Tyrosine phosphorylation of vav protooncogene product in primary human myelogenous leukemic cells stimulated by granulocyte colony-stimulating factor.

Granulocyte colony-stimulating factor(G-CSF), but not granulocyte-macrophage CSF(GM-CSF), induced tyrosine phosphorylation of 95-kDa protein in 13 cases of primary human acute myelogenous leukemic cells. Electrophoretic mobility of 95-kDa phosphoprotein and the protooncogene product p95vav was identical. In addition, p95vav was tyrosine-phosphorylated only in G-CSF-stimulated cells. In contrast to primary leukemic cells, amount of p95vav was under detectable level and G-CSF did not induce tyrosine phosphorylation of 90-100-kDa proteins in human neutrophils. These results indicate specific involvement of vav product in signaling pathway of G-CSF in primary human leukemic cells.

[Penetrating keratoplasty for keratoconus in a case of Down's syndrome].

We report a Down's syndrome patient who underwent penetrating keratoplasty (PKP) surgery. The patient was a 62-year-old female who had Down's syndrome with severe bilateral keratokonus and cataract. Her visual acuity was very poor as she did everything by touch before the surgery. We performed a triple procedure surgery, i.e., PKP, extracapsular cataract extraction, and posterior chamber intraocular lens implantation in her left eye. After the surgery her visual behavior improved markedly. This case shows that PKP surgery can be performed on such handicapped patients who are difficult handle in emergencies and need general anesthesia, because we have been able to keep the donor cornea longer than usual. We conclude that we should actively perform the PKP surgery for the handicapped if the patient does not have self-damaging behavior and if there is cooperation of the family and the medical staff.

Prolonged hyperalimentation as a possible cause of renal tubular dysfunction: evaluation of 1,5-anhydro-D-glucitol resorption and N-acetylglucosaminidase excretion in humans.

1. A major polyol found in the sera and other tissues of humans, 1,5-anhydro-D-glucitol, is mainly ingested in the diet and is excreted in urine. We compared the influence of the long-term administration of total parenteral nutrition free of 1,5-anhydro-D-glucitol with that of total enteral nutrition on the serum level of 1,5-anhydro-D-glucitol in 46 patients who could not take food by mouth. 2. The serum concentration of 1,5-anhydro-D-glucitol and its kinetics remained unchanged in the group receiving total enteral nutrition (n = 21) over a period of 12 months. However, after 1 month on total parenteral nutrition (n = 25), the serum level of 1,5-anhydro-D-glucitol decreased, falling to about one-sixth the pretreatment level in the 12th month. Because the serum level of 1,5-anhydro-D-glucitol continued to decline, falling below the limit at which its renal reabsorption is normally activated, this decrease did not seem to be caused directly by a nutritional deficiency of this substance. 3. The urinary excretion of 1,5-anhydro-D-glucitol was closely correlated (r = 0.792) with that of N-acetyl-beta-glucosaminidase; but not with the serum creatinine level or of the urinary excretion of microalbumin or of urinary beta 2-microglobulin. We observed no glucosuria, hyperuricuria or changes in serum electrolytes during total parenteral nutrition. 4. The reduction in the serum level of 1,5-anhydro-D-glucitol and the urinary excretion of N-acetyl-beta-glucosaminidase were correlated with the duration of total parenteral nutrition administration.(ABSTRACT TRUNCATED AT 250 WORDS)

[Early phase II clinical study of RP56976 (docetaxel) in patients with primary pulmonary cancer. Docetaxel Cooperative Study Group for Lung Cancer].

