We have established an Adriamycin (ADM)-resistant small cell lung cancer (SCLC) cell line, SBC-3/ADM 100, which shows multifactorial mechanisms of resistance to ADM, such as over-expression of P-glycoprotein, an enhanced detoxifying system and a decrease in topoisomerase II activity. In the present study, we confirmed that SBC-3/ADM 100 showed collateral sensitivity to methotrexate and TNP-351, a new antifolate, though this cell line showed a typical multidrug resistance (MDR) pattern. We also demonstrated a faster uptake and higher accumulation (1.3-fold) of TNP-351 in the SBC-3/ADM 100 cells than those in the parent SBC-3 cells. These results explain one of the mechanisms for collateral sensitivity in the resistant cells. Furthermore, this cell line was found to have no cross-resistance to edatrexate and minimal cross-resistance to trimetrexate, 254-S (cisplatin analog), 5-fluorouacil and 4-hydroperoxyifosfamide. These drugs will have clinical importance in patients with SCLC who were previously treated with an ADM-containing regimen. Thus, antifolates, especially TNP-351 and edatrexate, can be expected to eradicate residual multidrug resistant SCLC cells selected by ADM.

Animals↗

PubMed1997

Spontaneous remission of desquamative interstitial pneumonia.

We report a case of spontaneous remission of desquamative interstitial pneumonia (DIP) in a 50-year-old male. The histological diagnosis of DIP was based on open lung biopsy. A chest X-ray revealed reticulo-nodular shadows in the bilateral lung fields, and the patient had mild dyspnea on exertion. Without treatment, these shadows decreased gradually and disappeared after several months. The patient recovered completely within one year, and recurrence of the disease has not been observed for 4 years. Recently, DIP has rarely been described, and the spontaneous remission of DIP has not been reported since Carrington et al in 1978 (1).

Biopsy↗

PubMed1997

Epidermal cell cultures from involved skin of patients with mammary and extramammary Paget's disease.

In involved epidermis, Paget cells are completely enclosed by the surrounding keratinocytes, which appear to be intact and unaltered. It is possible that the surrounding keratinocytes inhibit Paget cell proliferation. Accordingly, Paget cells might proliferate differently when cultured as an epidermal cell suspension. In this study, primary monolayer cultures of epithelial cells from involved epidermis of patients with mammary and extramammary Paget's disease were carried out to investigate whether Paget cells proliferate in the same manner as other malignant cells. Skin samples were obtained from one patient with mammary Paget's disease, and from 2 patients with extramammary Paget's disease. The epidermis was separated from the dermis with dispase, and epidermal cell suspensions were obtained with ethylenediamine tetraacetate and trypsin. A commercially available serum-free media, Keratinocyte-SFM, was used. Epithelial monolayers from the involved skin could be maintained for approximately 45 days, while keratinocytes from normal skin were maintained for approximately 35 days. The mechanism for the longer survival of the mixed cell culture of keratinocytes and Paget cells is not known. Permanent cell lines were not developed from these primary cultures. Paget cells could not be distinguished from keratinocytes by phase-contrast microscopy. The proportion of carcinoembryonic antigen (CEA) positive cells in the culture did not increase, but instead decreased. In certain areas of the dish, the CEA positive cells proliferated and accumulated like mushrooms. However, at the periphery of the dish, the Paget cells identified by immunostaining for CEA were dispersed and not clustered. These findings indicate that the influence of keratinocytes on Paget cells also occurs in cultured cells, which may explain why Paget cells survive longer than keratinocytes. In conclusion, the Paget cells in the involved epidermis do not proliferate like other malignant cells.

Aged↗

PubMed1997

Expression of desmogleins in Paget cells of mammary and extramammary Paget's disease.

