Electron microscopic study of muscle spindle in human interarytenoid muscle

Using transmission electron microscopy, the fine structure of the muscle spindle in the interarytenoid muscle was studied. The specimen was made from a fresh adult male larynx which had been surgically removed. The muscle spindle showed the following characteristic features: (1) the capsule was thin, with only a small number of layers of capsular sheet cells; (2) the periaxial space was narrow and there were abundant collagenous fibrils; (3) the sensory endings consisted of irregularly coiled terminal axons with varicose swellings, and some endings penetrated the sarcoplasm; (4) one nuclear chain fiber terminated on the capsule, while the other branched into two bundles; and (5) special sarcoplasmic inclusions, possibly related to the sensory endings, were also observed. These findings suggest that the muscle spindle in the interarytenoid muscle is not only a very sensitive stretch receptor, but also a pressure receptor.     

Clinical Course and Autopsy Findings of a Patient with Clival Chordoma Who Underwent Multiple Surgeries and Radiation during a 10-Year Period.

The management of clival chordoma remains problematic. We present the case of a 48-year-old woman with clival chordoma who underwent multiple surgeries and radiation therapy, including gamma knife stereotactic radiosurgery (GK-SRS), during a 10-year clinical course. The tumor was initially removed by gross total resection via the trans-sphenoidal approach, followed by external linac radiation therapy. The tumor recurred at the clivus 5 years after the initial operation. After repeated trans-sphenoidal removal of recurrent tumors, she twice underwent GK-SRS for a tumor remnant adjacent to the brainstem. Although this part of the tumor was controlled by GK-SRS, there was further tumor extension toward the sphenoid and maxillary sinuses. Ultimately, lower cranial nerve dysfunction developed due to tumor extension into the lower part of the clivus and the patient died of respiratory failure. Autopsy revealed the tumor to extend from the lower clivus to the bilateral middle fossae. The lower part of the tumor extended to the nasal cavity and to the posterior wall of the pharynx, resulting in compression of the upper pharyngeal region. The tumor around the jugular foramen compressed the lower cranial nerves bilaterally. Tumor cells did not, however, invade the intradural space microscopically. Although chordoma is not biologically malignant, this tumor can show massive extension with destruction of bony structures and extracranial invasion of connective tissues. Therefore, the optimal treatment strategy is to remove the tumor mass as extensively as possible, including normal bony structures and connective tissues surrounding the tumor, using skull base surgical techniques.     

Potentiation of vincristine and actinomycin D by a new synthetic imidazole anti-tumor agent YM534 active against human cancer cells and multidrug-resistant cells

Ethyl 6-p-5-(l-imidazolyl) pentyloxyphenoxy-2, 2-dimethylhexanoate hydrochloride (YM534) is a new synthetic anti-tumor compound. Combinations of YM534 with other anti-cancer agents were examined to ascertain whether YM534 potentiated other anti-cancer agents against the KB cell line and its multidrug-resistant counterpart, VJ-300. YM534 potentiated the cytotoxic action of vincristine and actinomycin D about 2-fold against KB cells, but not those of daunomycin and adriamycin. By contrast, YM534 only slightly reversed drug-resistance to adriamycin and daunomycin in VJ-300 while it reversed 5-fold vincristine resistance and 60-fold actinomycin D resistance in VJ-300. The reversal effect of YM534 on actinomycin D and vincristine-resistance in VJ-300 cells appeared to be due to enhanced accumulation of [3H] actinomycin D and [3H] vincristine in VJ-300 cells by YM534. YM534 inhibited efflux of actinomycin D and vincristine from VJ-300 cells, and it also enhanced cellular uptake of these anti-cancer agents. YM534 enhanced cellular accumulation of both actinomycin D and vincristine in the sensitive KB cells. YM534 is thus a unique anti-cancer agent since combinations of other anti-cancer agents with YM534 are expected to augment anti-tumor activity of them. By contrast, YM212, a carboxy analog of YM534, had much less activity to potentiate vincristine and actinomycin D). YM534 at 100-1000 microM almost completely inhibited the photoaffinity labeling of [3H] azidopine to the 170-kD P-glycoprotein of VJ-300 cell membranes, but YM212 showed much less inhibitory action on the photoaffinity labeling. YM534 could also inhibit the photoaffinity labeling of deglycosylated P-glycoprotein.     

The role of glutathione on placental amino acid transport (using microvillous membrane vesicles)

To elucidate the role of glutathione (GSH) on placental amino acid transport, we investigated L-lysine transport using microvillous membrane vesicles prepared from full term human placenta. 1. The transport of L-lysine into microvillous membrane vesicles was not affected by glutathione. 2. The transport of L-lysine into microvillous membrane vesicles was inhibited by inorganic mercury (Hg2+), and 0.1mM Hg2+ inhibited 34% of this transport and 1mM Hg2+ inhibited 50%. 3. The transport of L-lysine inhibited by Hg2+ was almost completely restored when glutathione was added simultaneously. These results indicated that glutathione defended the inhibitory action of inorganic mercury on L-lysine transport across microvillous membrane.     