An early phase II clinical study of RP56976 (Docetaxel), a new anticancer agent of plant origin, was conducted in patients with primary pulmonary cancer as a multicentered study involving 28 Japanese institutions. Docetaxel was administered at an intravenous dose of 60 mg/m2 based on the results of a phase I clinical study, and efficacy and safety were examined. Of the 65 patients enrolled, 57 patients were evaluated to have completed the scheduled course of treatment by the Evaluation Committee. The antitumor effect in patients with non-small cell lung cancer was 21.4% (9/42). In patients not previously treated, the antitumor effect was 30.0% (6/20), in patients previously treated the antitumor effect was 13.6% (3/22), and in 13.3% (2/15) of patients with small cell lung cancer. This shows that docetaxel had an efficacy for non-small cell lung cancer. Hematological adverse reactions included leukopenia and neutropenia of Grade III or more as specified in the Adverse Event Reporting Form proposed by the Japan Society for Cancer Therapy in 53.3% (32/60) and 78.3% (47/60) patients, respectively. Other major adverse reactions included alopecia and anorexia. Neurological symptoms developed at a low frequency and were mild in severity.

Prevention of diabetes by thymic hormone in alloxan-treated rats.

We investigated the effects of facteur thymique sérique (FTS), a thymic peptide hormone, on alloxan- and streptozotocin-induced diabetes in rats. Pretreatment with intravenous injection of FTS significantly suppressed both alloxan- and streptozotocin-induced hyperglycemia. The effects of FTS were time dependent. FTS suppressed hyperglycemia in a dose range of 1-6600 micrograms/kg. Alloxan-induced hyperglycemia was completely prevented when FTS was injected in doses of 40-50 micrograms/kg 1 min before injection of alloxan. Histological examination of islet areas showed that alloxan-induced destruction of beta-cells was inhibited by FTS. FTS had no significant effects on lymphocyte subsets and immunity-related cells or on plasma superoxide dismutase activity and total glutathione level. The blood half-life time of exogenously injected FTS was short (2-3 min), indicating acute internalization of FTS into pancreatic beta-cells. Our results suggested that FTS acutely and directly blocks some initial effect of alloxan, preventing the destruction of beta-cells.

A rise in antineutrophil cytoplasmic antibody in a patient with systemic vasculitis in remission.

We report a 42-year-old man who showed alveolar hemorrhage and glomerulonephritis as well as episcleritis and skin rash. He had an extremely high titer of cytoplasm-staining antineutrophil cytoplasmic antibody (C-ANCA) and was diagnosed as having systemic vasculitis based on histological findings of kidney and skin biopsies. After immunosuppressive therapy clinical manifestations resolved within several weeks and C-ANCA titers commensurably declined. C-ANCA titers, however, increased again and remained high despite clinical remission. In general, there is a close relationship between ANCA titers and clinical activities in ANCA-associated diseases, but they displayed a large discrepancy in this patient. Indeed, the serum of the patient in remission contained the antibody against 29-kD neutrophil extracts which was detected by immunoblot analysis. These findings suggest that C-ANCA may not necessarily be, by itself, pathogenetic for the development of the vasculitis.

Embolotherapy for persistent hemoptysis: the significance of pleural thickening.

Elective embolotherapy for recurrent hemoptysis was evaluated for its effectiveness. Forty embolotherapeutic procedures were performed in 30 patients. In the short term, complete hemostasis was achieved in 16 of 40 procedures (40%) and significant improvement in another 16 procedures (40%). Long-term, complete hemostasis was achieved in 14 of 34 procedures (41%) and significant improvement in 12 (35%). Embolotherapy was consistently more effective in patients who had no pleural abnormalities compared with those with pleural thickening. Long-term complete hemostasis was achieved in 7 of 10 procedures (70%) for the patients without pleural thickening and only 7 of 24 (29%) in patients with pleural thickening. Thus, pleural abnormalities negatively influence long-term effectiveness of embolotherapy.

Origin and disposal of 1,5-anhydroglucitol, a major polyol in the human body.

