In order to determine the primary site of calmodulin (CaM) interaction on calcineurin (CN), a CaM-dependent protein phosphatase, recombinant forms of the mouse brain alpha-subunit were prepared and expressed in bacteria. A series of ordered deletions in the protein coding region were constructed systematically using ligation of PCR-generated fragments. A total of 12 recombinants, having successive deletions from the amino and carboxyl termini, were analyzed for their ability to interact on Western blots with biotinylated CaM and antibodies against the bovine brain enzyme. In addition, the recombinant peptides were purified by affinity chromatography on CaM-Sepharose and their free-solution interacts assessed using Dansyl-CaM. These studies indicate that a region of 64 amino acids, adjacent to and including the putative CaM-binding site, which was predicted by Kincaid, et al, was necessary and sufficient for CaM interaction.

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We studied the immunocytochemical distribution of amyloid β protein precursor (APP) in the nervous systems of the mouse and the rat, and changes with aging and brain damage induced by intraventricular injection of kainic acid in the rat brains. We used three different antisera against synthetic peptides of APP and one monoclonal antibody against APP. On Western blot analysis, both antisera against carboxyl-and amino-terminal regions of APP recognized the same 106-122 KDa proteins from mouse brain. Immunocytochemically, APP immunoreactivity was located in all types of neurons and some glial cells in both the central and peripheral nervous systems. In the brains of normal aged rats, APP accumulated in swollen neurites, most of which were axons. These swollen neurites appeared throughout the central nervous system. In the rat brains injected with kainic acid, APP positive dystrophic neurites appeared around the track of the cannula after 3 h, neurons near the lesion showed increased APP immunoreactivity after 6 h, and reactive astrocytes expressed APP with Kunitz-type protease inhibitor domain in the lesion and ipsilateral hippocampus after 3 days. APP was expressed by neurons and glial cells throughout nervous systems, and these distributions changed with aging and brain damage.

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Transient hypertrophic cardiomyopathy in human infants of diabetic mothers has been reported by various investigators. In order to clarify the pathogenesis of this unique type of myocardial disease, streptozotocin-induced diabetic rats were used in our study.
Obvious asymmetrical septal hypertrophy (ASH), with thickened myocytes and immature intercellular connections, was observed in newborns of diabetic rats. Daily administration of NPH insulin to mother rats did not prevent the development of ASH. However, ASH was no longer seen 4 weeks after the birth. On the other hand, symmetrical cardiac hypertrophy developed when 4 week old rats were treated with NPH insulin for 4 weeks.
Thus, transient ASH developed in infants of experimental diabetic rats. Clearly, this cardiac hypertrophy is not genetically transmitted. The author considers the cardiac hypertrophy in infants of diabetic mothers to possibly be a cardiac manifestation of generalized organomegaly caused by hyperinsulinism and/or catecholamine excess. The asymmetry of hypertrophy in this unique myocardial disease might represent only immaturity of the cardiac architecture.

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We investigated the utility of a depot preparation of the luteinizing hormone-releasing hormone agonist (LH-RHA) in treating patients with prostate cancer, and how to prevent flare up which occur at the first administration of LH-RHA.
One hundred and five patients with previously untreated prostate cancer were treated with the depot preparation of LH-RHA. Tumor response, time to progression and survival were assessed, and the results were comparable to the routine endocrine therapy. Side effects were mild and only 1 patient needed to discontinue the LH-RHA administration. Four patients experienced flare up.
In order to prevent flare up, we investigated the efficacy of short term concomitant use of diethylstilbestrol (DES-P) or chlormadinone acetate (CMA). There were no patients with flare up in either group. However, 1 of the 4 patients in CMA group showed increased prostatic acid phosphatase after the administration of LH-RHA. The regimen with DES-P prevented testosterone surge almost completely. It took a shorter time for the mean values of testosterone to decrease to the castration level in the DES-P group. From these observations, we concluded that pretreatment with DES-P could prevent flare up and hasten the appearance of theraputic effects in patients with prostate cancer treated with LH-RHA.

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The effects of activin and FSH on inhibin secretion were studied in rat granulosa cell cultures. Inhibin released into the culture medium was measured by specific inhibin radioimmunoassay system. The minimum effective dose of activin alone was 125ng/ml, and that of FSH was 500ng/ml, respectively. However, when activin was coincubated with 30ng/ml of FSH, even a dose of 15.6ng/ml of activin significantly augmented inhibin secretion. In the presence of 300ng/ml of FSH, activin increased inhibin secretion in a dose dependent manner from 0.49ng/ml to 15.6ng/ml. Thus, concomitant addition of activin and FSH to granulosa cell culture medium acts synergistically on inhibin secretion. Epidermal growth factor (EGF) markedly reduced inhibin secretion stimulated by activin and FSH even in low concentration of 0.49ng/ml. Inhibin secreted in granulosa cell culture medium was biologically active, namely it decreased FSH secretion from rat pituitary cell culture. These data indicate that inhibin secretion is under the direct control of both activin and FSH in granulosa cells, and inhibin in turn regulates FSH secretion from the pituitary.

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Panceraticoduodenectomy is a complex procedure associated with considerable mortality and morbidity. Pancreaticojejunostomy is the main cause of morbidity, and controversy concerning the best type of reconstruction persists. In this report we describe a modified pancraticojejunostomy technique for Billroth I reconstruction. An Fourend-to-side anastomosis of the pancreatic duct and jejunal mucosal layer was performed. Four patients whose pancreatic duct was less than 2 mm in diameter, the duct and the jejunal mucosal layer were anastomosed with a continuous running suture made of Polyglyconate absorbable material. An anastomosis between the pancreas and the jejunal seromuscular layer, using interrupted suture made of a monofilament material, and fibrin glue attachment was performed without complications. This pancreaticojejunostomy technique is reasonable for patients with soft glands and small ducts following pancreaticoduodenectomy.

