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Biomedical subjects

S Hitomi

Publications and source records attributed to S Hitomi.

At least 19 recordsLinked to original sources

Correlation of expression of H/Le(y)/Le(b) antigens with survival in patients with carcinoma of the lung.

BACKGROUND: The level of expression of H/Le(y)/Le(b) antigens is high in various histologic types of lung cancer, a feature that may be related to deletion of A and B blood-group antigens. We evaluated the possibility that expression of this antigen, which can be defined by the monoclonal antibody MIA-15-5, might be of prognostic value, as suggested by our previous observation that MIA-15-5 inhibits tumor-cell motility and metastasis. METHODS: We used MIA-15-5 to stain tissue sections from 149 patients with primary lung cancer whose clinico-pathological histories were well documented. The survival curves for patients whose tumors stained positively were compared with the curves for those whose tumors stained negatively. Multivariate analyses were performed with a Cox proportional-hazards regression model. RESULTS: Among the 149 patients studied, five-year survival in the 91 patients with MIA-positive tumors was significantly lower than survival in the 58 with MIA-negative tumors (20.9 percent vs. 58.6 percent, P less than 0.001). Among the 67 patients with squamous-cell carcinoma, the rates also differed significantly (10.5 percent vs. 62.1 percent, P less than 0.001). The difference in survival between patients with MIA-positive tumors and those with MIA-negative tumors was significant among patients with blood groups A and AB (P less than 0.001), but not among those with blood group B or O (P = 0.071 and 0.068, respectively). Multivariate analysis with the Cox regression model indicated that positivity best correlated with five-year mortality, followed by lymph-node status (N stage) and tumor size status (T stage), whereas sex, age, and blood group did not correlate with mortality. CONCLUSIONS: Positivity for MIA (i.e., immunohistologic staining by MIA-15-5, which defines H/Le(y)/Le(b) antigens) is inversely correlated with survival among patients with primary lung cancer and may be of prognostic value.

ABO Blood-Group System

First establishment of a human monoclonal antibody directed to sulfated glycosphingolipids SM4s-Gal and SM4g, from a patient with lung cancer.

Several human monoclonal antibodies directed to tumor-associated glycolipid antigens have been established, but more than one-half of them react with gangliosides and the others react with neutral glycolipids. We report here the first establishment of a human IgM monoclonal antibody directed to the sulfated glycolipid. This monoclonal antibody, M14-376, did not react with SM3 and SB1a which have a terminal HSO3----3Gal beta 1----R1, but with the simple sulfolipids SM4s-Gal and SM4g which contain a terminal HSO3----3Gal beta 1----O----CH2----R2; however, lyso-SM4s-Gal and lyso-SM4g did not bind M14-376. These results suggest that terminal HSO3----3Gal and part of the hydrophobic region of the glycolipid are recognized by M14-376. Directly biotinylated M14-376 was used for immunohistochemical staining of 140 formalin-fixed, paraffin-embedded lung cancer tissue sections to study the distribution of the antigen. A high incidence of positive staining was found in adenocarcinoma (39.5%, 17 of 43), followed by large cell carcinoma (20.0%, 5 of 25), while this antigen was rarely detected in small cell carcinoma (4.7%, 1 of 21) and squamous cell carcinoma (3.9%, 2 of 51). Thin layer chromatography immunostaining of glycolipids extracted from lung cancer tissues showed the presence of only SM4s-Gal in adenocarcinoma, but SM4g was not found in any subtype of lung cancer. Immunohistochemical staining revealed that this antigen was expressed in normal kidney, testis, and brain, but erythrocytes, granulocytes, and lymphocytes were negative in cytofluorometric analysis.

Adenocarcinoma

Omentopexy for revascularization of free tracheal grafts in rats.