The origin and disposal of 1,5-anhydro-D-glucitol (AG), one of the main polyols found in the human body, was studied in normal subjects and diabetic patients. AG was detected in various kinds of foods. The mean AG supplement through foods was estimated to be approximately 4.38 mg/day, which was compatible with that calculated in a food analysis (average 0.22 mg AG/100 kcal in Japanese foods) on eight healthy subjects. The mean AG excretion in urine was approximately 4.76 mg/day in these subjects. Excretion into stools was negligible. From observations on the patients without oral supplement of AG, 0.4 mg of daily de novo synthesis of AG was strongly suggested. It was also implied that urinary AG excretion occurred soon after food ingestion and that its amount was closely correlated with daily supplement through foods. Thus the fundamental kinetics of AG were recognized as follows: 1) AG in the body originates mainly from foods and is well absorbed in the intestine, 2) AG is little degraded and metabolized in the body, and 3) an equilibrium exists between oral supplement plus a small but steady amount of de novo synthesis and excretion in urine.

Estimation of plasma glucose fluctuation with a combination test of hemoglobin A1c and 1,5-anhydroglucitol.

We investigated the effect of plasma glucose fluctuation on hemoglobin A1c (HbA1c) and plasma 1,5-anhydroglucitol (AG) levels, especially in insulin-dependent diabetes mellitus (IDDM). Plasma AG is a new marker that provides sensitive and analytical information on glycemic control. The basic mechanisms underlying both the reduction and recovery of the plasma AG level, ie, the excretion into urine with glucosuria and the amount supplied to the body, were presumed to be similar in IDDM and non-insulin-dependent diabetes mellitus (NIDDM) patients. The correlation coefficient for mean plasma glucose and AG was -.591, and it was .578 for mean plasma glucose and HbA1c in IDDM patients. In NIDDM, the correlation between mean plasma glucose and AG was -.869, and between mean plasma glucose and HbA1c, .875. The plasma AG levels in the IDDM group showed a lower range than in the NIDDM group, even with similar HbA1c levels. All the cases showing lower plasma AG levels among those with similar HbA1c levels manifested greater fluctuation of plasma glucose and a larger amount of urinary glucose. The lower AG level in IDDM patients was reversible to the level in NIDDM patients when the greater fluctuation of plasma glucose was corrected. Thus, it was suggested that because urinary glucose excretion is intermittently high in IDDM patients, plasma AG is frequently low, even though the mean plasma glucose and HbA1c levels suggest good control.(ABSTRACT TRUNCATED AT 250 WORDS)

[Interstitial pneumonia developed after combination chemotherapy with (CDDP, VDS, MMC) and radiotherapy].

Reported is a case of interstitial pneumonia that developed after CDDP, VDS, and MMC combination chemotherapy and radiotherapy. The patient, a 68-year-old male, had received chemotherapy three times, beginning with CDDP + VDS, followed by CDDP, VDS, and MMC, in that sequence, after which he was given radiotherapy. The interstitial pneumonia developed one day after a dose of 54 Gy. It is felt that MMC played the leading role and the radiation the inducing role in the development of his interstitial pneumonia.

[Radiotherapy combined with cis-diammine-dichloro platinum (II) plus vindesine in the treatment of non-small cell lung cancer: a comparison with treatment by radiation alone].

The effect of CDDP + VDS has been evaluated in 39 cases of non-small cell lung cancer, compared with those treated with radiation alone. Nineteen cases consisted of a combined radiation and chemotherapy group, while twenty cases were classed a the radiation therapy only group. CDDP was given at a dosage of 60 to 110 mg/m2 every 4 weeks, and VDS at a dosage of 3 mg/m2 3 times weekly. Radiation was given at a fraction dose of 1.5 to 2 Gy 5 times per week with a mean total dose of 56 Gy in the radiation only group, and 50 Gy in the combined therapy group. There were no significant difference in both the response rate and the survival time between the two groups. This suggests that combined chemotherapy was not effective for the treatment of non-small cell lung cancer.

[A case of pneumococcal arthritis in a patient with gout].

