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We performed electron microscopic studies of eight nonfunctioning adrenocortical adenomas (NFA) and nine aldosterone-producing adenomas (APA) obtained from surgical specimens. A comparison of these two types of adenomas was conducted by morphometric analysis of random electron micrographs. The organelles measured included mitochondria (M), smooth-surfaced endoplasmic reticulum (SER), rough-surfaced endoplasmic reticulum (RER), lipid vacuoles (LV), and lysosomes (Ly). The content of steroid hormones, including 17-alpha hydroxyprogesterone (17-OHP), aldosterone (Ald), and other steroid hormones, was measured in adenoma tissue from six NFA and eight APA. The percentages of the areas of the organelles M, SER, and RER per total cell area in the NFA were significantly lower than those in the APA. The average content of Ald in adenoma tissues in APA was markedly higher than that in the NFA, while the mean content of 17-OHP in the NFA was significantly higher than that in APA. In conclusion, NFA are morphometrically characterized by a reduction in organelles such as M, SER, and RER, compared with findings in APA. From the quantitative analysis of steroid hormones, it was suggested that NFA produce more precursor substances with less hormone activity than APA and that steroidgenesis in NFA is shifted to a glucocorticoid pathway, as indicated by the elevated 17-OHP concentration.

A 42-year-old woman had been given a diagnosis of malignant lymphoma, follicular, small cleaved cell. She had undergone chemotherapy including etoposide (1,500 mg/total) and was in her second complete remission. Four years and 4 months later, refractory anemia with excess of blasts (RAEB) with dup(11) (q21q23) x 2 developed in the patient and progressed to acute myeloid leukemia (AML-M5b). Despite regression of the AML to RAEB, a clone with the additional abnormality of del(20) (q11q13.1) appeared and transformed the RAEB into AML-M6. Rearrangement of the MLL gene was observed, and FISH analysis demonstrated that the signal sequences from the gene's 5' and 3'-terminal regions had detached. RT-PCR techniques detected a tandem duplication of MLL gene exons 2 through 8. This was considered to be one of the mechanisms behind the formation of the 11q23 abnormality observed in this patient.

Peripheral T cell neoplasms originating from gamma/delta T cells are rarely reported, despite the development of hepatosplenic lymphoma from gamma/delta T cells. We report a case of multiple generated gamma/delta T cell lymphomas presenting in the subcutaneous tissue and small intestine in a patient with accompanying capillary leak syndrome. The patient, a 43-year-old male presented with remarkable systemic edema, pleural effusion, and ascites. Widespread tumors were evident in the subcutaneous tissue and in the small intestine. A biopsy revealed anaplastic large cell lymphoma in these lesions. Phenotypic examination showed that the neoplastic cells were positive for the surface markers CD3 and TCR delta, but negative for CD4, CD8 and TCR beta. Genomic analysis revealed a clonal rearrangement of the TCR genes encoding the gamma, delta, and beta chains. A polymerase chain reaction analysis of the gene encoding the TCR delta chain showed that the rearrangement occurred between V delta 3 and J delta 1, suggesting that neoplastic cells were generated in the early stages of T cell differentiation.

A 32-year-old female was admitted due to splenomegaly and leukocytosis in September, 1993. The leukocyte count was 26,900/microliter with 29% monocytes (7,800/microliter). A diagnosis of the chronic phase of chronic myelomonocytic leukemia was made. On November 19, 1993, splenic arterial embolization was performed. After the embolization, the leukocyte count rapidly increased, and acute respiratory failure developed. The respiratory condition was improved by methylprednisolone (m-PRED) pulse therapy. Subsequently, the effectiveness of chemotherapy gradually decreased, and there was an increase in the leukocyte count. Respiratory failure developed again but was successfully treated with m-PRED pulse therapy in addition to aclarubicin. On July 4, 1995, splenectomy was performed. The leukocyte count rapidly increased, and acute respiratory failure again developed. She did not respond to m-PRED pulse therapy, but the respiratory condition was markedly improved by leukoplasmapheresis. The respiratory failure in this patient may be associated with capillary leak syndrome due to neutrophilia. In addition, stasis of increased monocytes in the pulmonary capillaries and their infiltration into the pulmonary parenchyma and alveoli was thought to have occurred.

