Decreased expression of c-myc family genes in thymuses from myasthenia gravis patients.

The thymus is a critical organ for the elimination of autoreactive T cells by apoptosis. We studied the expression of apoptosis-associated genes, bcl-xL, bad, caspase-3, and c-myc family genes in myasthenia gravis (MG) thymuses. We observed that the mRNA levels of myc family genes, c-myc and max, were markedly reduced in MG thymuses. These results indicate that c-myc-mediated signaling is abnormal in MG thymuses. The levels of molecules whose expressions are associated with myc, such as STAM, prothymosin-alpha, and NFkappaB, were also analyzed.

Elevated serum soluble CD44 level in sarcoidosis.

Sarcoidosis is a chronic multi-organ granulomatous disease of unknown etiology. Several studies have suggested an involvement of immunologic background in sarcoidosis. The lymphocyte surface marker CD44 is a multifunctional molecule which mediates the adhesion of lymphocytes to the extracellular matrix. Recently, we developed a system to quantitate soluble CD44 (sCD44) which we employed to determine serum and bronchoalveolar lavage fluid (BALF) levels of sCD44 to obtain further insights into immunologic aspects of sarcoidosis. Serum sCD44 levels were measured in 13 consecutive patients with sarcoidosis and 56 normal healthy controls using enzyme-linked immunoabsorbent assay. BALF sCD44 levels were also measured in 11 patients with sarcoidosis and 10 normal healthy controls. In patients with sarcoidosis, the serum sCD44 level was significantly higher than that of normal controls (348.5+/-164.2 ng/ml vs 145.4+/-22.9 ng/ml; p<0.001). Also BALF sCD44 levels tended to be higher in sarcoidosis than in normal controls (23.7+/-13.4 ng/ml vs 18.1+/-8.4 ng/ml), but no statistically significant difference was recognized. We also found that there was a positive correlation between the serum sCD44 and angiotensin converting enzyme (r=0.78). Our data indicate that sCD44 may be related to immunologic background and may be a useful new marker of sarcoidosis.

Acute fracture of the neck of the femur. An assessment of perfusion of the head by dynamic MRI.

We performed dynamic MRI of the femoral head within 48 hours of injury on 22 patients with subcapital fracture of the neck of the femur and on a control group of 20 of whom ten were healthy subjects and ten were patients with an intertrochanteric fracture. Three MRI patterns emerged when the results between the fractured side and the contralateral femoral head were compared. In all of the control group and in those patients who had undisplaced fractures (Garden stages I and II), perfusion of the femoral head was considered to be at the same level as on the unaffected side. In patients with displaced fractures (Garden stages III and IV) almost all the femoral heads on the fractured side were impaired or totally avascular, although some had the same level of perfusion as the unaffected side. We conclude that dynamic MRI, a new non-invasive imaging technique, is useful for evaluating the perfusion of the femoral head.

[A case of systemic lupus erythematosus developed with intestinal perforation].

A case of intestinal perforation associated with SLE is presented. A 54-year-old woman was diagnosed as having SLE twenty-five years ago when she had facial erythema, photosensitivity, oral aphtha, polyarthraliga, leukopenia, positive LE cell and positive antinuclear antibody. She had been treated with prednisolone and admitted to Kushiro City General Hospital because of one month history of fever and anorexia in February 1996. Laboratory findings did not reveal activity of SLE, and a diagnosis of urinary tract infection was made based on the findings of urinalysis. After severe diarrhea, disseminated intravascular coagulation (DIC) developed. A rectal perforation was revealed by endoscopic and radiological examination. An emergency laparotomy revealed necrosis of the rectum and sigmoidostomy was performed. The biopsied specimen of the rectum were diagnosed as gangrene of ischemic colitis histologically. Because of a penetration to the urinary bladder, an ureterocutaneostomy was performed. She died of sepsis and DIC on the 127th day of admission. Only 11 cases of intestinal perforation associated with SLE have been reported in Japan, and the association of vasculitis has been considered. In the present case, the prolonged use of prednisolone might cause the necrotizing ischemic colitis.

[An evaluation of a therapy with antibacterial and antifungal agents infections with hematological disorders].