A 62 year-old man had suffered from gout and mild renal insufficiency since he was 40 years old. He was admitted to our hospital complicated by a productive cough, high fever and a right swollen knee joint. The chest radiographs demonstrated a left upper lobe infiltration shadow. Streptococci pneumoniae were found in the sputum, arterial blood and synovial fluid of the right knee joint, suggesting a severe pneumonia followed by pneumococcal septicemia which led to purulent arthritis. He was treated with cefamandole (CMD) and penicillin G (PC-G) for one week, but the chest X-ray findings were not improved. After treatment with cefbuperazone (CBPZ) and latamoxef (LMOX), his fever and other symptoms gradually resolved. Streptococcus pneumoniae is an uncommon organism of septic arthritis. Pneumococcal arthritis in a patient without immunodeficiency such as this case is very rare, and has not been reported in Japan.

[Results of surgical treatment in patients aged 80 years and over].

Surgical treatments were performed in 31 patients over 80-year-old with lung cancer. Men were 25 and women were 6, the eldest patient was 92-year-old male. Pneumonectomy was carried out in 3, lobectomy in 19, carinal resection in 1, Segmentectomy in 4, and partial resection of lung in 2. Histologies of resected specimen in 31 included 11 epidermoid carcinoma, 15 adenocarcinoma and 5 other cell types. There was no patients died within 30 days postoperatively. The cumulative 5 year-survival rate was 53.9%.

Plasma 1,5-anhydro-D-glucitol as new clinical marker of glycemic control in NIDDM patients.

To elucidate the value of using plasma 1,5-anhydro-D-glucitol (AG) as a marker of glycemic control in diabetic patients, the relationship between the plasma concentration of AG and glucosuria was examined in 152 patients with non-insulin-dependent diabetes mellitus (NIDDM). After recovery from the deterioration of glycemic control in NIDDM patients had started, AG began to increase day by day. The recovery of plasma AG showed a constant linear increase curve when excellent glycemic control was attained. The ordinary daily recovery rate of plasma AG was estimated to be 0.3 microgram/ml, which was independent of body weight, sex, age, the difference in treatment, the duration of diabetes, or the level of plasma AG among NIDDM patients. This rate decreased according to the increase in urinary glucose. When we calculated the decrease rate of plasma AG (delta AG), assuming 0.3 microgram/day to be the maximum increase rate in a day, we found a high correlation between delta AG and urinary glucose at almost all AG levels except the normal range and observed that plasma AG (A) times urinary glucose (G) was relatively constant. The formula A x G = 16 is a simple equation for rough estimation of urinary glucose from the plasma AG concentration in a stable glycemic-controlled NIDDM patient, and we call it the A.G index. The plasma AG also correlated significantly with fasting plasma glucose (r = -.810) and glycosylated hemoglobin (r = -.856) in the same stable glycemic-controlled NIDDM patients. Based on these observations, we propose that plasma AG can serve as a new marker that may provide sensitive and analytical information about glycemic control.

Results of resection for bronchogenic carcinoma in patients over the age of 80.

Thirty three patients aged over 80 years underwent resection for bronchogenic carcinoma. The operations performed were: lobectomy (21), segmentectomy (4), wedge resection (2), pneumonectomy (3), carinal resection (1). In two patients no resection was feasible. Three patients died within two months of surgery. The cumulative five year survival rate was 55%, 79% for patients with stage I carcinoma and 31% for stage III. It is considered that resection has an acceptable outcome in patients over 80 years.

[A phase II study of carboplatin in small cell lung cancer].

A phase II clinical trial of carboplatin for small cell lung cancer was conducted in 20 institutions of the National Chest Hospital lung cancer cooperative study group. Carboplatin was administered by three dosing schedule of 300 mg/m2, 400 mg/m2 and 450 mg/m2. Out of 30 patients registered in this trial, 29 patients were evaluable for response and toxicity. Seven patients achieved PR with the response rate of 24.1%. The response rates for 300 mg/m2, for 400 mg/m2 and for 450 mg/m2 were 25.0%, 8.3% and 44.4%, respectively. Thrombocytopenia (less than 7 x 10(4)/mm3) and leukopenia (less than 3,000/mm3) were observed at 25.9% and 17.2% of cases, respectively. Nausea/vomiting was also observed at an incidence of 55.2% with mild degree. No renal and ototoxic damage was observed.