Sagebiel (1969) electronmicroscopically observed that desmosomes are present between adjacent Paget cells, as well as between Paget cells and adjacent keratinizing epidermal cells. Desmosomes contain the proteins desmoglein (Dsg) and desmocollin as their transmembrane components, and Dsg has three isotypes. Among the three isotypes of Dsg, Dsg1 and Dsg3 are autoantigens for pemphigus foliaceus and pemphigus vulgaris (PV), respectively. We examined the expression of Dsgs in Paget cells of mammary and extramammary Paget's disease. Skin samples were obtained from one patient with mammary Paget's disease, and from 2 with extramammary Paget's disease. One part of the samples was cut into small pieces and epidermal sheets were separated with dispase, then treated with a mixture of EDTA and trypsin. The resulting cell suspensions were cultured in low Ca++ medium, then the cells were incubated in high Ca++ medium. Paget cells identified with anti-epithelial membrane antigen (EMA) antibody were positive for serum from a PV patient which was confirmed to react with both Dsg1 and Dsg3. However, the intensity of fluorescence of Paget cells was weaker than that of EMA-negative keratinocytes. In the cryostat sections, Paget cells identified with anti-EMA antibody showed the same staining pattern as cultured cells in high Ca++ medium. The data presented in this study confirm that Paget cells express Dsgs, and are consistent with the electronmicroscopical data by Sagebiel (1969). However, our data do not support the hypothesis that Paget cells are of keratinocyte origin, because sweat ducts or sweat glands could be positive for sera from PV patients. It is necessary to confirm whether or not sweat ducts or sweat glands express Dsgs, because sera from PV patients exhibit high background in the dermis.

Aged↗

PubMed1997

[Right atrial flap method for repair of partial anomalous pulmonary venous drainage into the high superior vena cava--case report].

We report an alternative method of repairing partial anomalous pulmonary venous return (PAPVR) wherein anomalous veins drain into the high portion of superior vena cava (SVC). A six year old girl, weighing 19 kg underwent cardiac catheterization for cardiomegaly. The study showed sinus venous defect and pulmonary veins anomalously drained from the right upper and middle lobe into the high SVC. Under cardiopulmonary bypass with aortic and bicaval direct cannulation, a 2-cm-wide pedicled flap made from the middle part of the right atrium (RA), was pulled into the SVC. The atrial flap divided the SVC from the ostium of the uppermost pulmonary vein (PV) to the ASD. This posterior tunnel drained anomalous PV blood into the left atrium. Postoperative echocardiogram and magnetic resonance imaging showed adequate space in the SVC and the PV channel. The patient maintained normal sinus rhythm after surgery. The advantage of this method is to minimize the risk of injuring the sinus node or sinus node artery, and to easily reconstruct both the SVC and PV channel without using prosthetic materials, even in patients with small RA.

Child↗

PubMed1997

[Preservation of anal transitional zone in restorative proctocolectomy].

Since 1980, restorative proctocolectomy has been established for surgical therapy to ulcerative colitis. The crucial points of this procedure are mucosectomy of the anorectal mucosa and pouch anal anastomosis. Mucosectomy is often difficult due to long standing acute and chronic inflammation and incomplete microscopically and leakage of pouch anal anastomosis is relatively high probably due to steroid given prior to surgery or direct effect of anorectal mucosal inflammation. Regards to postoperative bowel function, nocternal soiling is frequently recognized in the patients who received this operation. To overcome these technical and functional disadvantages, anal transitional zone preservation without mucosectomy and stapled anastomosis between pouch and the upper rim of the puborectalis muscle has been performed. Our series of 84 cases with this modified method, anastomotic leakage was significantly decreased and nocternal soiling was completely disappeared within 7 months postoperatively. And one stage procedure became possible unless severe, or high doses of steroid given prior to surgery. Only one case of mild dysplasia was experienced in the remaining rectal mucosa which was disappeared at the next examination. Medical treatment to the remaining lesion was not necessary in the most of cases. Anal canal preservation is superior to mucosectomy in the points of bowel function and minimizing postoperative complications.

Anal Canal↗

PubMed1997

[Juvenile onset of idiopathic interstitial pneumonia].

A 22-year-old first man came to our hospital because of dyspnea on exertion in February 1993, and was admitted in September 1994 because of progression of dyspnea. A chest roentgenogram showed diffuse ground-glass-opacities in the middle and lower lung fields, and an elevated diaphragm. Pulmonary-function testing revealed a low %VC and a low diffusing capacity. Examination of a specimen obtained by thoracoscopic lung biopsy revealed usual interstitial pneumonia. Immunohistochemical examinations showed the expression of intercellular adhesion molecule-1 on vascular endothelial cells and on alveolar epithelial cells. Dust inhalation and collagen vascular disease were ruled out and the diagnosis was idiopathic interstitial pneumonia. This condition develops only rarely in patients under 60 years old.

