Ultrastructure of lentigo maligna in the oral cavity

A rare case of lentigo maligna in the oral cavity was investigated by light and electron microscopy. Cutaneous lentigo malignas often develop to malignant melanomas. However, the electron microscopic examination revealed that even though there were a large number of melanosomes, most of them were late stage and had membrane structure, and positive staining with HMB-45 was not recognized. From our findings, it is difficult to conclude that oral lentigo malignas develop malignant melanomas, and thus further studies are needed.     

IgG Anti-GM1 antibody is associated with reversible conduction failure and axonal degeneration in guillain-barré syndrome

To investigate the pathophysiological role of anti-GM1 antibody in Gullain-Barre syndrome (GBS), we reviewed sequential nerve conduction studies of 345 nerves in 34 GBS patients. Statistically significant correlation between IgG anti-GM1 antibodies and electrodiagnoses was found. Sixteen IgG anti-GM1-positive patients were classified as having acute motor sensory axonal neuropathy (AMAN or AMSAN) (12 patients), as having acute inflammatory demyelinating polyneuropathy (AIDP) (3 patientsrpar;, or as undetermined (1 patient) by electrodiagnostic criteria. Besides axonal features, there was rapid resolution of conduction slowing and block. In 3 patients initially diagnosed as having AIDP, conduction slowing was resolved within days, and 1 of them and 3 AMAN patients showed markedly rapid increases in amplitudes of distal compound muscle action potentials that were not accompanied by prolonged duration and polyphasia. The time courses of conduction abnormalities were distinct from those in IgG anti-GM1-negative AIDP patients. Rapid resolution of conduction slowing and block, and the absence of remyelinating slow components, suggest that conduction failure may be caused by impaired physiological conduction at the nodes of Ranvier. Reversible conduction failure as well as axonal degeneration constitutes the pathopsiological mechanisms in IgG anti-GM1)positive GBS. In both cases, immune-mediated attack probably occurs on the axolemma of motor fibers.     

Percutaneous hepatic venous isolation and extracorporeal charcoal hemoperfusion for high-dose intraarterial chemotherapy in patients with colorectal hepatic metastases

The results of treating 12 consecutive patients with unresectable colorectal hepatic metastases with a hepatic arterial infusion of high-dose Adriamycin, 100–120 mg/m², using hepatic venous isolation (HVI) and charcoal hemoperfusion (CHP) are reported herein. Adriamycin was administered over 5–15 min under extracorporeal drug elimination by HVI-CHP. HVI was percutaneously accomplished by either the double-balloon technique using a Fogarty occlusion catheter (8/22F) or a balloon-tipped catheter (16F). During the infusion, isolated hepatic venous blood was filtered by CHP and pumped into the left axillary vein. There were no lethal complications, and good hemodynamic tolerance to HVI-CHP was confirmed. Tumor liquefaction accompanied by a sharp decrease in serum carcinoembryonic antigen levels by more than 50% of pretreatment levels was observed in 6 of the 12 patients 1 month after treatment. Apart from chemical hepatitis, which developed in 11 (92%) of the patients, the Adriamycin toxicities were well controlled following the development of nausea and vomiting in 2 patients (17%), leukopenia <2,000/mm³ in 3 (25%), and gastric ulcer in 1 (8%). These results indicate that this method is a safe and useful procedure for otherwise hazardous high-dose intraarterial chemotherapy in patients with unresectable hepatic tumors.     

Recent Trends in the Treatment and Prognosis of Adult Leukemia with Characteristics of Patients in Japan: Transition during the Fifteen Years from 1971 to 1985

Patients with acute (2,569) and chronic (957) leukemia diagnosedat 19 institutes took part in the study on the "MultidisciplinaryTreatment of Leukemia" between 1971 and 1985 and were investigatedretrospectively. By dividing the 15 years into three five-yearperiods, we were able to compare patient ratios in the differentperiods. The proportions of acute to chronic leukemia casesshowed no obvious change; however, the proportions of casesdiagnosed as acute lymphocytic leukemia in acute leukemia showeda significant increase. The main chemotherapeutic drugs usedduring the three time periods were cytarabine or its analogues,the anthracyclines, 6-mercaputopurine and prednisolone, againstacute myelogenous leukemia, and the vinca alkaloids, prednisoloneand the anthracyclines against acute lymphocytic leukemia. Therate of complete remission from acute myelogenous leukemia mademarked progress, from 45.1% during 1971–1975 to 62.3%during 1981–1985, but that of acute lymphocytic leukemiashowed no significant progress, being 65% during 1971–1975and 69.7% during 1981–1985. The durations of remission,however, and the survival times for patients with acute lymphocyticleukemia, as well as for those with acute myelogenous leukemia,became significantly longer over the three periods. Median survivaltimes from chronic myelocytic leukemia were 37–40 mo inall three periods, showing no progress. There was a better prognosisin cases of chronic myelocytic leukemia with, than without,Philadelphia chromosome. Except for a low incidence of chroniclymphocytic leukemia in Japan, adult leukemia patients' characteristicsand prognoses seem to be almost the same in Japan as in theU.S.A. and Europe.     

