Increased circulating interleukin-12 (IL-12) p40 in pulmonary sarcoidosis.

In sarcoidosis, a T helper 1 (Th1) response is an essential event and the up-regulation of interleukin-12 (IL-12) has been detected in affected disease sites. In order to investigate the clinical usefulness of circulating IL-12, we measured the serum concentrations of IL-12 by ELISA and performed immunohistochemistry using specific MoAbs for IL-12 in the lungs and scalene lymph nodes of patients with sarcoidosis. The serum concentration of IL-12 p40 was detectable in all 45 patients with pulmonary sarcoidosis and 18 normal controls, whereas that of IL-12 p70 was undetectable. The serum concentrations of IL-12 p40 in pulmonary sarcoidosis were significantly higher than those of the normal controls, especially in cases with abnormal intrathoracic findings detected by chest roentogenogram. The serum concentrations of interferon-gamma (IFN-gamma) also increased compared with those of normal controls and there was a significant positive correlation between the serum concentrations of IL-12 p40 and IFN-gamma. Furthermore, serum angiotensin-converting enzyme (ACE) and lysozyme, which are known to be useful markers for disease activity in sarcoidosis, correlated well with the serum concentrations of IL-12 p40. The positive 67Ga scan group (for lung field) had significantly elevated serum IL-12 p40 levels compared with those of the negative group. No bioactivity of IL-12 p70 was detected in three sarcoid cases sera by using the IL-12 responsive cell line. Finally, the immunohistochemical approach revealed that IL-12 p40 was expressed in the epithelioid cells and macrophages of sarcoid lungs and lymph nodes. We concluded that the production of IL-12 p40 was far greater in the sera and we have demonstrated this to be a useful clinical marker for disease activity and the Th1 response in pulmonary sarcoidosis.

[Good response in case of hepatocellular carcinoma with portal tumor thrombs--a case report of interdisciplinary local therapy].

A 56-year-old male patient with chronic C type hepatitis had HCC which invaded right portal vein trunk (Vp3). In August 2000, we performed intrahepatic artery infusion chemotherapy with CDDP and 5-FU under subcutaneous interferon alpha treatment. In addition, we used chemoradiation therapy for portal tumor thrombus in HCC. As the result of such therapy, the size of HCC and portal tumor thrombus reduced and the level of PIVKA-II decreased. There were no side effects except fever due to interferon alpha treatment. In February 2001, we performed devascularization and RFA therapy for HCC in S7 of liver under laparoscope. The level of PIVKA-II was within the normal range. It is important to perform interdisciplinary therapy appropriate for the HCC status.

[Intra-arterial infusion chemotherapy with docetaxel for locally advanced breast cancer and inflammatory breast cancer].

From 1998 to 2000, we performed neoadjuvant intra-arterial infusion chemotherapy using docetaxel (60 mg/m2) a few times with 5 patients with local advanced breast cancer and inflammatory breast cancer. Therapeutic effects included 3 cases of PR among the breast tumor patients and downstaging was obtained 2 cases. No critical side effects were found due to this chemotherapy. We could perform mastectomy in all the cases. We consider intra-arterial infusion using docetaxel to be highly effective with few side effects in cases of advanced breast cancer.

Association of Clara cell 10-kDa protein, spontaneous regression and sarcoidosis.

Sarcoidosis is a systemic granulomatous disorder with a high rate of spontaneous regression. Clara cell 10-kDa protein (CC10), the predominant product of nonciliated bronchiolar epithelial cells, is a potent immunoregulatory and anti-inflammatory agent. CC10 levels were measured in sera and bronchoalveolar lavage (BAL) fluids from 31 sarcoidosis patients (nine progressive disease and 22 regressive disease) and their relevance to spontaneous regression investigated. The inhibitory effects of recombinant CC10 on interferon gamma (IFN-gamma) production were examined using lipopolysaccharide (LPS)-stimulated sarcoid BAL fluid cells, and the blocking effects of monoclonal antibody TY-5, directed against CC10, on CC10 function were also tested. Serum and BAL fluid CC10 levels in the regressive disease group were significantly higher than those in the progressive disease group (serum, p<0.05; BAL fluid, p<0.005) and healthy subjects (serum, p<0.0001; BAL fluid, p<0.005). CC10 inhibited, in part, IFN-gamma production from LPS-stimulated sarcoid BAL fluid cells (CC10 inhibition: 1,000 ng x mL(-1), 30%; 100 ng x mL(-1), 14%). TY-5 restored IFN-gamma production by blocking CC10 function. Sarcoidosis patients with regressive disease showed increased Clara cell 10-kDa protein levels in their sera and bronchoalveolar lavage fluids. Clara cell 10-kDa protein may be a regulator of the inflammatory process in sarcoidosis.

