Effects of surgery and chronic disease states on the concentrations and phenotype distribution of α1-acid glycoprotein: studies in patients with breast cancer and patients with chronic inflammatory disease.

OBJECTIVE: Although the concentration of α1-acid glycoprotein (AGP) in serum increases under some conditions, the behavior of the individual genetic variants is not well understood. Therefore, we studied the relative changes in AGP variants pre- and postoperatively in patients with cancer and patients with chronic inflammatory disease states, as well as the distribution of AGP phenotypes in a Japanese population. METHODS: Serum samples were taken before and after surgery from 25 female patients with early breast cancer. Serum samples were also obtained from 134 patients with rheumatoid arthritis (RA) and 33 with systemic lupus erythematosus (SLE), and from 103 healthy subjects. The relative concentrations of the individual genetic variants in the serum samples were determined by isoelectric focusing after desialylation with neuraminidase. RESULTS: The postoperative AGP concentrations in patients with early breast cancer were 2-fold higher than before surgery. The relative concentrations of the F1 and S variants were significantly increased, whereas that of the A variant was not changed significantly. The relative concentrations of all the AGP variants in patients with RA and SLE were significantly higher than those in healthy subjects. The distribution of the AGP phenotypes did not differ significantly among the groups examined in this study. CONCLUSIONS: The F1/S variants of AGP, but not the A variant, were significantly increased after early breast cancer surgery, but all the variants were increased in patients with chronic inflammatory states such as RA and SLE. The distribution of the AGP phenotypes did not differ significantly among the disease groups studied.

Features of retinal arterial macroaneurysms in patients with uveitis.

AIM: To determine the frequency and clinical characteristics of retinal arterial macroaneurysms in patients with uveitis. METHODS: A retrospective review of the clinical, photographic, and angiographic records of 1007 patients with uveitis, examined at the Osaka University Hospital uveitis clinic between January 1995 and April 2002, was performed. All of the records were examined to determine whether macroaneurysms were present, and when present, to determine the laterality, type, location, clinical course, and the presence of associated systemic and ocular diseases. RESULTS: Of the 1007 patients with uveitis, only 14 (1.4%) had macroaneurysms. 12 of these 14 patients had peripheral multifocal chorioretinitis (PMC), and five of these 12 were diagnosed with sarcoidosis and the other seven without sarcoidosis. There was only one case with sarcoidosis without PMC, and the remaining case was uveitis of unknown origin. There were 18 macroaneurysms in all cases and 17 (94.4%) were the exudative type, and the remaining one was the haemorrhagic type. Two patients had been treated for systemic hypertension but the others had no signs of systemic hypertension or cardiovascular disease. CONCLUSIONS: Macroaneurysms are not characteristically found in patients with uveitis, but the majority are found in patients with PMC. The majority of the macroaneurysms were the exudative type, and the conclusion is that patients with PMC should be carefully examined for exudative macroaneurysms.

[Indication and effectiveness of endoscopic percutaneous gastrostomy as a route of parenteral alimentation for the home care patient].

We are managing 8 home care patients who have a gastrostomy made using an endoscopic percutaneous technique as a route of parenteral alimentation. Based on our experience, the preconditions for an endoscopic percutaneous gastrostomy as a route of parenteral alimentation are 1. normal gastrointestinal function, 2. difficulty in swallowing, 3. possibility that the caregiver can manage the gastrostomy. When we performed an endoscopic percutaneous gastrostomy as a route of parenteral alimentation for 8 home care patients, we obtained the several advantages mentioned below. 1. Swallowing pneumonia was prevented. 2. Adequate amount of alimental liquid could be infused. 3. Patient could take a bath or shower with the gastrostomy, and good QOL was realized. 4. The home care patient with the gastrostomy could have a satisfactorily long life.

Inhibitory effect of retinoid on esophageal carcinogenesis in rats induced by N-nitroso-N-methylbutylamine in relation to cellular retinoic acid-binding protein.