The primary objective of this study is to confirm the efficacy and safety of combination therapy with antibacterial and antifungal drugs for patients with hematological disorders complicated with infections of unknown causative organisms. The subjects consisted of 55 patients with hematological disorders, 28 males and 27 females, ranging from 1 to 78 years of age, with an average age of 34 years. The breakdown of the patients by disease was: 41 leukemias, 10 malignant lymphomas, 3 myelodysplastic syndromes and an aplastic anemia. All patients were treated with sulbactam/cefoperazone (SBT/CPZ) and aminoglycoside (AG) plus fluconazole (FLCZ) as an empiric therapy. Overall efficacy rate was 54.5% for all the patients: 57.7% for patients with suspected sepsis and 0% for those with pneumonia from which unknown organisms were detected. The efficacy rate was 59.4% for patient who had been previously treated with other antibiotics and 47.8% for those who had not previously been treated. The above results suggested that this combination therapy might be effective for severe infections of unknown causative organisms associated with hematological disorders.

[Adult T-cell leukemia/lymphoma, histologically presenting Ki-1 positive anaplastic large cell lymphoma].

A 48-year-old woman was admitted with neck tumors and cutaneous nodules. On the histological basis of the skin nodule biopsy, a metastatic anaplastic carcinoma was suspected. Immunohistochemical studies showed the presence of Ki-1 antigen, IL-2 receptor antigen, leukocyte common antigen (LCA), CD3 and CD4 on the tumor cells compatible with Ki-1 positive anaplastic large-cell lymphoma. This case was, however, finally diagnosed as adult T cell lymphoma (ATL) of a helper/inducer phenotype. She was born in Kagoshima. The serum anti-ATL associated antigen (ATLA) was positive. Southern blot analysis on the DNA extracted from the skin tumor cells showed a monoclonal integration of HTLV-1 proviral DNA. The results suggested that Ki-1 positive lymphomas may include a subset of ATL with a large-cell histology.

Butyrylcholinesterase-rich neurons in rat brain demonstrated by a sensitive histochemical method.

Butyrylcholinesterase (BChE) is a highly active enzyme in brain, but little is known about its physiological functions. One obstacle has been the lack of a sensitive and specific method for determining its cellular localization. We report here on a histochemical technique that has permitted BChE to be detected in neuronal, glial, and vascular structures. The method, which utilizes butyrylthiocholine iodide as the substrate, is a modification of our previously described method for acetylcholinesterase (AChE) histochemistry. BChE-rich neuronal somata stained much more intensely than capillaries or glia. Prominent neuronal groups were located in the anterodorsal, laterodorsal, anteroventral, reuniens, centrolateral, paratenial, and periventricular thalamic nuclei, the laterodorsal tegmental nucleus, the pedunculopontine tegmental nucleus, and the dorsal motor nucleus of vagus. Several other areas of the forebrain and brainstem showed modest numbers of positive cells. No positive cells were detected in the striatum, hippocampus, and most parts of the hypothalamus, which are regions containing numerous AChE-rich neurons. Although the distribution pattern of BChE-rich neurons differed from that of AChE-rich neurons, some neuronal groups contained both esterases. The results suggest that BChE may play a unique role in neuronal function, particularly since many BChE-rich neurons have not been identified as to neurotransmitter type.

Serial changes of SPECT in periodic synchronous discharges in a case with Creutzfeldt-Jakob disease.

We conducted serial EEG and SPECT studies on one female with Creutzfeldt-Jakob disease (CJD). In an analysis of EEG, a periodic synchronous discharge (PSD) was observed in the middle of the third stage (terminal stage) of Bernoulli's classification. The frequency of PSD was the highest at the beginning of the third stage, followed by a gradual decrease and disappeared at the end of the third stage. In the middle of the third stage, SPECT disclosed blood flow differences between the cerebrum and other regions (the cerebellum and the brainstem), while no such difference was observed by SPECT at the end of the third stage. It was suggested that the appearance of PSD requires the presence of a pathological change in the cerebrum precedent to other regions.

[Study of IgE.IgG4 antibodies on eczema in infants. II. Clinical characteristics of infants with egg white.RAST 4+].

