglycerols which are important ligands that bind to protein kinase C. Three typical phorbol esters, phorbol 13-[1-11C]butyrate, phorbol 12,13-[1-11C]dibutyrate and 12-deoxyphorbol 13-isobutyrate-20-[1-11C]butyrate, were synthesized by using [11C]ethylketene with a high specific activity (186GBq/mumol). Their in vivo autoradiograms demonstrated a heterogenous distribution in rat brain. 12-deoxyphorbol 13-isobutyrate-20-[1-11C]butyrate was particularly suited for in vivo use due to its nontumor-promoting activity and its ready permeability to the blood-brain barrier. High optical density was observed in the cortex, amygdala and hippocampus. The in vivo binding properties of this compound to protein kinase C were confirmed by in vivo displacement studies with unlabeled 12-deoxyphorbol 13-isobutyrate-20-butyrate and unlabeled phorbol 12,13-dibutyrate. This suggests that 12-deoxyphorbol 13-isobutyrate-20-[1-11C] butyrate has a specific binding affinity for protein kinase C.

Animals↗

Complete excision and panpleuropneumonectomy resulting in long-term survival for a teenager with invasive thymoma: report of a case.

An 18-year-old girl with invasive thymoma and pleural dissemination underwent a complete removal of the tumor with combined resection of the pericardium and a panpleuropneumonectomy of the left lung. At the time of writing, 70 months later, she was doing well under the classification of grade I performance status with no signs of recurrence. Thus, complete surgical removal of this tumor can prolong the survival time of patients with invasive thymoma and pleural dissemination.

Adolescent↗