Search

Anopheles maculatus of Thailand were distinguished morphologically into densely and sparsely scaled types and cross-mating experiments between these types revealed a substantial amount of genetic divergence. Progeny of wild females of An. maculatus collected throughout Thailand from north to south were examined morphologically with respect to adult tergal pale scales. Northern progeny broods could be separated into densely scaled (willmori) and sparsely scaled (maculatus) types, or W and M types, respectively. Using these two types of An. maculatus from Chiang Rai and Nakhon Phanom, cross-mating experiments were conducted, which resulted in sterile F1 male hybrids in one direction of cross and very low survival rate of F1 male hybrids in the reciprocal cross. However, southern broods could not be separated clearly because of intergradation of scaling. These results indicate that Thai An. maculatus involves at least 2 forms differentiated morphologically, as well as by incomplete reproductive isolation.

Amelioration of cisplatin (CDDP)-induced vomiting and anorexia by methylprednisolone (MP) was studied using conscious dogs. The incidence of vomiting was 88.9% and the mean number of emetic episodes was 8.22 +/- 1.25/dog during 5 hours after i.v. administration of 1.5 mg/kg CDDP in 9 dogs. In control dogs, food intake on the day after administration of CDDP was markedly reduced to 60 +/- 22.4 g/day from 461 +/- 23 g. Continuous high-dose infusion of MP (10 mg/kg, 10 min before the start of CDDP infusion and 50 mg/kg/h for 5 h) markedly reduced the incidence (33%) and mean number of vomiting episodes (2.00 +/- 1.51/dog) and also mitigated the reduction of food intake (350 +/- 30.6 g/day). However, continuous low-dose infusion of MP (5 mg/kg, 10 min before CDDP infusion and 16.6 mg/kg/h for 5 h) showed a little effect on CDDP-induced vomiting. Plasma MP levels after the high-dose and the low-dose regimens were 6.20 +/- 0.628 micrograms/ml and 4.66 +/- 1.72 micrograms/ml, respectively, 30 min after CDDP infusion. In both cases, MP levels gradually increased and reached to those more than twice 5 hours after CDDP infusion. Bolus administrations of MP (30 mg/kg, each time) 2 hr and 30 min before CDDP infusion also significantly reduced the mean number of emetic episodes (3.22 +/- 1.33/dog) and mitigated the reduction of food intake (325 +/- 37.3 g/day). No significant changes in catecholamines, prostaglandins, vasopressin, plasma renin activity, Na+, K+, Mg++ and osmolality in peripheral blood were noted after administration of CDDP and/or MP. The results suggest that administration of MP was effective against CDDP-induced vomiting and anorexia in dogs.

The motor end plate of the cat posterior cricoarytenoid muscle is examined by using electron microscope and histochemical method. Furthermore, we studied the localization of acetylcholine receptors by fluorescent staining of snake neurotoxins (alpha-bungarotoxin and erabutoxin b) and autoradiography of 125I-labeled alpha-bungarotoxin. The fine structure of the motor end plate of this muscle is approximately identical to that of other singly innervated skeletal muscles. The subneural apparatus is activated by cholinesterase (ChE). ChE reaction appears markedly in primary and secondary synaptic clefts. No remarkable difference is found between TMR-labeled neurotoxin and FITC-conjugated neurotoxin. Fluorescent staining is associated with subsynaptic muscle membranes and not with motor nerve terminals. The autoradiogram revealed heavy accumulations of grains at the junctional folds.

The clinical and pathological findings in a 58-year-old Japanese man suffering from type III Machado-Joseph disease are reported. The patient became affected at the age of 50 years and presented cerebellar ataxia, progressive external ophthalmoplegia and muscular atrophy, although extrapyramidal signs were never detected throughout the whole course of his disease. His mother, sister and son presented progressive ataxia in the third or fourth decade. The mode of inheritance is considered to be autosomal dominant. Pathological examination revealed severe involvement of the dentato-rubral, ponto-cerebellar and subthalamopallidal systems, spinocerebellar tracts and Clarke's column, cranial motor nuclei including the oculomotor systems and anterior horn cells. The involvement of the substantia nigra was relatively mild, and the nerve cells in the inferior olivary nucleus were well preserved. The distal portion of peripheral nerves was severely damaged. Although the striking feature of Machado-Joseph disease is a considerable variability in the individual clinical expression, there have not been many autopsied cases of this disease and efforts to clarify the clinico-pathological correlation in each phenotype have scarcely been made. Relatively mild changes in the substantia nigra and severe involvement of the peripheral nervous system, as in our case, may be the pathological hallmarks of the type III disorder.