The inhibitory effect of a synthetic retinoid, ethyl alltrans-9-(4-methoxy-2, 3, 6-trimethyl-phenyl)-3, 7-dimethyl-2, 4, 6, 8-nonatetraenoate (Tigason), on esophageal carcinogenesis in F344 rats induced by N-nitroso-N-methylbutylamine (NMBA) was evaluated. The animals were given NMBA daily in their drinking water for 21 weeks at a concentration of 15 mg per liter ad libitum starting at 8 weeks of age. One week before the beginning of NMBA treatment, the rats were divided randomly into Tigason-fed and -unfed groups. Thirty-five rats were fed a diet supplemented with Tigason at a concentration of 30 mg per kg of diet, and 80 rats were given a basal diet alone. In NMBA-treated rats, multiple papillomas were seen 11 weeks after NMBA treatment and squamous cell carcinoma developed 12 weeks after NMBA; the tumors increased in number thereafter, and the numbers of papillomas and carcinomas were the same at 17 and 21 weeks after NMBA. At 21 weeks after NMBA treatment, the number of papillomas was similar, regardless of the dietary Tigason supplement, however, the number of esophageal squamous cell carcinomas was significantly lower in the Tigason-fed rats than in -unfed animals (p < 0.025). In normal esophageal tissues, a small amount of cellular retinoic acid-binding protein (cRABP) was detected throughout the experimental period, while during carcinogenesis, the levels of cRABP increased continuously until 16 weeks after NMBA; the cRABP level was higher in papillomas than in squamous cell carcinomas. As Tigason specificially blocked the progression of papillomas to carcinomas, it may be a promising candidate chemopreventive agent in esophageal carcinogenesis.

[Combined lung resection for advanced thoracic esophageal carcinoma].

We performed lung resection together with esophagectomy in 2 patients with advanced thoracic esophageal cancer. Both patients survived more than 2 years with no evidence of disease. The first case was a 60-year-old man who had a cancer lesion in middle of the intra-thoracic esophagus (Im) and the right lower lobe of the lung was involved. In March 1989, right lower lobectomy of the lung was performed with esophagectomy. Pathologic examination showed well differentiated squamous cell carcinoma invading the lung parenchyma and intrapulmonary lymph node. Postoperatively, 44 Gy of radiation and Peplomycin cancer chemotherapy was performed. The patient survived 51 months after surgery and died of chronic myelogenous leukemia. The second case was a 60-year-old man who underwent thoracic esophagectomy with resection of the involved pericardium and right lung in February 1992. Pathologic examination showed N3 lymph node metastasis. Postoperatively, the patient received 48 Gy of radiation and was free from cancer after 30 months. In conclusion, better surgical results are expected in cases of advanced thoracic esophageal cancer with lung involvement which can be completely resected en bloc with the primary tumor even in a3 cases than in those with aortic or tracheobronchial involvement.

[A case of metachronous primary cancer of the lung, rectum and trachea].

We reported a metachronous primary triple cancer of lung, rectum and trachea. Patient was a 64-year-old male, who was admitted with a episode of bloody sputum. A chest X-ray and rentogen tomogram showed a irregularity and narrowing of the upper trachea. Transbronchoscopic biopsy specimen showed squamous cell carcinoma. December '92, trachea was resected in the length of five cartilages and end-to-end anastomosis was performed. Microscopic examination demonstrated a moderately differentiated squamous cell carcinoma with mediastinal lymph node metastasis. Therefore, he received a course of 30 Gy of radiation to the upper mediastinum after surgery. Three years before the tracheal resection, he had undergone left pneumonectomy for moderately differentiated squamous cell carcinoma of the lung. Nineteen months after the pulmonary resection, he had undergone low anterior resection of the colon for the rectum carcinoma.

[Physicochemical properties of sputum from patients with immotile cilia syndrome].

Sputum samples were collected from 15 immotile cilia syndrome (ICS) cases, 12 diffuse panbronchiolitis (DPB) cases, and 11 bronchiectasis without ICS (BE) cases, during stable clinical state, to clarify the physicochemical properties of sputum from patients with ICS and to compare them with the properties of sputum from patients with DPB and BE. We measured sputum rheological properties and concentrations of several biochemical components. In ICS, spinnability was higher than that in DPB. No significant difference was seen between ICS and the other cases regarding other rheological properties. Albumin was lower, but fucose, sialic acid, and IgA were higher in ICS than in DPB. Although no significant difference was seen between ICS and BE, the sialic acid/albumin ratio was higher and the sialic acid/fucose ratio was lower in ICS than in BE. These results revealed that sputum from ICS cases was characterized by an absolutely or relatively increased mucus component with high spinnability and by a decreased extravascular transudate component. In view of these rheological properties, sputum from ICS cases was not always indicated to be associated with efficiency in cough clearance. The results suggested that chronic airway inflammation in ICS is not such a serious problem compared with DPB and BE.

Transplant arteriosclerosis in a rat aortic model.

