Possible factors affecting the cholesterol nucleation time in human bile: A filtration study

This study examined the hypothesis that filtration through the MW 300 kD cut-off membrane (XM-300) may influence factors affecting the cholesterol nucleation time (the appearance time of cholesterol monohydrate crystal). Differences in biliary lipids, biliary protein, mucous glycoprotein and vesicular composition were examined before and after the XM-300 filtration in control and cholesterol gallstone patients. The nucleation time in the cholesterol gallstone patients was significantly faster than that in the control patients. However, the nucleation time in the gallstone patients was significantly prolonged following the XM-300 filtration resulting in a similar value to that of the control patients. No differences in concentrations of total protein, mucous glycoprotein or lipids composition were observed. The nucleation time did not correlate with the total lipid concentration, the concentrations of biliary mucous glycoprotein or total protein. The prolonged nucleation time of gallstone bile by the XM-300 filtration was primarily ascribed to the removal of vesicles, which was confirmed by gel chromatography. It was concluded that vesicles greater than MW 300 kD are primarily responsible for the rapid nucleation time.     

CD34 expression in endothelial cells of small hepatocellular carcinoma: Its correlation with tumour progression and angiographic findings

The angiogenic process plays an important role in tumour growth and metastasis during hepatocarcinogenesis, but it is still uncertain when the process begins during tumour formation. Forty-two small hepatocellular carcinomas (HCC) that measured either less than or equal to 2 cm in diameter were studied by comparing the histologic findings with the angiographic findings, and with immunohistochemical expression of endothelial marker QB-end/10 (QB), a new monoclonal antibody raised against CD34, in the sinusoidal wall. Twenty (91%) of 22 moderately or poorly differentiated HCC revealed a positive reaction for QB, while only eight (40%) of 20 well differentiated HCC demonstrated a positive reaction (P < 0.01). In the tumours showing a ‘nodule in nodule’ appearance, the less differentiated areas were more reactive for QB. Twenty-three (82%) of 28 QB positive tumours were hypervascular, while only three of 14 (21%) QB negative tumours were hypervascular (P < 0.01) by angiography. All six of the poorly differentiated and 13 (81%) of the 16 moderately differentiated tumours were hypervascular, while only seven (35%) of 20 well differentiated HCC were hypervascular (P < 0.01). These results indicate that as the tumour becomes less differentiated, the QB positive areas become wider and angiography demonstrates hypervascularity. We therefore speculate that the HCC sinusoids acquire the characteristics of capillary and precapillary blood vessels during de-differentiation from well to moderate, and thus the tumour begins to reveal hypervascularity on angiography. The above process may be correlated with the stepwise progression of HCC.     

Correlation between Dose and Tumor Response in the Radiotherapy of Lung Cancer of Various Histological Types

Correlation between dose and tumor response by cell types wasdetermined in 50 patients with lung cancer in order to predictthe possibility of further tumor regression. The TDF (time-dose-fractionation)concept was used as dose factor. The radiation source was a cobalt-60 -ray or linear accelerator10 MV X-ray. As a routine regime a fraction dose of 2 Gy fivetimes per week was given to 39 of the 50 patients, but a doseof 2 Gy three times per week or of 1.5 Gy five times per weekwas given to seven and four patients, respectively. Radiation response was the best in small cell carcinoma andbetter in adenocarcinoma than in squamous cell carcinoma, showinga tumor regression rate of 50% or more in 90%, 80% and 58% ofthe patients, respectively. The correlation between tumor regression rate and TDF valueswas good in squamous cell carcinoma (r=0.73) and small cellcarcinoma (r=- 0.72), but poor in adenocarcinoma (r=- 0.10).These results suggest that in squamous cell carcinoma improvementof tumor regression can be expected by increasing TDF values,and in adenocarcinoma and small cell carcinoma the optimal TDFvalues are about J00 and 60 to 80, respectively.     

Diagnosis of Early Gastric Cancer Seen as Less Malignant Endoscopically

Jn order to make the endoscopic diagnosis of early gastric cancermore accurate, we determined the endoscopic and clinicopathologicalcharacteristics of the 129 cases of early gastric cancer withless malignant appearance among the 978 cases of the diseasewith a solitary lesion detected at the National Cancer CenterHospital during the period between 1962 and 1981. Accordingto findings required to make a differential diagnosis, the endoscopicappearance of the 978 cases were divided into the followingfour groups: 170 cases of polypoid, 587 of ulcerative, 119 ofgastritis-like and 102 of advanced cancer-like. Among the fourgroups, the frequency of cases with less malignant appearancewas quite high in the gastritis-like group. The lesion in thisgroup was defined as the cancerous lesion which shows only superficialmucosal abnormality, not associated with any polypoid or ulcerativecomponents. Chronologically, it has been rapidly increasingin recent years. These two paradoxical phenomena in the gastritis-likegroup, that is, "high frequency of less malignant appearance"and "increase in number of cases" not only indicate the inadequacyof the conventional criteria for the recent cases but also showthat the gastritis-like malignancy is detectable. New additionalendoscopic criteria for the gastritis-like malignancy, for example,irregular margin of the shallow mucosal depression, disproportionof the mucosal granularity, irregularity on the erythematouschange and discoloration are essential in order to detect muchmore cases with less malignant appearance.     