Growth fractions of transitional cell carcinomas of the bladder defined by the monoclonal antibody Ki-67

We used an immunohistochemical technique with the monoclonal antibody Ki-67, which recognizes nuclear antigen expressed in proliferating cells to determine the growth fractions of 5 normal mucosa specimens and 55 transitional cell carcinomas of the bladder. Normal mucosa had a mean value of 0.37 +/- 0.35% cells positive for Ki-67, whereas 9 histological grade 1 tumors showed 2.2 +/- 1.5%, 31 grade 2 tumors averaged 10.1 +/- 7.5% and 15 grade 3 tumors yielded 19.5 +/- 9.0%. These values were significantly different from each other (p less than 0.01), with Ki-67 indexes for grade 2 varying from 0.3 to 24.6%. Nonpapillary tumors had significantly higher indexes than papillary tumors (20.1 +/- 8.0 versus 6.7 +/- 5.9, p less than 0.01). The Ki-67 indexes were 4.6 +/- 4.5% for stage Ta (20 cases), 7.8 +/- 4.7% for stage T1 (14) and 20.2 +/- 7.8% for stages equal to or higher than T2 (21). Significant differences were noted between stages Ta and T1 (p less than 0.05) and between stages T1 and T2 or greater (p less than 0.01). Tumors with muscle layer invasion often showed more than 15% Ki-67 positive cells. Our results imply that Ki-67 indexes not only provide objective information to determine a malignant potential but also help to select the treatment.     

The effect of donor specific blood transfusion (DST) on graft survival--intermittent coverage of cyclophosphamide

Donor specific blood transfusion (DST), given prior to living related kidney transplantation has resulted in significant improvement in graft survival. This improvement, however, has been accomplished with a high rate of adverse sensitization against the donor. In an attempt to reduce the incidence of sensitization, we have employed DST with intermittent coverage of cyclophosphamide. A comparative study was done between 2 methods of DST with or without the coverage of immunosuppressant for prospective kidney transplant recipients from living related donors. In addition, the beneficial effect of DST on graft survival was evaluated in our recent series of living related transplantation using cyclosporine A (CsA) as postoperative immunosuppression. Twenty-nine prospective kidney transplant patients received 200 ml of fresh whole blood 3 times at 2 week intervals from HLA one-haploidentical living related donors. The first 13 patients received DST alone, while the remaining 16 were given cyclophosphamide (CPM 1.5 mg/kg/day) for 3 days prior to each DST. In patients with CPM coverage, 6.3% (1 of 16) developed positive T-warm antibody against donor and 15% of patients (2 of 13) with DST alone developed it. Like-wise 19% (3 of 16) of the former and 38% (5 of 13) of the latter became positive B-warm crossmatch. The difference in sensitization rates between these 2 groups was not statistically significant. Nineteen patients receiving DST were compared to 21 non-DST patients in incidence of acute rejection, graft function and graft survival with the same immunosuppressive regimen, such as CsA, prednisolone, and mizoribine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endothelium-dependent and -independent mechanisms of action of acetylcholine in monkey and dog isolated arteries

In helical strips of monkey coronary and mesenteric arteries and dog mesenteric arteries partially contracted with prostaglandin (PG)F2 alpha, the mechanism of action of acetylcholine (ACh) has been analyzed by the use of pharmacological antagonists and by the endothelium-derived relaxing factor (EDRF) bioassay and the 6-keto PGF1 alpha radioimmunoassay. In conclusion, ACh releases vasodilator substance(s) from endothelium (EDRF) and also PGs from subendothelial tissues. Vasoconstrictor PGs appear to counteract the dilator action of EDRF in monkey coronary arteries, whereas vasodilator PG, possibly PGI2, appears to facilitate the relaxation caused by EDRF in monkey and dog mesenteric arteries.     

Intraperitoneal high-dose cisplatinum chemotherapy (CDDP-ip) in patients with carcinomatous peritonitis

Immediately after CDDP-ip, the level of free Pt in ascites reached nearly 100 micrograms/ml, and the AUC (area under the curve) for ascites was 20-140 times greater than that for serum. The free Pt in serum following CDDP-ip administration was detected for several hours, and interestingly, the AUC for serum after ip therapy was 0.4-2.2 times greater than that after iv therapy. As a result, free Pt was found to act on cancer cells in the abdominal cavity directly at a high concentration. At the same time, the possibility of an antitumor effect from the vascular side of the tumor was also suggested. On the other hand, cases of ovarian cancer had various levels of peritoneal clearance (CLp), which depended on the severity of their carcinomatous peritonitis. The CLp had a great influence on the peak plasma concentration and on the AUC of free Pt in serum. In particular, the peak plasma concentration produced by CDDP-ip was 40-80% of the plasma concentration produced by CDDP-iv. These findings indicate that high-dose CDDP-ip is possibly effective and useful for advanced ovarian cancer, producing only very mild side effects.     

Cholinergic neurons contain Calbindin-D28k in the monkey medial septal nucleus and nucleus of the diagonal band: an immunocytochemical study

The distribution patterns of choline acetyltransferase (CAT), as a marker for cholinergic neurons, and Calbindin-D_28k (CaBP) immunoreactivities in the forebrain basal ganglia of the Japanese monkeyMacaca fuscata were compared. Similar distribution patterns of CAT and CaBP immunoreactivities were found in the medial septal nucleus (MS) and the nucleus of the diagonal band of Broca (DBB). Double-labeling fluorescence immunocytochemistry revealed that most, but not all, cholinergic neurons were CaBP-immunoreactive in the MS and DBB. The results suggest that CaBP may play a role in the septohippocampal cholinergic neuron system of the monkey.