Cefteram pivoxil (CFTM-PI, T-2588) was administered to pediatric patients with acute infectious diseases, and a summary of the results obtained are as follows. 1. Pharmacokinetic parameters determined in 1 patient appears to be comparable to those of adults. 2. Clinical efficacy was studied on 16 children with acute urinary tract infections, acute upper respiratory infections, acute sinusitis, acute otitis media and acute cervical lymphadenitis. Responses to the treatment were excellent in 7 (43.8%) and good in 9 (56.3%). 3. No adverse reactions were noted in this study.

We demonstrated the ultrastructures of the nasal mucosa of the rat by rapid freezing and freeze substitution with OsO4. Liquid helium was used for the rapid freezing. The depth of the good preservation was approximately 20 micron below the cut surface of the tissue. The characteristic features of the nasal mucosa obtained here are as follows: 1) The cross-section profiles of the cilium were round and smooth. 2) Mitochondrial matrix was electron dense and a few dense granules were observed in it. 3) Secretory granules of the goblet cells were enclosed by a limited membrane. 4) Extracellular space was of variable widths. 5) Cytoplasmic filaments were well preserved.

We studied the pleomorphic adenoma of the salivary gland ultrastructurally and cytochemically [Mg2+-activated adenosine triphosphatase (Mg2+-ATPase)], compared it with normal human fetal and adult salivary glands, and evaluated the histogenesis of this tumor. In the adult salivary gland, reaction products shows Mg2+-ATPase activity were localized in the plasma membranes of myoepithelial cells adjacent to the acinar cells or intercalated duct cells. However, in the salivary gland of the 16-week fetus, they were seen along all adjoining plasma membranes of the cells of terminal buds and duct-like structures. The present case of pleomorphic adenoma comprised two histological components: solid and myxomatous areas. Reaction products were seen along adjoining plasma membranes of both light and dark cells in solid areas.

Based on the cell types in bronchogenic carcinoma, we treated 123 patients with different regimens of combination chemotherapy. The chemotherapy regimens consisted of CAP (cyclophosphamide + adriamycin + platinum) for 60 patients with adenocarcinoma and large cell carcinoma, PP (peplomycin + platinum) for 29 patients with squamous cell carcinoma and CAV (cyclophosphamide + adriamycin + vincristine) for 35 patients with small cell carcinoma. These regimens were repeated every 4 weeks for at least 2 cycles. The response rates for CAP, PP and CAV were 18.3% (11 PR), 20.7% (6 PR) and 60% (10 CR + 11 PR), respectively. Median survival time (MST) was 12.5 months for CAP, 8.5 months for PP and 9.5 months for CAV. Responders had a significantly (P less than 0.002) improved survival (MST, 15.5 months) compared to non-responders (MST, 7.5 months) in small cell carcinoma. However, there was no significant difference between responders and non-responders in CAP and PP. Survival of patients with PS 0-1 was significantly better than that with PS 2-3 in all treated patients. Nausea and vomiting were severe in patients treated with platinum-based polychemotherapy. There was no renal failure although a transient increase of serum creatinine was noted in CAP and PP. Myelosuppression was mild to moderate in all patients treated with CAP, PP and CAV.

Monkey B-lymphotropic papovavirus (LPV) DNA present as free copies in LPV-transformed hamster embryo cells was molecularly cloned in Escherichia coli. Twenty-two of 24 cloned DNAs were 4.9 kilobases long and shorter than the wild-type LPV DNA (5.1 kilobases). The shorter DNA was nondefective and generated infectious virus (designated LPV-76) upon transfection of human B-lymphoblastoid BJA-B cells. LPV-76 DNA had a small deletion in the early region and a deletion and an insertion in the control region for transcription. LPV-76 VP-1 was apparently larger than that of the wild-type LPV. LPV-76 could grow in human T-lymphoblastoid MOLT-4 cells, whereas the wild-type LPV replicated only in B-lymphoblastoid cells. Characterization of constructed recombinant viruses between wild-type LPV and LPV-76 showed that the mutation responsible for the extended host range of LPV-76 was within the PstI B fragment, which includes the VP-1 coding region. These data strongly suggest that the mutation of VP-1 altered the host range of LPV.

