P-glycoprotein expression in soft-tissue sarcomas

Multidrug resistance (MDR) is an important problem in chemotheraphy for neoplastic disease. In humans, MDR is mainly mediated by P-glycoprotein (P-gp), a product of theMDR1 gene, which acts as a transmembrane protein pump and eliminates chemotherapeutic agents from the cells. Expression of P-gp was immunohistochemically studied by using two monoclonal antibodies, JSB-1 and C-219, on paraffin-embedded sections from 55 patients with soft-tissue sarcoma. The histological diagnosis of tumors was malignant fibrous histiocytoma in 24 cases, liposarcoma in 9, synovial sarcoma in 7, malignant neurogenic tumors in 6, leiomyosarcoma in 5, others in 4. The histological grade was determined on the basis of criteria previously proposed by us. Out of 55 cases, 34 (62%) were positive for P-gp expression. There was a significant difference in P-gp expression between high-grade (90%) and intermediate and low-grade tumors (46%) (P<0.005). Tumors expressing P-gp had a less favorable prognosis than P-gp-negative tumors in the high- and intermediate-grade tumors. The current study demonstrated that the estimation of P-gp expression could be used to select appropriate therapeutic modalities.Abbreviations MDR multidrug resistance - P-gp P-glyco-protein     

Effect of hyaluronan on the healing of partially ruptured anterior cruciate ligament of rabbits

The midportion of the anterior cruciate ligament (ACL) of rabbits was partially transected, and the effect of hyaluronan (HA) on its healing was determined. A 1% solution of HA (HA group) or physiological phosphate-buffered saline (control group) was administered intraarticularly, at 0.1 ml/kg body weight, once a week from 1 week after the operation. Two, 4, and 6 weeks after the initiation of HA administration, the ACLs were examined grossly, histologically and immunohistochemically. At 2 weeks, the lacerated portions were completely covered with scar-like tissue in both groups. These tissue areas were smaller in the HA group than in the control group. Histologically in the HA group, the regularity of collagen fibers (indicating the maturity of regenerated collagen fibers) had increased compared to findings in the control group, and the number of fibroblastic cells decreased gradually at a significantly faster rate. The number of inflammatory cells and blood vessels decreased gradually in both groups, with these values being lower in the HA group at each time point but not significantly so. Immunohistochemical examination of the repaired tissue revealed strong staining with anti-chondroitin sulfate proteoglycan antibody in the HA group 2 weeks after the first HA administration. The staining gradually became reduced, with the rate of reduction being faster in the HA group than in the control group. The stimulation of chondroitin sulfate proteoglycan production and the faster reduction of it in the HA group suggests that HA facilitated tissue repair and inhibited the formation of scar tissue.     

Effect of magnetic field on pineal gland volume and pinealocyte size in the rat

Abstract: Light microscopic observations on the superficial pineal gland of Wistar-King rats were made to examine whether or not pineal volume and pinealocyte size, expressed as nuclear density, at daytime or nighttime are affected by long-term exposure to 50 Hz rotating magnetic field (MF) at 5.0 μT. Determinations of pineal volume and pinealocyte size were repeated twice (April and October) during the year. Size of pinealocytes in MF-exposed and sham-exposed rats exhibited, in addition to the difference between peripheral and central regions, regional differences in a proximodistal direction; pinealocytes in the distal and middle-peripheral regions were usually larger than those in the proximal and middle-central regions at daytime or nighttime. In October, distal and proximal pinealocytes showed significant day-night changes in size in sham-exposed rats, but not in MF-exposed animals. The situations in the two groups were almost reversed in April. Significant day-night differences were scarcely found in pinealocyte size in the middle region in the two groups. Throughout the study, pineal volume and pinealocyte size in each region were generally the same between MF-exposed and sham-exposed rats at daytime or nighttime. The results suggest that pinealocytes in the distal and proximal regions, but not those in the middle region, are affected by MF-exposure; day-night differences in sizes of distal and proximal pinealocytes appear in April and disappear in October under the influence of MF. MF may exert an effect on mechanisms controlling day-night rhythms of pinealocyte size in the rat.     