Adult↗

PubMed1997

[Repair of D-transposition of the great arteries associated with double aortic arch].

We report a case of D-transposition of the great arteries associated with double aortic arch. An aortic root angiogram revealed that the left-sided aortic arch was anterior and smaller than the right one and the descending thoracic aorta located on the left side of the spine. Balloon atrial septostomy was performed at one day of age. The patient underwent a simultaneous arterial switch procedure and division of the vascular ring at the isthmus of the left aortic arch through a median sternotomy incision at the age of 16 days. There was persistent postoperative difficulty in weaning the patient from the ventilator. Magnetic resonance images showed re-formation of pseudovascular ring by the connective tissue grown around the divided arch. At the age of 23 days, resection of the remnant of left aortic arch including the left subclavian artery and the diverticulum concomitant with vascular suspension procedure was performed through a left lateral thoracotomy. The patient was subsequently extubated without difficulty and was discharged from the hospital. It is though that a vascular suspension procedure and resection of the subclavian artery are necessary to avoid respiratory obstruction when the great arteries are in an anteroposterior position and Lecompte procedure is performed.

Aorta, Thoracic↗

PubMed1997

[A successful Konno's operation for subaortic stenosis progressed after total correction of partial atrioventricular septal defect associated with polysplenia].

Konno's operation was successfully performed on a small infant, weighing 3.8 kg. She underwent pulmonary artery banding on the 29th day of life under the diagnosis of partial atrioventricular septal defect with a small left ventricle, associated with polysplenia. Intracardiac repair was subsequently performed on the 45th day of life, which included atrial partition and mitral valvuloplasty. Eleven months after the second operation, wedge resection on the narrow subaortic fibrous lesion was done concomitant with mitral revalvuloplasty. However, repeated echocardiac study disclosed progression of subaortic stenosis. Cardiac catheterization performed at 2 years of age showed the pressure gradinet of 90 mmHg between the aorta and the LV. The aortic annulus and the subaortic lesion measured 10 mm and 4 mm in diameter respectively. Severe subaortic stenosis was created by protrusion of abnormal mitral tissue to the LV outflow, in addition by secondary circumferential fibrous tissue growth and hypertrophy of the ventricular septum. Konno's operation using on 18A Carbomedics valve was chosen for the certain relief of the subaortic stenosis. Although the operation required extensive ventriculotomy and septostomy because of the small aortic annulus, the postoperative course was uneventful. Two months after the operation echocardiography showed good LV function and low RV pressure of about 40 mmHg.

Aortic Valve Stenosis↗

PubMed1997

[An experience of the modified Norwood's operation for hypoplastic left heart syndrome with aberrant origin of right subclavian artery and persistent left superior vena cava--the procedure without total circulatory arrest and cardiac arrest].

We reported a successful case of the modified Norwood operation for a 21-day-old neonate with hypoplastic left heart syndrome (MS and AS) associated with an aberrant right subclavian artery and a persistent left superior vena cava. The modified Norwood operation was performed without total circulatory arrest and Cardiac arrest. A 4 mm Gore-Tex graft, which was anastomosed between the right carotid artery and the right pulmonary artery for systemic-pulmonary shunt, was used for cerebral perfusion during aortic arch reconstruction. Coronary perfusion was performed with a small cannula placed on the relatively large ascending aorta during anastomosis between the main pulmonary artery and the ascending aorta. Equine pericardial patch was used for aortic arch reconstruction and the ascending aorta was directly anastomosed to a part of the main PA. Postoperative course was uneventful and postoperative MRI revealed no stenosis of the aortic arch and the pulmonary artery.

Aorta, Thoracic↗

PubMed1997

Acute hemorrhagic gastritis associated with acetazolamide intoxication in a patient with chronic renal failure.