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For the patient needing palliative treatment, and for the aged patient with non-Hodgkin's lymphoma, prognoses remain poor. This study was designed to investigate the pathological conditions found in non-Hodgkin's lymphoma in the terminal stage, especially those causing death, mainly by using autopsied material. The materials were obtained from 75 patients in whom investigation, histological and immunohistologic chemistry was possible. These patients were selected from among all of the non-Hodgkin's lymphoma patients autopsied during the 10-year period from 1981 to 1990 in the Department of Pathology, Gunma University School of Medicine. The findings were : B-cell lymphoma in 47 patients (63%) and T-cell lymphoma in 28 patients (37%). We did not, however, find a true T-cell leukemia/lymphoma.
The causes of death were : the tumor itself in 38 patients (51%) and causes other than the tumor in 37 patients (49%). The findings from the group whose death was due to some factor other than the tumor itself were : infectious disease in 26 patients, interstitial pneumoniain in 6 patients, bleeding tendencies in 2 patients, myocardial insufficiency due to drugs in 2 patients and undeterminable etiology in 1 patient. The findings from the group whose cause of death was the tumor itself were manifested by many remaining tumor cells which kept their shape relatively intact in all specimens. The detailed findings from this group were as follows : pulmonary insufficiency due to pulmonary infiltration, cardiac insufficiency due to cardiac infiltration, infection and bleeding tendencies due to bone marrow infiltration, bleeding of the digestive system due to infiltration of the digestive system, and infiltration of the meninges. In addition, some patients had complications accompanying tumor infiltration. These complications were : infectious diseases in 15 patients and interstitial pneumonia in 5 patients. The number of patients who showed complications of infectious disease was 44 (59%). The causes of the infectious diseases, in descending order of frequency, were : mycosis, bacteria, viruses, and tubercle bacilli. Also, in some of these non-Hodgkin's lymphoma patients, susceptibility to disease and white blood cell counts did not necessarily correlate with each other. The number of patients who showed complications of interstitial pneumonia was 23 (30%). In the histological-pathological examination we found various stages of lesions, from the acute stage to the chronic stage. Most of these were mixed. The causes of interstitial pneumonia are numerous, but we considered opportunistic infection to have been a major factor in the acute stage of interstitial pneumonia, the etiology of which is difficult to determine.
Our study revealed the following : In the future, it will be important for the non-Hodgkin' s lymphoma patient that we not only develop more effective therapy, but that we also develop supportive therapy to counterat side effects, which can be predicted.

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Allogeneic bone marrow transplantation (BMT) with major ABO blood-group incompatibility is reported. The patient was a 12 year-old-boy with acute myelomonocytic leukemia who underwent allogeneic BMT from an HLA-matched sibling with major ABO blood-group incompatibility. Erythrocyte depletion of marrow cells using the COBE 2991 blood cell processor was carried out. Engraftment was successful with no sign of hemolysis, and confirmed on day 26 after transplantation. He is now being followed with no additional chemotherapy. A technique for rapid isolation of bone marrow mononuclear cells using Ficoll-Conray and the COBE 2991 blood cell processor is described.

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A 54 year old woman was admitted with hypertension and abnormal liver function tests. A small tumor was revealed at the fundus of the gallbladder by ultrasonography. Cholecystectomy, including liver bed resection and lymph node dissection (R 2), was performed because of the possibility of carcinoma.
The solid, globular tumor was present at the fundus of the gallbladder, and on the cut surface of the tumor small Rokitansky Ashoff Sinus (RAS) cysts were observed. Microscopically, hypertrophy and proliferation of the RAS was demonstmated and was associated with hypertrophy of the muscle layer. No malignant invasion could be found, however.
Three types of adenomyomatosis, viz, a generalized (diffuse) type, a segmental (annular) type and a localized (fundal) type have been reported and our case belongs to the localized (fundal) type.
The patient has made satisfactory postoperative progress for the 2 years since the operation and has returned to work.
A case of adenomyomatosis of the gallbladder, with specific histophthological features, is presented and discussed with regard to the literature.

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Acute cardiac tamponade secondary to perforation of the right ventricle during a transient transvenous electrode catheter insertion, occurred in a 79-year-old man. This perforation may have occurred because the apexical tissue of the right ventricle was fragile. Prompt recognition and treatment of this potentially lethal complication of pacemaker electrode catheter insertion are essential.

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An autopsy case of pleural malignant mesothelioma was reported with histopathologically and ultrastructurally. The patient was 51 year-old female. She was admitted to Gunma Cancer Center Hospital because of respiratory disturbance. She died of respiratory failure caused by marked pleural and abdominal effusion and cachechitic change six months after the admission. Autopsy findings showed multiple metastases : lungs, pericardium, mediastinum, diaphragma, abdominal serous menbrane, lymph nodes. Histologically, the tumor was diffuse type malignant mesothelioma of biphagic pattern. Immunohisto-chemistry showed positive reaction for keratin, vimentin, and EMA, but negative for CEA. Ultrastructural findings showed the charcterictics of mesothelial cells. In order to make accurate pathological diagnosis, we should use immunohisto-chimistry and electronmicroscopy.

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