Thio-sugars. IV. Synthesis of carbohydrate 1,3-glycol (six-membered) thionocarbonates and their attempted O-S rearrangement.

Four six-membered cyclic thionocarbonates (two sec-sec and two prim-sec) were prepared and their radical-promoted O-S rearrangement reaction was examined. The results revealed that the reaction in six-membered rings is difficult compared with the simple rearrangement in five-membered rings. In the course of syntheses of the substrates, interesting acyl migration during the stannylation process occurred.

Clinical and pathologic findings in 52 consecutively autopsied cases with multiple myeloma.

We studied clinical features and pathologic findings in 52 consecutively autopsied patients with multiple myeloma in our center between 1979 and 1998. Distant extraosseous involvement was found in 33 patients (63.5%). Thirty-one patients (59.6%) were proven to have infection at autopsy, among which pneumonia was most common site of infection. Amyloidosis was shown in 8 patients. Second malignancies were observed in 4 cases. The three major causes of death were hemorrhage, infection, and renal failure, which accounted for death in approximately 70% of the patients. Advances in the anticancer and antimicrobial chemotherapies might have decreased deaths due to myeloma itself or infection.

[Anaplastic thyroid carcinoma with lung metastasis producing CA 19-9 and GM-CSF].

A 68-year-old Japanese woman was admitted to our hospital because of hoarseness, dysphagia and a mass on the right side of her neck. Chest radiographs showed multiple nodular shadows in both lung fields. Detailed investigations resulted in a diagnosis of multiple lung metastasis of anaplastic thyroid carcinoma transformed from papillary adenocarcinoma. Both serum CA 19-9 and GM-CSF levels were elevated, to 70.5 U/ml (normal range: 0-37 U/ml) and 343.4 pg/ml (normal range: 0-8 pg/ml), respectively. Immunostaining disclosed that the primary and metastatic tumors were positive for CA 19-9, but not for GM-CSF antigens. Serum levels of these two parameters slowly decreased after chemo-radiotherapy, suggesting that the tumor may have produced GM-CSF as well as CA 19-9. Recent studies have indicated that the prognosis is poor for non-small cell lung cancers that produce G-CSF or CA 19-9. To our knowledge, this is the first case report of anaplastic thyroid carcinoma characterized by high serum levels of both CA 19-9 and GM-CSF, with metastasis to the lung and other organs.

[Legionella pneumonia caused by aspiration of hot spring water after sarin exposure].

A 72-year-old man was exposed to the sarin gas attack in a Tokyo subway on March 20 th, 1995. After exposure, he noticed eye discomfort, chest tightness, headache and weakness of the lower limbs and oropharyngeal muscles. Despite these symptoms, he visited a hot spring on the same day with his family. On March 25 th, his muscle weakness progressed, and a low grade fever appeared. His muscle weakness disappeared 8 days after exposure to sarin, but respiratory failure rapidly developed, necessitating artificial ventilation within four day after hospitalization on March 28th. Chemotherapy with erythromycin, imipenem/cilastatin, and steroid pulse therapy was begu. PCR and culture of sputum collected by bronchofiberscopy were positive for Legionella pneumophila, serogroup I. His respiratory state improved, but subsequent infection with Pseudomonous aeruginosa. Enterobacter cloacae, and Candida tropicalis/glabrata caused his death 71 days after admission. Oropharyngeal muscle weakness caused by sarin-mediated cholinesterase inhibition was strongly suspected as the cause of hot spring water aspiration. Transbronchial lung biopsy revealed organizing pneumonia with fibrosis. Bronchoscopic findings included redness, edema and fragility of all visible areas of the airway, which was thought to be due to bronchitis caused by Legionellosis.

[Malignant recurrence of solitary fibrous tumor of the pleura developed 20 years after the surgery: a case report of re-extirpation].