In rats, we examined the effect of an omentum wrapping on the vascularization of the trachea and on regeneration of the mucosal epithelium in the very early stage after free tracheal grafting. Two pieces of trachea were obtained from each donor rat. One piece was transplanted into the peritoneal cavity of the recipient rat and wrapped with omentum. The other piece was transplanted subcutaneously into the abdominal wall, without omentopexy. Recipients were sacrificed at random on days 1, 2, 3, and 4 after operation (5 rats/day). The increase of blood vessels rose significantly earlier in the omentopexy tracheas than in those without omentopexy (p less than 0.01), with all the former showing a normal ciliated, columnar epithelium in the membranous region of the trachea on day 4, accompanied by excellent epithelial regeneration in the cartilaginous region. These results suggest that omentopexy causes revascularization to occur earlier and to be completed in a shorter time, and that it also promotes epithelial regeneration following free tracheal grafting.

Animals

Laser Doppler velocimetry measurement of canine mucosal circulation response to bronchial artery reperfusion after lung transplantation.

Left lung transplantation accompanied by reestablishment of the circulation of the bronchial arteries by simultaneous transplantation of part of the aorta was performed on seven dogs. Mucosal circulation of the bronchi at the anastomosis was evaluated using laser Doppler velocimetry (LDV). Since the donor lung must maintain blood supply through the bronchial arteries, the donor aorta from its ascending portion to the descending portion below the outlet for the last bronchial artery was retained with the lung graft. The distal end of the left brachiocephalic artery was sutured to the side of the recipient aorta when the blood supply to the bronchial arteries was to be restored. The LDV values before reperfusion of the bronchial arteries were 20 to 65% (mean: 42.8%) of the preoperative value. Since the LDV values increased to 36 to 125% (mean: 79.9%) of the control, blood flow to the bronchial mucosa increased evidently. Four out of seven dogs died one to two days after the operation due to bleeding and operative stress. One dog was sacrificed on the 4th postoperative day and another on the 16th. The last dog died 40 days after surgery. The unfavorable course of the LDV values in these three dogs suggest that the method used does not ensure an adequate blood supply to the bronchial arteries in the long term.

Animals

Neovascularization effect with He-Ne laser in the rat trachea.

The tracheal tissue of a rat was heterotopically transplanted beneath the abdominal skin of a syngenetic rat, and the transplanted graft was irradiated with a He-Ne laser (2.41 J/cm2). Four or seven days following transplantation, Chinese ink staining was used to ascertain the number of newly generated vessels. Rats sacrificed on day 4 were divided into 3 groups, according to the number of laser irradiation treatments: A0, A2, and A4. Similarly, rats sacrificed on day 7 were divided into groups B0, B2, and B4. Among the A groups, vascular counts were 49.5 +/- 31.1 in group A0 (n = 6), 108.9 +/- 34.7 in group A2 (n = 7), and 90.9 +/- 24.6 in group A4 (n = 4). Neovascularization was significantly more pronounced in the irradiated groups that in the non-irradiated group. In the B groups, vascular counts were 148 +/- 58 in group B0 (n = 6), 146 +/- 56 in group B2 (n = 5), and 147 +/- 49 in group B4 (n = 5). There was no significant difference between the irradiated and non-irradiated B groups. Laser irradiation was determined to stimulate neovascularization, and the possibility of a clinical application for this procedure was suggested.

Animals

The effects of cromolyn sodium in dogs undergoing high-frequency oscillation superimposed on conventional mechanical ventilation.

The effects on gas exchange of superimposition of high-frequency oscillation (HFO) (40 Hz) on conventional mechanical ventilation were investigated in mongrel dogs with eucapnic gas exchange on conventional mechanical ventilation (CMV). The dogs were anesthetized, paralyzed, and ventilated with CMV until stable. Oscillation was then superimposed for 15 min, followed by CMV alone for a further 30 min. During HFO superimposed on CMV (CMV-HFO), the arterial carbon dioxide tension (PaCO2) increased from 43.6 +/- 1.2 mm Hg to 47.2 +/- 1.4 mm Hg (p less than 0.02), whereas the arterial oxygen tension (PaO2) did not change at all. The change was inhibited completely by administration of intravenous cromolyn sodium (CS) (6 mg/kg/min). The mean pulmonary arterial pressure (mPAP), cardiac output (CO), pulmonary capillary wedge pressure (PCWP), and pulmonary vascular resistance (PVR) did not change during the experiment. These results demonstrate that CMV-HFO appears to cause CO2 accumulation and eliminates the impaired O2 transfer, and that these effects are inhibited completely by CS administration.