An infertile man with a 45X karyotype

We describe an infertile man with normal secondary sexual characteristics and a 45X karyotype. Physical examination showed bilateral soft small testes and the semen contained no sperm. Serum testosterone, estrogen and gonadotropin levels were within normal range. Biopsy of the testis showed germinal aplasia.     

Acute hemodynamic effects of intravenous bolus injection of isosorbide dinitrate in aged patients with congestive heart failure]

In order to investigate whether intravenous bolus injection of isosorbide dinitrate (ISDN) is a safe and efficient therapy in aged patients with congestive heart failure, we studied acute hemodynamic effects in 11 patients. Peak effects on preload were observed after 5 to 10 minutes of bolus injection and unloading effects continued effectively for 60 minutes. At peak effect, pulmonary systolic pressure decreased from 50.2 +/- 2.6 to 36.2 +/- 2.6 mmHg (-28.5%, p less than 0.01) and pulmonary end diastolic pressure decreased from 25.0 +/- 2.2 to 18.5 +/- 2.1 mmHg (-26.0%, p less than 0.01). Mean pulmonary artery wedge pressure decreased from 23.4 +/- 2.2 to 16.0 +/- 2.1 mmHg (-31.6%, p less than 0.01). Mean right atrial pressure decreased from 10.5 +/- 1.8 to 7.4 +/- 2.0 mmHg (-29.5%, p less than 0.01). Blood pressure, heart rate, cardiac index, systemic and pulmonary vascular resistance showed no significant changes. Thus, intravenous bolus injection of ISDN showed a potent vasodilator effects on preload, and may be a safe and useful treatment for aged patients with acute congestive heart failure.     

A case of humidifier lung associated with BHL]

We encountered a rare case of hypersensitivity pneumonitis associated with bilateral hilar lymphadenopathy (BHL). The patient was a 53-year-old male, who developed dry cough and shortness of breath when using a humidifier since 1982. He was admitted to our hospital for further evaluation in 1987. Chest X-ray films showed BHL and ground glass appearance in the bilateral lung fields. Pulmonary function test indicated disturbance of diffusing capacity. Transbronchial lung biopsy revealed interstitial pneumonitis, and lymph node biopsy by mediastinoscopy showed lymphoid sinus histiocytosis without noncaseating granuloma. Provocation test using the humidifier was positive, and the diagnosis of humidifier lung with BHL was made.     

A case of severe summer-type hypersensitivity pneumonitis treated with high-dose administration of steroid]

A 40-year-old man who lived in a wooden house built 30 years ago presented with complaints of fever, dry cough and dyspnea. Chest X-ray findings showed interstitial shadows throughout bilateral lung fields. After admission, high-dose administration of 3000 mg of methylprednisolone was performed because of deterioration of chest X-ray shadows and symptoms. In a week, clinical data and symptoms improved. Findings of BAL fluid on admission revealed a relative increase of lymphocytes, neutrophils and mast cells, and pathological findings of transbronchial lung biopsy revealed non-caseous granulation and alveolitis. Precipitating antibodies and indirect fluorescent antibodies against Trichosporon cutaneum and Cryptococcus neoformans had positive reactions and T. cutaneum was isolated and identified from the patient's house. A diagnosis of summer-type hypersensitivity pneumonitis was made according to the criteria advocated by Ando et al. This seemed to be a rare case of summer-type hypersensitivity pneumonitis prolonged after isolation from his normal living environment, successfully treated by high-dose administration of steroid.     