A 63-year-old female developed the chest wall tumor protruding into the right thoracic cavity. She consulted our hospital complaining of chest pain. 20 years before this episode, she had undergone tumor extirpation combined with the partial resection of adherent anterior chest wall and the diaphragm for large benign solitary fibrous tumor of the pleura. Because of the difficulty in making diagnosis by needle biopsy, operation (re-tumor extirpation combined with the chest wall) was done. Histological examination revealed that the tumor was malignant solitary fibrous tumor. We concluded that the tumor was the malignant recurrence of the benign solitary fibrous tumor resected 20 years before. Occasionally, benign solitary fibrous tumor of the pleura recurs and behaves more aggressively than primary, but such a long latent period as 20 years is quite uncommon. So we present the case and the review of the literature.

[A case of desquamative interstitial pneumonia with increased numbers of eosinophils in the bronchoalveolar lavage fluid].

A 76-year-old man was admitted to our hospital with a diffuse reticulo-nodular shadow on chest X-ray. He had no symptoms. Transbronchial lung biopsy specimens revealed alveolitis and small numbers of lymphocytes. Bronchoalveolar lavage fluid (BALF) analysis revealed an increased number of eosinophils. Few eosinophils were seen in the alveolar lumen on biopsy. The patient had no symptoms, and was discharged without therapy. He was followed as an outpatient. Dyspnea on effort gradually developed June 1995. The diffuse infiltrative shadows on chest CT worsened and the patient was again admitted. Laboratory data revealed an elevation of serum LDH. Tumor markers were negative. Desquamative interstitial pneumonia (DIP) was diagnosed on open lung biopsy. Corticosteroid therapy (1 mg/kg/day) was administered. After treatment with corticosteroid, chest CT findings and pulmonary function tests improved remarkably. DIP is less common in Japan than elsewhere. The characteristic findings of BALF taken from patients with DIP are still inperfectly characterized. Our patient exhibited an increased number of eosinophils. To the best of our knowledge, BALF findings were reported for six cases of DIP in Japan. In five out of the seven cases (including our case), BALF findings demonstrated an increased number of eosinophils. This finding may be one of the characteristic features in patients with DIP.

[Repeated pneumonia in the middle lobe caused by congenital bronchoesophageal fistula].

A 52-year-old woman was admitted to our hospital because of repeated episodes of pneumonia in the middle lobe. She had also experienced coughing during meals. The history and chest CT findings suggested the presence of a bronchoesophageal fistula. An upper GI series revealed a fistula between an esophageal diverticulum and the superior segment bronchus of the right lower lobe. Fiberoptic bronchoscopy done immediately after the upper GI series revealed barium sulfate leaking from the superior segment bronchus of the right lower lobe into the middle lobe bronchus. These findings indicated that the repeated pneumonia in the middle lobe was caused by a congenital bronchoesophageal fistula. Examination of the resected fistula showed that it was a Braimbridge type I bronchoesophageal fistula. Although of at least 49 cases of congenital bronchoesophageal fistulas with esophageal diverticula have been reported in the Japanese medical literature, we know of no previous case in which such a fistula was associated with middle-lobe pneumonia.

[Tracheal carcinoma causing severe tracheal stenosis].

A 47-year-old woman was admitted to our hospital because of shortness of breath. She had wheezed for a long time before admission. A flow-volume curve showed a pattern consistent with a fixed obstruction of the trachea. CT findings also revealed severe stenosis of the trachea caused by a tumor mass. Tracheal carcinoma was diagnosed after transbronchoscopic biopsy. The patient received chemotherapy and radiation therapy concurrently for about six weeks. Her symptoms resolved, and a second flow-volume curve had a normal pattern. Tracheal carcinoma should be included in the differential diagnosis of airway obstruction. In such cases, the flow-volume curve can be useful as a screening test.

[Metastatic lung cancer from renal cell carcinoma effectively treated by bronchial artery embolization].