Transplant arteriosclerosis (TA) has emerged as an obstacle to the long-term survival of transplanted organs, especially cardiac transplants. The animal models that have been used to study TA have not been fully characterized with regard to features such as the time course of cell proliferation and the sequence of cell types arriving in the developing intimal lesion. We present a model of TA based on a transplanted segment of abdominal aorta that helps address these questions. Two strains of rats (PVG x DA) underwent orthotopic aortic transplantation without immunosuppression and were killed at 14, 20, 40, and 60 days after transplantation. The within-strain control group displayed minimal evidence of cellular rejection with minimal to absent intimal lesions. In contrast, the allograft group showed a linearly increasing intimal lesion, up through 60 days after transplantation. The mechanism of intimal thickening was by an increase in cell number at the earlier time points with the later deposition of extracellular matrix. The early intimal lesion consisted mostly of mononuclear inflammatory cells (45%) with gradually increasing presence of smooth muscle cells (SMC) in the intima between 20 and 60 days. Conversely, the media showed gradual infiltration by macrophage-type cells with virtual loss of all SMC from the media by 40 days. The proliferative index showed a peak of 6% and 8% at 20 days in both the intima and media, respectively, and was preceded by the presence of macrophages. In fact, most of the proliferating cells at the earlier time points were either monocytes/macrophages, or were immediately adjacent to monocyte-/macrophage-rich regions. This straight artery segment model of transplant arteriosclerosis provides an easily quantifiable system in which the effects of different interventions (e.g., immunosuppressive regimens) can be tested.

[Clinical epidemiology of bronchial asthma in children report. No. III. Comparison of prevalence of asthma with 1982 and 1990 and environmental factors].

UNLABELLED: In 1982, our group carried out a survey by the questionnaires and on the site medical check-ups to observe and occurrence of asthma and other allergic symptoms in elementary and junior high school children in Izu Ohshima island. Same procedure was repeated in 1990 for 1145 children of the same age group to see any data fluctuation. The occurrence of allergic symptoms with relation to living conditions was also researched. RESULT: 114 students (11.0%) had either suffered from asthma in the past, or were still currently exhibiting symptoms, this marked a 7.5% rise (108 students) over the 1982 research data. However, patients in need of current treatment numbered 48 (4.5%), which was similar to the 1982 data of 82 (4.3%). For other allergic symptoms, rhinitis showed a marked increase over the 1982 data. The relation between living conditions and asthma was analyzed by Multiple Factor Analysis Quantification Theory. RESULT: 1) Family history of allergy, 2) Selection of food products upon starting solids during infancy, 3) Infection of lower bronchus during infancy all seemed to have had much influence on the occurrence of asthma.

Proliferating cell nuclear antigen. A marker for cell proliferation in autopsy tissues.

Antibodies to the proliferating cell nuclear antigen allow identification of proliferating cells in fresh tissue specimens using routine immunocytochemical methods. However, the use of such proliferation markers has not been verified for autopsy-derived tissue specimens, in which there is often a significant delay between the time of death and tissue specimen fixation. To assess the reliability of anti-proliferating cell nuclear antigen antibodies to identify proliferating cells in autopsy tissue specimens, an autopsy simulation was performed using fresh monkey and rat tissue specimens. These tissue specimens were kept at room temperature for predetermined numbers of hours before fixation. The proliferation specific staining was most reliable for tissue specimens obtained within 6 hours of death. There was reliable staining of proliferating regions up to 12 hours, although sensitivity was decreased. The only exception was skin, which was able to withstand much longer periods. Quantitative data from monkey spleen white-pulp regions showed 63% of the cells to stain for proliferating cell nuclear antigen when fixed immediately; this decreased to 29% of the cells after 12 hours and only 19% by 18 hours of postmortem simulation. Representative tissue specimens obtained from human autopsy material revealed similar postmortem staining patterns. Rapid procurement and fixation of tissue specimens and the use of control tissue specimens derived from the same autopsy material (eg, lymph node tissue) are recommended. These studies do suggest that anti-proliferating cell nuclear antigen antibodies can be used to identify proliferating cells in human autopsy tissue specimens obtained within approximately 12 hours of death, with some compromise in overall sensitivity.

Structure-activity relationship of yohimbine and its related analogs in blocking alpha-1 and alpha-2 adrenoceptors: a comparative study of cardiovascular activities.

