An autopsied case of primary intracranial squamous cell carcinoma (PISCC) is reported, and 25 previously reported cases of PISCC, followed by the Garcia's criteria, are reviewed. A 72-year-old female was admitted to our service with chief complaints of headache and nausea on March 30, 1988. She had no neurological deficits on admission. However, CT examination revealed a round mass lesion in the left hypothalamus with dislocation of the brain stem. The cerebrospinal fluid (CSF) examination showed squamous cell carcinoma cytologically, and slightly higher levels of beta-HCG (13.0 ng/ml) and CEA (14.2 ng/ml). Because of progressive worsening in the level of her consciousness, total removal of a suprasellar tumor was performed on April 19, 1988. Gross appearance of the tumor was yellowish, soft and encapsulated. Histologically, it was squamous cell carcinoma. She did well for several days after the operation, then deteriorated. Finally she expired because of dissemination of the carcinoma on May 14, 1988. Postmortem examination revealed a large mass of squamous cell carcinoma in her right cerebellopontine angle. Except for that in the brain, no cancer was found in her body. Immunohistological study of the tumor specimen demonstrated positive for HCG in some of the large-sized neoplastic cells. Twenty-six cases of PISCC have been reported previously, so far. However, 21 cases out of the 26 PISCC were thought to have originated from intracranial epidermoid, one from the dermoid and the other one from craniopharyngioma. In the other three cases of PISCC, including the present case, the origin of the tumor was not able to be identified.(ABSTRACT TRUNCATED AT 250 WORDS)

Embryoglycan is a high molecular weight glycopeptide, found abundantly in the cell surface of F9, stem cell clone derived from mouse teratocarcinoma. Many differentiation-associated antigens and receptors for lectins have been shown to be carried by embryoglycan. Furthermore, antibodies reacting with embryoglycan have been detected in the sera of patients with ovarian germ cell tumor. We investigated anti-embryoglycan antibodies in the sera of patients with uterine cervical cancer, considering the possibility of the appearance of embryoglycan-like antigen accompanied by malignant changes in the uterine cervix. Reaction between the patients' sera and embryoglycan (or F9 cells) was assayed by Farr's assay and an indirect immunofluorescence method. Among the patients with uterine cervical cancer (squamous cell carcinoma), 16 of 61 cases (26%) were positive in invasive cases, whereas early cases (14 cases) were all negative. Cases of benign ovarian tumor (23 cases), uterine myoma (25 cases) and 50 normal volunteers were all negative. The antigenic determinant of embryoglycan was found to be alpha-galactosyl residue since alpha-galactosidase-treated embryoglycan lost the activity to bind these antisera. However, the antigenic structure of alpha-galactosyl residue was shown to be distinct from the antigenic determinant of erythrocytes blood type B, but to some degree cross reacted with it, in an absorption test. These results indicate that an unusual alpha-galactosyl residue carried by embryoglycan is expressed on at least some uterine cervical cancer cells. Furthermore the immune system of patients produces antibodies reacting with the alpha-galactosyl residue of embryoglycan. It would be possible to use this method in monitoring patients' specific immune response.

The 6-day subrenal capsule assay for determining chemotherapeutic sensitivities of brain tumors was studied. Rat glioma 9L and ACNU resistant 9L-2 were transplanted under the renal capsule of normal immunocompetent WKA rats for laboratory investigation. Evaluation of implanted tumor growth till 12 days was performed. The effects of chemotherapeutic agents administered intravenously were evaluated by measuring the growth rate of implanted tumor specimens. The results obtained from SRC were compared with the results from colony forming assay. Both were correlated to each other. On the other hand, histological investigation revealed that implanted human tumor cells had been diminished and implanted tumor was replaced by immunoreactive cells from the host in many cases. These results threw doubt on a reliability of SRC. To avoid this immunoreaction, cyclophosphamide was injected as immunosuppressive agent subcutaneously 24 hours before implantation. In such cases, the growth rates of implanted tumors were increased and histologically the implanted tumor cells existed for 6 days after implantation. Twenty-three malignant brain tumors (malignant astrocytomas 16, metastatic tumors 5, malignant lymphoma 2) were obtained as surgical specimens. Evaluable assay rate of our study were 89%. 15 patients with malignant astrocytomas were studied about correlation between the sensitivities of ACNU and post-operative clinical courses. Overall clinical correlation of 15 cases of malignant astrocytomas was 47%. These results from subrenal capsule assay are not seemed to be beneficial for clinical use. Immunoreactive response when using immunocompetent rats must be solved in future.