The effects of oral adsorbent (AST-120) in the experimental model of chronic renal failure--pathophysiological study on renal function, glomerular hypertrophy, mesangial function and glomerular histology

Oral adsorbent (AST-120) reduces blood levels of urea and creatinine in experimental studies. It has also been shown to retard the progression of chronic renal failure in clinical studies. In the present study, the effect of AST-120 was examined in the rat model of subtotal nephrectomy (sNPX). This experimental model of chronic renal failure is characterized by glomerular hyperfunction, glomerular hypertrophy, increased mesangial trapment of macromolecules and subsequent glomerular sclerosis. We report the effect of AST-120 on glomerular hyperfunction, glomerular hypertrophy and mesangial trapment of macromolecules in the early stage and glomerular function and histology in the late stage of the rat model of sNPX. From 2 days after sNPX, rats were fed regular rat chow with (AST group: AST) or without (control) AST-120. At 2 weeks, iron dextran (ID) was injected intravenously. Three days after the injection, mesangial trapment of ID was largely ameliorated in AST when compared with control (p less than 0.02). The value of mean planar area of glomerulus (PAmean) in AST was significantly lower than that in control (p less than 0.05). At 2 and 9 weeks, the values of GFR and RPF in AST were all statistically higher than those in control. At 9 weeks, whereas average glomerular sclerosis index (SI: 0-4 scale) was 1.07 in control, significantly lower SI (0.57) was noted in AST (p less than 0.05). Thus, AST-120 has effects on glomerular hypertrophy, increased mesangial trapment of macromoleculus and finally the progression of chronic renal failure in the rat model of sNPX. The effects are not through reducing glomerular hyperfunction.(ABSTRACT TRUNCATED AT 250 WORDS)     

HTLV-I seroprevalence in patients with malignancy

Since many malignancies often occur in patients with smoldering type adult T-cell leukemia (ATL) (5 of 18 cases in this report), the relationship between HTLV-I (human T-cell leukemia virus type I) infection, which is closely associated with ATL, with other malignancies in an HTLV-I endemic area was examined. Among the 394 patients with malignancies and who had not had blood cell transfusions, 61 (15.5%) tested positive for HTLV-I antibody. The prevalence was significantly higher in males older than age 40 years and females of all ages compared to age- and sex-matched healthy individuals. The overall seroprevalence (26.1%) in 291 patients with malignancies and who had had blood cell transfusions was higher than that of those who had not had blood transfusions. There was no significant correlation between the site of malignancy and antibody prevalence. These results suggest the possibility that development of malignancy may contribute to expression of latent HTLV-I infection and that HTLV-I infection may contribute to the risk of other malignancies.     

Clinical evaluation of tumor markers in breast cancer patients

During the past 4 years, the performances of various tumor markers such as CA15-3, CEA, ferritin, beta 2-microglobulin and TPA have been evaluated in 78 cases of mammary cancer. The results were categorised according to differences in stages, difference in values from patients with recurrent tumors, the incidence of abnormal values and differences in values before and after surgery. When the incidence of values higher than the cutoff value was determined for each of stage I, II and III + IV, the rates for CEA were 14.3%, 4.9% and 27.8%, respectively, whereas those for TPA were 25.0%, 22.2% and 26.7%, respectively. In addition, for CA15-3, the incidences were 0% in stage I, 5.0% in stage II and 57.1% for combined stages III + IV. The average values for patients with recurrent tumors were 3.2 ng/ml CEA, 194.5 ng/ml ferritin, 316.2 U/l TPA and 81.3 U/ml CA15-3. The rates of abnormal values were 40.0% for CEA, 40.0% for ferritin, 85.7% for TPA and 63.6% for CA15-3. Differences in the values after surgical removal of the tumor were observed with these tumor markers: the CEA value was reduced from 1.6 +/- 1.4 to 1.1 +/- 0.5 (p less than 0.01) and the CA15-3 value from 12.2 +/- 8.4 to 9.3 +/- 4.1 (p less than 0.05), respectively, whereas that for ferritin was conversely increased from 48.9 +/- 48.0 to 74.0 +/- 70.0 (p less than 0.01). However, the values for TPA, despite showing a tendency to decrease, did not show any statistically significant alteration. The fluctuations of these marker levels in patients with recurrent tumors reflects the progress of the disease, with a sudden elevation in values indicating imminent death. The diagnostic significance of these markers is not high, but they are considered to be useful in detecting the progress or condition of a recurrent tumor.