We investigated the selectivities and structure requirements for alpha-1 and alpha-2 adrenoceptor blocking activities of yohimbine (YO) and its 12 related analogs, such as beta-yohimbine (beta-YO), dihydrocorynantheine (DHC) and (-)indoloquinolizidine ((-)IQ). The affinity of YO analogs to alpha-adrenoceptor was assessed by measuring their blockade of pressor responses to epinephrine in pithed rats. Among YO structure groups, the potency order was YO greater than DHC = beta-YO greater than geissoschizine methylether greater than 14 beta-hydroxy YO greater than 14 beta-benzoyloxy YO (inactive). (-)IQ was slightly less potent than YO, but much stronger than (+)IQ. Among (+/-)IQ structure groups, the potency order was (+/-)IQ greater than (+/-)1,12b-trans-1-hydroxy IQ much greater than (+/-)1,12b-cis-1-hydroxy IQ (inactive). (+/-)Borrerine was active, but (+/-)desmethylborrerine was inactive. The alpha-1 blocking activities of the four compounds YO, beta-YO, DHC and (-)IQ, were assessed in experiments of pressor responses to methoxamine in pithed rats and contractile responses to methoxamine in the rat vas deferens. The potency order was (-)IQ greater than YO greater than DHC greater than beta-YO. Furthermore, the alpha-2 blocking activities of the four analogs were assessed in experiments of pressor responses to clonidine and inhibition of electrically driven cardioacceleration by clonidine, in pithed rats. The potency order was YO greater than beta-YO greater than (-)IQ greater than DHC. Based on the potency ratio between alpha-1 and alpha-2 blocking activities, DHC or YO was most selective for alpha-1 or alpha-2 subtype, respectively, among the four YO analogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Monoclonal antibodies for detection of occult carcinoma cells in bone marrow of breast cancer patients.

Metastases develop in 30% to 40% of patients with operable breast cancer. Investigators have reported on the detection of occult micrometastases in bone marrow using an antibody to epithelial membrane antigen (EMA) and have since reported prognostic significance for these antibody-detected cells. In this study, two anti-cytokeratin monoclonal antibodies (35 beta H11 and 34 beta E12) were used to examine bone marrow specimens from patients with breast cancer. The technique was first studied in a test system in which human or monkey bone marrow was seeded with MCF-7 cells, and was determined to be sensitive enough to detect fewer than one cancer cell in 10(4) hematopoietic cells. An immunoglucose oxidase method was used for patient specimen antibody localization and was found to be free of false-positive staining. Marrow specimens from 25 patients with breast cancer of various stages were examined. No correlation with disease stage was observed. We conclude that the technique is feasible, but prognostic import remains to be determined.

[The effect of intravenous administration of xylocaine for the treatment of tinnitus].

One hundreds and forty-nine patients (221 ears) suffering from tinnitus were treated by an intravenous administration of Xylocaine. Xylocaine, 1mg per kg, was administered once a week. The immediate effect of Xylocaine on tinnitus was evaluated subjectively for all the patients. The long term effect in 57 patients who received Xylocaine administration more than 12 times was also analyzed. The results can be summarized as follows. 1. Short and long term relief of tinnitus was obtained in 165 of 221 ears (74.7%) and in 35 of 57 cases (61.4%), respectively. 2. This therapy was more effective in old patients and in the patients with low pitch tinnitus, or with positive residual inhibition. 3. The numbers of the effective cases increased after the 8th time administration of Xylocaine. Thus we recommend the Xylocaine administration at least 8 times. 4. The results of the loudness balance test were not correlated with the change of the subjective improvements. 5. The suppressive effect of tinnitus by injecting saline solution intravenously was recognized in 24 of 73 cases. At present, repeated administration of Xylocaine would be one of the most significant therapies of tinnitus.

Structure specificities of yohimbine and indoloquinolizidine derivatives in blocking alpha-adrenoceptor and calcium channel.

1,12b-Cis-1-p-nitrobenzoyloxyindoloquinolizidine as well as 14 beta-p-nitrobenzoyloxyyohimbine possessed potent calcium channel blocking activities in the isolated rat perfused mesenteric vascular bed. Introduction of the bulky substituents to C-14 of yohimbine or to C-1 of indoloquinolizidine resulted in enhancement of the calcium channel blocking activities. By comparison of chemical structures between yohimbine and indoloquinolizidine, it was found that the E ring of yohimbine had no association with the calcium channel blocking activities. On the other hand, alpha 1- and alpha 2-adrenoceptor antagonistic activities which were tested in the rat mesenteric vascular bed and in the rat vas deferens, respectively, were markedly reduced by such introduction of the bulky substituents to yohimbine and indoloquinolizidine. From these results, it is expected that chemical modifications of indoloquinolizidine at the C-1 position provide new types of agents with calcium channel blocking activities.

Implantable hearing aid in fourteen patients with mixed deafness.