It has been reported that cochlea is the lesion of hearing loss in FSH. However, the details of this lesion are not yet sufficiently known. We performed detailed audiologic studies to examine hearing loss in FSH. We experienced 2 cases of FSH associated with hearing loss. Case 1 was a girl aged 5 years, and case 2 a boy aged 15 years. Clinical findings, EMG and muscle biopsy gave a diagnosis of FSH in both cases. Hearing loss was evaluated by pure tone audiography, speech audiography, tympanometry, stapedial reflex, auditory brain stem response and electrocochleography. In case 1, pure tone audiograms revealed high tone hearing loss without an A-B gap. On speech audiography, the maximum articulation score was 100% and proved normal. The tympanogram was type A. Stapedial reflex was normal bilaterally. The threshold of the 5th wave increased markedly on auditory brain stem response. On electrocochleography, the H-curve of the input-output function curves of action potential was recorded, but the L-curve was absent. There were no complaints of hearing loss in case 2, but pure tone audiograms revealed high-tone hearing loss without an A-B gap. The tympanogram was type A. Stapedial reflex was normal bilaterally. On auditory brain stem response, threshold was increased and latency was prolonged when intensity was lowered. The electrocochleograms were almost normal. It has been reported that, in electrocochleography, the L-curve represents the function of the outer hair cells and the H-curve that of the inner hair cells. The electrocochleograms in case 1 showed damage to the outer hair cells.(ABSTRACT TRUNCATED AT 250 WORDS)

We used the human monocyte/macrophage-like tumor cell line U937 to examine whether tumor necrosis factor-alpha (TNF-alpha) induces differentiation of monocyte/macrophage progenitors. Incubation of these cells with recombinant human tumor necrosis factor-alpha (rhTNF-alpha) resulted in an increase in Fc rosette formation by the cells. RhTNF-alpha increased the rosette formation in dose- and culture time-dependent manners. And the highest Fc rosette formation was observed in culture medium supplemented with 10% serum. However, U937 cell growth was not inhibited by rhTNF-alpha. The stimulatory effect of rhTNF-alpha was completely inhibited when the factor and indomethacin (10(-6) M) were added simultaneously to the cells. Also, rhTNF-alpha increased NBT reducing activity of the cells. Additionally, rhTNF-alpha-treated U937 cells produced interleukin-1 in the cell density- and culture time-dependent fashions. These results demonstrate that rhTNF-alpha is a potent inducer of the differentiation of the monocyte/macrophage-like tumor cell line U937.

Methylcellulose culture study revealed that the potency of recombinant granulocyte-colony stimulating factor (G-CSF) or granulocyte/macrophage (GM)-CSF to support the growth of purified target cell populations from peripheral blood of patients undergoing peripheral blood stem cell (PBSC) autotransplantation was inferior to that of PHA-stimulated lymphocyte conditioned medium (PHA-LCM) or interleukin-3 (IL-3). In liquid-suspension limiting dilution assay the cells responded directly to IL-3 by proliferation with single-hit kinetics. Hence, optimal culture for PBSC should include the use of PHA-LCM or IL-3. Further study disclosed a linear relationship between the number of CFU-GM infused into the patients and days required to achieve a granulocyte count above 0.5 x 10(9)/l.

The cellular DNA content was measured with flow cytometry from paraffin-embedded material in 329 patients and metastatic tumors of the liver from the rectum in 11 patients. The classification of the DNA ploidy pattern is as follows: A stem cell peak with a DNA index of 0.9-1.1 is defined as DNA diploid tumor and DNA aneuploid tumor is that with a DNA index greater than or equal to 1.1. There was a good correlation of DNA indices (r = 0.997) obtained from flesh and corresponding paraffin-embedded specimens. It is concluded that accurate determination of DNA index from paraffin-embedded materials is possible in the majority of cases. DNA ploidy of primary tumor cells correlated with clinicopathological findings such as lymphatic invasion, vascular invasion, lymph node metastasis and hepatic metastasis (p less than 0.01), but did not correlate with extramural carcinoma invasion. The cumulative survival rate (Kaplan-Meier) of curatively resected rectal carcinomas was worse in DNA aneuploid than in DNA diploid tumors (p less than 0.01). These observation showed that the determination of DNA ploidy in rectal carcinomas may prove to be of prognostic value.