[Fulminant Mycoplasma pneumoniae pneumonia resulting in respiratory failure and a prolonged pulmonary lesion].

A previously healthy 26-year-old woman presented with a fever and coughing on October 1, 1995. Despite treatment with beta-lactam antibiotics at another hospital, she had a high fever, coughing, and dyspnea. A chest roentgenogram showed diffuse infiltrates in both lung fields. On October 9, she was transferred to our hospital. On admission, a chest X-ray film showed marked diffusely infiltrates in both lung fields and a effusion in the left lung. Arterial blood gas analysis after inhalation of 4 liters per minute of oxygen via a nasal cannula revealed a PaO2 of 39.0 torr. Despite treatment with various antibiotics, including minocyclin and gamma-globulin, her respiratory condition rapidly deteriorated. She was mechanically ventilated by with intermittent mandatory ventilation and positive end-experiatory pressure, and received antibiotics and methylprednisolone pulse therapy. He chest X-ray and arterial blood gase findings, gradually improved. The passive hemagglutination titer for Mycoplasma rose from 1:4 on October 9, to 1:2,560 on the 14th hospital day. Acute respiratory failure due to Mycoplasma pneumoniae pneumonia was diagnosed. A chest X-ray film obtained 2 months after admission showed linear-reticular shadows in both lung fields and pulmonary-function tests revealed abnormally low vital capacity and diffusing capacity. Examination of a specimen obtained by transbronchial lung biopsy revealed focal intraalveolar exudate with fibrin and macrophages. Very mild interstitial thickening was also noted. The lymphocyte stimulation responses to PPD, PHA, and Con A were low early in the illness and became normal after recovery. Several reports have said that an enhanced pulmonary cellular immune response may be responsible for the development of severe Mycoplasma pneumoniae, resulting in a temporary decrease in the cell-mediated immune response. This case supports that hypothesis. We believe that in severe cases, steroid therapy including pulse therapy should be started as soon as possible.

[Clinical evaluation of intra-arterial infusion of hyperthermo-chemotherapy in gastric cancer].

We performed intra-arterial infusion hyperthermochemotherapy by retaining an intra-arterial reservoir in 17 lesions of 12 patients with non-resectable, metastatic or recurrent gastric cancers. The 12 patients consisted of one with a primary gastric cancer lesion, 6 with a solitary gastric cancer lesion metastasizing to the liver, 4 with gastric cancer accompanied by hepatic metastasis, lymph node metastasis or local recurrence, and one with a gastric cancer lesion metastasizing to Douglas' pouch. A catheter was retained in the hepatic artery of all 6 patients with a solitary gastric cancer lesion metastasizing to the liver, and a catheter was retained in the aorta of the patient with a primary lesion, 3 of the 4 patients with two or more metastatic lesions, and the patient with a lesion metastasizing to Douglas' pouch. The duration of each hyperthermia session was 50 minutes, and one or two sessions were performed within a week. One course consisting of 5 or 6 sessions was repeated. Antineoplastic drugs such as MMC, 5-FU, ADR, epi-ADR, CDDP and VP-16 were injected in bolus form or administered serially through the reservoir. Nine of the 12 patients had polypharmacy. One to 3 courses or 4 to 20 sessions at maximum (average 9.8 sessions) were given. The rate of efficacy of intra-arterial infusion hyperthermochemotherapy was 44% for hepatic metastasis and 25% for lymph node metastasis. The local recurrent lesions, the lesion metastasizing to Douglas' pouch and the primary lesion did not respond to therapy.

A study on the distribution of G-cells in human gastric mucosa.

The distribution of G-cells in the gastric glands was studied quantitatively using the indirect immunoperoxidase method in 37 resected stomachs: 11 for esophageal cancer, 14 for gastric cancer, 4 for gastric ulcer, 7 for duodenal ulcer, and 1 for atypical epithelium. G-cells were seen in the pyloric glands and in the pseudopyloric glands in the atrophic fundic gland area. No G-cells were found in the fundic glands or in the cardiac glands. There was a significant correlation between the number of G-cells and the pyloric and/or pseudopyloric glandular tubes (p less than 0.01). The number of G-cells per glandular tube was 1.9 +/- 0.5 in the pyloric glands and 1.2 +/- 0.4 in the pseudopyloric glands on the pyloric part of the atrophic fundic gland area. G-cells were rarely seen in the pseudopyloric glands on the cardiac part of the atrophic fundic gland area. It is suggested that the pseudopyloric glands without G-cells in the cardiac region are akin to cardiac glands.