Animals

Combination use of suboptimal dose of FK 506 and cyclosporine in canine lung transplantation.

The immunosuppressive potency and the side effects of combination therapy with FK 506 and cyclosporine A were studied in dogs that had undergone lung transplantation. The animals were divided into four groups: group A (one third optimal FK 506 dose: FK 506, 0.03 mg/kg intramuscularly) (n = 5), group B (one third optimal cyclosporine dose: cyclosporine 6 mg/kg orally) (n = 5), group C (one third FK 506 and one third cyclosporine optimal doses): FK 506, 0.03 mg/kg intramuscularly plus cyclosporine 6 mg/kg orally) (n = 5), and group D (half FK 506 plus half cyclosporine optimal doses: FK 506, 0.05 mg/kg intramuscularly, plus cyclosporine, 10 mg/kg orally) (n = 10). Assessments including chest x-ray film, fiberoptic bronchoscopy, hematologic and biochemical tests, FK 506 and cyclosporine blood trough level measurement, right pulmonary artery occlusion test, and histopathologic observations were performed. In group A two of five dogs survived 28 days and three died on postoperative days 7, 14, and 21. In group B one dog survived 28 days and four died on postoperative days 9 (two dogs), 14, and 21. Histologic examination showed severe rejection in both group A and group B. In group C all five dogs survived 28 days but showed mild rejection. In group D one dog died of intestinal bleeding on postoperative day 7 and nine survived 28 days. No pathologic changes were observed except in one case of mild rejection. The ventilation function of the transplanted lung was poor in groups A, B, and C but good in group D. No abnormal rise of FK 506 and cyclosporine trough levels was observed. There were no significant side effects and abnormal hematologic and biochemical data except in one dog in group D. We concluded (1) the combination of FK 506, 0.03 mg/kg, and cyclosporine, 6 mg/kg, is much more effective than either drug used singly, (2) the combination of FK 506, 0.05 mg/kg, and cyclosporine, 10 mg/kg, prevents rejection with tolerable side effects, and (3) no worse side effects are caused by combination therapy with FK 506 and cyclosporine than by either one used singly.

Animals

[Clinical study of bioabsorbable PGA sheets for suture reinforcement and use as artificial pleura].

Bioabsorbable PGA non-woven fabric sheets were used to treat 103 patients who underwent pulmonary surgery in three hospitals, and their handleability, applicability, drainage time after surgery and subsequent side effects were studied. For suture reinforcement, these sheets showed satisfactory handleability, applicability and effectiveness for hemostasis and prevention of air leakage at the suture sites. Since this material has good compatibility with fibrin glue, use of these two materials in combination reduced both the operation time and postoperative drainage period. For small fistula and pleural defects, attachment of the sheets with fibrin glue to create an artificial pleura was sufficient for prevention air leakage without suturing. No side effects or complications were observed, and the postoperative courses of all 103 patients were uneventful. These findings suggest that PGA sheets are acceptable for suture reinforcement in the pulmonary surgery, and that when used with fibrin glue, can simplify surgery for emphysematous lung disease and shorten the period of postoperative air leakage.

Absorption

The immunosuppressive effect of FK 506 on canine lung transplantation.