This report elucidates our experiences on acoustic neuroma surgery, in which auditory function was lost postoperatively, although conservation of hearing had been intended preoperatively. Five ears from four patients (two ears: unilateral, three ears from bilateral acoustic neuromas) were operated on via standard retromastoid route, with monitoring of auditory evoked potentials. Abolition of ABR occurred when surgical manipulations were performed within the internal auditory canal. Pulling tumor tissue away from the cochlea toward the brain stem has proved to be a hazardous procedure. Recognizing the condition of tumor tissue within the internal auditory canal is prerequisite for hearing preservation. For this purpose, MRI is very useful because tumor tissue within the internal auditory canal can be clearly visualized. The preoperative criteria in selecting candidates for hearing preservation operations should be more strict because most acoustic neuromas with a diameter of more than 10mm cannot be resected without causing loss of hearing, and, even in such small tumors, the cochlear nerves are infiltrated by tumor cells. Most ABR changes during operations seem to be explicable from avulsion of the cochlear nerve fibers and/or the internal auditory artery from the fundus of the internal auditory canal-the tractus spiralis foraminosus. Postoperative recordings of ABR indicated that progression of degeneration of the cochlear nerve fibers occurred after surgery. This phenomenon may explain postoperative delayed hearing loss observed clinically.

The chemical structure and immunomodulating activities of the cell wall peptidoglycans isolated from Actinobacillus actinomycetemcomitans were investigated. Peptidoglycans were isolated from A. actinomycetemcomitans strains Y4 and ATCC 29522 by boiling in 4% sodium dodecyl sulfate and by digestion with pronase, trypsin and alpha-amylase. Analysis of amino acids and amino sugars of the peptidoglycans revealed that glucosamine, muramic acid, D-glutamic acid, D-alanine, and meso-2, 6-diaminopimelic acid (A2pm) were the principal components. Serine and glycine were not found. Dinitrophenylation method revealed that about half of A2pm residue had a free aminogroup, and analysis by hydrazinolysis showed that a small part of alanine and A2pm located at the C-terminal. The above results indicate that one of the amino groups of A2pm residue at one strand of the stem peptide subunit crosslinked to the carboxyl group of alanine of the neighboring strand. It was thus revealed that the peptidoglycans of A. actinomycetemcomitans belonged to the Al gamma type of the classification by Schleifer and Kandler. Peptidoglycans isolated from A. actinomycetemcmitans strain Y4 and ATCC 29522 were found to be definitely adjuvant-active in induction of delayed type hypersensitivity against ovalbumin when administered to guinea pigs as water-in oil emulsion and stimulation of increase serum antibody levels was found in both peptidoglycans. Regarding mitogenicity on splenocytes of BALB/c and BALB/c nu/nu mice, peptidoglycans from two strains of A. actinomycetemcomitans were markedly enhanced the uptake [3H] thymidine in dose of 10 micrograms/10(5) cells, however thymocytes were not reactive. Stimulation effects on peritoneal macrophages from a guinea pig to incorporation of 14C-glucosamin were not exhibited on addition of 100 micrograms of both peptidoglycans. These findings indicate that peptidoglycan of A. actinomycetemcomitans might eventually be responsible for destruction of periodontal tissue by host mediated activities.

The developmental potential of various teratocarcinomas of different origins was examined by making chimeras with mouse embryos. Of 7 teratocarcinoma lines examined, only 2 were found to contain stem cells having the ability to form live-born chimeras; one was experimentally induced OTTBALB-2 and the other was spontaneously occurring STT-3. The latter showed remarkable ability to colonize mid-gestational fetuses and adults. This result not only demonstrates that EC cells of male primordial germ cells have the ability to form viable chimeras but also suggest that this kind of tumor is a useful source of EC cells to make chimeras. The advantage of using pluripotent cell lines such as EC cells or embryonic stem (ES) cells as a vector for introducing foreign genes into mouse embryos was discussed in relation to the study on gene function and on gene regulation during development.

Mast cells are a progeny of the multipotential hematopoietic stem cell. Most of progenies of the stem cell complete their differentiation within the bone marrow, but precursors of mast cells leave the bone marrow, migrate in blood, and invade into tissues. After the invasion, precursors proliferate and differentiate into mast cells. An appreciable proportion of mast cells retain proliferative potential after differentiation, and even after degranulation, some mast cells can proliferate and recover the original morphology. Proliferation of mast cells are regulated by both T cell-derived factors (i.e., IL-3 and IL-4) and fibroblast-derived factor(s). Mice of either W/Wv or Sl/Sld genotype lack mast cells, but mast cells do develop when bone marrow cells of W/Wv or Sl/Sld mice were cultured in the presence of T cell-derived factors. Mast cells derived from W/Wv mice cannot respond fibroblast-derived factor(s) and fibroblasts derived from Sl/Sld mice cannot support mast cells of normal mouse origin. Phenotypes of mast cells are determined by the environment in which the mast cells differentiated. However, when mast cells are transplanted into a new environment which is different from the original one, the mast cells acquire the phenotype which are dependent on the second environment.