Acetazolamide (Diamox) is a carbonic anhydrase inhibitor commonly used in patients with glaucoma in order to reduce intraocular pressure. Acetazolamide (AZ) is mostly excreted in the urine, therefore, the blood levels of AZ often tend to increase in patients with chronic renal failure. We experienced a case of chronic renal failure in a patient suffering from acute hemorrhagic gastritis associated with AZ intoxication. A 66-year-old female with chronic renal failure was referred to our hospital because of drowsiness and an acute deterioration of renal function. She had been treated with AZ, 500 mg per every day for eleven days for the treatment of glaucoma. Laboratory studies showed leukocyturia, thrombocytopenia, severe anemia, and tarry stools. The serum concentration of AZ was elevated to a maximum of 76.5 mg/ml. She was thus diagnosed as having AZ intoxication. On further examination, acute extensive hemorrhagic gastritis was also found by gastroscopy. Despite of the administration of intensive therapies, she died of disseminated intravascular coagulation (DIC) and septic shock due to bone marrow depression 6 days after admission. It is generally known that excessive blood levels of AZ inhibit not only the gastric juices but also prostaglandin levels and HCO3- excretion in the gastric mucosal barrier. We thus concluded that an excessive dose of AZ had probably destroyed the gastric mucosal barrier or thrombocytopenia due to bone marrow disorder and thus eventually led to the development of hemorrhagic gastritis. As far as we know, this is the first case report of acute hemorrhagic gastritis associated with AZ intoxication. Even though AZ tends to strongly bind to plasma protein and its clearance is generally poor by hemodialysis (HD), in our patient, HD was observed to be rather effective since the clearance of AZ was 45.8 ml/min on HD and 66 ml/min on direct hemoperfusion (DHP). DHP often reduces the number of platelets, also DHP needs a lot of heparin, therefore, we should have performed HD alone instead of DHP. In patients with an impaired renal function, AZ should therefore be administered very carefully in order to avoid an accumulation of the drug. In addition, HD alone should be used to remove any excessive amounts of AZ from the blood.

Acetazolamide↗

PubMed1997

[A patient with bronchial asthma and mucoid impaction who presented with a high concentration of carcinoembryonic antigen in serum].

We encountered a patient with bronchial asthma and mucoid impaction who presented with a high concentration of carcinoembryonic antigen (CEA) in serum. The patient was a 46-year-old woman. One year after resection of a uterine myoma and an ovarian cyst, examination of serum revealed a high concentration of CEA (24.1 ng/ml). Further examination revealed no evidence of malignant disease, but an abnormal shadow was seen on a chest X-ray film, and was thought to be compatible with mucoid impaction. Fiberoptic bronchoscopy revealed mucoid impaction in the right lower-lobe bronchus. The concentration of CEA in bronchoalveolar lavage fluid was also high (6100 ng/ml). Lavage was done five times and the impaction was removed completely. The concentrations of CEA in serum and in bronchoalveolar lavage fluid decreased to 3.4 ng/ml and 621.9 ng/ml, respectively.

Adult↗

PubMed1997

[Usefulness of exercise electro-cardiography in a THP (Total Health Promotion Plan)].

We conducted ergometer exercise electrocardiography (ergometry) on 3,477 subjects in a THP (Total Health Promotion Plan). One hundred cases in which abnormal findings were detected by ergometry were analyzed. In the hundred cases there were 3 patterns: abnormal ST change, 50 cases; abnormal reaction, 22 cases; and extreme increase in blood pressure, 28 cases. Electrocardiograms (ECG) in 78 of these 100 cases indicated no abnormalities. Of the 31 subjects who underwent further examinations, in 18 cases abnormal findings were detected, and further observation or treatment was necessary. They were over two thirds of the 26 cases requiring observation or treatment on further examination. In other words, exercise electrocardiography revealed more than 3 times as many problem cases as electrocardiography only. One hundred and four cases were analyzed, and among them abnormal findings on ECG made further examination or treatment necessary. Of 68 subjects with an abnormal ECG and who needed to undergo exercise electrocardiography, 51 (75%) had no need to undergo further examinations, because there were no abnormal findings on ergometry in the THP. Of the 104 subjects who underwent ECG examination at rest, 51 no longer needed to waste time, effort and expense on further medical evaluation. Ergometry in a THP serves as a medical check and as a means to decide the strength of exercise before the initiation of exercise training, which is very important in preventing coronary artery disease, rather than in detecting the disease. Ergometry is expensive and it takes a lot of time and labor, but it is necessary in ensuring the safety of exercise training and in prescribing proper exercise. This analysis has shown that ergometry in THP is very useful and cost effective in improving the accuracy of health examinations.

Adult↗