The author made an assessment in his first report, regarding relationship to the degree of skin involvement. As a result, it was suggested that the extent of eczema is a good index for determining the severity of the allergy and also that the severity of the allergy early in the infancy has a good correlation with egg white.specific IgE antibody. Therefore, an assessment had been made this time regarding the clinical characteristics of 32 infants who have strong reactions (egg white.RAST 4+) to egg white. The results were as follows; 1. All the infants with egg white.RAST 4+ had a systemic eczema, and their IgE antibodies showed high values of 445.6 +/- 626.9 IU/ml. 2. There were many cases with positive multiple allergens. Particularly, all the infants with egg white.RAST 1+ - 2+ were negative to rice and wheat, while 7 cases positive RAST score to rice and 9 cases to wheat were seen out of the 32 who showed the RAST 4+ to egg.white early in the infancy (rice; p less than 0.02 and wheat; p less than 0.01). 3. If the growth curves of the group from which egg and milk were completely eliminated are compared with the curves of the healthy infants, the height and head circumference were entirely in the normal range while the weight and Kaup index had a trend of being a little low, though they were within the normal range. 4. Regarding family history of allergies, past histories of atopic dermatitis on the mother's side were observed at a high rate.

[IgE.IgG4 antibody in eczema in infants between 5-7 months of age. I. Relationship to the degree of eczema involvement].

Assessments have been made of serum IgE and IgA value, specific IgE and IgG4 antibody titers to foods, house dust, mite and percent peripheral++ eosinophil count in 191 infants with and without eczema between 5-7 months of age. Eczema patients were divided into 4 groups according to the degree of eczema involvement and laboratory data were compared between these and not eczematous group. The results were as follows; 1) IgE antibody titers were higher as the degree of eczema involvement increased. 2) RAST positive rates to foods increased with the degree of eczema involvement. Positive rate was highest to egg white followed by milk, soybean, wheat and rice. 3) Only 9 cases were RAST-positive to rice or wheat and all of them had IgE antibodies to other allergens tested. 4) A value of 10 IU/ml, which is the lowest measurable value of IgE in infants was considered to be a little too high to speculate allergy to some foods. 5) Specific IgG4 antibodies were positive only to milk. 6) All the 18 cases with positive milk-specific IgG4 antibody were all negative in milk-specific IgE antibody, and conversely all the 14 cases with positive milk-specific IgE antibody were negative in milk-specific IgG4 antibody. From these results, it was concluded that food allergy is related to the degree of eczema involvement in infants between 5-7 months of age.

[Adult T cell leukemia/lymphoma with hyperprolactinemia: successful treatment by OK432 and PSK].

A 48-year-old woman was admitted in September 1987, because of lumbago and galactorrhea. Peripheral blood analysis showed neutrophilia and eosinophilia without abnormal lymphocytes. The antibody to adult T-cell leukemia (ATL) virus-associated antigen was detected and a hyperprolactinemia was observed. The blastogenic responses to PHA, ConA and PWM were lowered. Brain CT and MRI scannings showed no abnormalities in the hypophysis and hypothalamus, but abdomen CT revealed markedly enlarged abdominal lymph nodes. Two months after the administration of OK432 and PSK, the lymph node swellings disappeared and the responses to PHA, ConA and PWM were normalized, but hyperprolactinemia and galactorrhea persisted. After four months of the remission period, the patient developed lymph node swellings again, and was diagnosed from the biopsy specimen of the retroperitoneal lymph node as having malignant lymphoma of diffuse mixed cell type. Southern blot analysis showed a monoclonal integration of HTLV-I proviral DNA. Despite repeated combination chemotherapies, she died of pneumonia in February 1989. Autopsy revealed marked infiltrations of lymphoma cells in the liver, spleen and lungs, but no abnormality accounting for hyperprolactinemia was detected in the suprasellar regions. This case was of interest in that immunotherapy was effective in achieving a remission and in normalizing immuno-parameters in ATLL.

[An evaluation of combination antibiotic therapy in infections with hematological disorders. Hyogo Cooperative Study Group of Infectious Diseases Complicating Hematological Disorders].

A clinical study was undertaken to determine the effects of combination antibiotic therapy in 104 patients with infections associated with hematological disorders. All patients were treated with sulbactam/cefoperazone (SBT/CPZ) plus an aminoglycoside as an empiric therapy for fever. The overall efficacy rate of the therapy was 63.5%. Efficacy rates were 61.2% and 71.9% when initial neutrophil counts were less than 500/mm3 and over 500/mm3, respectively. No significant difference was found between the cases in which initially used antibiotics were continued (efficacy rate 62.5%) and those in which antibiotics were switched during the course of therapy (65.6%). Antibiotic therapy with SBT/CPZ plus an aminoglycoside provides adequate antibiotic coverage against infections associated with hematological disorders. This combination was highly effective even in the neutropenic periods of febrile patients.

Choline acetyltransferase immunopositive neurons in the lateral septum.