Certain uremic metabolites are recognized to have high affinity to serum protein and some of them have been identified as hippuric acid (HA), quinolinic acid (QA) and indoxyl sulfate (IS). Cell toxicity and effect on renal function of these substances were examined by means of erythroid colony formation, lymphocyte blast formation and isolated perfused rat kidney. These substances inhibited the binding of diphenylhydantoin to albumin, depending on the concentration of the substances. At the same concentration of 10 mg/dl, IS was most potent and QA was the second. QA and IS suppressed the erythroid colony formation, depending on the concentration of QA and IS. On the other hand, HA had no suppressive effect even at the higher concentration. The suppressive effect of QA and IS were attenuated by increasing erythropoietin concentration. QA and IS had strong suppressive effect of lymphocyte blast formation and interleukin 2 production at the concentration of uremic serum. However, they did not suppress the increase of intracellular calcium concentration of lymphocytes after stimulation by mitogen. This might indicate the possibility that these substances act not only on cell surface but on intracellular protein. HA and IS inhibited para-aminohippurate secretion and QA suppressed tubular reabsorption of sodium in isolated perfused rat kidney. These results show that the uremic protein binding inhibitors may influence renal regulation of fluid and electrolyte homeostasis. It is concluded that some of the protein binding inhibitors have toxic effects on cell function of various tissues and play a role in pathophysiology of uremia.

Results from phase I/II studies of Granulocyte-colony stimulating factor (G-CSF) for bone marrow transplantation were reported. G-CSF in 200-800 micrograms/m2 was administered from day 3 or 5 daily for 14 days. A very rapid recovery of granulocytes was observed in most cases. Stem cell exhaustion was considered not serious. Stimulation on myeloid leukemic cells was observed in vitro tests, but relapse was observed in only 2 out of 17 myeloid leukemia patients. There was no marked difference in the grade and incidence of GVHD from historical control patients. As side effects, 3 cases of bone pain and 2 of skin rash were observed. All these symptoms were slight, reversible and tolerated for further administration. As a whole, courses of BMT with G-CSF seemed very smooth and uneventful with very rapid and steady recovery of granulocytes. G-CSF seemed promising for bone marrow transplantation in which the severe granulocytopenic stage is inevitable and normal stem cells without contact with cytostatic agents are procured.

The achievement of complete response in cancer chemotherapy is most important for prolongation of survival period and improvement of quality in patient's life. Because of the above, chemosensitivity-oriented chemotherapy is required. Human tumor clonogenic assay (HTCA) and subrenal capsule assay (SRCA) provide relatively precise in vitro and in vivo methods for determining the chemosensitivity of individual cancer patients. The success rates are 52% in HTCA and 77% in SRCA. HTCA has an initiative for an evaluation using fluid samples and SRCA can be used against lymphomas and sarcomas which show low success rates in HTCA. Until now both methods show high predictivity of drug response in clinical situation and especially high true positive rate in SRCA is striking.

It has been suggested that one of most important parameters for predicting individual tumor treatment response in both radiotherapy and chemotherapy is intrinsic cellular sensitivity of tumor stem cells. The rationale behind the hypothesis and recent progress in the method of the assay were discussed in this review article. Since there have been no clinical data for the usefulness of the radiobiological approaches in predicting the clinical outcomes, multivariate analysis of the factors affecting prognosis seems most important to determine independent prognostic indicators. Addition of the assay data in the clinical testing may significantly improve the accuracy of the prediction if they are independent of known clinical prognosticators. Close cooperation between radiobiologists and therapeutic radiologists is certainly required for this goal.

The effects of recombinant human interferon (IFN) alpha-2b and gamma on the bone marrow megakaryocyte progenitors (CFU-Meg) were compared between eight patients in the chronic phase of Ph1-positive chronic myelocytic leukemia (CML) and five hematologically normal patients. CFU-Meg was assayed in plasma clot culture added with phytohemagglutinin-stimulated leukocyte-conditioned medium as a source of colony stimulating activity. The average count of CFU-Meg colonies formed from the bone marrow of CML patients was 5.5 times that of normal controls. Spontaneous CFU-Meg colonies were grown in seven of eight CML patients, but in none of five controls. Colony formation by CFU-Meg in CML as well as normal bone marrow was suppressed by the two preparations of IFN in a dose dependent fashion. Their suppressive influence on colonies from CFU-Meg was comparable between CML and normal bone marrow at lower concentrations, but was less marked for CML than normal bone marrow at higher concentrations. The formation of CFU-Meg colonies from CML bone marrow was more severely suppressed by IFN-gamma than IFN-alpha-2b. Depletion of either T lymphocytes or adherent cells from the CML bone marrow cells diminished the suppressive effects of IFN-gamma, but had no influence on the effects of IFN-alpha-2b.