"Flare" Followed by Successful Tamoxifen Therapy in Two Cases of Advanced Breast Cancer

An antiestrogen, tamoxifen, is an effective drug in the treatmentof advanced breast cancer. The drug is generally very well toleratedand serious side effects such as the so-called "flare in thetumor" have rarely been observed. We have had two patients withadvanced breast cancer who showed the "flare" soon after theinitiation of tamoxifen therapy, and both patients finally achievedpartial response to tamoxifen. It is important not to misinterpretthe "flare" as progressive disease during tamoxifen therapy.     

Comparison of Survival of Patients With Lung Cancer Between Elderly (greater double equals70) and Younger (70>) Age Groups

Results of radiotherapy for lung cancer in the elderly werecompared with those in younger patients. A total of 129 patientswere treated by radiation therapy with or without chemotherapy.Fifty-six patients (43.4%) were 70 years old or more (elderlygroup) at the time of treatment, and the remaining 73 patientswere below age 70 (younger group). Treatment results in the elderly group were nearly the sameas those in the younger group in all stages of the disease.Survival time was longer for patients with performance status(PS) of 0 to 2 than for those with PS 3 or 4 regardless of age(p < 0.05). The survival time of the elderly group was nearlythe same as that of the younger group for squamous cell carcinoma,but somewhat shorter for adenocarcinoma although the differencewas not statistically significant. There was no difference insurvival between the two groups when they were treated by combinedradiation therapy and chemotherapy. Our results suggest thatelderly patients can be treated as safely as younger patientsby radiotherapy alone or combined radiation therapy and chemotherapy.     

Colony-Stimulating Factor Producing Carcinoma of the Gallbladder

A patient with an anaplastic carcinoma of the gallbladder accompaniedby marked neutrophilia was found to have high colony-stimulatingfactor (CSF) activity in the urine and serum. The supernatantof the cultured tumor cells (6th passage) showed high and specificCSF activity. These specimens induced the formation of granulocytecolonies, macrophage colonies or granulocyte macrophage mixedcolonies by both human and C57BL mouse bone marrow cells insoft agar. These results suggest that this tumor is a human granulocyte-macrophage(GM)-CSF producing tumor.     

Enzymatic semisynthesis of [Leu B30] insulin

Experimental conditions for the preparation of [Leu^B30] insulin by coupling of des-Ala^B30 insulin with Leu-OBu^t were determined using Achromobacter protease I and trypsin as catalysts. Successful coupling required a large excess of the amine component (0.8 M), a high concentration of organic cosolvent (35–50%) and neutral pH of the reaction mixture. The coupling yield of Achromobacter protease I after 24 h at 37°C was almost the same or a little higher than that at 25°C. With trypsin, the coupling yield at 37°C after 24 h was considerably lower than at 25°C. This was partly ascribed to the difference in concentration of organic cosolvent at 37°C and 25°C; 35% and 50%, respectively, or possibly of enzyme stability at these temperatures. The maximum product yield was about 90% with both enzymes under optimal conditions. A preparative scale experiment was performed with Achromobacter protease I; the yield of [Leu^B30] insulin was 51% using porcine insulin as the starting material. This semisynthetic insulin was identified by HPLC and amino acid analysis. No difference was observed in CD spectra between [Leu^B30] insulin and human insulin.     

Hemoglobin FHouston: A Fetal Variant

A fetal hemoglobin variant, designated hemoglobin F_Houston, was found inthe cord blood sample of a healthy, term Negro infant. The variant, comprising about 15 per cent of the total cord blood hemoglobin, diminished concomitantly with hemoglobin F, and it was barely detectable in the blood whenthe infant was 4 months old. The hemolysates of the parents and two siblingsresolved into the usual adult pattern, but a trace amount of a fraction similarto hemoglobin F_Houston was present in the father’s hemolysates and not in themother’s.

The ultraviolet absorption spectrum indicates that hemoglobin F_HOUSTON contains polypeptide chains, and immunologic studies reveal the presence ofboth and chains. In hybridization tests the alteration appears in the chain.

Peptide chromatograms of hemoglobin F_Houston indicated the presence of and chains, but failed to reveal an abnormality. Amino acid analyses suggestthat there may be a substitution of an alanyl for a glutamyl residue.

Submitted on August 3, 1965 Accepted on October 12, 1965     

Ovarian mixed germ cell tumor composed of dysgerminoma, endodermal sinus tumor, choriocarcinoma and mature teratoma in a 44-year-old woman: Case report and literature review

A case of ovarian mixed germ cell tumor In a 44-year-old woman was examined. The tumor was well circumscribed, measured 15 times 11 times 10cm and appeared solid and partly cystic on the cut surface. Light microscopic examinations revealed that the tumor was composed of four different neoplastic germ cell elements, Intermingled with each other. They are: (i) choriocarcinoma, immunohistochemically positive for human placental lactogen (hPL) and human chorionic gonadotropin (hCG); (ii) dysgerminoma, positive for placental alkaline phosphatase; (iii) endodermal sinus tumor positive for α-fetoproteln (AFP); and (lv) mature teratoma. Among these histological types, dysgermlnoma occupied more than 50% of the neoplasm. The patient was diagnosed as a stage la ovarian mixed germ cell tumor and was subsequently treated with chemotherapy. A second-look laparotomy after completion of chemotherapy revealed no residual tumors in the abdomen and the patient Is alive and well 15 months after operation. This Is the fourth reported case of ovarian mixed germ cell tumor arising In patients over 40 years old.