SOLITARY GASTRIC POLYPS IN THE FUNDIC GLAND AREA A Histochemical Study

Six solitary gastric polyps in the acid-secreting fundic mucosa were histo-chemically investigated using the mucin histochemistry, immunoperoxidase method, and silver methods for endocrine cells. Histologically, the polyps were grouped into three types : they largely consisted of either hyperplastic foveolar cells (group 1), normal-appearing fundic gland cells with mild cystic changes (group 2) or hyperplastic fundic gland cells with cystic dilatation (group 3). The presence of parietal cells and mucous neck cells was confirmed in all polyps by the immunoperoxidase method using parietal cell autoantibody and the paradoxical Concanavalin A staining, respectively. Regarding the endocrine component, somatostatin-containing cells, Grimelius-positive argyrophil cells, and Fontana-Masson-positive enterochromaffin cells were scattered in the fundic gland area of the polyps as well as in the surrounding normal-appearing fundic mucosa. Gastrin-containing cells were absent. In one of the group 2 polyps and both group 3 polyps, a varying number of glicentin-containing cells were found among the fundic gland components : In one polyp in group 3, glucagon immunoreactivity was detected in the glicentin-containing cells. These findings suggest that some of the polyps express characteristics of the fetal fundic mucosa, since glicentin and glucagon immunoreactivities in normal human stomach have been detected exclusively in the fetal fundus. ACTA PATHOL. JPN. 35: 831–840, 1985.     

GAMMA HEAVY CHAIN DISEASE

Electron microscopic and immunohistochemical studies were carried out on materials obtained from three patients of gamma heavy chain disease ( λ -HCD). Electron microscopically, proliferating cells showed various stages of maturation from immunoblast to plasma cell, and the majority of proliferating cells were proplasmacytes and plasma cells. From the intracytoplasmic immunoglobulin studies by immunoperoxidase method (PAP method) and electron microscopical enzyme-labeled antibody technique, proliferating cells, such as the immunoblast, plasmablast, proplasmacyte, and plasma cell, showed positive reaction to anti- λ -heavy chain serum and anti-Fc fragment (IgG) serum, and also in a third case with Bence Jones protein, proliferating cells showed positive reaction to anti_-K light chain serum. We would conclude that proliferating cells in λ -HCD might be a single clone proliferation of B-cell synthesizing λ -HCD protein, and the predominant proliferation cells are proplasmacytes and plasma cells situated near mature plasma cells in the B-cell line.     

Vascularization in vivo caused by the controlled release of fibroblast growth factor-2 from an injectable chitosan/non-anticoagulant heparin hydrogel

Addition of various heparinoids to the lactose-introduced, water-soluble chitosan (CH-LA) aqueous solution produces an injectable chitosan/heparinoid hydrogel. In the present work, we examined the capability of the chitosan/non-anticoagulant heparin (periodate-oxidized (IO(4)-) heparin) hydrogel to immobilize fibroblast growth factor (FGF)-2, as well as the controlled release of FGF-2 molecules from the hydrogel in vitro and in vivo. The hydrogel was biodegraded in about 20 days after subcutaneous injection into the back of a mouse. When the FGF-2-incorporated hydrogel was subcutaneously injected into the back of both mice and rats, a significant neovascularization and fibrous tissue formation were induced near the injected site. These results indicate that the controlled release of biologically active FGF-2 molecules is caused by biodegradation of the hydrogel, and that subsequent induction of the vascularization occurs.     

Kanamycin ototoxicity in glutamate transporter knockout mice

Glutamate-aspartate transporter (GLAST), a powerful glutamate uptake system, removes released glutamate from the synaptic cleft and facilitates the re-use of glutamate as a neurotransmitter recycling system. Aminoglycoside-induced hearing loss is mediated via a glutamate excitotoxic process. We investigated the effect of aminoglycoside ototoxicity in GLAST knockout mice using the recorded auditory brainstem response (ABR) and number of hair cells in the cochlea. Kanamycin (100 mg/mL) was injected directly into the posterior semicircular canal of mice. Before the kanamycin treatment, there was no difference in the ABR threshold average between the wild-type and knockout mice. Kanamycin injection aggravated the ABR threshold in the GLAST knockout mice compared with the wild-type mice, and the IHC degeneration was more severe in the GLAST knockout mice. These findings suggest that GLAST plays an important role in preventing the degeneration of inner hair cells in aminoglycoside ototoxicity.     

Oral squamous cell carcinoma: electron microscopic and immunohistochemical characteristics

Oral squamous cell carcinoma is the most common oral malignancy, and we performed electron microscopic and immunohistochemical investigation of the tumor. In patients with cervical metastasis, microvilli were developed and a small number of desmosomes were found, regardless of the width of the intercellular spaces. In patients without the metastasis, few microvilli were found in relatively wide intercellular spaces, or numerous microvilli were found in narrow intercellular spaces, and a large number of desmosomes were shown. However, these findings were different from those of tumors that had received radiotherapy, in which numerous microvilli and a small number of desmosomes were found in the nonmetastatic cases. Transferrin receptor, which is a marker of cell proliferation, was localized on the cell membrane, especially in microvilli. Ultrastructural similarity between the primary tumor and the metastatic tumor was recognized, however, the features of microvilli, desmosomes, and the intercellular spaces differed between them in most cases. It is suggested that microvilli might be related to the metastasis of oral squamous cell carcinoma cells. Immunohistochemically, the protein expression of p53 and pRb2/p130 was related to the clinical course of the patients with oral squamous cell carcinoma; the mechanism of the synthesis of these proteins should be investigated in order to understand the biological behavior of the tumor.