The immunosuppressive potency of FK 506 was studied after left lung transplantation in adult mongrel dogs in comparison with cyclosporine. Fiberoptic bronchoscopy, bronchial mucosal blood flow measurement with laser Doppler velocimetry, and chest x-ray and pathologic examinations were performed. Group A had no immunosuppression (n = 5); group B received FK 506 (0.10 mg/kg/day intramuscularly (n = 5); group C received cyclosporine (20 mg/kg/day orally) (n = 5). In group A four dogs died of rejection on the seventh to the twenty-first postoperative days. Another one was killed on the fourteenth postoperative day because bronchial dehiscence occurred at the anastomosis. In group B one died of alveolar rejection on the seventh postoperative day. The remaining four survived 28 days and were put to death. In group C all five dogs survived 28 days and were put to death. In group A bronchial stenosis or dehiscence at the anastomosis was found in every one during the early postoperative period. In group B stenosis did not develop in any of the dogs, including the one that died on the seventh postoperative day. In group C slight stenosis was seen in one dog, severe narrowing in another, and good healing in the remaining three. The transplanted lungs were almost normal histologically in four animals of group B, and one showed alveolar phase rejection. In all animals of group A severe rejection was observed, and in group C two of five animals showed vascular phase rejection, two latent phase, and one fibrosis. Histologic examination of the bronchial anastomosis in group B showed almost normal bronchial epithelium and slight submucosal infiltration of mononuclear cells. In group A there was desquamation of epithelium and mild to moderate mononuclear cell infiltration. In group C hyperplasia of the epithelium was observed in two animals, an abscess at the site of anastomosis in one, and mild to moderate mononuclear cell infiltration in all five. With use of laser Doppler velocimetry, bronchial blood flow in group B was found to be the same as in group C. Laser Doppler velocimetry values reached preoperative levels by the twenty-eighth postoperative day in both groups. Although diarrhea developed in two dogs of group B, no other significant side effect of FK 506 was seen.

Animals

[Congenital absence of the right main pulmonary artery--a case report].

A 32-year-old man was admitted to hospital for investigation of bloody sputum. Chest roentgenogram showed a decrease in the volume of the right lung, with mediastinal shift to the right. Chest CT examination revealed narrowing of the right main pulmonary artery. Bronchofiberscopic examination was normal. Pulmonary arteriogram demonstrated complete absence of the right pulmonary artery. Cardiac catheterization showed no concomitant cardiac malformation. Therefore, this case was diagnosed as congenital absence of the right main pulmonary artery.

Adult

[Surgical treatment for tuberculous spondylitis; a case report].

A 64-year-old woman was admitted with the chief complaints of severe back pain. Chest X-ray film on admission showed an abnormal mass lesion in the right upper mediastinum. Chest tomography and chest CT films revealed destruction of thoracic vertebrae (Th 2 and 3) and paravertebral abscess. Chemotherapy containing RFP was started under diagnosis of active tuberculous spondylitis of thoracic vertebrae. Three months later, curative operation for spondylitis were performed. She underwent the resection of necrotic bone and the anterior spinal fusion using transplanted bone autograft. Her post-operative course was good and she discharged three months after curative operation. Tuberculous spondylitis is still important diseases at the differential diagnosis from metastatic vertebral tumors. This report describes a successful case of surgical treatment for tuberculous spondylitis of thoracic vertebrae.

Female

[A case of thyroid medullary carcinoma-like tumor of the lung with amyloid stroma].

A 58-year-old man with history of productive cough and mild exertional dyspnea for several years was admitted to our hospital because of abnormal shadow on chest radiograph. Bronchofiberscopic examination revealed a polypoid tumor almost completely obstructing the right main bronchus. Bronchoscopic biopsy specimens showed amyloid-like deposits in the connective tissue surrounded by epithelium-like tumor cells with squamous metaplasia, but no diagnostic findings. Malignant tumor was suspected and right upper lobectomy was performed. The surgical specimen revealed nests of tumor cells surrounded by amorphous eosinophilic substance, which was confirmed to include amyloid fibrils by electron microscopy. A few tumor cells contained argyrophil granules by Grimelius staining, and some showed PAP staining for calcitonin. There was no evidence of involvement of other organs including the thyroid gland during the four year postoperative follow-up period. This case was diagnosed as thyroid medullary carcinoma-like tumor of the lung, which is a bronchopulmonary carcinoid-related tumor.