An implantable hearing aid (IHA) in which the stapes was directly driven by a ceramic vibrator of bimorph design was applied to fourteen patients with mixed deafness of varying degree due to chronic otitis media. In the partial IHA system, only the output transducer and secondary coil are implanted, the remainder of the components such as microphone, amplifier, battery and primary induction coil remain in the location behind the auricle. The vibrator was activated by an electric signal transmitted electromagnetically through the induction system from the outer unit. All the patients admitted that sound quality provided by the IHA was natural, clear and easy to hear without causing fatigue in long-term use. Speech discrimination test under noise circumstance showed that acoustic perception by the IHA was superior to that by a conventional hearing aid. In four patients, however, the implanted unit was replaced with a new one due to recurrence of cholesteatoma, head trauma, and accidental disruption of wire by manipulating the ear canal. They regained good hearing after re-implantation.

Implantable hearing aid. Report of the first human applications.

To our knowledge, this is the first report of human application of the partial implantable hearing aid. Direct driving of the stapes by an ossicular vibrator of piezoelectric ceramic bimorph is the fundamental mechanism of this device. Acoustic signals received by a microphone were transmitted to the external link coil after amplification. By means of electromagnetic induction, the internal coil placed under the retroauricular skin excited electroacoustic energy, which is transmitted to the vibrator directly coupled with the stapes. The device used in this first patient has been functioning for longer than one year. Excellent frequency response of the vibrator and highly efficient direct transmission of electroacoustic signals to the inner ear gave rise to acoustic perception of superior quality that could not be obtained by other surgical or rehabilitative measures.

Ca2+ channel-blocking effect of the yohimbine derivatives, 14 beta-benzoyloxyyohimbine and 14 beta-pho-nitrobenzoyloxyyohimbine.

Yohimbine possesses a relatively selective alpha 2-adrenoceptor antagonistic effect and a weak Ca2+ channel blocking activity, so two derivatives, 14 beta-benzoyloxyyohimbine and 14 beta-rho-nitrobenzoyloxyyohimbine were compared with yohimbine using those parameters. The two derivatives blocked Ca2+-induced contraction of the rat perfused mesenteric vascular bed at 3 X 10(-6) M, and developed dose-dependent shifts of the dose-response curve to the right in concentrations from 3 X 10(-6) to 10(-5) M. Yohimbine showed a weak Ca2+ channel-blocking effect only at a concentration of 10(-5) M. On the other hand, both derivatives at 3 X 10(-6) M did not affect the dose-response curve to noradrenaline-induced vasoconstriction. Furthermore, at 10(-8) M they had no effect on the dose-response curve to clonidine-induced inhibition of the twitch response of the rat isolated vas deferens evoked by electric stimulation, whereas yohimbine significantly attenuated clonidine-induced inhibition. These results indicate that introduction of bulky substituents into the 14-position of yohimbine intensely potentiated the Ca2+ channel-blocking effects and reduced alpha-adrenoceptor antagonistic effects compared with those of yohimbine, and suggest that chemical modifications of yohimbine may lead to structurally new types of Ca2+ channel-blockers.

Implantable hearing aid using an ossicular vibrator composed of a piezoelectric ceramic bimorph: application to four patients.

Direct driving of the stapes by an ossicular vibrator composed of a piezoelectric ceramic bimorph is the key functional mechanism of the partially implantable hearing aid reported in this article. Acoustic signals from a microphone are transmitted to the vibrator by means of electromagnetic induction. The devices were implanted into four patients with mixed deafness due to chronic otitis media. In the first patient, the device has continued to function for two years. The highly efficient sound transmission achieved by the direct driving of the stapes produced excellent sound perception. The functional principle, surgical procedure, and indications for this new device for hearing rehabilitation are described together with the clinical results obtained in the four patients.

Avidin-biotin-immunoglucose oxidase: use in single and double labeling procedures.

We have investigated the use of an avidin-biotin-immunoglucose oxidase (AB-GO) technique for single and double antigen localization in conjunction with the avidin-biotin-immunoperoxidase (AB-P) technique in fixed, embedded specimens, using sequential monoclonal and polyclonal antibodies of the same species. The optimal technique for double labeling requires the first antibody to be applied and localized with the AB-P technique using 3,3'-diaminobenzidine (DAB) as the chromogen, followed by an optional elution step and/or incubation with mild detergent (0.01% Triton). The second antigen is localized with the AB-GO technique with nitro blue tetrazolium (NBT) as a chromogen. Effects of antigen concentration, intermediate elution steps, and the relative efficiency of the two methodologies are described.