We examined a patient with anaplastic large-cell lymphoma (Ki-1 lymphoma) showing eosinophilic invasion of the tumor tissues. The number of eosinophils in the peripheral blood changed as a function of the stage of the disease. The IL-5 gene was expressed in the tumor tissues, suggesting that the eosinophilic invasion and eosinophilia were caused by IL-5 derived from the lymphoma cells.

We studied the relationship between clinical stage and tumor infiltrating lymphocytes (TIL) in 26 cases of renal cell carcinoma. In 10 patients, interferon-gamma (IFN-gamma) was administered preoperatively (administration group); 5 patients had low stage (Robsonor = I), and the remaining 5 patients had high stage (Robsonor = II) tumors. The other 16 patients underwent nephrectomy alone without preoperative IFN administration (control group); 11 patients had low stage, and the remaining 5 patients had high stage tumors. Immunohistochemical studies of tumor infiltrating lymphocytes in renal cell carcinoma showed a significantly high incidence of CD3, CD8, CD11b and ICAM-1 in the administration group, while CD4, LFA-1 and Ber-MAC3 were increased without significance (p0.05). Concerning clinical stage (Robson), a significant increase in CD3, CD8, CD11b and ICAM-1 was observed in the patients with high-stage tumors in the administration group compared to those in the control group (p0.05). This suggested that TIL could be changed by preoperative administration of IFN-gamma.

Immunological effect of recombinant interferon gamma (IFN-gamma) was studied in 18 cases of renal cell carcinoma. Sixteen of them were administered IFN-gamma as post-operative adjuvant therapy. Two of them were administered IFN-gamma for metastatic renal cell carcinoma. All of them were followed for at least 1 year. We divided the patients into two groups. One group subcutaneously received IFN-gamma every other day for 16 days, then 4 weeks later every week for one year (group A), and the other group, received alternate subcutaneous IFN-gamma every other day for 16 days and every week for 4 weeks (group B). For immunological testing, peripheral blood lymphocytes were obtained before treatment on day 1, 2 weeks later, 6 months later and 12 months later. The cells were tested for natural killer activity (NK), antibody dependent cellular cytotoxicity (ADCC), positive lymphocytes of CD3, CD4, CD8 and CD11b. Both ADCC and NK activity were increased after therapy, especially in group B. CD3, CD4 and CD8 positive lymphocytes were increased by means of IFN-gamma. On the other hand, CD11b-positive lymphocytes could not be elicited in group B. Tumor regression was observed in 2 cases of metastatic renal cell carcinomas. When clinical responses were observed, both ADCC and NK were elicited as compared with the pretreatment values. Our findings indicated that ADCC and NK could be elicited in group B.

PDGF is a glycoprotein composed of A and B chains, and induced the expression not only in platelets but also in many types of cells. By stimulation inducing cell proliferation, transcription of the A chain is activated, resulting in an increase in mRNA. By stimulation inducing cell differentiation, the A chain is activated at the post-transcriptional level, and the B chain at the transcriptional level, resulting in an increase in both mRNA. The 5' region of the A chain shows a mosaic pattern of positive and negative regulatory elements, suggesting complicated regulation. Also the fragments of the first intron are bond by 110Kd and 90Kd nuclear proteins and regulate the A chain expression. Mechanisms of regulation of the A and B chain gene expression differ markedly. The role of PDGF was then investigated on the mechanism of myelofibrosis frequently observed in myeloproliferative disorders (MPD). In the chronic phase of MPD PDGF was suggested to be leaked or released from megakaryocytes. In the accelerated and blast phase of CML with fibrosis, PDGF-AB or PDGF-BB was found to be secreated from myeloid blasts. These results suggest the importance of PDGF in the pathogenesis of myelofibrosis associated with MPD.