Carcinoma

[Complications of Nd-YAG laser treatment on tracheobronchial lesions].

Neodymium-yttrium-aluminum-garnet (Nd-YAG) laser was clinically introduced to the treatment of tracheobronchial lesions 10 years ago. Since then, the apparatus of the laser therapy and the flexible bronchoscopy have been improved, and the indication for its treatment has been established. Nd-YAG laser is useful at the field of the treatment of the tracheobronchial stenotic or obstructed lesions. But various complications occur, because of the lesions occupying in the narrow tracheo and bronchial lumen. In our institute, 83 cases have been treated in 196 sessions (from one to fifteen sessions per patient) for the past ten years. The stenotic or obstructed lesions were divided into three etiologies, 64 cases with malignant lesion, 8 cases with post operative granulation at the suture line and 11 cases with benign lesion. All procedures were performed under local anesthesia by using flexible bronchoscope. Among them, complications were noticed in eleven cases. They involved hemorrhage (6 cases) and respiratory disturbances (2 cases) during operative period, and massive hemorrhage (2 cases) and edema of the tumor (1 case) in the adjacent period of laser treatments.

Adult

Biodegradation and antitumour effect of adriamycin-containing poly(L-lactic acid) microspheres.

Adriamycin-containing poly (L-lactic acid) microspheres were prepared to develop a slow-releasing and long-acting adriamycin delivery system. An almost constant release of adriamycin from the adriamycin-containing poly(L-lactic acid) was achieved in Tris buffer and adriamycin disappeared within 20 d. Adriamycin was not detected in serum for up to 14 d, when the suspension of the adriamycin-containing poly(L-lactic acid) microspheres was injected into lung parenchyma, the femoral muscles of rabbits or the peritoneal cavity of mice. However, adriamycin remained in the rabbit muscles for up to 10 d under formation of scar tissue. When free adriamycin was added to P815 tumour cells in culture, the cell survival rate decreased with the exposure time. The treatment with the adriamycin-containing poly(L-lactic acid) microspheres showed a higher survival rate for mice bearing P815 tumour cells than with free adriamycin. In addition, the systemic side effects were insignificant when the adriamycin-containing poly(L-lactic acid) microspheres were given to mice instead of free adriamycin.

Animals

Immunohistochemical study on gastrin-releasing peptide-containing peripheral nerve fibers in rat, macaque and human.

Distribution of gastrin-releasing peptide (GRP)-containing peripheral nerve fibers in the respiratory organs, digestive tracts and hearts of rat, monkey and human was studied with immunohistochemical method. In the trachea, GRP-immunoreactive nerve fibers were observed in the lamina propria and surrounded ducts and acini of tracheal serous glands with a basket-like appearance. In the lung, immunoreactive nerve fibers were scattered in the lamina propria of bronchi and bronchioles, and also the adventitia of veins. In the digestive organs, such as esophagus, duodenum and jejunum, numerous GRP-immunoreactive nerve fibers were distributed in the lamina propria and muscle layer; especially in the former layer where they were seen running up to the apical part of villi. GRP-containing nerve bundles and branched fibers were also observed in the atrial muscle layer. These results gave a morphological basis to future studies of the functional significance of GRP on autonomic mechanisms.

Aged

A new method for carinal reconstruction: an experimental study.

We developed a new procedure for carinal reconstruction which can be used for lesions of the carina invading the left main bronchus. Twelve mongrel dogs were used. A Y-shaped bronchial graft was autotransplanted from the bifurcation of the right upper bronchus to form a new carina with or without an omentopexy. Six animals survived 10 days to 11 months. In these animals healing of the bronchial anastomotic sites was excellent, and the integrity of the grafts was well preserved. Although the results of this preliminary report were not satisfactory in all cases, intensive perioperative care will improve the outcome of this new procedure.

Animals