A 55-year-old man was admitted to the International Medical Center of Japan because of obstructive pneumonia in the right middle and lower lobes. His left kidney had been removed 3 years earlier because of renal cell carcinoma. Metastatic lung cancer from renal cell carcinoma was diagnosed. Bronchial artery embolization was done twice with sponges, because the tumor was thought to be resistant to interferon. Three days after the second embolization, the tumor was removed through the trachea, and atelectasis was relieved. Bronchial artery embolization may be useful for treatment of metastatic lung cancer from renal cell carcinoma.

Using H2(15)O and C15O in noninvasive pulmonary measurements.

Regional pulmonary blood flow (PBF), regional pulmonary extravascular water (PEW), and regional pulmonary blood volume (PBV) were measured quantitatively with positron emission tomography (PET) using H2(15)O and C15O in normal human subjects and patients before and after thoracotomy. The method was based on the Kety's model and a modification of the Mintun's method of measuring regional PBF with H2(15)O. The method consisted of intravenous injection of H2(15)O and dynamic PET scanning of the lung field and the right heart blood pool. Another scan following C15O inhalation was performed to visualize the blood pool, and the influence of the blood pool radioactivity to the H2(15)O image was subtracted. A mathematic model was applied to the data analysis, and the least-square fitting procedure was used with a computer for obtaining the optimal parameters. The mean values of the measured PBF, PEW, and PBV in two normal human subjects were 67.2 +/- 23 ml/min/100 ml, 17 +/- 5 ml/100 ml, and 19 +/- 6 ml/100 ml, respectively. The PBF, PEW, and PBV increased in the direction of gravity in the transverse cross-section image of the lung. Using this method, we studied the condition of patients who underwent lung surgery with thoracotomy. The PEW increased and the PBF decreased in the patients after surgery. This condition lasted for a few days, and the patients then recovered. The well-known phenomenon of pulmonary edema occurring after thoracotomy, which is usually recognized by symptoms and radiologically, was thus confirmed quantitatively by our method.

Acute leukemia of megakaryocyte lineage with tumor formation. An autopsy case of patient with Down's syndrome.

In this report we present the autopsy findings of acute megakaryoblastic leukemia with tumor formation in a 2-year-old female infant with Down's syndrome. Chromosomal analysis of blast cells revealed constitutional anomaly of trisomy 21 and two other related types of abnormal clones. Flow cytometric examination revealed blast cells expressing Ia-like or HLA-DR antigens. Postmortem examination showed extensive infiltration of leukemic cells in most of the examined organs, including the bone marrow with myelofibrosis. Tumor masses in the maxillary, frontal and femoral bones and the atria of the heart had undergone massive infiltration of atypical blast cells with an increase in the reticulin network. The final diagnosis was confirmed by ultrastructural cytochemistry of the platelet peroxidase reaction as well as by immunological staining utilizing anti-platelet glycoprotein IIb/IIIa, antiplatelet factor 4 and anti-beta-thromboglobulin antibodies for the blast cells. It seems likely that platelet-derived growth factor, secondary to an increase in the reticulin network, plays a major role in myelofibrosis of acute megakaryoblastic leukemia with tumor formation.

Synthesis and antibacterial activity of 2,2'-dithiobis(benzamide) derivatives against Mycobacterium species.

A series of compounds, which are analogues of 2,2'-dithiobis(benzamide), were synthesized and tested for in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv including resistant strains against streptomycin, kanamycin, or isonicotinic acid hydrazide. MICs of these compounds against atypical mycobacteria, Mycobacterium kansasii and Mycobacterium intracellulare were also examined. Structure-activity relationships were found in a series of (acyloxy)alkyl ester derivatives depending upon the length of alkyl carbon chain. The MIC of the most potent compound, 2,2'-dithiobis[N-[3-(decanoyloxy)propyl]benzamide] [56] was superior or at least equivalent to streptomycin, kanamycin, and ethanbutol. All the compounds showed no cross-resistance between the current antitubercular agents.