We encountered a patient with anaplastic large cell lymphoma (Ki-1 lymphoma) that originated in the stomach and showed histiocytic lymphoma-like morphology. CD43 antigen was positive, and rearrangement of TCR-beta gene was observed. The lymphoma was the T-cell type. Though no atypical lymphocytes or histological images specific to adult T-cell leukemia were observed, clonal integration of HTLV-1 proviral DNA was noted. Viruses such as HTLV-1 appear to be involved in the development of some anaplastic large cell lymphomas.

Transrectal linear ultrasonography was performed on 59 male patients with dysuria, and voiding movement of the posterior urethra was observed with a videomonitor. Uroflowmetry was performed simultaneously, and the results were compared with those obtained in a previous study. On the image synchronized with maximum flow rate, the diameter of the bladder neck, and the center of the prostatic urethra were measured as parameters and the correlation with maximum flow rate, average flow rate, and residual urine rate, was examined. The forward movement of the ventral side of the posterior urethra was found to play a more important role in the opening of the posterior urethra, than the opening of the bladder neck, and the width of the prostatic urethra to play a more important role in the efficiency of urination than the width of the bladder neck.

Eight cases with Ph1 positive acute leukemia (7 of acute lymphocytic leukemia: ALL, and one of acute myelocytic leukemia: AML) were studied molecular biologically to identify location of breakpoints on BCR gene in each patient. Six of the 8 patients (5 of ALL and 1 of AML) had rearrangements at bcr (M-BCR) region. Their locations of the breakpoint in M-BCR were similar to those of 59 chronic myelocytic leukemia patients. One of the remaining two patients had gene rearrangements at m-BCR-1 region in BCR intron 1, and the last patient did not have gene rearrangements at any site of m-BCR-1 and IgL C lambda region. Two cases had gene deletion at either 3' or 5' side of the bcr. A patient with bcr rearrangement was also analyzed by PCR method with reverse transcriptase (RT-PCR) and had simultaneous expressions of bcr3-abl and bcr2-abl chimeric mRNAs. These results indicate that Ph1 positive acute leukemia have heterogeneous characteristics in terms of the molecular biology. The molecular analysis will help for classifying the leukemic types and for elucidating the pathogenesis in Ph1 positive acute leukemia.

The relationship between immunophenotype, histopathology and clinical stage in influencing prognosis was evaluated in 99 cases of non-Hodgkin's lymphoma (NHL). All cases were histopathologically classified according to the system of the international conference on working formulation (WF), immunologically analysed by flow cytometry with a panel of monoclonal antibodies and clinically staged by the Ann Arbor scheme. Eighty eight percent of T- and 87.7% of B-phenotype NHLs respectively received combination chemotherapies with or without radiotherapy. Early stages I and II showed higher response rates (86% for T- and B-NHL) compared to the advanced ones III and IV (58% for T-NHL and 65% for the B-NHLs), p less than 0.05. Higher overall survival rates were observed in low and intermediate grade NHLs, p less than 0.05. The early stages further showed relatively higher survival rates in T- than in B-phenotype of intermediate grade NHL. Low grade NHL had the highest survival rates in both early and advanced stages, whereas the survival rate was the lowest in high grade NHL irrespective of the clinical stages. Immunophenotype, pathological grade and clinical stage jointly displayed varied predictive values in the prognosis of NHL. Since the present prognostic models are based on histological and staging criteria only, the results suggest that, phenotype should be included in the classification systems or prognostic models for the NHLs, thus facilitating the establishment of effective lineage specific therapies.