Biopsy specimens of the sural nerve obtained from 28 middle-aged and elderly diabetics suffering from neuropathy were studied morphometrically. Myelinated nerve fiber density, especially large fibers, was decreased, and the bimodal distribution of myelinated fiber diameter shifted to unimodal distribution containing only a small fiber peak and the mean diameter of myelinated fiber was decreased. An insulin-treated group and a group with severe retinopathy showed a prominent decrease of myelinated fiber density; the severity and duration of diabetes may be a factor in this decrease. Large unmyelinated nerve fibers were also decreased and the mean diameter of unmyelinated fibers was reduced. Three patients with prominent autonomic nervous system symptoms showed a significant reduction of total unmyelinated fibers. The linear correlation between the square root of the transverse axis cylinder area and the number of myelin lamellae was obscured, and the plots were towards two directions, axonal atrophy and remyelination in diabetes. The latter process tended to be dominant in the middle-aged patients, but the importance of these two processes was reversed with age. To discuss the morphological changes of the sural nerve in diabetic neuropathy, the influence of aging as well as the duration, severity and clinical symptoms should be considered.

A clinical trial of a new semi-synthetic podophyllotoxin, VP-16, was undertaken in patients with primary lung cancer; 56 of the 81 evaluable patients had small cell carcinoma, 9 adenocarcinoma, 8 epidermoid carcinoma, 7 large cell carcinoma, and 1 adenosquamous carcinoma. A dose of 200 mg/body/day orally for 5 consecutive days was administered every 3 to 4 weeks. Partial response (PR) was attained in 19 out of 81 (23%) and PR + MR was 35 out of 81 (43%). PR and minor response (MR) were seen as follows; small cell carcinoma, 17 PR (30%), 13 MR; epidermoid carcinoma, 2 PR (25%), 1 MR; adenocarcinoma, 1 MR; adenosquamous carcinoma, 1 MR. The dose-limiting factor was leukopenia, while thrombocytopenia was experienced in 2 cases. Clinical toxicities noted were anorexia, nausea, vomiting, stomatitis, diarrhea and alopecia, but these were well tolerated in all cases. The result indicated that VP-16 has considerable efficacy in small cell carcinoma and epidermoid carcinoma of the lung and hence its usefulness in combination chemotherapy was suggested.

A rare case of a neurinoma of the left facial nerve was investigated on the electron microscopic level. The tumor developed in a 27 years old man and induced a facial paresis by nerve compression. Ultrastructurally the tumour cells were characterized by markedly notched nuclei and a well developed organized cytoplasm with multiple organelles (lysosomes, Golgi's complex, mitochondria, rough endoplasmic reticulum). Fibroblasts were frequently observed in the interstice. So-called "long spacing collagen" was not detected in the interstice. The arrangement of the tumour cells represents the Antoni A type.

A new endo-cellulase component of carboxymethyl cellulase (CMCase) type (En-1) was obtained by gel filtration and column chromatography from Driselase, a commerical enzyme preparation from Irpex lacteus (Polyporus tulipiferae). The enzyme behaved as a single protein on polyacrylamide disc electrophoresis in the presence of sodium dodecyl sulfate (SDS). Its molecular weight was estimated to be 15,500 and it contained only 0.73% carbohydrate as glucose. The pattern of its amino acid composition is similar to those of other cellulases in respect of high contents of acidic amino acids, glycine, serine, and threonine. The cellulase was most active at pH 4.0 and was very stable in the pH range of 3.0 to 6.0, but was completely inactivated by heating at 70 degrees C for 10 min. A series of cellooligosacharides, including cellobiose, was formed by this enzyme from sodium carboxymethyl cellulose (CMC) as well as from water-insoluble celluloses. In the hydrolysis of CMC, the increase in the fluidity of the substrate was relatively large as compared with the simultaneous increase in reducing power. From this result and the pattern of hydrolysis products, En-1 was elucidated to be an endo-cellulase, and it showed the highest randomness among the cellulase components obtained so far from Irpex lacteus.

The study was carried out to confirm the effect of MDP-Lys (L 18) on the neutrophil number and function in the patients with lung cancer. The patients were enrolled only in case of leukopenia (equal or less than 3,000/mm3 after anticancer chemotherapy) and subcutaneously given 200 mcg of MDP-Lys (L 18) for 7 days. Mean leukocyte counts were found to be 3,900/mm3 and 5,500/mm3 one day and one week after MDP-Lys (L 18) treatment, respectively. The rate of "markedly effective" and "effective" was 53% (8/15). Chemiluminescence by zymosan showed a significant increase after MDP-Lys (L 18) treatment. However, no change of neutrophil function was observed in the tests of chemiluminescence by phorbol myristate acetate, superoxide (O2-) production, hydrogen peroxide (H2O2) production, chemotaxis, bacterial killing and opsonization. Transient fever was observed in 6 cases and eruption accompanied with one fever case. It was concluded that MDP-Lys (L 18) could prevent infection in cancer-bearing immunocompromised patients by increasing the neutrophil number and function.