A small cluster of choline acetyltransferase (ChAT)-positive neurons was identified immunohistochemically in rat and monkey brain in the ventral portion of the lateral septal nucleus. These multipolar neurons were smaller and much less intensely staining than the medial septal nucleus ChAT-immunopositive group.

Occurrence of diffuse amyloid deposits in the presubicular parvopyramidal layer in Alzheimer's disease.

Silver staining by a modified Bielschowsky's technique and immunostaining for beta-amyloid protein BAP have revealed the occurrence of diffuse amyloid deposits bilaterally in the presubiculum in each of fourteen Alzheimer's disease cases examined. Observations on serial blocks show these deposits to be localized in the parvopyramidal layer of the presubiculum proper and the transsubiculum. They are also observed in the cellular islands within the molecular layer of the subiculum but not in the parasubiculum. These amyloid deposits are not accompanied by neurofibrillary tangles, neuropil threads, or the aggregated microglial reaction which is characteristically associated with classic senile plaques. Convergence of input from limbic and cortical areas might play a significant role in the formation of these diffuse amyloid deposits.

Distribution of choline acetyltransferase immunopositive structures in the rat brainstem.

The distribution of neurons, fibers and terminal fields in rat brainstem displaying positive immunoreactivity to a polyclonal antiserum to human placental choline acetyltransferase (ChAT) is described. The antiserum was used at the high dilution of 1:10,000 and was coupled with a sensitive detection system using the nickel ammonium sulfate intensification method. In addition to previously described ChAT immunopositive groups of large cells in the cranial motor nuclei, and the parabrachial and reticular complexes, many small or medium size, weakly immunopositive neurons were identified. Some of these appeared in structures in the region of the fourth ventricle, including the area postrema. Others were in structures associated with the superior olivary complex, including the lateral superior olive, and the medioventral, lateroventral and superior periolivary nuclei. Scattered, weakly positive cells were seen in numerous other structures, including the ventral tegmental area of Tsai, central gray, superior colliculus, spinal nucleus of nerve 5, dorsal cochlear nucleus and non-motor regions of the spinal cord. The prominent ascending fiber tract of the laterodorsal tegmental pathway was traceable from the parabrachial area to the subgeniculate region of the thalamus. Prominent terminal fields were seen in a number of brainstem structures, including the superior colliculus, pontine nuclei, anterior pretectal nucleus, interpeduncular nucleus and spinal nucleus of nerve 5. The association of small ChAT positive cells and terminal fields with many sensory structures suggests a significant cholinergic participation in the physiology of sensory function.

[CALLA-positive leukemic multiple myeloma of IgA-kappa type].

A 73-year-old man was admitted into the hospital because of lumbago in October, 1986. Laboratory examination on admission showed anemia, an IgA-kappa Bence Jones proteinemia. The bone marrow picture disclosed a marked involvement by the neoplastic cells, followed by leukemic conversion 2 weeks later. The leukemic cells displayed a lymphoblastoid appearance on light microscopy, but rather compatible with plasma cells on electron microscopy, showing some strands of rough endoplasmic reticulum and a prominent Golgi apparatus in the cytoplasm. The cells expressed a wide spectrum of surface markers, including those of plasma cell (PCA-1, OKT10), B cell (B1, sIg) and CALLA. Reverse hemolytic plaque assay disclosed the immunoglobulin production of monoclonal kappa chain, but a heavy chain production was recognized only in a small proportion of the cells. Under the diagnosis of multiple myeloma, he was treated with vincristine, cyclophosphamide, and prednisolone. But he died of renal failure complicating hypercalcemia after only three months of the admission in accordance with previous reports that CALLA-positive myeloma was associated with poor prognosis. This case may also represent the clinical, morphological and phenotypic diversity in multiple myeloma.

[Clinical evaluation of monotherapy with ceftazidime for severe infections complicating hematological disorders. Hyogo Cooperative Study Group of Infectious Diseases Complicating Hematological Disorders].

Clinical effects of the monotherapy with ceftazidime (CAZ) were evaluated in patients with severe infections associated with febrile granulocytopenia in hematological disorders in 10 institutions. CAZ (4-6g/day) was administered intravenously by drip infusion divided into 2 to 4 doses. 83% of the underlying diseases were hematological malignancies. Infections mainly consisted of documented sepsis (10%), presumed sepsis (60%). Overall efficacy rate was 65%, and that of septic patients was 83.3%. Adverse reactions were minimal, and this study revealed safety of CAZ.