E-643, a newly developed alpha 1-adrenergic blocker with a postsynaptic action, was tried on 17 subjects, 10 patients with neurogenic bladder and 7 patients with lower urethral obstruction. The results of treatment were excellent in 5, good in 7, and poor in 5 of them, the rate of effectiveness therefore being 70.6%. The inhibitory effect of E-643 on the contractility of the detrusor was no stronger than that of other alpha-blockers. The rate of effectiveness for neurogenic bladders was as high as 80% whereas that for lower urethral obstruction was much lower: 57%. Concerning benign prostatic hyperplasia (B.P.H.) alone, this agent was markedly beneficial. In the case of B.P.H the urethra pressure in the prostatic urethra tends to drop and urination is facilitated even without a change in maximum urethral closure pressure, which reduces the amount of residual urine, this sequence of events taking place on condition that the contractility of the detrusor is adequate. According to urodynamic criteria, the underlying causes of the so-called bladder neck contracture can be classified into organic and functional obstruction, but it is mistaken to use this term for functional disturbance of the bladder neck. It seems worthwhile to determine the clinical effect of alpha-blockers on functional urethral obstruction. E-643 produced few if any appreciable signs or symptoms of side effects either subjectively or objectively.

The clinical effectiveness of KL 007 (oxybutynin hydrochloride) was studied on patients with urinary disturbance, mostly complaints of urinary frequency, who were suffering from nervous pollakisuria, irritable bladder or neurogenic bladder. Fifty two patients were administered KL 007 three times daily at the dose of 6 mg, 9 mg, or 12 mg per day for one or two weeks. An overall clinical effectiveness of KL 007 was seen in the cases of hypertonic bladder. As to the clinical effectiveness of subjective symptoms, KL 007 improved the symptoms of urinary frequency, urinary incontinence, discomfort upon micturition, urinary urgency and sense of residual urine. Transient side effects were observed in 23 cases (41.4%), and dry mouth was most observed. No severe side effects were noticed.

A near-tetraploid clone was observed at the 5th relapse in a 34 year-old female with acute granulocytic leukemia. She was referred to Hiroshima University Hospital presenting with palpitation in May 1978. On admission she had a WBC count of 2,900/microliters with 31.5% blasts, platelet count of 2.4 x 10(4)/microliters and hemoglobin of 2.8 g/dl. A bone marrow aspirate showed hypercellular with 88.5% blasts. Most of them were weakly positive for peroxidase reaction. Occasional Auer rod and/or fine azurophilic granules were observed. DCMP therapy (daunorubicin, cytosine arabinoside, 6-mercaptopurine, and prednisone) was started and the first complete remission was achieved in August 1978. Afterward, the 5th relapse occurred in August 1986 and several kinds of drugs were given without effects. She died 8 years and 9 months after the diagnosis. Karyotype prior to treatment showed a normal diploidy without tetraploid mitoses. However, cells with near-tetraploid (mode: 91) were observed predominantly on the 5th relapse sample and almost all mitoses were occupied with near-tetraploidy at the terminal stage. Results of serial cytogenetic and hematologic study showed a close correlation between the incidence of near-tetraploid mitoses and that of very large blast cells. The significance of tetraploidy in previously reported 44 cases including our case was discussed.

Adenoid cystic carcinoma is an uncommon tumor, especially in cases of its extension into the cranial cavity. Two cases of this tumor involving Gasserian ganglion were reported. The first case was a 47 year old female who developed paresis of the right side fifth cranial nerve. The plain skull X-ray of the axial view demonstrated enlargement of the right sided foramen ovale. The tumor was removed exploring the middle fossa extradurally, however its extention through the foramen ovale remained behind. A small induration was found at the base of the oral cavity postoperatively, and the biopsy revealed characteristic findings of adenoid cystic carcinoma histologically. Radiation therapy was followed by considerable clinical improvement.

Forty milligrams papaverine HCl was intracavernously injected to 28 patients with erectile dysfunction for diagnosis and treatment in 14 cases in which it was injected a few times. We designed a brief manual method for measurement of penile hardness by artificial erection. Twenty of the patients corresponding to 71.4%, reacted, but only 16 (57.1%) had efficient erection for possibility of coitus. It was useful for the diagnosis of vascular dysfunction with dorsal penile arterial pulse sound examination in impotence. It was useful for the cases of small vascular impediment with preservation of nerve supply after the operation of intrapelvic malignancies, and self injection might be possible, but on the other hand, it had no effect for the patients of advanced age with vascular impediment and diabetes mellitus neuropathy, and with arteriosclerosis.