To elucidate the mechanism of interferon (IFN) induction on virus infection, we constructed two types of plasmids by inserting a part of the cDNA of the Sendai virus into a simian virus 40-derived expression vector (pSV2-0). One, pSV2-PC, contained the P + C gene, which codes for the P and C proteins in overlapping reading frames, and the other, pSV2-C, contained only the C gene. After transfecting the plasmids into mammalian cells, we determined the IFN activity in the culture medium. We found that the level obtained with pSV2-PC was significantly positive but very low, whereas that obtained with pSV2-C was as high as or even higher than that observed in the culture medium after Sendai virus infection. By cleaving pSV2-C between the simian virus 40 promotor and the C gene or by inserting a stop codon within the C gene [pSV2-C(stop)], induction of IFN was greatly diminished. In Northern blot analyses of the transcripts obtained from the cells transfected with the plasmids with cDNA to the P + C gene as a probe, the transcript having the expected size was detected with both pSV2-C and pSV2-C(stop), whereas none was detected with cleaved pSV2-C or pSV2-0. The results indicate that both transcription and translation of the C gene seem to be required for IFN induction after Sendai virus infection.

Mouse class I antigens are the major targets of cytolytic T lymphocytes in both major histocompatibility complex (MHC)-restricted and allogeneic responses. Considerable evidence has recently accumulated demonstrating that MHC class I molecules encoded by genes whose alpha 1 and alpha 2 coding exons were interchanged are not recognized by T lymphocytes specific for parental class I products. Along with the loss of T-cell reactivity, there is a loss of recognition by some, but not all monoclonal antibodies. In this communication we report that the loss of reactivity by monoclonal antibodies is accompanied by the gain of new epitopes caused by the interaction of alpha 1 and alpha 2 domains. These epitopes are immunodominant. They are the major determinant recognized by polyclonal antisera raised by immunization with L cells transfected with exon-shuffled class I genes. Four new monoclonal antibodies have been produced which recognize at least two separate epitopes caused by the interaction of the alpha 1p and alpha 2d domains.

Infection of HTLV-1 during childhood may be the most probable cause of leukemogenesis of ATL. The possibility of mother to child transmission of HTLV-1 was studied. Our epidemiological investigation disclosed that almost all mothers of HTLV-1 carrier children were positive for anti-HTLV-1 antibody and children born from carrier mothers showed statistically higher positive rate for anti-HTLV-1 antibody than control groups. A large number of HTLV-1 positive lymphocytes were detected in the milk from carrier mother, but not in the cord blood from newborn babies delivered from carrier mothers. We inoculated the fresh milk collected from carrier mothers into the oral cavity of a common marmoset to prove the oral infection. The marmoset was found to be seroconverted and viral antigen expression was detected in short term cultures of its peripheral T lymphocytes. These results suggest that we can prevent the transmission of HTLV-1 by prohibiting the breast-fed [corrected] by carrier mother. We have so far followed up 55 children born from carrier mothers but fed with compound milk only. None of the children in this group became a carrier of HTLV-1, whereas breast-fed group was found to have higher incidence of sero-positivity for HTLV-1. Therefore the trial prevention of HTLV-1 transmission is now undertaken in Nagasaki district.

A case of glycogen-rich adenocarcinoma of the parotid gland of a 23 years old man was investigated ultrastructually. The cytoplasm of the tumour cells was abundantly filled with glycogen-rich particles. Among these particles well developed cytoplasmic organelles were observed, too. In addition, another tumour all type could be found, i.e. a tumour cell of basal cell origin with tonofibris in the cytoplasm, attached to the glycogen-rich tumour cell type by desmosomes.

We have utilized a group of MHC class I genes produced by in vitro recombination between Dp and Dd to study recognition of MHC class I molecules by cytolytic T cells (CTLs). Both polyclonal allo-specific and H-2-restricted CTLs require that alpha 1 and alpha 2 of the target class I molecule be derived from the same haplotype for efficient killing. By using T-cell lines we showed that within the bulk population there must exist a fraction of T cells which can recognize epitopes in alpha 1 or alpha 2. Critical residues for T-cell recognition have been identified using these chimeric genes.